Main Page/SlicerCommunity/2018

From Slicer Wiki
Revision as of 17:35, 12 October 2018 by JChris.FillionR (talk | contribs) (Created page with "=2018= ==Simple and Robust Referencing System Enables Identification of Dissolved-phase xenon Spectral Frequencies== {|width="100%" | '''Publication:''' [http://www.ncbi.nlm....")
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to: navigation, search
Home < Main Page < SlicerCommunity < 2018



Simple and Robust Referencing System Enables Identification of Dissolved-phase xenon Spectral Frequencies

Publication: Magn Reson Med. 2018 Aug;80(2):431-41. PMID: 29266425

Authors: Antonacci MA, Zhang L, Burant A, McCallister D, Branca RT.

Institution: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, NC, USA.


To assess the effect of macroscopic susceptibility gradients on the gas-phase referenced dissolved-phase 129 Xe (DPXe) chemical shift (CS) and to establish the robustness of a water-based referencing system for in vivo DPXe spectra.

METHODS: Frequency shifts induced by spatially varying magnetic susceptibility are calculated by finite-element analysis for the human head and chest. Their effect on traditional gas-phase referenced DPXe CS is then assessed theoretically and experimentally. A water-based referencing system for the DPXe resonances that uses the local water protons as reference is proposed and demonstrated in vivo in rats.

RESULTS: Across the human brain, macroscopic susceptibility gradients can induce an apparent variation in the DPXe CS of up to 2.5 ppm. An additional frequency shift as large as 6.5 ppm can exist between DPXe and gas-phase resonances. By using nearby water protons as reference for the DPXe CS, the effect of macroscopic susceptibility gradients is eliminated and consistent CS values are obtained in vivo, regardless of shimming conditions, region of interest analyzed, animal orientation, or lung inflation. Combining in vitro and in vivo spectroscopic measurements finally enables confident assignment of some of the DPXe peaks observed in vivo.

CONCLUSION: To use hyperpolarized xenon as a biological probe in tissues, the DPXe CS in specific organs/tissues must be reliably measured. When the gas-phase is used as reference, variable CS values are obtained for DPXe resonances. Reliable peak assignments in DPXe spectra can be obtained by using local water protons as reference.

"Each region was then assembled into a standard tessellation language mesh using 3D Slicer."

Diffusion Weighted And Dynamic Contrast Enhanced MRI as an Imaging Biomarker for Stereotactic Ablative Body Radiotherapy (SABR) of Primary Renal Cell Carcinoma

Publication: PLoS One. 2018 Aug 16;13(8):e0202387. PMID: 30114235 | PDF

Authors: Reynolds HM, Parameswaran BK, Finnegan ME, Roettger D, Lau E, Kron T, Shaw M, Chander S, Siva S.

Institution: Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Abstract: PURPOSE: To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI.

METHODS: Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman's rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT.

RESULTS: Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation.

CONCLUSION: DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.

Baseline ADC map with tumour contour in red for patient 3 and associated histogram showing the frequency of ADC values in each MRI scan. ADC maps were read into 3D Slicer software and the tumour volume contoured directly onto ADC map image slices by an experienced radiologist.

Toward a Real-time System for Temporal Enhanced Ultrasound-guided Prostate Biopsy

Publication: Int J Comput Assist Radiol Surg. 2018 Aug;13(8):1201-1209. PMID: 29589258

Authors: Azizi S, Van Woudenberg N, Sojoudi S, Li M, Xu S, Abu Anas EM, Yan P, Tahmasebi A, Kwak JT, Turkbey B, Choyke P, Pinto P, Wood B, Mousavi P, Abolmaesumi P.

Institution: The University of British Columbia, Vancouver, BC, Canada.

Abstract: PURPOSE: We have previously proposed temporal enhanced ultrasound (TeUS) as a new paradigm for tissue characterization. TeUS is based on analyzing a sequence of ultrasound data with deep learning and has been demonstrated to be successful for detection of cancer in ultrasound-guided prostate biopsy. Our aim is to enable the dissemination of this technology to the community for large-scale clinical validation.

METHODS: In this paper, we present a unified software framework demonstrating near-real-time analysis of ultrasound data stream using a deep learning solution. The system integrates ultrasound imaging hardware, visualization and a deep learning back-end to build an accessible, flexible and robust platform. A client-server approach is used in order to run computationally expensive algorithms in parallel. We demonstrate the efficacy of the framework using two applications as case studies. First, we show that prostate cancer detection using near-real-time analysis of RF and B-mode TeUS data and deep learning is feasible. Second, we present real-time segmentation of ultrasound prostate data using an integrated deep learning solution.

RESULTS: The system is evaluated for cancer detection accuracy on ultrasound data obtained from a large clinical study with 255 biopsy cores from 157 subjects. It is further assessed with an independent dataset with 21 biopsy targets from six subjects. In the first study, we achieve area under the curve, sensitivity, specificity and accuracy of 0.94, 0.77, 0.94 and 0.92, respectively, for the detection of prostate cancer. In the second study, we achieve an AUC of 0.85.

CONCLUSION: Our results suggest that TeUS-guided biopsy can be potentially effective for the detection of prostate cancer.

Innovations in Preoperative Planning: Insights into Another Dimension using 3D Printing for Cardiac Disease

Publication: J Cardiothorac Vasc Anesth. 2018 Aug;32(4):1937-1945. PMID: 29277300

Authors: Farooqi KM, Mahmood F.

Institution: Division of Pediatric Cardiology, New York Presbyterian-Columbia University Medical Center, New York, NY, USA.


Two-dimensional visualization of complex congenital heart disease has limitations in that there is variation in the interpretation by different individuals. Three-dimensional printing technology has been in use for decades but is currently becoming more commonly used in the medical field. Congenital heart disease serves as an ideal pathology to employ this technology because of the variation of anatomy between patients. In this review, the authors aim to discuss basics of applicability of three-dimensional printing, the process involved in creating a model, as well as challenges with establishing utility and quality.

3D-constructive Interference into Steady State (3D-CISS) Labyrinth Signal Alteration in Patients with Vestibular Schwannoma

Publication: Auris Nasus Larynx. 2018 Aug;45(4):702-10. PMID: 28947096

Authors: Wagner F, Herrmann E, Wiest R, Raabe A, Bernasconi C, Caversaccio M, Vibert D.

Institutions: Department of Diagnostic and Interventional Neuroradiology, University Hospital, University of Bern, Bern, Switzerland.


Objective: To evaluate signal intensity of the inner ear using 3D-CISS imaging and correlated signal characteristics in patients with vestibular schwannoma to neuro-otological symptoms.

Methods: Sixty patients with unilateral vestibular schwannoma were retrospectively reviewed. All patients had had initial and follow-up magnetic resonance imaging (MRI). Individual treatment strategies consisted of "wait-and-watch", surgical tumour resection, stereotactic radiosurgery or both surgery and stereotactic radiosurgery. For all patients a complete baseline and treatment course neuro-otological examination was re-studied. For the semi-automatic volumetric tumour measurement we used 3D Slicer 4.4.0.

Results: On initial MRI, 3D-CISS sequence signal loss of the membranous labyrinth was present in 20 patients (33.3%); signal loss of cochlea in 20 (33.3%) and coincident signal loss of sacculus/utriculus in 17 (85%) of them. Sequential analysis of follow-up MRI series demonstrated slightly increased labyrinthine signal degradation, independently of the chosen therapy. Correlation of initial MRI results with initial neuro-otological symptoms showed significance only for cochlear obstruction versus vertigo (p=0.0397) and sacculus/utriculus obstruction versus vertigo (p=0.0336). No other statistically significant relationships were noted.

Conclusion: 3D-constructive interference into steady state (3D-CISS) is appropriate for observing inner ear signal loss in patients with vestibular schwannoma. However, except for vertigo, no significant correlation was noted between initial neuro-otological symptomatology and signal loss of the inner ear.

Computed Tomography Trachea Volumetry in Patients with Scleroderma: Association With Clinical and Functional Findings

Publication: PLoS One. 2018 Aug 1;13(8):e0200754. PMID: 30067820 | PDF

Authors: Silva BRA, Rodrigues RS, Rufino R, Costa CH, Vilela VS, Levy RA, Guimarães ARM, Carvalho ARS, Lopes AJ.

Institution: Postgraduate Programme in Medical Sciences, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract: BACKGROUND: In scleroderma, excessive collagen production can alter tracheal geometry, and computed tomography (CT) volumetry of this structure may aid in detecting possible abnormalities. The objectives of this study were to quantify the morphological abnormalities in the tracheas of ​​patients with scleroderma and to correlate these findings with data on clinical and pulmonary function.

METHODS: This was a cross-sectional study in which 28 adults with scleroderma and 27 controls matched by age, gender and body mass index underwent chest CT with posterior segmentation and skeletonization of the images. In addition, all participants underwent pulmonary function tests and clinical evaluation, including the modified Rodnan skin score (mRSS).

RESULTS: Most patients (71.4%) had interstitial lung disease on CT. Compared to controls, patients with scleroderma showed higher values ​​in the parameters measured by CT trachea volumetry, including area, eccentricity, major diameter, minor diameter, and tortuosity. The tracheal area and equivalent diameter were negatively correlated with the ratio between forced expiratory flow and forced inspiratory flow at 50% of forced vital capacity (FEF50%/FIF50%) (r = -0.44, p = 0.03 and r = -0.46, p = 0.02, respectively). The tracheal tortuosity was negatively correlated with peak expiratory flow (r = -0.51, p = 0.008). The mRSS showed a positive correlation with eccentricity (r = 0.62, p < 0.001) and tracheal tortuosity (r = 0.51, p = 0.007), while the presence of anti-topoisomerase I antibody (ATA) showed a positive correlation with tracheal tortuosity (r = 0.45, p = 0.03).

CONCLUSIONS: In a sample composed predominantly of scleroderma patients with associated interstitial lung disease, there were abnormalities in tracheal geometry, including greater eccentricity, diameter and tortuosity. In these patients, abnormalities in the geometry of the trachea were associated with functional markers of obstruction. In addition, tracheal tortuosity was correlated with cutaneous involvement and the presence of ATA.

Measurement of the tortuosity of the trachea. Images in the coronal (A) and sagittal (B) planes are shown. In this scheme, L is the length of the trachea (the total length of 'ab', shown in blue) and vd is the vectorial distance between the points at the extremities (the length of the shortest possible path between 'a’ and ‘b', shown in red).The airways were segmented using 3D Slicer v.4.4.0 with the aid of its AirwaySegmentation extension.

Comparison of Modified Two-point Dixon and Chemical Shift Encoded MRI Water-fat Separation Methods for Fetal Fat Quantification

Publication: J Magn Reson Imaging. 2018 Jul;48(1):274-82. PMID: 29319918

Authors: Giza SA, Miller MR, Parthasarathy P, de Vrijer B, McKenzie CA.

Institution: Department of Medical Biophysics, Western University, London, Ontario, Canada.


BACKGROUND: Fetal fat is indicative of the energy balance within the fetus, which may be disrupted in pregnancy complications such as fetal growth restriction, macrosomia, and gestational diabetes. Water-fat separated MRI is a technique sensitive to tissue lipid content, measured as fat fraction (FF), and can be used to accurately measure fat volumes. Modified two-point Dixon and chemical shift encoded MRI (CSE-MRI) are water-fat separated MRI techniques that could be applied to imaging of fetal fat. Modified two-point Dixon has biases present that are corrected in CSE-MRI which may contribute to differences in the fat measurements.

PURPOSE: To compare the measurement of fetal fat volume and FF by modified two-point Dixon and CSE-MRI.

STUDY TYPE: Cross-sectional study for comparison of two MRI pulse sequences.

POPULATION: Twenty-one pregnant women with singleton pregnancies.

FIELD STRENGTH/SEQUENCE: 1.5T, modified two-point Dixon and CSE-MRI.

ASSESSMENT: Manual segmentation of total fetal fat volume and mean FF from modified 2-point Dixon and CSE-MRI FF images.

STATISTICAL TESTS: Reliability was assessed by calculating the intraclass correlation coefficient (ICC). Agreement was assessed using a one-sample t-test on the fat measurements difference values (modified two-point Dixon - CSE-MRI). The difference scores were tested against a value of 0, which would indicate that the measurements were identical.

RESULTS: The fat volume and FF measured by modified two-point Dixon and CSE-MRI had excellent reliability, demonstrated by ICCs of 0.93 (P < 0.001) and 0.90 (P < 0.001), respectively. They were not in agreement, with CSE-MRI giving mean fat volumes 180 mL greater and mean FF 3.0% smaller than modified two-point Dixon.

DATA CONCLUSION: The reliability between modified two-point Dixon and CSE-MRI indicates that either technique can be used to compare fetal fat measurements in different participants, but they are not in agreement possibly due to uncorrected biases in modified two-point Dixon.

"Total fetal fat from the entire fetal volume was manually segmented from all the PDFF/FSF images using 3D Slicer v.4.7.0."

Genetic Mapping of Molar Size Relations Identifies Inhibitory Locus for Third Molars in Mice

Publication: Heredity (Edinb). 2018 Jul;121(1):1-11. PMID: 29302051

Authors: Navarro N, Murat Maga A.

Institution: EPHE, PSL Research University Paris, F-21000, Dijon, France.


Molar size in Mammals shows considerable disparity and exhibits variation similar to that predicted by the Inhibitory Cascade model. The importance of such developmental systems in favoring evolutionary trajectories is also underlined by the fact that this model can predict macroevolutionary patterns. using backcross mice, we mapped QTL for molar sizes controlling for their sequential development. Genetic controls for upper and lower molars appear somewhat similar, and regions containing genes implied in dental defects drive this variation. We mapped three relationship QTLs (rQTL) modifying the control of the mesial molars on the focal third molar. These regions overlap Shh, Sostdc1, and Fst genes, which have pervasive roles in development and should be buffered against new variation. It has theoretically been shown that rQTL produces new variation channeled in the direction of adaptive changes. Our results provide evidence that evolutionary/disease patterns of tooth size variation could result from such a non-random generating process.

"A random set of 79 individuals was segmented using the 3D Slicer with a specific threshold."


  • R00 DE021417/DE/NIDCR NIH HHS/United States

Characterization of Adrenal Lesions on Unenhanced MRI Using Texture Analysis: A Machine-Learning Approach

Publication: J Magn Reson Imaging. 2018 Jul;48(1):198-204. PMID: 29341325

Authors: Romeo V, Maurea S, Cuocolo R, Petretta M, Mainenti PP, Verde F, Coppola M, Dell'Aversana S, Brunetti A.

Institution: Department of Advanced Biomedical Sciences, University of Naples "Federico II,", Naples, Italy.


BACKGROUND: Adrenal adenomas (AA) are the most common benign adrenal lesions, often characterized based on intralesional fat content as either lipid-rich (LRA) or lipid-poor (LPA). The differentiation of AA, particularly LPA, from nonadenoma adrenal lesions (NAL) may be challenging. Texture analysis (TA) can extract quantitative parameters from MR images. Machine learning is a technique for recognizing patterns that can be applied to medical images by identifying the best combination of TA features to create a predictive model for the diagnosis of interest.

PURPOSE/HYPOTHESIS: To assess the diagnostic efficacy of TA-derived parameters extracted from MR images in characterizing LRA, LPA, and NAL using a machine-learning approach.

STUDY TYPE: Retrospective, observational study.


FIELD STRENGTH/SEQUENCE: Unenhanced T1 -weighted in-phase (IP) and out-of-phase (OP) as well as T2 -weighted (T2 -w) MR images acquired at 3T.

ASSESSMENT: Adrenal lesions were manually segmented, placing a spherical volume of interest on IP, OP, and T2 -w images. Different selection methods were trained and tested using the J48 machine-learning classifiers.

STATISTICAL TESTS: The feature selection method that obtained the highest diagnostic performance using the J48 classifier was identified; the diagnostic performance was also compared with that of a senior radiologist by means of McNemar's test.

RESULTS: A total of 138 TA-derived features were extracted; among these, four features were selected, extracted from the IP (Short_Run_High_Gray_Level_Emphasis), OP (Mean_Intensity and Maximum_3D_Diameter), and T2 -w (Standard_Deviation) images; the J48 classifier obtained a diagnostic accuracy of 80%. The expert radiologist obtained a diagnostic accuracy of 73%. McNemar's test did not show significant differences in terms of diagnostic performance between the J48 classifier and the expert radiologist.

DATA CONCLUSION: Machine learning conducted on MR TA-derived features is a potential tool to characterize adrenal lesions.

"Images and VOIs were successively imported on 3D Slicer (HeterogeneityCAD module) to extract a total of 138 first-order, GLCM, and RLM texture parameters, 46 for each MR sequence.

Technique Development and Measurement of Cross-Sectional Area of the Pubovisceral Muscle on MRI Scans of Living Women

Publication: Int Urogynecol J. 2018 Jul 5. PMID: 29974138

Authors: Masteling M, Ashton-Miller JA, DeLancey JOL.

Institution: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA.

Abstract: INTRODUCTION AND HYPOTHESIS: Measurements of the anatomic cross-sectional area (CSA) of the pubovisceral muscle (PVM) in women are confounded by the difficulty of separating the muscle from the adjacent puborectal (PRM) and iliococcygeal (ICM) muscles when visualized in a plane orthogonal to the fiber direction. We tested the hypothesis that it might be possible to measure the PVM CSA within a defined region of interest based on magnetic resonance images (MRI).

METHODS: MRI scans of 11 women with unilateral PVM tears and seven primiparous women with intact muscles following elective C-section were used to identify the PVM injury zone defined by the mean location of its boundaries with the adjacent intact PRM and ICM from existing anatomic reference points using 3D Slicer and ImageJ software. Then, from the 15 or more 2-mm transverse slices available, the slice with the maximum anatomic CSA of the left and right PVM was found in 24 primiparous women with bilaterally intact muscles who had delivered via C-section.

RESULTS: Mean [± standard deviation (SD)] of the maximum left or right PVM cross-section areas for the 24 women, measured by two different raters, was 1.25 ± 0.29 cm2 (range 0.75-1.86). The 5th, 50th, and 95th percentile values were 0.77, 1.23, and 1.80 cm2, respectively. Inter- and intrarater measurement repeatability intraclass correlation coefficients exceeded 0.89 and 0.90, respectively.

CONCLUSIONS: It is possible to use MRI to identify the volume of interest with the maximum anatomic cross section of the PVM belly while minimizing the inadvertent inclusion of adjacent PRM or ICM in that measurement.

Validation of a Windowing Protocol for Accurate In Vivo Tooth Segmentation Using i-Cat Cone Beam Computed Tomography

Publication: Adv Clin Exp Med. 2018 Jul 12. PMID: 29999253

Authors: Rastegar B, Thumilaire B, Odri GA, Siciliano S, Zapała J, Mahy P, Olszewski R.

Institution: Service de Parodontologie, Université libre de Bruxelles, Brussels, Belgium.

Abstract: BACKGROUND: Validation of three-dimensional (3D) reconstructions of full dental arches with crowns and roots based on cone beam computed tomography (CBCT) imaging represents a key issue in 3D digital dentistry.

OBJECTIVES: The aim of the study was to search for the most accurate in vivo windowing-based manual tooth segmentation using CBCT. The null hypothesis was that all applied windowing protocols were equivalent in terms of in vivo tooth volume measurement using CBCT.

MATERIAL AND METHODS: This retrospective study was based on preoperative CBCT images from patients who underwent further tooth extractions for reasons independent of this study. Written informed consent was obtained from all the participants, and the study was approved by the Ethics Committee of Cliniques Universitaires Saint Luc (Brussels, Belgium). The radiological protocol was I-CAT CBCT, 0.3 mm slice thickness, 8 cm × 16 cm field of view, 120 kVp, and 18 mAs. A total of 36 teeth were extracted from 14 patients between the ages of 18 and 68 years. Using 3D Slicer software, segmentations were performed twice by 2 independent observers, with a 1-month time period between the 2 segmentations to study intraand inter-observer repeatability and reproducibility. Four windowing protocols (level/window) were applied: 1. 1131/1858, 2. 2224/4095, 3. 1131/4095, and 4. AUTO, an automatic protocol provided by default by the software. A total of 576 segmentations were performed. Tooth volumes were automatically calculated using the software. To compare the volumes obtained from CBCT segmentations with a gold-standard method, we laser-scanned the extracted teeth.

RESULTS: Excellent intraand inter-observer intraclass correlations were found for all of the protocols used. The best windowing protocol was 1131/1858 for both observers. Tooth volumes were obtained by manual segmentation of the CBCT images and using windowing protocol 1131/1858. No significantly different tooth volumes were found by laser scanning.

CONCLUSIONS: Our null hypothesis was rejected. Only windowing protocol 1131/1858 allowed for significantly closer 3D in vivo segmentation of a tooth compared to I-CAT CBCT, with excellent intra-observer repeatability and inter-observer reproducibility.

Automatic Segmentation of Stereoelectroencephalography (Seeg) Electrodes Post-Implantation Considering Bending

Publication: Int J Comput Assist Radiol Surg. 2018 Jun;13(6):935-46. PMID: 29736800 | PDF

Authors: Granados A, Vakharia V, Rodionov R, Schweiger M, Vos SB, O'Keeffe AG, Li K, Wu C, Miserocchi A, McEvoy AW, Clarkson MJ, Duncan JS, Sparks R, Ourselin S.

Institution: Wellcome/EPSRC Centre for Interventional and Surgical Sciences, UCL, London, UK.

Abstract: PURPOSE: The accurate and automatic localisation of SEEG electrodes is crucial for determining the location of epileptic seizure onset. We propose an algorithm for the automatic segmentation of electrode bolts and contacts that accounts for electrode bending in relation to regional brain anatomy.

METHODS: Co-registered post-implantation CT, pre-implantation MRI, and brain parcellation images are used to create regions of interest to automatically segment bolts and contacts. Contact search strategy is based on the direction of the bolt with distance and angle constraints, in addition to post-processing steps that assign remaining contacts and predict contact position. We measured the accuracy of contact position, bolt angle, and anatomical region at the tip of the electrode in 23 post-SEEG cases comprising two different surgical approaches when placing a guiding stylet close to and far from target point. Local and global bending are computed when modelling electrodes as elastic rods.

RESULTS: Our approach executed on average in 36.17 s with a sensitivity of 98.81% and a positive predictive value (PPV) of 95.01%. Compared to manual segmentation, the position of contacts had a mean absolute error of 0.38 mm and the mean bolt angle difference of [Formula: see text] resulted in a mean displacement error of 0.68 mm at the tip of the electrode. Anatomical regions at the tip of the electrode were in strong concordance with those selected manually by neurosurgeons, [Formula: see text], with average distance between regions of 0.82 mm when in disagreement. Our approach performed equally in two surgical approaches regardless of the amount of electrode bending.

CONCLUSION: We present a method robust to electrode bending that can accurately segment contact positions and bolt orientation. The techniques presented in this paper will allow further characterisation of bending within different brain regions.


  • WT106882/Health Innovation Challenge Fund/
  • 203145Z/16/Z/Wellcome/EPSRC/
  • NIHR BRC UCLH/UCL High Impact Initiative/National Institute for Health Research University College London Hospitals Biomedical Research Centre
Generalisability and robustness tests. Our proposed algorithm using data from a different centre: a with smaller bolt heads, b contacts very close to each other, and c electrodes inserted deeply (pink electrode with insertion depth of 110 mm); Our data in SEEGA: d segmented contact positions (green fiducials) and implantation plan (pink fiducials). "We randomly chose 3 of our data sets to test the method proposed in [2, 16] and implemented in SEEGA 3D Slicer v4.6.2."]

Low-Cost Three-Dimensional Printed Phantom for Neuraxial Anesthesia Training: Development and Comparison to a Commercial Model

Publication: PLoS One. 2018 Jun 18;13(6):e0191664. PMID: 29912877 | PDF

Authors: Mashari A, Montealegre-Gallegos M, Jeganathan J, Yeh L, Qua Hiansen J, Meineri M, Mahmood F, Matyal R.

Institution: Department of Anesthesia and Pain Management, Toronto General Hospital, Toronto, Ontario, Canada.

Abstract: METHODS: Anonymized CT DICOM data was segmented to create a 3D model of the lumbar spine. The 3D model was modified, placed inside a digitally designed housing unit and fabricated on a desktop 3D printer using polylactic acid (PLA) filament. The model was filled with an echogenic solution of gelatin with psyllium fiber. Twenty-two staff anesthesiologists performed a spinal and epidural on the 3D printed simulator and a commercially available Simulab phantom. Participants evaluated the tactile and ultrasound imaging fidelity of both phantoms via Likert-scale questionnaire.

RESULTS: The 3D printed neuraxial phantom cost $13 to print and required 25 hours of non-supervised printing and 2 hours of assembly time. The 3D printed phantom was found to be less realistic to surface palpation than the Simulab phantom due to fragility of the silicone but had significantly better fidelity for loss of resistance, dural puncture and ultrasound imaging than the Simulab phantom.

CONCLUSION: Low-cost neuraxial phantoms with fidelity comparable to commercial models can be produced using CT data and low-cost infrastructure consisting of FLOS software and desktop 3D printers.

ITK-SNAP interface after segmentation of the spine with the automated active contour tool. Each colour represents a different layer-mask indicating different regions for the segmented 3D model. "We used the FLOS software ITK-SNAP and 3D Slicer for image segmentation".]

Improvement of Quality of 3D Printed Objects by Elimination of Microscopic Structural Defects in Fused Deposition Modeling

Publication: PLoS One. 2018 Jun 7;13(6):e0198370. PMID: 29879163 | PDF

Authors: Gordeev EG, Galushko AS, Ananikov VP.

Institution: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia.

Abstract: Additive manufacturing with fused deposition modeling (FDM) is currently optimized for a wide range of research and commercial applications. The major disadvantage of FDM-created products is their low quality and structural defects (porosity), which impose an obstacle to utilizing them in functional prototyping and direct digital manufacturing of objects intended to contact with gases and liquids. This article describes a simple and efficient approach for assessing the quality of 3D printed objects. Using this approach it was shown that the wall permeability of a printed object depends on its geometric shape and is gradually reduced in a following series: cylinder > cube > pyramid > sphere > cone. Filament feed rate, wall geometry and G-code-defined wall structure were found as primary parameters that influence the quality of 3D-printed products. Optimization of these parameters led to an overall increase in quality and improvement of sealing properties. It was demonstrated that high quality of 3D printed objects can be achieved using routinely available printers and standard filaments. "preparing the model for printing in the 3D Slicer program."

Objects of various shapes made of PLA by 3D printing (A) cylinder, (B) cone, (C) sphere, (D) joined cylinder/cone, (E) pyramid, (F) cube.

Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with Osimertinib

Publication: Clin Cancer Res. Clin Cancer Res. 2018 Jun 1;24(11):2594-604. PMID: 29298799 | PDF

Authors: Liu S, Li S, Hai J, Wang X, Chen T, Quinn MM, Gao P, Zhang Y, Ji H, Cross D, Wong KK.

Institution: Laboratory for Percutaneous Surgery, School of Computing, Queen's University, Kingston, ON, Canada.


Purpose: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2-6 percent of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in non-small cell lung cancer (NSCLC) patients, we performed a comprehensive pre-clinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291). Experimental Design:Three genetically modified mouse models (GEMMs) mimicking individual HER2 alterations in NSCLC were generated and osimertinib was tested for its efficacy against these HER2 aberrations in vivo.

Results: Osimertinib treatment showed robust efficacy in HER2wt overexpression and EGFR del19/HER2 models but not in HER2 exon 20 insertion tumors. Interestingly, we further identified that combined treatment with osimertinib and the BET inhibitor JQ1 significantly increased the response rate in HER2-mutant NSCLC while JQ1 single treatment did not show efficacy.

Conclusions: Overall, our data indicated robust anti-tumor efficacy of osimertinib against multiple HER2 aberrations in lung cancer, either as a single agent or in combination with JQ1. Our study provides a strong rationale for future clinical trials using osimertinib either alone or in combination with epigenetic drugs to target aberrant HER2 in NSCLC patients.

"...Lung tumors were monitored by MRI and 3D Slicer was used to quantify the lung tumors."

Plasma Membrane LAT Activation Precedes Vesicular Recruitment Defining Two Phases of Early T-cell Activation

Publication: Nat Commun. 2018 May 22;9(1):2013. PMID: 29789604 | PDF

Authors: Balagopalan L, Yi J, Nguyen T, McIntire KM, Harned AS, Narayan K, Samelson LE.

Institution: Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Abstract: The relative importance of plasma membrane-localized LAT versus vesicular LAT for microcluster formation and T-cell receptor (TCR) activation is unclear. Here, we show the sequence of events in LAT microcluster formation and vesicle delivery, using lattice light sheet microscopy to image a T cell from the earliest point of activation. A kinetic lag occurs between LAT microcluster formation and vesicular pool recruitment to the synapse. Correlative 3D light and electron microscopy show an absence of vesicles at microclusters at early times, but an abundance of vesicles as activation proceeds. Using TIRF-SIM to look at the activated T-cell surface with high resolution, we capture directed vesicle movement between microclusters on microtubules. We propose a model in which cell surface LAT is recruited rapidly and phosphorylated at sites of T-cell activation, while the vesicular pool is subsequently recruited and dynamically interacts with microclusters.


  • HHSN261200800001C/RC/CCR NIH HHS/United States
  • HHSN261200800001E/CA/NCI NIH HHS/United States

Correlative 3D light and FIB-SEM of activated T cells. Jurkat cells transfected with emerald-VAMP7 (green) were dropped onto stimulatory coverslips and fixed after 2 min a–h or 5 min i–n of activation and immunostained for pLAT (red), nucleus (blue), and plasma membrane (purple). a Images were collected of the whole cell activated for 2 min using confocal microscopy. "In the absence of correlative fiducial markers, “slabs” of volumetric data corresponding to the immune synapse from the confocal and FIB-SEM volumes were aligned using simple transforms in 3D Slicer."]

Advances in Stereotactic Navigation for Pelvic Surgery

Publication: Surg Endosc. 2018 Jun;32(6):2713-20. PMID: 29214516 | PDF

Authors: Wijsmuller AR, Romagnolo LGC, Agnus V, Giraudeau C, Melani AGF, Dallemagne B, Marescaux J.

Institution: IRCAD/ EITS, Department of General, Digestive and Endocrine Surgery, Nouvel Hôpital Civil, University Hospital of Strasbourg, Strasbourg, France.


BACKGROUND: Stereotactic navigation could improve the quality of surgery for rectal cancer. Critical challenges related to soft tissue stereotactic pelvic navigation include the potential difference in patient anatomy between intraoperative lithotomy and preoperative supine position for imaging. The objective of this study was to determine the difference in patient anatomy, sacral tilt, and skin fiducial position between these different patient positions and to investigate the feasibility and optimal set-up for stereotactic pelvic navigation.

METHODS: Four consecutive human anatomical specimens were submitted to repeated CT-scans in a supine and several degrees of lithotomy position. Patient anatomy, sacral tilt, and skin fiducial position were compared by means of an image computing platform. In two specimens, a 10-degree wedge was introduced to reduce the natural tilt of the sacrum during the shift from supine to lithotomy position. A simulation of laparoscopic and transanal surgical procedures was performed to assess the accuracy of the stereotactic navigation.

RESULTS: An up-to-supracentimetric change in patient anatomy was noted between different patient positions. This observation was minimized through the application of a wedge. When switching from supine to another position, sacral retroversion occurred independent of the use of a wedge. There was considerable skin fiducial motion between different positions. Accurate stereotactic navigation was obtained with the least registration error (1.9 mm) when the position of the anatomical specimen was registered in a supine position with straight legs, without pneumoperitoneum, using a conventional CT-scan with an identical specimen positioning.

CONCLUSION: The change in patient anatomy is small during the sacral tilt induced by positional changes when using a 10-degree wedge, allowing for an accurate stereotactic surgical navigation. This opens up new promising opportunities to increase the quality of surgery for rectal cancer cases where it is difficult or impossible to identify and dissect along the anatomical planes.

"each skin fiducial were marked by using an image computing platform, 3D Slicer.

Markers were manually placed in the center of the skin fiducials in each CT-scan by using an image computing platform 3D Slicer (B). The other markers S1-6 (C) and P1-6 (D) were placed at the anatomical landmarks as depicted in Table 2. ]

New Approach of Ultra-focal Brachytherapy for Low- and Intermediate-risk Prostate Cancer with Custom-linked I-125 Seeds: A feasibility Study of Optimal Dose Coverage

Publication: Brachytherapy. 2018 May - Jun;17(3):544-55. PMID: 29525514

Authors: Brun T, Bachaud JM, Graff-Cailleaud P, Malavaud B, Portalez D, Popotte C, Aziza R, Lusque A, Filleron T, Ken S.

Institution: Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopôle, Department of Engineering and Medical Physics, Toulouse, France.

Abstract: PURPOSE: To present the feasibility study of optimal dose coverage in ultra-focal brachytherapy (UFB) with multiparametric MRI for low- and intermediate-risk prostate cancer.

METHODS AND MATERIALS: UFB provisional dose plans for small target volumes (<7 cc) were calculated on a prostate training phantom to optimize the seeds number and strength. Clinical UFB consisted in a contour-based nonrigid registration (MRI/Ultrasound) to implant a fiducial marker at the location of the tumor focus. Dosimetry was performed with iodine-125 seeds and a prescribed dose of 160 Gy. On CT scans acquired at 1 month, dose coverage of 152 Gy to the ultra-focal gross tumor volume was evaluated. Registrations between magnetic resonance and CT scans were assessed on the first 8 patients with three software solutions: VariSeed, 3D Slicer, and Mirada, and quantitative evaluations of the registrations were performed. Impact of these registrations on the initial dose matrix was performed.

RESULTS: Mean differences between simulated dose plans and extrapolated Bard nomogram for UFB volumes were 36.3% (26-56) for the total activity, 18.3% (10-30) for seed strength, and 22.5% (16-38) for number of seeds. Registration method implemented in Mirada performed significantly better than VariSeed and 3D Slicer (p = 0.0117 and p = 0.0357, respectively). For dose plan evaluation between Mirada and VariSeed, D100% (Gy) for ultra-focal gross tumor volume had a mean difference of 28.06 Gy, mean values being still above the objective of 152 Gy. D90% for the prostate had a mean difference of 1.17 Gy. For urethra and rectum, dose limits were far below the recommendations.

CONCLUSIONS: This UFB study confirmed the possibility to treat with optimal dose coverage target volumes smaller than 7 cc.

Evaluating the Association between Enlarged Perivascular Spaces and Disease Worsening in Multiple Sclerosis

Publication: J Neuroimaging. 2018 May;28(3):273-7. PMID: 29226505

Authors: Cavallari M, Egorova S, Healy BC, Palotai M, Prieto JC, Polgar-Turcsanyi M, Tauhid S, Anderson M, Glanz B, Chitnis T, Guttmann CRG.

Institution: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.


BACKGROUND AND PURPOSE: Enlarged perivascular spaces (EPVSs) have been associated with relapses and brain atrophy in multiple sclerosis (MS). We investigated the association of EPVS with clinical and MRI features of disease worsening in a well-characterized cohort of relapsing-remitting MS patients prospectively followed for up to 10 years.

METHODS: Baseline EPVSs were scored on 1.5T MRI in 30 converters to moderate-severe disability, and 30 nonconverters matched for baseline characteristics.

RESULTS: EPVS scores were not significantly different between converters and nonconverters, nor associated with accrual of lesions or brain atrophy.

CONCLUSIONS: Our preliminary findings from a relatively small study sample argue against a potential use of EPVS as early indicator of risk for disease worsening in relapsing-remitting MS patients in a clinical setting. Although the small sample size and clinical 1.5T MRI may have limited our ability to detect a significant effect, we provided estimates of the association of EPVS with clinical and MRI indicators of disease worsening in a well-characterized cohort of MS patients.

"Outputs from the automated image analysis workflow were manually edited by a physician expert in image analysis (SE) in 3D Slicer"

Clinical Evaluation of Semi-Automatic Open-Source Algorithmic Software Segmentation of the Mandibular Bone: Practical Feasibility and Assessment of a New Course of Action

Publication: PLoS One. 2018 May 10;13(5):e0196378. PMID: 29746490 | PDF

Authors: Wallner J, Hochegger K, Chen X, Mischak I, Reinbacher K, Pau M, Zrnc T, Schwenzer-Zimmerer K, Zemann W, Schmalstieg D, Egger J.

Institution: Department of Oral & Maxillofacial Surgery, Medical University of Graz, Graz, AT.

Abstract: INTRODUCTION: Computer assisted technologies based on algorithmic software segmentation are an increasing topic of interest in complex surgical cases. However-due to functional instability, time consuming software processes, personnel resources or licensed-based financial costs many segmentation processes are often outsourced from clinical centers to third parties and the industry. Therefore, the aim of this trial was to assess the practical feasibility of an easy available, functional stable and licensed-free segmentation approach to be used in the clinical practice.

MATERIAL AND METHODS: In this retrospective, randomized, controlled trail the accuracy and accordance of the open-source based segmentation algorithm GrowCut was assessed through the comparison to the manually generated ground truth of the same anatomy using 10 CT lower jaw data-sets from the clinical routine. Assessment parameters were the segmentation time, the volume, the voxel number, the Dice Score and the Hausdorff distance.

RESULTS: Overall semi-automatic GrowCut segmentation times were about one minute. Mean Dice Score values of over 85% and Hausdorff Distances below 33.5 voxel could be achieved between the algorithmic GrowCut-based segmentations and the manual generated ground truth schemes. Statistical differences between the assessment parameters were not significant (p<0.05) and correlation coefficients were close to the value one (r > 0.94) for any of the comparison made between the two groups.

DISCUSSION: Complete functional stable and time saving segmentations with high accuracy and high positive correlation could be performed by the presented interactive open-source based approach. In the cranio-maxillofacial complex the used method could represent an algorithmic alternative for image-based segmentation in the clinical practice for e.g. surgical treatment planning or visualization of postoperative results and offers several advantages. Due to an open-source basis the used method could be further developed by other groups or specialists. Systematic comparisons to other segmentation approaches or with a greater data amount are areas of future works.

Axial Algorithmic (GrowCut) segmentation in 3D Slicer. (a) Fore- (green) and background (yellow) initialization of GrowCut in the lower jawbone in an axial, sagittal and coronal slice around the anterior mandible (symphysis / para-symphysis). (b) Slicer based algorithmic (GrowCut) segmentation: Fore- (green) and background (yellow) initialization of GrowCut in the lower jawbone in an axial, sagittal and coronal slice around parts of the mandible.

Subthalamic Oscillatory Activity and Connectivity during Gait in Parkinson's Disease

Publication: Neuroimage Clin. 2018 May 3;19:396-405. PMID: 30035024 | PDF

Authors: Hell F, Plate A, Mehrkens JH, Bötzel K.

Institution: Department of Neurology, Ludwig-Maximilians University, Munich, Germany.

Abstract: Local field potentials (LFP) of the subthalamic nucleus (STN) recorded during walking may provide clues for determining the function of the STN during gait and also, may be used as biomarker to steer adaptive brain stimulation devices. Here, we present LFP recordings from an implanted sensing neurostimulator (Medtronic Activa PC + S) during walking and rest with and without stimulation in 10 patients with Parkinson's disease and electrodes placed bilaterally in the STN. We also present recordings from two of these patients recorded with externalized leads. We analyzed changes in overall frequency power, bilateral connectivity, high beta frequency oscillatory characteristics and gait-cycle related oscillatory activity. We report that deep brain stimulation improves gait parameters. High beta frequency power (20-30 Hz) and bilateral oscillatory connectivity are reduced during gait, while the attenuation of high beta power is absent during stimulation. Oscillatory characteristics are affected in a similar way. We describe a reduction in overall high beta burst amplitude and burst lifetimes during gait as compared to rest off stimulation. Investigating gait cycle related oscillatory dynamics, we found that alpha, beta and gamma frequency power is modulated in time during gait, locked to the gait cycle. We argue that these changes are related to movement induced artifacts and that these issues have important implications for similar research.

Shank rotation measurements, raw LFP recordings and electrode localization. A. Shank rotation velocity of two different goniometer sensors setups mounted at right and left leg of one patient during walking and raw LFP trace from a single STN recording with Activa PC + S sensing. B. Posterior dorsal view of DBS-electrode localizations in left and right STN. The motor region of the STN is depicted in dark red, the associative subregion in light blue and limbic subregion in yellow. The contact used for stimulation is colored in light red (see text for details). "MRT and CT were aligned manually using 3D Slicer software, co-registered using a two-stage linear registration (rigid followed by affine) as implemented in Advanced Normalization Tools"]

Complete Thoracolumbar Fracture-dislocation with Intact Neurologic Function: Explanation of a Novel Cord Saving Mechanism

Publication: J Spinal Cord Med. 2018 May;41(3):367-376. PMID: 28648115

Authors: Rahimizadeh A, Asgari N, Rahimizadeh A.

Institution: Department of Neurosurgery, Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Science, Tehran, Iran.


Background: The thoracolumbar junction from T11 to L2 is a common site of injury in which fracture and dislocations are the most prevalent ones occurring at this location. Fracture dislocation is defined as failure of all three columns of the spine with gross displacement. Considering the significant violence necessary to produce fracture dislocations, these injuries are often associated with major neural deficit, with the majority of casualties becoming paraplegic immediately. Preservation of neurological function following complete fracture dislocation is quite rare entity.

Objective: To represent the possibility of existence of a preservation mechanism for functional integrity of cord despite spinal gross fracture dislocation by reproducing the injury on a plastic model and simulating a corresponding model using 3D Slicer software, detailed description the pathomechanism of neurologic sparing.

Case Report: A 19-year-old female who sustained severe thoracolumbar fracture dislocation but with normal neurology is presented. Despite the severity of the condition, the diagnosis was initially missed due to associated vital injuries.

Results: Combined posterior and anterior surgery resulted in optimal coronal and sagittal alignment, as well as proper stabilization without any complication. At 9-year follow-up, the patient was found to be doing well.

Conclusion: The prognosis for complete recovery with preplanned surgical intervention in thoracolumbar injuries affecting all three columns but with normal neurologic function is promising based on images, plastic models and 3D simulated model based on digital images.

Optimization of 3D Print Material for the Recreation of Patient-Specific Temporal Bone Models

Publication: Ann Otol Rhinol Laryngol. 2018 May;127(5):338-43. PMID: 29667491

Authors: Haffner M, Quinn A, Hsieh TY, Strong EB, Steele T.

Institution: University of California, Davis, School of Medicine, Sacramento, CA, USA.

Abstract: OBJECTIVE: Identify the 3D printed material that most accurately recreates the visual, tactile, and kinesthetic properties of human temporal bone Subjects and Methods: Fifteen study participants with an average of 3.6 years of postgraduate training and 56.5 temporal bone (TB) procedures participated. Each participant performed a mastoidectomy on human cadaveric TB and five 3D printed TBs of different materials. After drilling each unique material, participants completed surveys to assess each model's appearance and physical likeness on a Likert scale from 0 to 10 (0 = poorly representative, 10 = completely life-like). The 3D models were acquired by computed tomography (CT) imaging and segmented using 3D Slicer software.

RESULTS: Polyethylene terephthalate (PETG) had the highest average survey response for haptic feedback (HF) and appearance, scoring 8.3 (SD = 1.7) and 7.6 (SD = 1.5), respectively. The remaining plastics scored as follows for HF and appearance: polylactic acid (PLA) averaged 7.4 and 7.6, acrylonitrile butadiene styrene (ABS) 7.1 and 7.2, polycarbonate (PC) 7.4 and 3.9, and nylon 5.6 and 6.7.

CONCLUSION: A PETG 3D printed temporal bone models performed the best for realistic appearance and HF as compared with PLA, ABS, PC, and nylon. The PLA and ABS were reliable alternatives that also performed well with both measures.

3-D Segmentation of Lung Nodules using Hybrid Level Sets

Publication: Comput Biol Med. 2018 May 1;96:214-26. PMID: 29631230

Authors: Shakir H, Rasool Khan TM, Rasheed H.

Institution: Department of Electrical Engineering, Bahria University, 13-National Stadium Road, Karachi, Pakistan.

Abstract: Lung nodule segmentation in CT images and its subsequent volume analysis can help determine the malignancy status of a lung nodule. While several efficient segmentation schemes have been proposed, only a few studies evaluated the segmentation's performance for large nodules. In this research, we contribute a semi-automatic system which is capable of performing robust 3-D segmentations on both small and large nodules with good accuracy. The target CT volume is de-noised with an anisotropic diffusion filter and a region of interest is selected around the target nodule on a reference slice. The proposed model performs nodule segmentation by incorporating a mean intensity based threshold in Geodesic Active Contour model in level sets. We also devise an adaptive technique using image intensity histogram to estimate the desired mean intensity of the nodule. The proposed system is validated on both lung nodules and phantoms collected from publicly available diverse databases. Quantitative and visual comparative analysis of the proposed work with the Chan-Vese algorithm and statistic active contour model of 3D Slicer platform is also presented. The resulting mean spatial overlap between segmented nodules and reference nodules is 0.855, the mean volume bias is 0.10±0.2 ml and the algorithm repeatability is 0.060 ml. The achieved results suggest that the proposed method can be used for volume estimations of small as well as large-sized nodules.

Prediction of Outcome using Pretreatment 18F-FDG PET/CT and MRI Radiomics in Locally Advanced Cervical Cancer Treated with Chemoradiotherapy

Publication: Eur J Nucl Med Mol Imaging. 2018 May;45(5):768-86. PMID: 29222685

Authors: Lucia F, Visvikis D, Desseroit MC, Miranda O, Malhaire JP, Robin P, Pradier O, Hatt M, Schick U.

Institution: Department of Radiation Oncology, University Hospital, Brest, France.


PURPOSE: The aim of this study is to determine if radiomics features from 18fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer.

METHODS: One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. 18F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control.

RESULTS: In the training cohort, median follow-up was 3.0 years (range, 0.43-6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I-II vs. III-IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non UniformityGLRLM in PET and EntropyGLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50-60% for clinical parameters).

CONCLUSIONS: In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.

Smoking Duration Alone Provides Stronger Risk Estimates of Chronic Obstructive Pulmonary Disease than Pack-years

Publication: Thorax. 2018 May;73(5):414-21. PMID: 29326298

Authors: Bhatt SP, Kim YI, Harrington KF, Hokanson JE, Lutz SM, Cho MH, DeMeo DL, Wells JM, Make BJ, Rennard SI, Washko GR, Foreman MG, Tashkin DP, Wise RA, Dransfield MT, Bailey WC; COPDGene Investigators.

Institution: Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.


Cigarette smoking is the strongest risk factor for COPD. Smoking burden is frequently measured in pack-years, but the relative contribution of cigarettes smoked per day versus duration towards the development of structural lung disease, airflow obstruction and functional outcomes is not known.

METHODS: We analysed cross-sectional data from a large multicentre cohort (COPDGene) of current and former smokers. Primary outcome was airflow obstruction (FEV1/FVC); secondary outcomes included five additional measures of disease: FEV1, CT emphysema, CT gas trapping, functional capacity (6 min walk distance, 6MWD) and respiratory morbidity (St George's Respiratory Questionnaire, SGRQ). Generalised linear models were estimated to compare the relative contribution of each smoking variable with the outcomes, after adjustment for age, race, sex, body mass index, CT scanner, centre, age of smoking onset and current smoking status. We also estimated adjusted means of each outcome by categories of pack-years and combined groups of categorised smoking duration and cigarettes/day, and estimated linear trends of adjusted means for each outcome by categorised cigarettes/day, smoking duration and pack-years.

RESULTS: 10 187 subjects were included. For FEV1/FVC, standardised beta coefficient for smoking duration was greater than for cigarettes/day and pack-years (P<0.001). After categorisation, there was a linear increase in adjusted means FEV1/FVC with increase in pack-years (regression coefficient β=-0.023±SE0.003; P=0.003) and duration over all ranges of smoking cigarettes/day (β=-0.041±0.004; P<0.001) but a relatively flat slope for cigarettes/day across all ranges of smoking duration (β=-0.009±0.0.009; P=0.34). Strength of association of duration was similarly greater than pack-years for emphysema, gas trapping, FEV1, 6MWD and SGRQ.

CONCLUSION: Smoking duration alone provides stronger risk estimates of COPD than the composite index of pack-years.

"... After segmentation and extrusion of the large and medium-sized airways, emphysema was quantified as the percentage of lung volume at TLC with attenuation <−950 Hounsfield units (HU) by density mask analyses using 3D Slicer software."

Using 3DSlicer, Z-Brush, and Slic3r to Turn CAT Scans Into Kidney 3D-Prints

Publication: Adafruit, May 24, 2018.

Authors: Andrew Krill

Read the article here


Development of White Matter Microstructure in Relation to Verbal and Visuospatial Working Memory-A Longitudinal Study

Publication: PLoS One. 2018 Apr 24;13(4):e0195540. PMID: 29689058 | PDF

Authors: Krogsrud SK, Fjell AM, Tamnes CK, Grydeland H, Due-Tønnessen P, Bjørnerud A, Sampaio-Baptista C, Andersson J, Johansen-Berg H, Walhovd KB.

Institution: Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.

Abstract: Working memory capacity is pivotal for a broad specter of cognitive tasks and develops throughout childhood. This must in part rely on development of neural connections and white matter microstructure maturation, but there is scarce knowledge of specific relations between this and different aspects of working memory. Diffusion tensor imaging (DTI) enables us to study development of brain white matter microstructure. In a longitudinal DTI study of 148 healthy children between 4 and 11 years scanned twice with an on average 1.6 years interval, we characterized change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD) in 10 major white matter tracts hypothesized to be of importance for working memory. The results showed relationships between change in several tracts and change in visuospatial working memory. Specifically, improvement in visuospatial working memory capacity was significantly associated with decreased MD, RD and AD in inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in the right hemisphere, as well as forceps major (FMaj). No significant relationships were found between change in DTI metrics and change in verbal working memory capacity. These findings yield new knowledge about brain development and corresponding working memory improvements in childhood.

FA and MD in specific tracts with age. Spaghetti plots of individual participant change in FA and MD in specific tracts with age (years). Females are plotted in red and males in blue. For each measure, an assumption-free general additive mixed model as a function of age was fitted to accurately describe change across the age range. Three-dimensional renderings illustrate ten atlas-based probabilistic tracts from the Mori atlas in anterior, left, and dorsal views, displayed on a semitransparent template brain. The color-coded titles for each scatterplot represent the color of each specific white matter tract. Color codes refer to: Light blue: Inferior longitudinal fasciculus (ILF), Yellow: Inferior fronto-occipital fasciculus (IFOF), Red: Forceps major (FMaj), Blue: Superior longitudinal fasciculus (SLF), Green: Uncinate fasciculus (UF), and Purple: Forceps minor (FMin). The 3D figures were made by the use of 3D Slicer. L = left and R = right.

Detailed T1-Weighted Profiles from the Human Cortex Measured in Vivo at 3 Tesla MRI

Publication: Neuroinformatics. 2018 Apr;16(2):181-96. PMID: 29352389 | PDF

Authors: Ferguson B, Petridou N, Fracasso A, van den Heuvel MP, Brouwer RM, Hulshoff Pol HE, Kahn RS, Mandl RCW.

Institution: Rudolf Magnus Brain Center, Brain Division, Department of Psychiatry, University Medical Center Utrecht, Utrecht University, The Netherlands.

Abstract: Studies into cortical thickness in psychiatric diseases based on T1-weighted MRI frequently report on aberrations in the cerebral cortex. Due to limitations in image resolution for studies conducted at conventional MRI field strengths (e.g. 3 Tesla (T)) this information cannot be used to establish which of the cortical layers may be implicated. Here we propose a new analysis method that computes one high-resolution average cortical profile per brain region extracting myeloarchitectural information from T1-weighted MRI scans that are routinely acquired at a conventional field strength. To assess this new method, we acquired standard T1-weighted scans at 3 T and compared them with state-of-the-art ultra-high resolution T1-weighted scans optimised for intracortical myelin contrast acquired at 7 T. Average cortical profiles were computed for seven different brain regions. Besides a qualitative comparison between the 3 T scans, 7 T scans, and results from literature, we tested if the results from dynamic time warping-based clustering are similar for the cortical profiles computed from 7 T and 3 T data. In addition, we quantitatively compared cortical profiles computed for V1, V2 and V7 for both 7 T and 3 T data using a priori information on their relative myelin concentration. Although qualitative comparisons show that at an individual level average profiles computed for 7 T have more pronounced features than 3 T profiles the results from the quantitative analyses suggest that average cortical profiles computed from T1-weighted scans acquired at 3 T indeed contain myeloarchitectural information similar to profiles computed from the scans acquired at 7 T. The proposed method therefore provides a step forward to study cortical myeloarchitecture in vivo at conventional magnetic field strength both in health and disease.


  • 13339/Nederlandse Organisatie voor Wetenschappelijk Onderzoek/
Result of deconvolution of 3 T and 7 T scans, coronal slice. Effect of deconvolution shown in a coronal section of the occipital lobe for one participant for the area of interest displayed in the white rectangle in (a). The four panels on the right indicate the area of interest in an original (a) and deconvoluted (b) 3 T T1w 0.8 mm isotropic scan and in an original (d) and deconvoluted (e) 7 T myelin-sensitive T1w 0.5 mm isotropic scan. Freesurfer white (red) and pial (yellow) surfaces are overlaid. Insets display signal intensity sampled along displayed orange ruler (marked by the white arrow), with 3D Slicer 4.4.0, which is 4.2 mm in length and runs from white matter to CSF. Please note that this sample is drawn in a 2D projection and is not necessarily perpendicular to the cortical mantle. (f) depicts the PSF used]

Estimating Shape Correspondence for Populations of Objects with Complex Topology

Publication: Proc IEEE Int Symp Biomed Imaging. 2018 Apr;2018:1010-3. PMID: 29973974 | PDF

Authors: Fishbaugh J, Pascal L, Fischer L, Nguyen T, Boen C, Goncalves J, Gerig G, Paniagua B.

Institution: NYU Tandon School of Engineering, NY, USA.

Abstract: Statistical shape analysis captures the geometric properties of a given set of shapes, obtained from medical images, by means of statistical methods. Orthognathic surgery is a type of craniofacial surgery that is aimed at correcting severe skeletal deformities in the mandible and maxilla. Methods assuming spherical topology cannot represent the class of anatomical structures exhibiting complex geometries and topologies, including the mandible. In this paper we propose methodology based on non-rigid deformations of 3D geometries to be applied to objects with thin, complex structures. We are able to accurately and quantitatively characterize bone healing at the osteotomy site as well as condylar remodeling for three orthognathic surgery cases, demonstrating the effectiveness of the proposed methodology.


  • R01 EB021391/EB/NIBIB NIH HHS/United States
Signed corresponding distance computed between a-e-h) T1 and T2 shapes, displayed on T1, b-f-i) T2 and T3, displayed on T2, c-f-i) T3 and T4, displayed on T3 and d) T4 and T5, displayed on T4. "Measurements were made using ModelToModelDistance [14], a surface to surface distance plugin in 3D Slicer."]

Development of a Hybrid Computational/Experimental Framework for Evaluation of Damage Mechanisms of a Linked Semiconstrained Total Elbow System

Publication: J Shoulder Elbow Surg. 2018 Apr;27(4):614-23. PMID: 29305101

Authors: Sharifi Kia D, Willing R.

Institution: Biomechanics and Orthopedic Design Laboratory, Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY, USA.


Background: Long-term durability of total elbow arthroplasty (TEA) is a concern, and bearing wear or excessive deformations may necessitate early revision. The current study used experimental wear testing and computational finite element modeling to develop a hybrid computational and experimental framework for the evaluation of TEA damage mechanisms.

Methods: Three Coonrad-Morrey (Zimmer-Biomet Inc., Warsaw, IN, USA) TEA implants were used for experimental wear testing for 200,000  cycles. Gravimetric measurements were performed before and after the tests to assess the weight change caused by wear. A finite element model of the implant was also developed to analyze ultrahigh-molecular-weight polyethylene (UHMWPE) damage.

Results: High localized contact pressures caused visible creep and plastic flow, deforming bushings and creating unintended UHMWPE-on-UHMWPE contact surfaces where considerably high wear rates were observed. Average experimentally measured vs. model-predicted wear was 9.5 ± 1.0 vs. 14.1 mg for the of the medial bushing, 8.5 ± 1.0 vs. 13.9 mg for the lateral humeral bushing, and 34.1 ± 0.7 vs. 36.9 mg for the ulnar bushings, respectively. Model predicted contact stresses on the surfaces of bushings were substantially higher than the yield limit of conventional UHMWPE (87 MPa for the humeral bushings and 83 MPa for the ulnar bushing).

Conclusions: Our study discovered that unintended wear at UHMWPE-UHMWPE contact surfaces, "fed" by excessive plastic flow may, in fact, be of more concern than wear that occurs at the intended metal-UHMWPE contact interfaces. Furthermore, formation of high localized contact stresses much above the yield limit of UHMWPE is another likely contributor to bushing failure for this implant.

"...files were imported into 3D Slicer for 3-dimensional (3D) model reconstruction."

Simulation of the Human Airways using Virtual Topology Tools and Meshing Optimization

Publication: Biomech Model Mechanobiol. 2018 Apr;17(2):465-77. PMID: 29105007

Authors: Fernández-Tena A, Marcos AC, Agujetas R, Ferrera C.

Institution: Central University Hospital of Asturias, Oviedo, Spain.


A method is proposed to improve the quality of the three-dimensional airway geometric models using a commercial software, checking the number of elements, meshing time, and aspect ratio and skewness parameters. The use of real and virtual topologies combined with patch-conforming and patch-independent meshing algorithms results in four different models being the best solution the combination of virtual topology and patch-independent algorithm, due to an excellent aspect ratio and skewness of the elements, and minimum meshing time. The result is a reduction in the computational time required for both meshing and simulation due to a smaller number of cells. The use of virtual topologies combined with patch-independent meshing algorithms could be extended in bioengineering because the geometries handling is similar to this case. The method is applied to a healthy person using their computed tomography images. The resulting numerical models are able to simulate correctly a forced spirometry.

"As all human tissues are classified under the Hounsfield scale, the 3D Slicer software was used to group similar grey values, identifying the threshold between the different tissues and extracting the human airways."

Planning of Skull Reconstruction Based on a Statistical Shape Model Combined with Geometric Morphometrics

Publication: Int J Comput Assist Radiol Surg. 2018 Apr;13(4):519-29. PMID: 29080945

Authors: Fuessinger MA, Schwarz S, Cornelius CP, Metzger MC, Ellis E 3rd, Probst F, Semper-Hogg W, Gass M, Schlager S.

Institution: Department of Oral and Maxillofacial Surgery, Albert-Ludwigs University, Freiburg, Germany.


Purpose: Virtual reconstruction of large cranial defects is still a challenging task. The current reconstruction procedures depend on the surgeon's experience and skills in planning the reconstruction based on mirroring and manual adaptation. The aim of this study is to propose and evaluate a computer-based approach employing a statistical shape model (SSM) of the cranial vault.

Methods: An SSM was created based on 131 CT scans of pathologically unaffected adult crania. After segmentation, the resulting surface mesh of one patient was established as template and subsequently registered to the entire sample. using the registered surface meshes, an SSM was generated capturing the shape variability of the cranial vault. The knowledge about this shape variation in healthy patients was used to estimate the missing parts. The accuracy of the reconstruction was evaluated by using 31 CT scans not included in the SSM. Both unilateral and bilateral bony defects were created on each skull. The reconstruction was performed using the current gold standard of mirroring the intact to the affected side, and the result was compared to the outcome of our proposed SSM-driven method. The accuracy of the reconstruction was determined by calculating the distances to the corresponding parts on the intact skull.

Results: While unilateral defects could be reconstructed with both methods, the reconstruction of bilateral defects was, for obvious reasons, only possible employing the SSM-based method. Comparing all groups, the analysis shows a significantly higher precision of the SSM group, with a mean error of 0.47 mm compared to the mirroring group which exhibited a mean error of 1.13 mm. Reconstructions of bilateral defects yielded only slightly higher estimation errors than those of unilateral defects.

Conclusion: The presented computer-based approach using SSM is a precise and simple tool in the field of computer-assisted surgery. It helps to reconstruct large-size defects of the skull considering the natural asymmetry of the cranium and is not limited to unilateral defects.

"Segmentation was done with 3D Slicer".

Contribution of 3D Printing to Mandibular Reconstruction after Cancer

Publication: Eur Ann Otorhinolaryngol Head Neck Dis. 2018 Apr;135(2):133-6. PMID: 29100719

Authors: Dupret-Bories A, Vergez S, Meresse T, Brouillet F, Bertrand G.

Institution: Chirurgie ORL et cervico-faciale, Institut Universitaire du Cancer Toulouse Oncopole, Institut Claudius-Regaud, Toulouse, France.


Three-dimensional (3D) printing is booming in the medical field. This technology increases the possibilities of personalized treatment for patients, while lowering manufacturing costs. To facilitate mandibular reconstruction with fibula free flap, some companies propose cutting guides obtained by CT-guided moulding. However, these guides are prohibitively expensive (€2,000 to €6,000). Based on a partnership with the CNRS, engineering students and a biomedical company, the authors have developed cutting guides and 3D-printed mandible templates, deliverable in 7days and at a lower cost. The novelty of this project is the speed of product development at a significantly lower price. In this technical note, the authors describe the logistic chain of production of mandible templates and cutting guides, as well as the results obtained. The goal is to allow access to this technology to all patients in the near future. "In order to demonstrate the feasibility and potential cost reduction, we preferred to use a free access software suite (3D Slicer, Blender, 3D Builder)"

Optimizing Image Quantification for Lu-177 SPECT/CT Based on a 3D Printed 2-Compartment Kidney Phantom

Publication: J Nucl Med. 2018 Apr;59(4):616-624. PMID: 29097409

Authors: Tran-Gia J, Lassmann M.

Institution: University of Würzburg, Germany.


Aims: The aim of this work was to find an optimal setup for activity determination of Lu-177-based single photon emission computed tomography (SPECT) / computed tomography (CT) imaging reconstructed with two commercially available reconstructions (xSPECT Quant and Flash3D, Siemens Healthcare). For this purpose, 3D printed phantoms of different geometries were manufactured, different partial volume correction (PVC) methods were applied, and the accuracy of the activity determination was evaluated.

Methods: A 2-compartment kidney phantom (70% cortical and 30% medullary compartment), a sphere, and an ellipsoid of equal volumes were 3D printed, filled with Lu-177, and scanned with a SPECT/CT system. Reconstructions were performed with xSPECT and Flash3D. Different PVC methods were applied to find an optimal quantification setup: 1) Geometry-specific recovery coefficient based on the 3D printing model. 2) Geometry-specific recovery coefficient based on the low-dose CT. 3) Enlarged volume-of-interest (VOI) including spilled-out counts. 4) Activity concentration in the peak milliliter applied to the entire CT-based volume. 5) Fixed threshold of 42% of the maximum in a large volume containing the object-of-interest. Additionally, the influence of post-reconstruction Gaussian filtering was investigated.

Results: While the recovery coefficients of sphere and ellipsoid only differed by 0.7%, a difference of 31.7% was observed between the sphere and renal cortex phantoms . Without post-filtering, the model-based recovery coefficients (methods 1 and 2) resulted in the best accuracies (xSPECT: 1.5%, Flash3D: 10.3%), followed by the enlarged volume (xSPECT: 8.5%, Flash3D: 13.0%). The peak-milliliter method showed large errors only for sphere and ellipsoid (xSPECT: 23.4%, Flash3D: 21.6%). Applying a 42%-threshold led to the largest quantification errors (xSPECT: 32.3%, Flash3D: 46.7%). After post-filtering, a general increase of the errors was observed.

Conclusion: In this work, 3D printing was used as prototyping technique for a geometry-specific investigation of SPECT/CT reconstruction parameters and PVC methods. An optimal setup for activity determination was found to be an unsmoothed SPECT/CT reconstruction in combination with a recovery coefficient calculated based on the low-dose CT. The difference between spherical and renal recovery coefficients suggests that the typically applied volume-dependent but only sphere-based recovery coefficient lookup tables should be replaced by a more geometry-specific alternative.

"The highly-resolved mask as well as the filling volume were extracted from the low-dose CT using 3D Slicer."

Endocardial Infarct Scar Recognition by Myocardial Electrical Impedance is not Influenced by Changes in Cardiac Activation Sequence

Publication: Heart Rhythm. 2018 Apr;15(4):589-96. PMID: 29197656

Authors: Amorós-Figueras G, Jorge E, Alonso-Martin C, Traver D, Ballesta M, Bragós R, Rosell-Ferrer J, Cinca J.

Institution: Department of Cardiology, Hospital de la Santa Creu, Autonomous University of Barcelona, Barcelona, Spain.


Background: Measurement of myocardial electrical impedance can allow recognition of infarct scar and is theoretically not influenced by changes in cardiac activation sequence, but this is not known.

Objectives: The objectives of this study were to evaluate the ability of endocardial electrical impedance measurements to recognize areas of infarct scar and to assess the stability of the impedance data under changes in cardiac activation sequence.

Methods: One-month-old myocardial infarction confirmed by cardiac magnetic resonance imaging was induced in 5 pigs submitted to coronary artery catheter balloon occlusion. Electroanatomic data and local electrical impedance (magnitude, phase angle, and amplitude of the systolic-diastolic impedance curve) were recorded at multiple endocardial sites in sinus rhythm and during right ventricular pacing. By merging the cardiac magnetic resonance and electroanatomic data, we classified each impedance measurement site either as healthy (bipolar amplitude ≥1.5 mV and maximum pixel intensity <40%) or scar (bipolar amplitude <1.5 mV and maximum pixel intensity ≥40%).

Results: A total of 137 endocardial sites were studied. Compared to healthy tissue, areas of infarct scar showed 37.4% reduction in impedance magnitude (P < .001) and 21.5% decrease in phase angle (P < .001). The best predictive ability to detect infarct scar was achieved by the combination of the 4 impedance parameters (area under the receiver operating characteristic curve 0.96; 95% confidence interval 0.92-1.00). In contrast to voltage mapping, right ventricular pacing did not significantly modify the impedance data.

Conclusion: Endocardial catheter measurement of electrical impedance can identify infarct scar regions, and in contrast to voltage mapping, the impedance data are not affected by changes in cardiac activation sequence.

"Processing of the LGE-CMR data was performed using the 3D Slicer software."

Regional Hippocampal Vulnerability in Early Multiple Sclerosis: Dynamic Pathological Spreading from Dentate Gyrus to CA1

Publication: Hum Brain Mapp. 2018 Apr;39(4):1814-24. PMID: 29331060

Authors: Planche V, Koubiyr I, Romero JE, Manjon JV, Coupé P, Deloire M, Dousset V, Brochet B, Ruet A, Tourdias T.

Institution: Universiry of Bordeaux, Bordeaux, France.



Whether hippocampal subfields are differentially vulnerable at the earliest stages of multiple sclerosis (MS) and how this impacts memory performance is a current topic of debate.


We prospectively included 56 persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year longitudinal study, together with 55 matched healthy controls at baseline. Participants were tested for memory performance and scanned with 3 T MRI to assess the volume of 5 distinct hippocampal subfields using automatic segmentation techniques.


At baseline, CA4/dentate gyrus was the only hippocampal subfield with a volume significantly smaller than controls (p < .01). After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively). CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2  = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as covariates). The volume of CA4/dentate gyrus at baseline was associated with MS diagnosis during follow-up, independently of T2-lesion load and demographic variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with memory scores at baseline, CA1 atrophy was an independent correlate of episodic verbal memory performance one year after CIS (ß = 0.87, p < .05).


The hippocampal degenerative process spread from dentate gyrus to CA1 at the earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis after CIS and will ultimately impact hippocampal-dependent memory performance.

"Binary maps of lesions were reviewed and corrected manually by two blinded experts (MR engineer and neurologist), using 3D Slicer 4.4.0."

Effects of Total Saponins from Trillium Tschonoskii Rhizome on Grey and White Matter Injury Evaluated by Quantitative Multiparametric MRI in a Rat Model of Ischemic Stroke

Publication: J Ethnopharmacol. 2018 Apr 6;215:199-209. PMID: 29309860

Authors: Li M, Ouyang J, Zhang Y, Cheng BCY, Zhan Y, Yang L, Zou H, Zhao H.

Institution: School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.


Ethnopharmacological Relevance: Trillium tschonoskii rhizome (TTR), a medicinal herb, has been traditionally used to treat traumatic brain injury and headache in China. Although the potential neuroprotective efficacy of TTR has gained increasing interest, the pharmacological mechanism remains unclear. Steroid saponins are the main bioactive components of the herb.

Aim of Study: To investigate the protective and repair-promoting effects of the total saponins from TTR (TSTT) on grey and white matter damages in a rat model of middle cerebral artery occlusion (MCAO) using magnetic resonance imaging (MRI) assay.

Materials and Methods: Ischemic stroke was induced by MCAO. TSTT and Ginaton (positive control) were administered orally to rats 6h after stroke and daily thereafter. After 15 days of treatment, the survival rate of each group was calculated. We then conducted neurological deficit scores and beam walking test to access the neurological function after ischemic stroke. Subsequently, T2-weighted imaging (T2WI) and T2 relaxometry mapping were performed to measure infarct volume and grey and white matter integrity, respectively. Moreover, diffusion tensor imaging (DTI) was carried out to evaluate the grey and white matter microstructural damage. Additionally, arterial spin labelling (ASL) - cerebral blood flow (CBF) and magnetic resonance angiography (MRA) images provided dynamic information about vascular hemodynamic dysfunction after ischemic stroke. Finally, haematoxylin and eosin (HE) staining was carried out to evaluate the stroke-induced pathological changes in the brain.

Results: The survival rate and neurological behavioural outcomes (Bederson scores and beam walking tests) were markedly ameliorated by TSTT (65mg/kg) treatment within 15 days after ischemic stroke. Moreover, T2WI and T2 relaxometry mapping showed that TSTT (65mg/kg) significantly reduced infarct volume and attenuated grey and white matter injury, respectively, which was confirmed by histopathological evaluation of brain tissue. The results obtained from DTI showed that TSTT (65mg/kg) not only significantly alleviated axonal damage and demyelination, but also promoted axonal remodelling and re-myelination. In addition, TSTT treatment also enhanced vascular signal density and increased CBF in rats after MCAO.

Conclusion: Our results suggested the potential protective and repair-promoting effects of TSTT on grey and white matter from damage induced by ischemia. This study provides a modern pharmacological basis for the application of TSTT in managing ischemic stroke.

"To determine the orientation and integrity of fibre systems, fibre tractography was conducted using 3D Slicer software."

Optimized Programming Algorithm for Cylindrical and Directional Deep Brain Stimulation Electrodes

Publication: J Neural Eng. 2018 Apr;15(2):026005. PMID: 29235446

Authors: Anderson DN, Osting B, Vorwerk J, Dorval AC, Butson CR.

Institution: Bioengineering, University of Utah, Salt Lake City, UT, USA.

Abstract: Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs.&#13; &#13; Approach: Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts).&#13; &#13; Main Results: The optimization algorithm returns patient-specific contact configurations in near real-time - less than ten seconds for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region whereas the Medtronic 3389 could only activate 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 only activated 2.9% of the STN.&#13; &#13; Significance: This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

"...used a deterministic streamline algorithm in 3D Slicer software package."

Temporomandibular Joint Regeneration: Proposal of a Novel Treatment for Condylar Resorption after Orthognathic Surgery using Transplantation of Autologous Nasal Septum Chondrocytes, and the First Human Case Report

Publication: Stem Cell Res Ther. 2018 Apr 7;9(1):94. PMID: 29625584 | PDF

Authors: de Souza Tesch R, Takamori ER, Menezes K, Carias RBV, Dutra CLM, de Freitas Aguiar M, Torraca TSS, Senegaglia AC, Rebelatto CLK, Daga DR, Brofman PRS, Borojevic R.

Institution: Centro de Medicina Regenerativa, Faculdade de Medicina de Petrópolis - FASE, Petrópolis, Brazil.

Abstract: BACKGROUND: Upon orthognathic mandibular advancement surgery the adjacent soft tissues can displace the distal bone segment and increase the load on the temporomandibular joint causing loss of its integrity. Remodeling of the condyle and temporal fossa with destruction of condylar cartilage and subchondral bone leads to postsurgical condylar resorption, with arthralgia and functional limitations. Patients with severe lesions are refractory to conservative treatments, leading to more invasive therapies that range from simple arthrocentesis to open surgery and prosthesis. Although aggressive and with a high risk for the patient, surgical invasive treatments are not always efficient in managing the degenerative lesions.

METHODS: We propose a regenerative medicine approach using in-vitro expanded autologous cells from nasal septum applied to the first proof-of-concept patient. After the required quality controls, the cells were injected into each joint by arthrocentesis. Results were monitored by functional assays and image analysis using computed tomography.

RESULTS: The cell injection fully reverted the condylar resorption, leading to functional and structural regeneration after 6 months. Computed tomography images showed new cortical bone formation filling the former cavity space, and a partial recovery of condylar and temporal bones. The superposition of the condyle models showed the regeneration of the bone defect, reconstructing the condyle original form.

CONCLUSIONS: We propose a new treatment of condylar resorption subsequent to orthognathic surgery, presently treated only by alloplastic total joint replacement. We propose an intra-articular injection of autologous in-vitro expanded cells from the nasal septum. The proof-of-concept treatment of a selected patient that had no alternative therapeutic proposal has given promising results, reaching full regeneration of both the condylar cartilage and bone at 6 months after the therapy, which was fully maintained after 1 year. This first case is being followed by inclusion of new patients with a similar pathological profile to complete an ongoing stage I/II study.

CT image three-dimensional reconstruction, being green before and red after the cell therapy injection. Note the filling of the bony defect in the right TMJ (black and yellow arrows). "After the segmentation, the next step of image analysis consisted of registering the scans and their respective three-dimensional volumetric models in a common coordinate system using a target region as the reference. This was done with 3D Slicer v.3.1 software."]

Validation of MRI to TRUS Registration for High-dose-rate Prostate Brachytherapy

Publication: Brachytherapy. 2018 Mar - Apr;17(2):283-90. PMID: 29331575

Authors: Poulin E, Boudam K, Pinter C, Kadoury S, Lasso A, Fichtinger G, Ménard C.

Institution: Laboratory for Percutaneous Surgery, School of Computing, Queen's University, Kingston, Canada.


PURPOSE: The objective of this study was to develop and validate an open-source module for MRI to transrectal ultrasound (TRUS) registration to support tumor-targeted prostate brachytherapy.

METHODS AND MATERIALS: In this study, 15 patients with prostate cancer lesions visible on multiparametric MRI were selected for the validation. T2-weighted images with 1-mm isotropic voxel size and diffusion weighted images were acquired on a 1.5T Siemens imager. Three-dimensional (3D) TRUS images with 0.5-mm slice thickness were acquired. The investigated registration module was incorporated in the open-source 3D Slicer platform, which can compute rigid and deformable transformations. An extension of 3D Slicer, SlicerRT, allows import of and export to DICOM-RT formats. For validation, similarity indices, prostate volumes, and centroid positions were determined in addition to registration errors for common 3D points identified by an experienced radiation oncologist.

RESULTS: The average time to compute the registration was 35 ± 3 s. For the rigid and deformable registration, respectively, Dice similarity coefficients were 0.87 ± 0.05 and 0.93 ± 0.01 while the 95% Hausdorff distances were 4.2 ± 1.0 and 2.2 ± 0.3 mm. MRI volumes obtained after the rigid and deformable registration were not statistically different (p > 0.05) from reference TRUS volumes. For the rigid and deformable registration, respectively, 3D distance errors between reference and registered centroid positions were 2.1 ± 1.0 and 0.4 ± 0.1 mm while registration errors between common points were 3.5 ± 3.2 and 2.3 ± 1.1 mm. Deformable registration was found significantly better (p < 0.05) than rigid registration for all parameters.

CONCLUSIONS: An open-source MRI to TRUS registration platform was validated for integration in the brachytherapy workflow.

Commissioning and Validation of Commercial Deformable Image Registration Software for Adaptive Contouring

Publication: Phys Med. 2018 Mar;47:1-8. PMID: 29609810

Authors: Jamema SV, Phurailatpam R, Paul SN, Joshi K, Deshpande DD.

Institution: Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.

Abstract: PURPOSE: To report the commissioning and validation of deformable image registration(DIR) software for adaptive contouring.

METHODS: DIR (SmartAdapt®v13.6) was validated using two methods namely contour propagation accuracy and landmark tracking, using physical phantoms and clinical images of various disease sites. Five in-house made phantoms with various known deformations and a set of 10 virtual phantoms were used. Displacement in lateral, anterio-posterior (AP) and superior-inferior (SI) direction were evaluated for various organs and compared with the ground truth. Four clinical sites namely, brain (n = 5), HN (n = 9), cervix (n = 18) and prostate (n = 23) were used. Organs were manually delineated by a radiation oncologist, compared with the deformable image registration (DIR) generated contours. 3D Slicer v4.5.0.1 was used to analyze Dice Similarity Co-efficient (DSC), shift in centre of mass (COM) and Hausdorff distances Hf95%/avg.

RESULTS: Mean (SD) DSC, Hf95% (mm), Hfavg (mm) and COM of all the phantoms 1-5 were 0.84 (0.2) mm, 5.1 (7.4) mm, 1.6 (2.2) mm, and 1.6 (0.2) mm respectively. Phantom-5 had the largest deformation as compared to phantoms 1-4, and hence had suboptimal indices. The virtual phantom resulted in consistent results for all the ROIs investigated. Contours propagated for brain patients were better with a high DSC score (0.91 (0.04)) as compared to other sites (HN: 0.84, prostate: 0.81 and cervix 0.77). A similar trend was seen in other indices too. The accuracy of propagated contours is limited for complex deformations that include large volume and shape change of bladder and rectum respectively. Visual validation of the propagated contours is recommended for clinical implementation.

CONCLUSION: The DIR algorithm was commissioned and validated for adaptive contouring.

Axial T2-weighted MR images of the thalamotomy lesion at the AC-PC plane at 24 hours and 1 year posttreatment, and volumetric segmentation of the lesion at 24 hours posttreatment (represented on T1-weighted sequences). Axial (Ax) are views bounded by AC, PC, midline, and insular cortex. Orange indicates zone I (necrotic core); yellow, zone II (cytotoxic edema); and blue, zone III (vasogenic edema). All axial images are shown at the AC-PC plane. Horizontal line across coronal (Cor) images represents the AC-PC plane. Arrows indicate the residual lesion at 1 year. Pt = patient.

Performance of Ultrafast DCE-MRI for Diagnosis of Prostate Cancer

Publication: Acad Radiol. 2018 Mar;25(3):349-58. PMID: 29167070

Authors: Chatterjee A, He D, Fan X, Wang S, Szasz T, Yousuf A, Pineda F, Antic T, Mathew M, Karczmar GS, Oto A.

Institution: Department of Radiology, The University of Chicago, Chicago, IL, USA.


Rationale and Objectives: This study aimed to test high temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for different zones of the prostate and evaluate its performance in the diagnosis of prostate cancer (PCa). Determine whether the addition of ultrafast DCE-MRI improves the performance of multiparametric MRI.

Materials and Methods: Patients (n = 20) with pathologically confirmed PCa underwent preoperative 3T MRI with T2-weighted, diffusion-weighted, and high temporal resolution (~2.2 seconds) DCE-MRI using gadoterate meglumine (Guerbet, Bloomington, IN) without an endorectal coil. DCE-MRI data were analyzed by fitting signal intensity with an empirical mathematical model to obtain parameters: percent signal enhancement, enhancement rate (α), washout rate (β), initial enhancement slope, and enhancement start time along with apparent diffusion coefficient (ADC) and T2 values. Regions of interests were placed on sites of prostatectomy verified malignancy (n = 46) and normal tissue (n = 71) from different zones.

Results: Cancer (α = 6.45 ± 4.71 s-1, β = 0.067 ± 0.042 s-1, slope = 3.78 ± 1.90 s-1) showed significantly (P <.05) faster signal enhancement and washout rates than normal tissue (α = 3.0 ± 2.1 s-1, β = 0.034 ± 0.050 s-1, slope = 1.9 ± 1.4 s-1), but showed similar percentage signal enhancement and enhancement start time. Receiver operating characteristic analysis showed area under the curve for DCE parameters was comparable to ADC and T2 in the peripheral (DCE 0.67-0.82, ADC 0.80, T2 0.89) and transition zones (DCE 0.61-0.72, ADC 0.69, T2 0.75), but higher in the central zone (DCE 0.79-0.88, ADC 0.45, T2 0.45) and anterior fibromuscular stroma (DCE 0.86-0.89, ADC 0.35, T2 0.12). Importantly, combining DCE with ADC and T2 increased area under the curve by ~30%, further improving the diagnostic accuracy of PCa detection.

Conclusion: Quantitative parameters from empirical mathematical model fits to ultrafast DCE-MRI improve diagnosis of PCa. DCE-MRI with higher temporal resolution may capture clinically useful information for PCa diagnosis that would be missed by low temporal resolution DCE-MRI. This new information could improve the performance of multiparametric MRI in PCa detection.

"… MR images from different pulse sequences were registered using rigid registration in 3D Slicer."

A Cost-Effective, In-House, Positioning and Cutting Guide System for Orthognathic Surgery

Publication: J Maxillofac Oral Surg. 2018 Mar;17(1):112-4. PMID: 29383005

Authors: McAllister P, Watson M, Burke E.

Institution: Department of Oral and Maxillofacial Surgery, St John's Hospital, Howden Road West, Livingston, UK.

Abstract: INTRODUCTION: Technological advances in 3D printing can dramatically improve orthognathic surgical planning workflow. Custom positioning and cutting guides enable intraoperative reproduction of pre-planned osteotomy cuts and can result in greater surgical accuracy and patient safety.

OBJECTIVES: This short paper describes the use of freeware (some with open-source) combined with in-house 3D printing facilities to produce reliable, affordable osteotomy cutting guides.

METHODS: Open-source software, 3D Slicer, is used to visualise and segment three-dimensional planning models from imported conventional computed tomography (CT) scans. Freeware (Autodesk Meshmixer ©) allows digital manipulation of maxillary and mandibular components to plan precise osteotomy cuts. Bespoke cutting guides allow exact intraoperative positioning. These are printed in polylactic acid (PLA) using a fused-filament fabrication 3D printer. Fixation of the osteotomised segments is achieved using plating templates and four pre-adapted plates with planned screw holes over the thickest bone. We print maxilla/ mandible models with desired movements incorporated to use as a plating template.

RESULTS: A 3D printer capable of reproducing a complete skull can be procured for £1000, with material costs in the region of £10 per case. Our production of models and guides typically takes less than 24 hours of total print time. The entire production process is frequently less than three days. Externally sourced models and guides cost significantly more, frequently encountering costs totalling £1500-£2000 for models and guides for a bimaxillary osteotomy.

CONCLUSION: Three-dimensional guided surgical planning utilising custom cutting guides enables the surgeon to determine optimal orientation of osteotomy cuts and better predict the skeletal maxilla/mandible relationship following surgery. The learning curve to develop proficiency using planning software and printer settings is offset by increased surgical predictability and reduced theatre time, making this form of planning a worthy investment.

Comparison of 3D Echocardiogram-Derived 3D Printed Valve Models to Molded Models for Simulated Repair of Pediatric Atrioventricular Valves

Publication: Pediatr Cardiol. 2018 Mar;39(3):538-47. PMID: 29181795

Authors: Scanlan AB, Nguyen AV, Ilina A, Lasso A, Cripe L, Jegatheeswaran A, Silvestro E, McGowan FX, Mascio CE, Fuller S, Spray TL, Cohen MS, Fichtinger G, Jolley MA.

Institution: Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.


Mastering the technical skills required to perform pediatric cardiac valve surgery is challenging in part due to limited opportunity for practice. Transformation of 3D echocardiographic (echo) images of congenitally abnormal heart valves to realistic physical models could allow patient-specific simulation of surgical valve repair. We compared materials, processes, and costs for 3D printing and molding of patient-specific models for visualization and surgical simulation of congenitally abnormal heart valves. Pediatric atrioventricular valves (mitral, tricuspid, and common atrioventricular valve) were modeled from transthoracic 3D echo images using semi-automated methods implemented as custom modules in 3D Slicer. Valve models were then both 3D printed in soft materials and molded in silicone using 3D printed "negative" molds. using pre-defined assessment criteria, valve models were evaluated by congenital cardiac surgeons to determine suitability for simulation. Surgeon assessment indicated that the molded valves had superior material properties for the purposes of simulation compared to directly printed valves (p < 0.01). Patient-specific, 3D echo-derived molded valves are a step toward realistic simulation of complex valve repairs but require more time and labor to create than directly printed models. Patient-specific simulation of valve repair in children using such models may be useful for surgical training and simulation of complex congenital cases.

A Preliminary Study on Precision Image Guidance for Electrode Placement in an EEG Study

Publication: Brain Topogr. 2018 Mar;31(2):174-85. PMID: 29204789

Authors: Trujillo P, Summers PE, Smith AK, Smith SA, Mainardi LT, Cerutti S, Claassen DO, Costa A.

Institution: Department of Robotics Engineering, DGIST, Daegu, Republic of Korea.


Conventional methods for positioning electroencephalography electrodes according to the international 10/20 system are based on the manual identification of the principal 10/20 landmarks via visual inspection and palpation, inducing intersession variations in their determined locations due to structural ambiguity or poor visibility. To address the variation issue, we propose an image guidance system for precision electrode placement. Following the electrode placement according to the 10/20 system, affixed electrodes are laser-scanned together with the facial surface. For subsequent procedures, the laser scan is conducted likewise after positioning the electrodes in an arbitrary manner, and following the measurement of fiducial electrode locations, frame matching is performed to determine a transformation from the coordinate frame of the position tracker to that of the laser-scanned image. Finally, by registering the intra-procedural scan of the facial surface to the reference scan, the current tracking data of the electrodes can be visualized relative to the reference goal positions without manually measuring the four principal landmarks for each trial. The experimental results confirmed that use of the electrode navigation system significantly improved the electrode placement precision compared to the conventional 10/20 system (p < 0.005). The proposed system showed the possibility of precise image-guided electrode placement as an alternative to the conventional manual 10/20 system. "An open-source software package, 3D Slicer was used as a basic visualization platform"


  • 17-BD-0401/Daegu Gyeongbuk Institute of Science and Technology/United States

Radiologic Factors Predicting Deterioration of Mental Status in Patients with Acute Traumatic Subdural Hematoma

Publication: World Neurosurg. 2018 Mar;111:e120-e134. PMID: 29248778

Authors: Won YD, Na MK, Ryu JI, Cheong JH, Kim JM, Kim CH, Han MH.

Institution: Department of Neurosurgery, Hanyang University Guri Hospital, Gyonggi-do, Korea.


OBJECTIVE: To evaluate whether subdural hematoma (SDH) volume and other radiologic factors predict deterioration of mental status in patients with acute traumatic SDH.

METHODS: SDH volumes were measured with a semiautomated tool. The area under the receiver operating characteristic curve was used to determine optimal cutoff values for mental deterioration, including the variables midline shift, SDH volume, hematoma thickness, and Sylvian fissure ratio. Multivariate logistic regression was used to calculate the odds ratio for mental deterioration based on several predictive factors.

RESULTS: We enrolled 103 consecutive patients admitted to our hospital with acute traumatic SDH over an 8-year period. We observed an increase in SDH volume of approximately 7.2 mL as SDH thickness increased by 1 mm. A steeper slope for midline shift was observed in patients with SDH volumes of approximately 75 mL in the younger age group compared with patients in the older age group. When comparing cutoff values used to predict poor mental status at time of admission between the 2 age groups, we observed smaller midline shifts in the older patients.

CONCLUSIONS: Among younger patients, an overall tendency for more rapid midline shift progression was observed in patients with relatively low SDH volumes compared with older patients. Older patients seem to tolerate larger hematoma volumes owing to brain atrophy compared with younger patients. When there is a midline shift, older patients seem to be more vulnerable to mental deterioration than younger patients.

"We measured hematoma volume with 3D Slicer software."

How to Precisely Measure the Volume Velocity Transfer Function of Physical Vocal Tract Models by External Excitation

Publication: PLoS One. 2018 Mar 15;13(3):e0193708. PMID: 29543829 | PDF

Authors: Fleischer M, Mainka A, Kürbis S, Birkholz P.

Institution: Division of Phoniatrics and Audiology, Department of Otorhinolaryngology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Abstract: Recently, 3D printing has been increasingly used to create physical models of the vocal tract with geometries obtained from magnetic resonance imaging. These printed models allow measuring the vocal tract transfer function, which is not reliably possible in vivo for the vocal tract of living humans. The transfer functions enable the detailed examination of the acoustic effects of specific articulatory strategies in speaking and singing, and the validation of acoustic plane-wave models for realistic vocal tract geometries in articulatory speech synthesis. To measure the acoustic transfer function of 3D-printed models, two techniques have been described: (1) excitation of the models with a broadband sound source at the glottis and measurement of the sound pressure radiated from the lips, and (2) excitation of the models with an external source in front of the lips and measurement of the sound pressure inside the models at the glottal end. The former method is more frequently used and more intuitive due to its similarity to speech production. However, the latter method avoids the intricate problem of constructing a suitable broadband glottal source and is therefore more effective. It has been shown to yield a transfer function similar, but not exactly equal to the volume velocity transfer function between the glottis and the lips, which is usually used to characterize vocal tract acoustics. Here, we revisit this method and show both, theoretically and experimentally, how it can be extended to yield the precise volume velocity transfer function of the vocal tract.

Printed and finite element models (A) Different views of the 3D-printed model of /a/. (B), (C) and (D) Finite element models of /a/, /u/ and /i/. For each model, the surface was partitioned into three regions representing the glottis, the lip region and the vocal tract walls. The merged voxel models for /a/, /u/ and /i/ were then converted back into triangle meshes using 3D Slicer. ]

Longitudinal Microstructural Changes of Cerebral White Matter and their Association with Mobility Performance in Older Persons

Publication: PLoS One. 2018 Mar 19;13(3):e0194051. PMID: 29554115 | PDF

Authors: Moscufo N, Wakefield DB, Meier DS, Cavallari M, Guttmann CRG, White WB3, Wolfson L.

Institution: Center for Neurological Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract: Mobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment.


  • M01 RR006192/RR/NCRR NIH HHS/United States
  • R01 AG022092/AG/NIA NIH HHS/United States
  • AG022092/NH/NIH HHS/United States
Relative spatial location of the regions of interest analyzed. Three-dimensional models of the sub-regions of the corpus callosum and corona radiata are illustrated. Models were produced in 3D Slicer using the MNI white matter parcellation map and they are shown overlaid on the MNI brain in sagittal (A), axial (B) and coronal (C) views. Regions shown are the anterior corona radiata (ACR, green), superior corona radiata (SCR, blue), posterior corona radiata (PCR, purple), genu of corpus callosum (GCC, red), body of corpus callosum (BCC, yellow), and splenium of corpus callosum (SCC, orange). Views are from left (A), top (B) and front (C) of head. For the regional assessment of the diffusion indices we used a mask with skeletonized ROIs in the subject native space.]

Micro-computed Tomographic Evaluation of the Shaping Ability of XP-endo Shaper, iRaCe, and EdgeFile Systems in Long Oval-shaped Canals

Publication: J Endod. 2018 Mar;44(3):489-95. PMID: 29273492

Authors: Versiani MA, Carvalho KKT, Mazzi-Chaves JF, Sousa-Neto MD.

Institution: Department of Restorative Dentistry, Dental School of Ribeirão Preto, University of São Paulo, Brazil.


INTRODUCTION: This study evaluated the shaping ability of the XP-endo Shaper (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland), iRaCe (FKG Dentaire SA), and EdgeFile (EdgeEndo, Albuquerque, NM) systems using micro-computed tomographic (micro-CT) technology.

METHODS: Thirty long oval-shaped canals from mandibular incisors were matched anatomically using micro-CT scanning (SkyScan1174v2; Bruker-microCT, Kontich, Belgium) and distributed into 3 groups (n = 10) according to the canal preparation protocol (ie, XP-endo Shaper, iRaCe, and EdgeFile systems). Coregistered images, before and after preparation, were evaluated for morphometric measurements of the volume, surface area, structure model index (SMI), untouched walls, area, perimeter, roundness, and diameter. Data were statistically compared between groups using the 1-way analysis of variance post hoc Tukey test and within groups with the paired sample t test (α = 5%).

RESULTS: Within groups, preparation significantly increased all tested parameters (P < .05). No statistical difference was observed in the mean percentage increase of the volume (〜52%) and surface area (10.8%-14.2%) or the mean percentage of the remaining unprepared canal walls between groups (8.17%-9.83%) (P > .05). The XP-endo Shaper significantly altered the overall geometry of the root canal to a more conical shape (SMI = 2.59) when compared with the other groups (P < .05). After preparation protocols, changes in area, perimeter, roundness, and minor and major diameters of the root canals in the 5 mm of the root apex showed no difference between groups (P > .05).

CONCLUSIONS: The XP-endo Shaper, iRaCe, and EdgeFile systems showed a similar shaping ability. Despite the XP-endo Shaper had significantly altered the overall geometry of the root canal to a more conical shape, neither technique was capable of completely preparing the long oval-shaped canals of mandibular incisors.

"...models of the canals were coregistered with their respective preoperative data sets using the rigid registration module of the 3D Slicer v.4.3.1 software"

Cerebral Radiation Necrosis: An Analysis of Clinical and Quantitative Imaging and Volumetric Features

Publication: World Neurosurg. 2018 Mar;111:e485-e494. PMID: 29288110

Authors: Feng R, Loewenstern J, Aggarwal A, Pawha P, Gilani A, Iloreta AM, Bakst R, Miles B, Bederson J, Costa A, Gupta V, Shrivastava R.


BACKGROUND: Radiation therapy (RT) is an effective treatment for primary brain tumors and intracranial metastases, but can occasionally precede new enhancing lesions on imaging studies that are difficult to discern between a tumor recurrence (TR) or radiation necrosis (RN). There is a need to identify clinical presentation and imaging patterns that may obviate the need for invasive definitive biopsy.

OBJECTIVE: To describe clinical and imaging characteristics of RN lesions compared to those from a TR.

METHODS: Patients who received RT and subsequently presented with a new intracranial lesion were reviewed from 2001-2016. Twenty-seven patients were identified with adequate records and confirmed pathology to have RN present or TR only. Patient and lesion characteristics were assessed utilizing univariate and multivariate logistic regression analyses. Sensitivity and specificities were calculated for imaging features and quantitatively segmented lesion and edema volumes for identifying RN.

RESULTS: Karnofsky Performance Status (KPS) at presentation significantly predicted pathological diagnosis on univariate analysis (p = 0.044). Radiation dosage and time from RT to lesion onset did not differ among pathological diagnosis groups. No differences existed between RN and TR on quantitative imaging analyses. Multivariate logistic regression found higher KPS to be an independent factor associated with TR relative to RN (OR = 1.26, 95% CI = 1.02-1.56, p = 0.030).

CONCLUSIONS: Diagnostic imaging can often be inaccurate in detecting RN alone, even with quantitative volume assessment. Functional status on re-presentation may increase the likelihood of accurate diagnosis prior to a definitive biopsy when neuroimaging remains unclear.

"...segmented for contrast-enhancement, lesion, and edema volumes using a semi-automatic image processing 3D Slicer software v.4.6."

Nonlinear Deformation of Tractography in Ultrasound-guided Low-grade Gliomas Resection

Publication: Int J Comput Assist Radiol Surg. 2018 Mar;13(3):457-67. PMID: 29299739

Authors: Xiao Y, Eikenes L, Reinertsen I, Rivaz H.

Institution: PERFORM Centre, Concordia University, Montreal, Canada.


Purpose: In brain tumor surgeries, maximum removal of cancerous tissue without compromising normal brain functions can improve the patient's survival rate and therapeutic benefits. To achieve this, diffusion MRI and intra-operative ultrasound (iUS) can be highly instrumental. While diffusion MRI allows the visualization of white matter tracts and helps define the resection plan to best preserve the eloquent areas, iUS can effectively track the brain shift after craniotomy that often renders the pre-surgical plan invalid, ensuring the accuracy and safety of the intervention. Unfortunately, brain shift correction using iUS and automatic registration has never been shown for brain tractography so far despite its rising significance in brain tumor resection.

Methods: We employed a correlation-ratio-based nonlinear registration algorithm to account for brain shift through MRI-iUS registration and used the recovered deformations to warp both the brain anatomy and tractography seen in pre-surgical plans. The overall technique was demonstrated retrospectively on four patients who underwent iUS-guided low-grade brain gliomas resection.

Results: Through qualitative and quantitative evaluations, the preoperative MRI and iUS scans were well realigned after nonlinear registration, and the deformed brain tumor volumes and white matter tracts showed large displacements away from the pre-surgical plans.

Conclusions: We are the first to demonstrate the technique to track nonlinear deformation of brain tractography using real clinical MRI and iUS data, and the results confirm the need for updating white matter tracts due to tissue shift during surgery.

"The results were visualized with the 3D Slicer software"

Lateral Ventricular Volume Asymmetry Predicts Poor Outcome After Spontaneous Intracerebral Hemorrhage

Publication: World Neurosurg. 2018 Feb;110:e958-e964. PMID: 29203311

Authors: Chen J, Zhang D, Li Z, Dong Y, Han K, Wang J, Hou L.

Institution: Department of Neurosurgery, Shanghai Institute of Neurosurgery, PLA Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.


Background: Midline shift (MLS) has been a known predictor for prognosis after spontaneous intracerebral hemorrhage (ICH), whereas it is secondary to lateral ventricular compression. In this study, we investigated whether lateral ventricular volume (LVV) asymmetry caused by ventricular compression was independently associated with poor outcome of ICH.

Methods: We retrospectively studied clinical patients with spontaneous ICH from January 2010 to January 2017. LVV was calculated using slicer software. LVV ratio (LVR) was then determined to quantitatively evaluate LVV asymmetry, and its relationship with poor outcome was tested by logistic regression model. Receiver operating characteristic (ROC) curve analysis was performed to identify the optimized baseline LVR cutoff point to predict poor outcome.

Results: 188 patients were included, of whom 41% (77/188) experienced a poor outcome. Multivariate logistic regression analysis identified baseline LVR as an independent predictor for poor outcome after ICH. The predictive value of baseline LVR was confirmed by ROC analysis (area under the curve = 0.742; P < 0.001). The optimized baseline LVR cutoff point was 3.7, with a sensitivity of 64.9% and specificity of 80.2%. using LVR >3.7 as an exposure factor yielded an odds ratio of 7.49 (P < 0.001), and a risk ratio of 2.98 (P < 0.001).

Conclusions: LVV asymmetry was associated with clinical prognosis after ICH, and high LVR (>3.7) might independently predict poor outcome.

"LVV and HV measurements were conducted using three dimensional 3D Slicer v. 4.0."

High Fidelity Virtual Reality Orthognathic Surgery Simulator

Publication: Proc SPIE Int Soc Opt Eng. 2018 Feb;10576. PMID: 29977103 | PDF

Authors: Arikatla VS, Tyagi M, Enquobahrie A, Nguyen T, Blakey GH, White R, Paniagua B.

Institution: Kitware Inc., Carrboro, NC, USA.

Abstract: Surgical simulators are powerful tools that assist in providing advanced training for complex craniofacial surgical procedures and objective skills assessment such as the ones needed to perform Bilateral Sagittal Split Osteotomy (BSSO). One of the crucial steps in simulating BSSO is accurately cutting the mandible in a specific area of the jaw, where surgeons rely on high fidelity visual and haptic cues. In this paper, we present methods to simulate drilling and cutting of the bone using the burr and the motorized oscillating saw respectively. Our method allows low computational cost bone drilling or cutting while providing high fidelity haptic feedback that is suitable for real-time virtual surgery simulation.


  • R43 DE027595/DE/NIDCR NIH HHS/United States
High-resolution model (obtained from CBCT) that illustrates the pre-surgical state of BSSO, with mandible rendered in full opening width. The model includes 3-dimensional reconstruction of craniofacial hard tissue (bone, in solid/semitransparent yellow) and soft tissue (vessels in solid red, gingiva in semitransparent pink) structures, rendered altogether with orthodontic appliances (brackets in solid blue). "In order to generate the 3D model of the bony structures of the patient we employed 3D Slicer Segmentation Module to threshold the scan of the patient."]

Volumetric Analysis of Magnetic Resonance-guided Focused Ultrasound Thalamotomy Lesions

Publication: Neurosurg Focus. 2018 Feb;44(2):E6. PMID: 29385921 | PDF

Authors: Harary M, Essayed WI, Valdes PA, McDannold N, Cosgrove GR.

Institution: Departments of Neurosurgery and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract: OBJECTIVE Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy was recently approved for use in the treatment of medication-refractory essential tremor (ET). Previous work has described lesion appearance and volume on MRI up to 6 months after treatment. Here, the authors report on the volumetric segmentation of the thalamotomy lesion and associated edema in the immediate postoperative period and 1 year following treatment, and relate these radiographic characteristics with clinical outcome. METHODS Seven patients with medication-refractory ET underwent MRgFUS thalamotomy at Brigham and Women's Hospital and were monitored clinically for 1 year posttreatment. Treatment effect was measured using the Clinical Rating Scale for Tremor (CRST). MRI was performed immediately postoperatively, 24 hours posttreatment, and at 1 year. Lesion location and the volumes of the necrotic core (zone I) and surrounding edema (cytotoxic, zone II; vasogenic, zone III) were measured on thin-slice T2-weighted images using 3D Slicer software. RESULTS Patients had significant improvement in overall CRST scores (baseline 51.4 ± 10.8 to 24.9 ± 11.0 at 1 year, p = 0.001). The most common adverse events (AEs) in the 1-month posttreatment period were transient gait disturbance (6 patients) and paresthesia (3 patients). The center of zone I immediately posttreatment was 5.61 ± 0.9 mm anterior to the posterior commissure, 14.6 ± 0.8 mm lateral to midline, and 11.0 ± 0.5 mm lateral to the border of the third ventricle on the anterior commissure-posterior commissure plane. Zone I, II, and III volumes immediately posttreatment were 0.01 ± 0.01, 0.05 ± 0.02, and 0.33 ± 0.21 cm3, respectively. These volumes increased significantly over the first 24 hours following surgery. The edema did not spread evenly, with more notable expansion in the superoinferior and lateral directions. The spread of edema inferiorly was associated with the incidence of gait disturbance. At 1 year, the remaining lesion location and size were comparable to those of zone I immediately posttreatment. Zone volumes were not associated with clinical efficacy in a statistically significant way. CONCLUSIONS MRgFUS thalamotomy demonstrates sustained clinical efficacy at 1 year for the treatment of medication-refractory ET. This technology can create accurate, predictable, and small-volume lesions that are stable over time. Instances of AEs are transient and are associated with the pattern of perilesional edema expansion. Additional analysis of a larger MRgFUS thalamotomy cohort could provide more information to maximize clinical effect and reduce the rate of long-lasting AEs.

Axial T2-weighted MR images of the thalamotomy lesion at the AC-PC plane at 24 hours and 1 year posttreatment, and volumetric segmentation of the lesion at 24 hours posttreatment (represented on T1-weighted sequences). Axial (Ax) are views bounded by AC, PC, midline, and insular cortex. Orange indicates zone I (necrotic core); yellow, zone II (cytotoxic edema); and blue, zone III (vasogenic edema). All axial images are shown at the AC-PC plane. Horizontal line across coronal (Cor) images represents the AC-PC plane. Arrows indicate the residual lesion at 1 year. Pt = patient.

SVA: Shape Variation Analyzer

Publication: Proc SPIE Int Soc Opt Eng. 2018 Feb;10578. PMID: 29780198 | PDF

Authors: de Dumast P, Mirabel C, Paniagua B, Yatabe M, Ruellas A, Tubau N, Styner M, Cevidanes L, Prieto JC.

Institution: University of Michigan, Ann Arbor, MI, USA.

Abstract: Temporo-mandibular osteo arthritis (TMJ OA) is characterized by progressive cartilage degradation and subchondral bone remodeling. The causes of this pathology remain unclear. Current research efforts are concentrated in finding new biomarkers that will help us understand disease progression and ultimately improve the treatment of the disease. In this work, we present Shape Variation Analyzer (SVA), the goal is to develop a noninvasive technique to provide information about shape changes in TMJ OA. SVA uses neural networks to classify morphological variations of 3D models of the mandibular condyle. The shape features used for training include normal vectors, curvature and distances to average models of the condyles. The selected features are purely geometric and are shown to favor the classification task into 6 groups generated by consensus between two clinician experts. With this new approach, we were able to accurately classify 3D models of condyles. In this paper, we present the methods used and the results obtained with this new tool.


  • R01 DE024450/DE/NIDCR NIH HHS/United States
  • R01 EB021391/EB/NIBIB NIH HHS/United States
  • U54 HD079124/HD/NICHD NIH HHS/United States

Manual segmentation of Condyles using ITK-SNAP. "Using EasyClip, a module included in 3D Slicer, the condylar models are simultaneously cropped to define the condylar region of interest. The cropped segmentation maps are used to generated regular tessellations."]

Automatic Quantification Framework to Detect Cracks in Teeth

Publication: Proc SPIE Int Soc Opt Eng. 2018 Feb;10578. PMID: 29769755 | PDF

Authors: Shah H, Hernandez P, Budin F, Chittajallu D, Vimort JB, Walters R, Mol A, Khan A, Paniagua B.

Institution: Kitware, Inc., Carrboro, NC, USA.

Abstract: Studies show that cracked teeth are the third most common cause for tooth loss in industrialized countries. If detected early and accurately, patients can retain their teeth for a longer time. Most cracks are not detected early because of the discontinuous symptoms and lack of good diagnostic tools. Currently used imaging modalities like Cone Beam Computed Tomography (CBCT) and intraoral radiography often have low sensitivity and do not show cracks clearly. This paper introduces a novel method that can detect, quantify, and localize cracks automatically in high resolution CBCT (hr-CBCT) scans of teeth using steerable wavelets and learning methods. These initial results were created using hr-CBCT scans of a set of healthy teeth and of teeth with simulated longitudinal cracks. The cracks were simulated using multiple orientations. The crack detection was trained on the most significant wavelet coefficients at each scale using a bagged classifier of Support Vector Machines. Our results show high discriminative specificity and sensitivity of this method. The framework aims to be automatic, reproducible, and open-source. Future work will focus on the clinical validation of the proposed techniques on different types of cracks ex-vivo. We believe that this work will ultimately lead to improved tracking and detection of cracks allowing for longer lasting healthy teeth.


  • R21 DE025306/DE/NIDCR NIH HHS/United States

Example of synthetic simulated dataset for a (a) healthy second molar, and(c) simulated crack sample. Data was post-processed to improve realism. (b) Healthy second molar after smoothing and (d) simulated crack sample after smoothing. Arrow points to the simulated crack. "Relevant anatomy of the teeth was segmented using 3D Slicer Segment Editor."]

Detection of Bone Loss via Subchondral Bone Analysis

Publication: Proc SPIE Int Soc Opt Eng. 2018 Feb;10578. PMID: 29769754 | PDF

Authors: Vimort JB, Ruellas A, Prothero J, Marron JS, McCormick M, Cevidanes L, Benavides E, Paniagua B.

Institution: Kitware, Inc., Carrboro, NC, USA.

Abstract: To date, there is no single sign, symptom, or test that can clearly diagnose early stages of Temporomandibular Joint Osteoarthritis (TMJ OA). However, it has been observed that changes in the bone occur in early stages of this disease, involving structural changes both in the texture and morphometry of the bone marrow and the subchondral cortical plate. In this paper we present a tool to detect and highlight subtle variations in subchondral bone structure obtained from high resolution Cone Beam Computed Tomography (hr-CBCT) in order to help with detecting early TMJ OA. The proposed tool was developed in ITK and 3D Slicer and it has been disseminated as open-source software tools. We have validated both our texture analysis and morphometry analysis biomarkers for detection of TMJ OA comparing hr-CBCT to μCT. Our initial statistical results using the multidimensional features computed with our tool indicate that it is possible to classify areas of demonstrated loss of trabecular bone in both μCT and hr-CBCT. This paper describes the first steps to alleviate the current inability of radiological changes to diagnose TMJ OA before morphological changes are too advanced by quantifying subchondral bone biomarkers. This paper indicates that texture based and morphometry based biomarkers have the potential to identify OA patients at risk for further bone destruction.


  • R21 DE025306/DE/NIDCR NIH HHS/United States

(left) NTotal, (center) NBone, highlighted in marron, and (right) NBoundary highlighted in marron lines.

Development of a Patient-specific Tumor Mold using Magnetic Resonance Imaging and 3-Dimensional Printing Technology for Targeted Tissue Procurement and Radiomics Analysis of Renal Masses

Publication: Urology. 2018 Feb;112:209-14. PMID: 29056576

Authors: Dwivedi DK, Chatzinoff Y, Zhang Y, Yuan Q, Fulkerson M, Chopra R, Brugarolas J, Cadeddu JA, Kapur P, Pedrosa I.

Institution: Department of Radiology, UT Southwestern Medical Center, Dallas, TX, USA.


Objective: To implement a platform for colocalization of in vivo quantitative multiparametric magnetic resonance imaging features with ex vivo surgical specimens of patients with renal masses using patient-specific 3-dimensional (3D)-printed tumor molds, which may aid in targeted tissue procurement and radiomics and radiogenomic analyses.

Materials and Methods: Volumetric segmentation of 6 renal masses was performed with 3D Slicer to create a 3D tumor model. A slicing guide template was created with specialized software, which included notches corresponding to the anatomic locations of the magnetic resonance images. The tumor model was subtracted from the slicing guide to create a depression in the slicing guide corresponding to the exact size and shape of the tumor. A customized, tumor-specific, slicing guide was then printed using a 3D printer. After partial nephrectomy, the surgical specimen was bivalved through the preselected magnetic resonance imaging (MRI) plane. A thick slab of the tumor was obtained, fixed, and processed as a whole-mount slide and was correlated to multiparametric MRI findings.

Results: All patients successfully underwent partial nephrectomy and adequate fitting of the tumor specimens within the 3D mold was achieved in all tumors. Distinct in vivo MRI features corresponded to unique pathologic characteristics in the same tumor. The average cost of printing each mold was US$160.7 ± 111.1 (range: US$20.9-$350.7).

Conclusion: MRI-based preoperative 3D printing of tumor-specific molds allow for accurate sectioning of the tumor after surgical resection and colocalization of in vivo imaging features with tissue-based analysis in radiomics and radiogenomic studies.

A Surface-based Approach to Determine Key Spatial Parameters of the Acetabulum in a Standardized Pelvic Coordinate System

Publication: Med Eng Phys. 2018 Feb;52:22-30. PMID: 29269225

Authors: Chen X, Jia P, Wang Y, Zhang H, Wang L, Frangi AF, Taylor ZA.

Institution: Institute of Biomedical Manufacturing and Life Quality Engineering, School of Mechanical Engineering, Shanghai Jiaotong University, Shanghai, China.

Abstract: Accurately determining the spatial relationship between the pelvis and acetabulum is challenging due to their inherently complex three-dimensional (3D) anatomy. A standardized 3D pelvic coordinate system (PCS) and the precise assessment of acetabular orientation would enable the relationship to be determined. We present a surface-based method to establish a reliable PCS and develop software for semi-automatic measurement of acetabular spatial parameters. Vertices on the acetabular rim were manually extracted as an eigenpoint set after 3D models were imported into the software. A reliable PCS consisting of the anterior pelvic plane, midsagittal pelvic plane, and transverse pelvic plane was then computed by iteration on mesh data. A spatial circle was fitted as a succinct description of the acetabular rim. Finally, a series of mutual spatial parameters between the pelvis and acetabulum were determined semi-automatically, including the center of rotation, radius, and acetabular orientation. Pelvic models were reconstructed based on high-resolution computed tomography images. Inter- and intra-rater correlations for measurements of mutual spatial parameters were almost perfect, showing our method affords very reproducible measurements. The approach will thus be useful for analyzing anatomic data and has potential applications for preoperative planning in individuals receiving total hip arthroplasty.

"Surface models are reconstructed from computed tomography (CT) data volumes through the threshold and region-growing segmentation method using 3D Slicer v.4.2."

Imaging of Concussion in Young Athletes

Publication: Neuroimaging Clin N Am. 2018 Feb;28(1):43-53. PMID: 29157852

Authors: Guenette JP, Shenton ME, Koerte IK.

Institution: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.


Conventional neuroimaging examinations are typically normal in concussed young athletes. A current focus of research is the characterization of subtle abnormalities after concussion using advanced neuroimaging techniques. These techniques have the potential to identify biomarkers of concussion. In the future, such biomarkers will likely provide important clinical information regarding the appropriate time interval before return to play, as well as the risk for prolonged postconcussive symptoms and long-term cognitive impairment. This article discusses results from advanced imaging techniques and emphasizes imaging modalities that will likely become available in the near future for the clinical evaluation of concussed young athletes.

"using a tool such as 3D Slicer (Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA), regions of interest within the brain can be manually segmented or parcellated."


  • R01 NS100952/NS/NINDS NIH HHS/United States
  • U01 NS093334/NS/NINDS NIH HHS/United States

Advantages and Disadvantages in Image Processing with Free Software in Radiology

Publication: J Med Syst. 2018 Jan 15;42(3):36. PMID: 29333590

Authors: Mujika KM, Méndez JAJ, de Miguel AF.

Institution: University Healthcare Complex of Salamanca, Salamanca, Spain.

Abstract: Currently, there are sophisticated applications that make it possible to visualize medical images and even to manipulate them. These software applications are of great interest, both from a teaching and a radiological perspective. In addition, some of these applications are known as Free Open Source Software because they are free and the source code is freely available, and therefore it can be easily obtained even on personal computers. Two examples of free open source software are Osirix Lite® and 3D Slicer®. However, this last group of free applications have limitations in its use. For the radiological field, manipulating and post-processing images is increasingly important. Consequently, sophisticated computing tools that combine software and hardware to process medical images are needed. In radiology, graphic workstations allow their users to process, review, analyse, communicate and exchange multidimensional digital images acquired with different image-capturing radiological devices. These radiological devices are basically CT (Computerised Tomography), MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography), etc. Nevertheless, the programs included in these workstations have a high cost which always depends on the software provider and is always subject to its norms and requirements. With this study, we aim to present the advantages and disadvantages of these radiological image visualization systems in the advanced management of radiological studies. We will compare the features of the VITREA2® and AW VolumeShare 5® radiology workstation with free open source software applications like OsiriX® and 3D Slicer®, with examples from specific studies.

WRIST: A WRist Image Segmentation Toolkit for Carpal bone Delineation from MRI

Publication: Comput Med Imaging Graph. 2018 Jan;63:31-40. PMID: 29331208

Authors: Foster B, Joshi AA, Borgese M, Abdelhafez Y, Boutin RD, Chaudhari A.

Institution: Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.


Segmentation of the carpal bones from 3D imaging modalities, such as magnetic resonance imaging (MRI), is commonly performed for in vivo analysis of wrist morphology, kinematics, and biomechanics. This crucial task is typically carried out manually and is labor intensive, time consuming, subject to high inter- and intra-observer variability, and may result in topologically incorrect surfaces. We present a method, WRist Image Segmentation Toolkit (WRIST), for 3D semi-automated, rapid segmentation of the carpal bones of the wrist from MRI. In our method, the boundary of the bones were iteratively found using prior known anatomical constraints and a shape-detection level set. The parameters of the method were optimized using a training dataset of 48 manually segmented carpal bones and evaluated on 112 carpal bones which included both healthy participants without known wrist conditions and participants with thumb basilar osteoarthritis (OA). Manual segmentation by two expert human observers was considered as a reference. On the healthy subject dataset we obtained a Dice overlap of 93.0 ± 3.8, Jaccard Index of 87.3 ± 6.2, and a Hausdorff distance of 2.7 ± 3.4 mm, while on the OA dataset we obtained a Dice overlap of 90.7 ± 8.6, Jaccard Index of 83.0 ± 10.6, and a Hausdorff distance of 4.0 ± 4.4 mm. The short computational time of 20.8 s per bone (or 5.1 s per bone in the parallelized version) and the high agreement with the expert observers gives WRIST the potential to be utilized in musculoskeletal research. v.4.6."

"Our work aimed at providing improved segmentation accuracy compared to existing methods while also having significantly decreased computational time. It was implemented as an open-source module for the popular image analysis tool, 3D Slicer."

Outer Wall Segmentation of Abdominal Aortic Aneurysm by Variable Neighborhood Search Through Intensity and Gradient Spaces

Publication: CJ Digit Imaging. 2018 Jan 19. PMID: 29352385

Authors: Siriapisith T, Kusakunniran W, Haddawy P2.

Institution: Department Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Abstract: Aortic aneurysm segmentation remains a challenge. Manual segmentation is a time-consuming process which is not practical for routine use. To address this limitation, several automated segmentation techniques for aortic aneurysm have been developed, such as edge detection-based methods, partial differential equation methods, and graph partitioning methods. However, automatic segmentation of aortic aneurysm is difficult due to high pixel similarity to adjacent tissue and a lack of color information in the medical image, preventing previous work from being applicable to difficult cases. This paper uses uses a variable neighborhood search that alternates between intensity-based and gradient-based segmentation techniques. By alternating between intensity and gradient spaces, the search can escape from local optima of each space. The experimental results demonstrate that the proposed method outperforms the other existing segmentation methods in the literature, based on measurements of dice similarity coefficient and jaccard similarity coefficient at the pixel level. In addition, it is shown to perform well for cases that are difficult to segment.

"Ground truth segmentations were also obtained by manual segmentation with the 3D Slicer version 4.7.0."

Enhanced Preoperative Deep Inferior Epigastric Artery Perforator Flap Planning with a 3D-Printed Perforasome Template: Technique and Case Report

Publication: Brachytherapy. Plast Reconstr Surg Glob Open. 2018 Jan 23;6(1):e1644. PMID: 29464169 | PDF

Authors: Chae MP, Hunter-Smith DJ, Rostek M, Smith JA, Rozen WM.

Institution: Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.

Abstract: Optimizing preoperative planning is widely sought in deep inferior epigastric artery perforator (DIEP) flap surgery. One reason for this is that rates of fat necrosis remain relatively high (up to 35%), and that adjusting flap design by an improved understanding of individual perforasomes and perfusion characteristics may be useful in reducing the risk of fat necrosis. Imaging techniques have substantially improved over the past decade, and with recent advances in 3D printing, an improved demonstration of imaged anatomy has become available. We describe a 3D-printed template that can be used preoperatively to mark out a patient's individualized perforasome for flap planning in DIEP flap surgery. We describe this "perforasome template" technique in a case of a 46-year-old woman undergoing immediate unilateral breast reconstruction with a DIEP flap. Routine preoperative computed tomographic angiography was performed, with open-source software (3D Slicer, Autodesk MeshMixer and Cura) and a desktop 3D printer (Ultimaker 3E) used to create a template used to mark intra-flap, subcutaneous branches of deep inferior epigastric artery (DIEA) perforators on the abdomen. An individualized 3D printed template was used to estimate the size and boundaries of a perforasome and perfusion map. The information was used to aid flap design. We describe a new technique of 3D printing a patient-specific perforasome template that can be used preoperatively to infer perforasomes and aid flap design.

3D-printed perforasome template placed on top of 3D-printed DIEP template of the same patient demonstrating their accurate alignment.

DCE-MRI Pharmacokinetic-Based Phenotyping of Invasive Ductal Carcinoma: A Radiomic Study for Prediction of Histological Outcomes

Publication: Contrast Media Mol Imaging. 2018 Jan 17;2018:5076269. PMID: 29581709 | PDF

Authors: Monti S, Aiello M, Incoronato M, Grimaldi AM, Moscarino M, Mirabelli P, Ferbo U, Cavaliere C, Salvatore M.

Institution: IRCCS SDN, Naples, Italy.

Abstract: Breast cancer is a disease affecting an increasing number of women worldwide. Several efforts have been made in the last years to identify imaging biomarker and to develop noninvasive diagnostic tools for breast tumor characterization and monitoring, which could help in patients' stratification, outcome prediction, and treatment personalization. In particular, radiomic approaches have paved the way to the study of the cancer imaging phenotypes. In this work, a group of 49 patients with diagnosis of invasive ductal carcinoma was studied. The purpose of this study was to select radiomic features extracted from a DCE-MRI pharmacokinetic protocol, including quantitative maps of ktrans, kep, ve, iAUC, and R1 and to construct predictive models for the discrimination of molecular receptor status (ER+/ER-, PR+/PR-, and HER2+/HER2-), triple negative (TN)/non-triple negative (NTN), ki67 levels, and tumor grade. A total of 163 features were obtained and, after feature set reduction step, followed by feature selection and prediction performance estimations, the predictive model coefficients were computed for each classification task. The AUC values obtained were 0.826 ± 0.006 for ER+/ER-, 0.875 ± 0.009 for PR+/PR-, 0.838 ± 0.006 for HER2+/HER2-, 0.876 ± 0.007 for TN/NTN, 0.811 ± 0.005 for ki67+/ki67-, and 0.895 ± 0.006 for lowGrade/highGrade. In conclusion, DCE-MRI pharmacokinetic-based phenotyping shows promising for discrimination of the histological outcomes.

"... dynamic motion-corrected sequence and the bounding box were given as input to the SegmentCAD module of dynamic motion-corrected sequence and the bounding box were given as input to the SegmentCAD module of 3D Slicer, which automatically segmented the lesion on the basis of the temporal dynamic of the signal."

MRI-Based Experimentations of Fingertip Flat Compression: Geometrical Measurements and Finite Element Inverse Simulations to Investigate Material Property Parameters

Publication: J Biomech. 2018 Jan 23;67:166-71. PMID: 29217092

Authors: Dallard J, Merlhiot X, Petitjean N, Duprey S.

Institution: University of Lyon, France.


Modeling human-object interactions is a necessary step in the ergonomic assessment of products. Fingertip finite element models can help investigating these interactions, if they are built based on realistic geometrical data and material properties. The aim of this study was to investigate the fingertip geometry and its mechanical response under compression, and to identify the parameters of a hyperelastic material property associated to the fingertip soft tissues. Fingertip compression tests in an MRI device were performed on 5 subjects at either 2 or 4 N and at 15° or 50°. The MRI images allowed to document both the internal and external fingertip dimensions and to build 5 subject-specific finite element models. Simulations reproducing the fingertip compression tests were run to obtain the material property parameters of the soft tissues. results indicated that two ellipses in the sagittal and longitudinal plane could describe the external fingertip geometry. The internal geometries indicated an averaged maximal thickness of soft tissues of 6.4 ± 0.8 mm and a 4 ± 1 mm height for the phalanx bone. The averaged deflections under loading went from 1.8 ± 0.3 mm at 2 N, 50° to 3.1 ± 0.2 mm at 4 N, 15°. Finally, the following set of parameters for a second order hyperelastic law to model the fingertip soft tissues was proposed: C01=0.59 ± 0.09 kPa and C20 = 2.65 ± 0.88 kPa. These data should facilitate further efforts on fingertip finite element modeling. "For each MRI acquisition, manual segmentations were performed using 3D Slicer.

Objective Assessment of Colonoscope Manipulation Skills in Colonoscopy Training

Publication: Int J Comput Assist Radiol Surg. 2018 Jan;13(1):105-14. PMID: 29086234

Authors: Holden MS, Wang CN, MacNeil K, Church B, Hookey L, Fichtinger G, Ungi T.

Institution: Laboratory for Percutaneous Surgery, School of Computing, Queen's University, Kingston, ON, Canada.


Objective: Manipulation of the colonoscope is a technical challenge for novice clinicians which is best learned in a simulated environment. It involves the coordination of scope tip steering with scope insertion, using a rotated image as reference. The purpose of this work is to develop and validate a system which objectively assesses colonoscopy technical skills proficiency in an arbitrary training environment, allowing novices to assess their technical proficiency prior to real patient encounters.

Methods: We implemented a motion tracking setup to objectively analyze and assess the way operators perform colonoscopies, including an analysis of wrist and elbow joint motions. Subsequently, we conducted a validation study to verify whether our motion analysis could discriminate novice colonoscopists from experts. Participants navigated a wooden bench-top model using a standard colonoscope while their motions were tracked.

Results: The developed motion tracking setup allowed colonoscopists of varying levels of proficiency to have their colonoscope manipulation assessed, and was able to be operated by a trained non-technical operator. Novice operators had significantly greater median times (101.5 vs. 31.5 s) and number of hand movements (62.0 vs. 21.5) than experts. Experts, however, spent a significantly greater proportion of time in extreme ranges of wrist and elbow joint motion than novices.

Conclusion: We have developed and implemented a hand and joint motion analysis system that is able to discriminate novices from experts based on objective measures of motion. These metrics could, thus, serve as proxies for technical proficiency during training. "The PLUS software library was used to acquire and send the tracking data to the 3D Slicer software."

Primary Trigeminal Neuralgia is Associated with Posterior Fossa Crowdedness: A Prospective Case-Control Study

Publication: J Clin Neurosci. 2018 Jan;47:89-92. PMID: 29066228

Authors: Cheng J, Meng J, Liu W, Zhang H, Hui X, Lei D.

Institution: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.


Neurovascular conflict (NVC) has been postulated to be the underlying cause of trigeminal neuralgia (TN). Does the posterior fossa crowdedness increase the chance of NVC? The aim of this study was to quantitatively measure the posterior fossa crowdedness in patients with TN and to perform a comparison with healthy controls. We conducted a prospective case-control study of 46 patients diagnosed with primary TN and 46 sex- and age-matched healthy controls. All subjects underwent high-resolution three-dimensional MRI, and the 3D Slicer software was used to measure the posterior fossa volume (PFV) and hindbrain volume (HBV). The posterior fossa crowdedness index (PFCI) was calculated as HBV/PFV × 100%. The results showed that patients with TN had a larger HBV (155.4 ± 23.2 cm3 versus 152.9 ± 13.5 cm3, P = .16) and a smaller PFV (182.7 ± 18.3 cm3 versus 186.1 ± 11.7 cm3, P = .42) as compared to control subjects, but these values were not significantly different. The mean PFCI was significantly higher in patients with TN than in controls (85.1% ± 3.4% versus 82.2% ± 5.3%; P = .03). Women had a more crowded posterior fossa than men (85.8% ± 2.1% versus 84.1% ± 2.6%; P = .023) in patients with TN. The correlation analysis showed that a higher PFCI was associated with younger age (P = .02), woman (P = .014), and TN disease (P = .001). From this study, we conclude that patients with TN have a more crowded posterior fossa than healthy subjects. Women, younger age and TN disease are associated with a higher PFCI. The posterior fossa crowdedness may be a risk factor of NVC, and thus more likely to result in the genesis of TN.

Bone Marrow Drives Central Nervous System Regeneration after Radiation Injury

Publication: J Clin Invest. 2018 Jan 2;128(1):281-93. PMID: 29202481 | PDF

Authors: Dietrich J, Baryawno N, Nayyar N, Valtis YK1, Yang B, Ly I, Besnard A, Severe N, Gustafsson KU, Andronesi OC5, Batchelor TT, Sahay A, Scadden DT.

Institution: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.

Abstract: Nervous system injury is a frequent result of cancer therapy involving cranial irradiation, leaving patients with marked memory and other neurobehavioral disabilities. Here, we report an unanticipated link between bone marrow and brain in the setting of radiation injury. Specifically, we demonstrate that bone marrow-derived monocytes and macrophages are essential for structural and functional repair mechanisms, including regeneration of cerebral white matter and improvement in neurocognitive function. Using a granulocyte-colony stimulating factor (G-CSF) receptor knockout mouse model in combination with bone marrow cell transplantation, MRI, and neurocognitive functional assessments, we demonstrate that bone marrow-derived G-CSF-responsive cells home to the injured brain and are critical for altering neural progenitor cells and brain repair. Additionally, compared with untreated animals, animals that received G-CSF following radiation injury exhibited enhanced functional brain repair. Together, these results demonstrate that, in addition to its known role in defense and debris removal, the hematopoietic system provides critical regenerative drive to the brain that can be modulated by clinically available agents.

"Before segmentation, the images were ... corrected for intensity nonuniformity using N4ITK algorithm (60) available in 3D Slicer."

Mice were sacrificed and brains sectioned for immunohistochemical evidence of GFP+ donor cells. Original magnification, ×20 (CC and DG); ×40 (choroid plexus and perivascular region). n = 3 independent biological replicates. Data are presented as mean ± SEM. (B) Quantification of GFP+ cells in different brain regions evaluated at 2 and 8 weeks after irradiation showing a significant increase in the total number of GFP+ cells after 8 weeks in CC, DG, SVZ, and cortex. (C and D) Significant change in morphology of GFP+ cells over time with signs of cellular maturation and increase in branched morphology in various regions. Original magnification, ×40, except ×60 in DG and perivascular region, left-sided panel. (E–G) Phenotypical analysis of GFP+ cells demonstrate that the majority of cells colabel the microglial marker Iba-1 (see Figure 5C) and the monocyte-macrophage marker F4/80. Upper panel original magnification: ×20. Lower panel original magnification: ×40 (E). In addition, many GFP+ cells colabeled with B-III tubulin Upper panel original magnification: ×20. Lower panel original magnification: ×40 (F). (G) Quantification of GFP+ cells colabeling with Iba-1, F4/80, and B-III tubulin. Asterisks indicate a significant change relative to control. *P < 0.05; **P < 0.01; ***P < 0.001, 1-way ANOVA. n = 3 mice/group. Data are presented as mean ± SEM of biological replicates.

Quantitative Spinal Cord MRI in Radiologically Isolated Syndrome

Publication: Neurol Neuroimmunol Neuroinflamm. 2018 Jan 17;5(2):e436. PMID: 29359174 | PDF

Authors: Alcaide-Leon P, Cybulsky K, Sankar S, Casserly C, Leung G, Hohol M, Selchen D, Montalban X, Bharatha A, Oh J.

Institution: Department of Surgery, St. Michael's Hospital, University of Toronto, ON, Canada.

Abstract: OBJECTIVES: To assess whether quantitative spinal cord MRI (SC-MRI) measures, including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer imaging metrics were different in radiologically isolated syndrome (RIS) vs healthy controls (HCs).

METHODS: Twenty-four participants with RIS and 14 HCs underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4 were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and parallel diffusivity (MD, λ⊥, and λ||) and magnetization transfer ratio (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM) areas were also manually segmented. Multivariable linear regression was performed to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for age and sex.

RESULTS: In this cross-sectional study of participants with RIS, 71% had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already evidence of brain atrophy (p = 0.05). There were no significant differences in SC-DTI metrics, GM, WM, or CSA between RIS and HCs.

CONCLUSION: The SC demonstrates minimal microstructural changes suggestive of demyelination and inflammation in RIS. These findings are in contrast to established MS and raise the possibility that the SC may play an important role in triggering clinical symptomatology in MS. Prospective follow-up of this cohort will provide additional insights into the role the SC plays in the complex sequence of events related to MS disease initiation and progression.

"Manual segmentation of SC lesions was performed on the PSIR sequence between C1 and C7 using 3D Slicer by an experienced neuroradiologist."

Quantitative spinal cord MRI maps and segmentations (A) Manual segmentation of the spinal cord cross-sectional area (black line) on high-resolution T2*-weighted, gradient-echo sequence with magnetization-transfer (MT) prepulse, (B) manual segmentation of spinal cord gray matter (black dashed line) on T2*-weighted, gradient-echo sequence without MT prepulse, (C) axial cross section of the map of fractional anisotropy with superimposed region of interest (black dashed line), and (D) axial cross section of the map of magnetization transfer ratio with superimposed region of interest (white line).

Radiogenomic Analysis of Hypoxia Pathway is Predictive of Overall Survival in Glioblastoma

Publication: Sci Rep. 2018 Jan 8;8(1):7. PMID: 29311558 | PDF

Authors: Beig N, Patel J, Prasanna P, Hill V, Gupta A, Correa R, Bera K, Singh S, Partovi S, Varadan V, Ahluwalia M, Madabhushi A, Tiwari P.

Institution: Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH, USA.

Abstract: Hypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-term (STS), mid-term (MTS), and long-term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).

"The registration was performed using the General Registration (BRIANSFIT) module of 3D Slicer 4.5. Skull stripping was done using the skull-stripping module in 3D Slicer."

(a)–(c) show a 2D Gd-T1w MRI slice with expert-annotated necrosis (outlined in green), enhancing tumor (yellow) and edematous regions (brown) in 3 different GBM patients that exhibited low, medium, and high HES respectively. The corresponding Haralick feature map has been overlaid on the manually annotated tumor regions, for HESlow (d), HESmedium (e), and HEShigh (f).

Comparing Damage on Retrieved Total Elbow Replacement Bushings with Lab Worn Specimens Subjected to Varied Loading Conditions

Publication: J Orthop Res. 2018 Jan 9. PMID: 29315772

Authors: Willing R.

Institution: Department of Mechanical Engineering, Thomas J. Watson School of Engineering and Applied Science, State University of New York at Binghamton, Binghamton, NY, USA.

Abstract: Complication rates following total elbow replacement (TER) with conventional implants are relatively high due to mechanical failure involving the UHMWPE bushings. Unfortunately, there are no standardized pre-clinical durability testing protocols for assessing the durability of TER components. This study examines the damage observed on retrieved humeral bushings, and then uses in vitro durability testing with two different loading protocols to compare resulting damage. Damage on 25 pairs of retrieved humeral bushings was characterized using micro-computed tomographic imaging techniques. The damage was compared with that of in vitro test specimens which were subjected to 200K cycles of either high joint reaction force (high JRF) or high varus moment (high VM) loading. Material removal (mass loss) from bushing components was measured using gravimetric techniques. Thinning was less for retrieved bushings which were still assembled in their humeral component, versus bushings which were loose (0.3 ± 0.3 mm versus 0.6 ± 0.3 mm, p = 0.02). Comparing in vitro test specimens, thinning due to high VM loading was 0.9 ± 0.3 mm, versus 0.2 ± 0.0 mm for high JRF loading (p = 0.08); however, the actual material removal rates from the humeral bushings were not different between the two protocols (48 ± 5 mm3 /Mc versus 43 ± 2 mm3 /Mc, p = 1). Neither loading protocol could produce damage patterns fully representative of the spectrum of damage patterns observed on clinical retrievals. Pre-clinical testing should employ multiple loading protocols to characterize implant performance under a broader spectrum of usage. This article is protected by copyright. All rights reserved.

"DICOM files were imported into 3D Slicer for three-dimensional (3D) model reconstruction."

Paracrine Osteoprotegerin and β-catenin Stabilization Support Synovial Sarcomagenesis in Periosteal Cells

Publication: J Clin Invest. 2018 Jan 2;128(1):207-18. PMID: 29202462 | PDF

Authors: Barrott JJ, Illum BE, Jin H, Hedberg ML, Wang Y, Grossmann A, Haldar M, Capecchi MR, Jones KB.

Institution: Departments of Orthopaedics and Oncological Sciences, University of Utah, Salt Lake City, UT, USA.

Abstract: Synovial sarcoma (SS) is an aggressive soft-tissue sarcoma that is often discovered during adolescence and young adulthood. Despite the name, synovial sarcoma does not typically arise from a synoviocyte but instead arises in close proximity to bones. Previous work demonstrated that mice expressing the characteristic SS18-SSX fusion oncogene in myogenic factor 5-expressing (Myf5-expressing) cells develop fully penetrant sarcomagenesis, suggesting skeletal muscle progenitor cell origin. However, Myf5 is not restricted to committed myoblasts in embryos but is also expressed in multipotent mesenchymal progenitors. Here, we demonstrated that human SS and mouse tumors arising from SS18-SSX expression in the embryonic, but not postnatal, Myf5 lineage share an anatomic location that is frequently adjacent to bone. Additionally, we showed that SS can originate from periosteal cells expressing SS18-SSX alone and from preosteoblasts expressing the fusion oncogene accompanied by the added stabilization of β-catenin, which is a common secondary change in SS. Expression and secretion of the osteoclastogenesis inhibitory factor osteoprotegerin enabled early growth of SS18-SSX2-transformed cells, indicating a paracrine link between the bone and synovial sarcomagenesis. These findings explain the skeletal contact frequently observed in human SS and may provide alternate means of enabling SS18-SSX-driven oncogenesis in cells as differentiated as preosteoblasts.


  • P30 CA042014/CA/NCI NIH HHS/United States
  • R01 CA201396/CA/NCI NIH HHS/United States

Expression of SS18-SSX2 in postnatal Prx1CreERT2 lineage induces synovial sarcomagenesis. "Reconstructed images were analyzed and visualized using 3D Slicer, v.4.6.2""]

A New Device for Fiducial Registration of Image-guided Navigation System for Liver RFA

Publication: Int J Comput Assist Radiol Surg. Int J Comput Assist Radiol Surg. 2018 Jan;13(1):115-24. PMID: 28718001

Authors: Doba N, Fukuda H, Numata K, Hao Y, Hara K, Nozaki A, Kondo M, Chuma M, Tanaka K, Takebayashi S, Koizumi N, Kobayashi A, Tokuda J, Maeda S.

Institution: Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.


Purpose: Radiofrequency ablation for liver tumors (liver RFA) is widely performed under ultrasound guidance. However, discriminating between the tumor and the needle is often difficult because of cavitation caused by RFA-induced coagulation. An unclear ultrasound image can lead to complications and tumor residue. Therefore, image-guided navigation systems based on fiducial registration have been developed. Fiducial points are usually set on a patient's skin. But the use of internal fiducial points can improve the accuracy of navigation. In this study, a new device is introduced to use internal fiducial points using 2D US.

Methods: 3D Slicer as the navigation software, Polaris Vicra as the position sensor, and two target tumors in a 3D abdominal phantom as puncture targets were used. Also, a new device that makes it possible to obtain tracking coordinates in the body was invented. First, two-dimensional reslice images from the CT images using 3D Slicer were built. A virtual needle was displayed on the two-dimensional reslice image, reflecting the movement of the actual needle after fiducial registration. A phantom experiment using three sets of fiducial point configurations: one conventional case using only surface points, and two cases in which the center of the target tumor was selected as a fiducial point was performed. For each configuration, one surgeon punctured each target tumor ten times under guidance from the 3D Slicer display. Finally, a statistical analysis examining the puncture error was performed.

Results: The puncture error for each target tumor decreased significantly when the center of the target tumor was included as one of the fiducial points, compared with when only surface points were used.

Conclusion: This study introduces a new device to use internal fiducial points and suggests that the accuracy of image-guided navigation systems for liver RFA can be improved by using the new device.

Uncoupling N-acetylaspartate from Brain pathology: Implications for Canavan Disease Gene Therapy

Publication: Acta Neuropathol. 2018 Jan;135(1):95-113. PMID: 29116375 | PDF

Authors: von Jonquieres G, Spencer ZHT, Rowlands BD, Klugmann CB, Bongers A, Harasta AE, Parley KE, Cederholm J, Teahan O, Pickford R, Delerue F, Ittner LM, Fröhlich D, McLean CA, Don AS, Schneider M, Housley GD, Rae CD, Klugmann M

Institution: Translational Neuroscience Facility and Department of Physiology, School of Medical Sciences, UNSW Sydney, Sydney, Australia.


N-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease-a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation. We show that NAA-deficiency causes neurological deficits affecting unconscious defensive reactions aimed at protecting the body from external threat. This finding suggests, while NAA reduction is pivotal to treat Canavan disease, abrogating NAA synthesis should be avoided. At the other end of the spectrum, while predicting pathological severity in Canavan disease mice, increased brain NAA levels are not neurotoxic per se. In fact, in transgenic mice overexpressing the NAA synthesising enzyme Nat8l in neurons, supra-physiological NAA levels were uncoupled from neurological deficits. In contrast, elimination of aspartoacylase expression exclusively in oligodendrocytes elicited Canavan disease like pathology. Although conditional aspartoacylase deletion in oligodendrocytes abolished expression in the entire CNS, the remaining aspartoacylase in peripheral organs was sufficient to lower NAA levels, delay disease onset and ameliorate histopathology. However, comparable endpoints of the conditional and complete aspartoacylase knockout indicate that optimal Canavan disease gene replacement therapies should restore aspartoacylase expression in oligodendrocytes. On the basis of these findings we executed an ASPA gene replacement therapy targeting oligodendrocytes in Canavan disease mice resulting in reversal of pre-existing CNS pathology and lasting neurological benefits. This finding signifies the first successful post-symptomatic treatment of a white matter disorder using an adeno-associated virus vector tailored towards oligodendroglial-restricted transgene expression.

"Whole brain and ventricle structures were segmented using thresholding and delineation methods provided by the 3D Slicer package."

Pathological consequences of manipulation of NAA metabolism. a qRT-PCR analysis of Aspa and Nat8l mRNA expression in CNS tissue from DKO and the parental single gene mutants (n = 3; expression relative to Hprt). Segmentation of images was performed in 3D Slicer outlining brain surface (yellow) and ventricles (blue). ]


Quantitative Texture Analysis in the Prediction of IDH Status in Low-grade Gliomas

Publication: Clin Neurol Neurosurg. 2017 Dec 5;164:114-20. PMID: 29220731 | PDF

Authors: Jakola AS, Zhang YH, Skjulsvik AJ, Solheim O, Bø HK, Berntsen EM, Reinertsen I, Gulati S, Förander P, Brismar TB.

Institution: Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract: OBJECTIVES: Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI).

PATIENTS AND METHODS: All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008-2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status.

RESULTS: In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p=0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion.

CONCLUSIONS: In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising.

"A radiologist experienced with LGG assessment and segmentation (H.K.B) performed the semiquantitative data interpretation and did the tumor segmentation in 3D Slicer.

Tumor with high homogeneity, 0.202 (upper) and low homogeneity, 0.065 (lower).

BRAF V600E Mutations a Significant Prognosticator of the Tumor Regrowth Rate in Brainstem Gangliogliomas

Publication: J Clin Neurosci. 2017 Dec;46:50-7. PMID: 28986151

Authors: Chen X, Pan C, Zhang P, Xu C, Sun Y, Yu H, Wu Y, Geng Y, Zuo P, Wu Z, Zhang J, Zhang L.

Institution: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.


BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.

A "Jail Escape Technique" (JET) for Distal Side Branch Wiring during Provisional Stenting: Feasibility and First-in-man Study

Publication: J Interv Cardiol. 2017 Dec;30(6):527-34. PMID: 29094411

Authors: Xiao H, Chen S, Wang G, Du R, Song Y, Jin J, Huang L, Jabbour R, Azzalini L, Zhao X.

Institution: Institution of Cardiovascular Research, Xinqiao Hospital, Third Military Medical University, Chongqing, China.


Objective: To evaluate the feasibility of a novel technique for achieving distal SB access and improve strut apposition during provisional stenting.

Background: While distal rewiring and stent expansion toward the side branch (SB) are associated with better results during provisional stenting of coronary artery bifurcation lesions, these techniques are technically challenging and often leave unopposed struts near the carina.

Methods: The "Jail Escape Technique" (JET) is performed by passing the proximal tip of the SB wire between the main vessel (MV) stent struts and balloon before implantation, allowing the MV stent to push the SB wire against the distal part of the carina. The MV stent can then be deployed without jailing the SB wire. Distal SB access and strut distribution at the carina were tested in phantom and swine models. Stent distortion, dislodgement forces, and material damage were evaluated with tensile testing. Human feasibility was then tested on 32 patients.

Results: Preclinical testing demonstrated that the SB wire was located at the most distal part of the carina and no strut malapposition at the carina was present after balloon inflation. Stent distortion, dislodgement forces, or material damage were not affected. JET was successfully performed in 30 of 32 patients. No major adverse cardiovascular events occurred in any patient at 6-month follow-up.

Conclusion: The "JET" enables distal SB access and eliminates strut malapposition at the carina. Further studies with larger numbers of patients are needed to further investigate this technique. "The images were segmented using 3D Slicer v3.6.3 to obtain both the lumen and stent geometry."

Effect of Temporomandibular Joint Articular Disc Repositioning on Anterior Open-bite Malocclusion: An 0rthodontic-surgical Approach

Publication: Am J Orthod Dentofacial Orthop. 2017 Dec;152(6):848-58. PMID: 29173864

Authors: Bianchi J, Pinto ADS, Ignácio J, Obelenis Ryan DP, Gonçalves JR.

Institution: Department of Pediatric Dentistry, Araraquara Dental School, Paulista State University, Araraquara, São Paulo, Brazil.


An anterior open bite is a challenge to orthodontic treatment; it has a multifactorial etiology and a wide range of intervention options. Temporomandibular joint (TMJ) disorders are a risk factor for the development of malocclusions such as the anterior open bite, especially in patients who have TMJ osteoarthritis with disc displacement. Articular disc repositioning surgery is an available option for treating this pathology, and it contributes to maintaining the condyles in a more stable position. The aim of this article was to report the case of a 20-year-old woman diagnosed with anterior open bite and TMJ osteoarthritis with bilateral disc displacement. The patient received both orthodontic treatment and TMJ disc repositioning surgery. Cone-beam computed tomography was used to create 3-dimensional models of the condyles with regional superposition, and assessment of bone remodeling was performed at different time intervals. Complete orthodontic and surgical treatment time was approximately 12 months. The results provided a stable correction of the patient's anterior open bite with a 2-year follow-up and favorable bone remodeling of the condyles due to functional improvement of the TMJ. "the same method of 3D model acquisition using 3D Slicer (SPHARM-PMD) and ITK-SNAP software during pretreatment was used for the 1-year posttreatment analysis."

Pool Size Ratio of the Substantia Nigra in Parkinson's Disease Derived from Two Different Quantitative Magnetization Transfer Approaches

Publication: Neuroradiology. 2017 Dec;59(12):1251-63. PMID: 28986653

Authors: Trujillo P, Summers PE, Smith AK, Smith SA, Mainardi LT, Cerutti S, Claassen DO, Costa A.

Institution: Department of Neuroradiology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milan, MI, Italy.


Purpose: We sought to measure quantitative magnetization transfer (qMT) properties of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease (PD) and healthy controls (HCs) using a full qMT analysis and determine whether a rapid single-point measurement yields equivalent results for pool size ratio (PSR).

Methods: Sixteen different MT-prepared MRI scans were obtained at 3 T from 16 PD patients and eight HCs, along with B1, B0, and relaxation time maps. Maps of PSR, free and macromolecular pool transverse relaxation times ([Formula: see text], [Formula: see text]) and rate of MT exchange between pools (k mf ) were generated using a full qMT model. PSR maps were also generated using a single-point qMT model requiring just two MT-prepared images. qMT parameter values of the SNc, red nucleus, cerebral crus, and gray matter were compared between groups and methods.

Results: PSR of the SNc was the only qMT parameter to differ significantly between groups (p < 0.05). PSR measured via single-point analysis was less variable than with the full MT model, provided slightly better differentiation of PD patients from HCs (area under curve 0.77 vs. 0.75) with sensitivity of 0.75 and specificity of 0.87, and was better than transverse relaxation time in distinguishing PD patients from HCs (area under curve 0.71, sensitivity 0.87, and specificity 0.50).

Conclusion: The increased PSR observed in the SNc of PD patients may provide a novel biomarker of PD, possibly associated with an increased macromolecular content. Single-point PSR mapping with reduced variability and shorter scan times relative to the full qMT model appears clinically feasible.

"Bilateral regions of interest (ROIs) in the SNc were segmented from the NM-MRI images using a thresholding method in the 3D Slicer v. 4.3.1 software package."


  • K23 NS080988/NS/NINDS NIH HHS/United States
  • R01 EY023240/EY/NEI NIH HHS/United States
  • R01 NS097783/NS/NINDS NIH HHS/United States
  • R21 NS087465/NS/NINDS NIH HHS/United States

Multiple Time Courses of Somatosensory Responses in Human Cortex

Publication: Neuroimage. 2017 Dec 14;169:212-6. PMID: 29248698

Authors: Avanzini P, Pelliccia V, Lo Russo G, Orban GA, Rizzolatti G.

Institution: CNR Institute of Neuroscience, National Research Council, Parma, Italy

Abstract: Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli.

"...multimodal scenes were built with the 3D Slicer software package."

Intracranial High-γ Connectivity Distinguishes Wakefulness from Sleep

Publication: Neuroimage. 2017 Dec 8;169:265-77. PMID: 29225064

Authors: Mikulan E, Hesse E, Sedeño L, Bekinschtein T, Sigman M, García MDC, Silva W, Ciraolo C, García AM, Ibáñez A.

Institution: Laboratory of Experimental Psychology and Neuroscience (LPEN), Institute of Cognitive and Translational Neuroscience (INCYT), INECO Foundation, Favaloro University, Buenos Aires, Argentina.

Abstract: Neural synchrony in the γ-band is considered a fundamental process in cortical computation and communication and it has also been proposed as a crucial correlate of consciousness. However, the latter claim remains inconclusive, mainly due to methodological limitations, such as the spectral constraints of scalp-level electroencephalographic recordings or volume-conduction confounds. Here, we circumvented these caveats by comparing γ-band connectivity between two global states of consciousness via intracranial electroencephalography (iEEG), which provides the most reliable measurements of high-frequency activity in the human brain. Non-REM Sleep recordings were compared to passive-wakefulness recordings of the same duration in three subjects with surgically implanted electrodes. Signals were analyzed through the weighted Phase Lag Index connectivity measure and relevant graph theory metrics. We found that connectivity in the high-γ range (90-120 Hz), as well as relevant graph theory properties, were higher during wakefulness than during sleep and discriminated between conditions better than any other canonical frequency band. Our results constitute the first report of iEEG differences between wakefulness and sleep in the high-γ range at both local and distant sites, highlighting the utility of this technique in the search for the neural correlates of global states of consciousness. "Electrode location was determined by co-registering the patient's post-implant CT and MRI scans in the3D Slicer software."

Preoperative Simulation Unveiled Undetected Surgical Difficulties in a Case of Cochlear Implantation

Publication: BMJ Case Rep. 2017 Dec 2;2017. PMID: 29197850

Authors: Matsumoto N, Yamashita M, Cho B, Hashizume M.

Institution: Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.


We herein report a case in which extensive preparation changed a difficult-to-treat patient into an easy one. We performed a revision cochlear implantation on a patient whose first procedure had been aborted due to unidentified difficulties. During a series of thorough three-dimensional simulations, we found that the patient in question had a normal cochlea but the cochlea was placed in an unusual position and orientation. This condition is difficult to detect on standard preoperative radiographic images. Through this simulation, we were able to propose a surgical plan to avoid making the same mistakes as the first surgeon. We present this case not as a rare difficult case of an unfortunate patient but instead emphasise the importance of performing surgical simulation and looking for non-obvious difficulties. This case is an example of the success that can be achieved with such extensive preparation. "We performed three-dimensional surgical simulation in the software program that we use for IGS 3D Slicer and Mimics, Materialise, Japan."

Investigating the Generalization of an Atlas-Based Synthetic-CT Algorithm to Another Centre and MR Scanner for Prostate MR-only Radiotherapy

Publication: Phys Med Biol. 2017 Nov 21;62(24):N548-N560. PMID: 29076457

Authors: Wyatt J, Dowling JA, Kelly CG, McKenna J, Johnstone E, Speight R, Henry A, Greer PB, McCallum HM.

Institution: Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, UK and Northern Ireland.


There is increasing interest in MR-only radiotherapy planning since it provides superb soft-tissue contrast without the registration uncertainties inherent in a CT-MR registration. However MR images cannot readily provide the electron density information necessary for radiotherapy dose calculation. An algorithm which generates synthetic CT's for dose calculations from MR images of the prostate using an atlas of 3 T MR images has been previously reported by two of the authors. This paper aimed to evaluate this algorithm using MR data acquired at a different field strength and a different centre to the algorithm atlas. 21 prostate patients received planning 1.5 T MR and CT scans with routine immobilisation devices on a flat-top couch set-up using external lasers. The MR receive coils were supported by a coil bridge. Synthetic CT's were generated from the planning MR images with (sCT<sub>1V</sub>) and without (sCT) a one voxel body contour expansion included in the algorithm. This was to test whether this expansion was required for 1.5 T images. Both synthetic CT's were rigidly registered to the planning CT (pCT). A 6 MV Volumetric Modulated Arc Therapy plan was created on the pCT and recalculated on the sCT and sCT1V The synthetic CT's dose distributions were compared to the dose distribution calculated on the pCT.&#13; &#13; The percentage dose difference at isocentre without the body contour expansion (sCT - pCT) was ΔD<sub>sCT</sub> = (0.9 ± 0.8) % and with (sCT<sub>1V</sub> - pCT) was ΔD<sub>sCT1V</sub> = (-0.7 ± 0.7) % (mean ± one standard deviation). The sCT<sub>1V</sub> result was within one standard deviation of zero and agreed with the result reported previously using 3 T MR data. The sCT dose difference only agreed within two standard deviations. The mean ± one standard deviation gamma pass rate was Γ<sub>sCT</sub> = 96.1 ± 2.9% for the sCT and Γ<sub>sCT1V</sub> = 98.8 ± 0.5% for the sCT<sub>1V </sub>(with 2% global dose difference and 2 mm distance to agreement gamma criteria). The one voxel body contour expansion improves the synthetic CT accuracy for MR images acquired at 1.5 T but requires the MR voxel size to be similar to the atlas MR voxel size. This study suggests that the atlas-based algorithm can be generalised to MR data acquired using a different field strength at a different centre.

"The gamma analysis was calculated using the SlicerRT toolkit within the open-source 3D Slicer application, version 4.6.2"

Correlation of Volumetric Growth and Histological Grade in 50 Meningiomas

Publication: Acta Neurochir (Wien). Acta Neurochir (Wien). 2017 Nov;159(11):2169-77. PMID: 28791500

Authors: Soon WC, Fountain DM, Koczyk K, Abdulla M, Giri S, Allinson K, Matys T, Guilfoyle MR, Kirollos RW, Santarius T.

Institution: Department of Neurosurgery, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Cambridge, UK.


Introduction: Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Methods: All histologically proven intracranial meningiomas that underwent resection in a single centre between April 2009 and April 2014 were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the CNS. Only patients who had two pre-operative scans that were at least 3 months apart were included in the study. Two authors performed the volumetric measurements using the 3D Slicer software independently and the inter-rater reliability was assessed. Multiple regression analyses of factors affecting the VGR and VDE of meningiomas were performed using the R statistical software with p < 0.05 considered to be statistically significant.

Results: Of 548 patients who underwent resection of their meningiomas, 66 met the inclusion criteria. Sixteen cases met the exclusion criteria (NF2, spinal location, previous surgical or radiation treatment, significant intra-osseous component and poor quality imaging). Forty-two grade I and 8 grade II meningiomas were included in the analysis. The VGR was significantly higher for grade II meningiomas. using receiver-operator characteristic (ROC) curve analysis, the optimal threshold that distinguishes between grade I and II meningiomas is 3 cm3/year. Higher histological grade, high initial tumour volume, MRI T2-signal hyperintensity and presence of oedema were found to be significant predictors of higher VGR.

Conclusion: Reliable tools now exist to evaluate and monitor volumetric growth of meningiomas. Grade II meningiomas have significantly higher VGR compared with grade I meningiomas and growth of more than 3 cm3/year is strongly suggestive of a higher grade meningioma. A larger, multi-centre prospective study to investigate the applicability of velocity of growth to predict the outcome of patients with meningioma is warranted.

Handgrip Strength in Chronic Obstructive Pulmonary Disease. Associations with Acute Exacerbations and Body Composition

Publication: Ann Am Thorac Soc. 2017 Nov;14(11):1638-45. PMID: 29090990

Authors: Martinez CH, Diaz AA, Meldrum CA, McDonald MN, Murray S, Kinney GL, Hokanson JE, Curtis JL, Bowler RP, Han MK, Washko GR, Regan EA; COPDGene Investigators.

Institution: Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.


Rationale: Handgrip strength (HGS) predicts mortality in the elderly, but its determinants and clinical significance in chronic obstructive pulmonary disease (COPD) has not been defined.

Objectives: We tested associations of HGS with pectoralis muscle area (PMA), subcutaneous adipose tissue (SAT), imaging characteristics, and lung function in smokers with COPD, and evaluated the cross-sectional and longitudinal associations of HGS with acute respiratory events.

Methods: We analyzed demographic, clinical, spirometry, HGS, and imaging data of 272 subjects with COPD, obtaining measures of airway thickness, emphysema, PMA, and SAT from chest computed tomography scans. We tested associations of lung function and imaging characteristics with HGS, using linear models. HGS association to acute respiratory events at enrollment and during follow-up (mean, 2.6 years) was analyzed using adjusted logistic models.

Results: HGS correlated with PMA, SAT, forced expiratory volume, and airway thickness, but not with body mass index or emphysema severity. In adjusted regression models, HGS was directly (β, 1.5; 95% confidence interval [CI], 0.1-3.0) and inversely (β, -3.3; 95% CI, -5.1 to -0.9) associated with one standard deviation of PMA and SAT, respectively, independent of body mass index and emphysema. In regression models adjusted for age, sex, body mass index, race, pack-years smoked, current smoking, chronic bronchitis, FEV1% predicted, emphysema, and airway metrics, HGS was associated with exacerbation risk; in cross-sectional analyses, there was an increment of 5% in the risk of exacerbations for each 1-kg decrement in HGS (risk ratio, 1.05; 95% CI, 1.01-1.08), and there was a similar risk during follow-up (risk ratio, 1.04; 95% CI, 1.01-1,07).

Conclusions: In ever-smokers with COPD, HGS is associated with computed tomography markers of body composition and airway thickness, independent of body mass index and emphysema. Higher HGS is associated with lower exacerbation frequency.

"Pectoralis muscle (PMA) and subcutaneous adipose tissue (SAT) areas were measured by trained analysts unaware of participants' clinical data, using 3D Slicer software."

3D Printing in Neurosurgery: A Specific Model for Patients with Craniosynostosis

Publication: Neurocirugia (Astur). 2017 Nov-Dec;28(6):260-5. PMID: 28666846

Authors: Sollmann N, Echlin PS, Schultz V, Viher PV, Lyall AE, Tripodis Y, Kaufmann D Hartl E, Kinzel P, Forwell LA, Johnson AM, Skopelja EN, Lepage C, Bouix S, Pasternak O, Lin AP, Shenton ME, Koerte IK.

Institution: School of Medicine, University of Navarra, Pamplona, Spain.


Introduction: Craniosynostosis is a rare condition and requires a personalised surgical approach, which is why we consider the use of 3D printed models beneficial in the surgical planning of this procedure.

Material and Methods: Acrylonitrile butadiene styrene plastic skull models were designed and printed from CT images of patients between 3 and 6 months of age with craniosynostosis of different sutures. The models were used to simulate surgical procedures.

Results: Four models of four patients with craniosynostosis were produced: two with closure of the metopic suture and two with sagittal suture closure. The mean age of the patients was 5 months (3-6m) and the mean duration of the surgery was 286min (127-380min). The acrylonitrile butadiene styrene plastic models printed for the project proved to be optimal for the simulation of craniosynostosis surgeries, both anatomically and in terms of mechanical properties and reaction to surgical instruments.

Conclusions: 3D printers have a wide range of medical applications and they offer an easy and affordable way to produce skull models. The acrylonitrile butadiene styrene material is suitable for the production of operable bone models as it faithfully reproduces the mechanical characteristics of bone tissue.

"Computed tomography images were processed using 3D Slicer software to extract only those data corresponding to bone density..."

Computational Radiomics System to Decode the Radiographic Phenotype

Publication: Cancer Res. 2017 Nov 1;77(21):e104-e107. PMID: 29092951 | PDF

Authors: van Griethuysen JJM, Fedorov A, Parmar C, Hosny A, Aucoin N, Narayan V, Beets-Tan RGH, Fillion-Robin JC, Pieper S, Aerts HJWL.

Institution: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract: Radiomics aims to quantify phenotypic characteristics on medical imaging through the use of automated algorithms. Radiomic artificial intelligence (AI) technology, either based on engineered hard-coded algorithms or deep learning methods, can be used to develop noninvasive imaging-based biomarkers. However, lack of standardized algorithm definitions and image processing severely hampers reproducibility and comparability of results. To address this issue, we developed PyRadiomics, a flexible open-source platform capable of extracting a large panel of engineered features from medical images. PyRadiomics is implemented in Python and can be used standalone or using 3D Slicer. Here, we discuss the workflow and architecture of PyRadiomics and demonstrate its application in characterizing lung lesions. Source code, documentation, and examples are publicly available at With this platform, we aim to establish a reference standard for radiomic analyses, provide a tested and maintained resource, and to grow the community of radiomic developers addressing critical needs in cancer research.

A, Overview figure of the process of PyRadiomics. First, medical images are segmented. Second, features are extracted using the PyRadiomics platform, and third, features are analyzed for associations with clinical or biologic factors. B, Stability of radiomics features for variation in manual segmentations by expert radiologists. C, Heatmap showing expression values of radiomics features (rows) of 429 lesions (columns). Note the four subtypes that could be identified from the expression values and their associations with malignancy. D, Area under the curve (AUC) showing the performance of the multivariate biomarker to predict malignancy of nodules.

Sex Differences in White Matter Alterations Following Repetitive Subconcussive Head Impacts in Collegiate Ice Hockey Players

Publication: Neuroimage Clin. 2017 Nov 21;17:642-649. PMID: 29204342 | PDF

Authors: Sollmann N, Echlin PS, Schultz V, Viher PV, Lyall AE, Tripodis Y, Kaufmann D Hartl E, Kinzel P, Forwell LA, Johnson AM, Skopelja EN, Lepage C, Bouix S, Pasternak O, Lin AP, Shenton ME, Koerte IK.

Institution: Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.


Objective: Repetitive subconcussive head impacts (RSHI) may lead to structural, functional, and metabolic alterations of the brain. While differences between males and females have already been suggested following a concussion, whether there are sex differences following exposure to RSHI remains unknown. The aim of this study was to identify and to characterize sex differences following exposure to RSHI.

Methods: Twenty-five collegiate ice hockey players (14 males and 11 females, 20.6 ± 2.0 years), all part of the Hockey Concussion Education Project (HCEP), underwent diffusion-weighted magnetic resonance imaging (dMRI) before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011-2012 and did not experience a concussion during the season. Whole-brain tract-based spatial statistics (TBSS) were used to compare pre- and postseason imaging in both sexes for fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Pre- and postseason neurocognitive performance were assessed by the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT).

Results: Significant differences between the sexes were primarily located within the superior longitudinal fasciculus (SLF), the internal capsule (IC), and the corona radiata (CR) of the right hemisphere (RH). In significant voxel clusters (p < 0.05), decreases in FA (absolute difference pre- vs. postseason: 0.0268) and increases in MD (0.0002), AD (0.00008), and RD (0.00005) were observed in females whereas males showed no significant changes. There was no significant correlation between the change in diffusion scalar measures over the course of the season and neurocognitive performance as evidenced from postseason ImPACT scores.

Conclusions: The results of this study suggest sex differences in structural alterations following exposure to RSHI. Future studies need to investigate further the underlying mechanisms and association with exposure and clinical outcomes.

"First, quality checks were performed by visually inspecting diffusion-weighted data sets using 3D Slicer version 4.5., Surgical Planning Laboratory, Brigham and Women's Hospital, Boston, MA, USA)"


  • I01 RX000928/RX/RRD VA/United States
  • R01 HD090641/HD/NICHD NIH HHS/United States
  • R01 NS100952/NS/NINDS NIH HHS/United States
  • U01 NS093334/NS/NINDS NIH HHS/United States

Evaluation of the Novel TSPO Radiotracer [18F] VUIIS1008 in a Preclinical Model of Cerebral Ischemia in Rats

Publication: EJNMMI Res. 2017 Nov 25;7(1):93. PMID: 29177913 | PDF

Authors: Pulagam KR, Colás L, Padro D, Plaza-García S, Gómez-Vallejo V, Higuchi M, Llop J, Martín A.

Institution: Radiochemistry and Nuclear Imaging, Molecular Imaging Unit, CIC biomaGUNE, San Sebastian, Spain.


Background: In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO.

Methods: Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats.

Results: MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008 and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats.

Conclusions: Altogether, these results suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.

"Regions of interest (ROIs) were manually defined using the Open Source software 3D Slicer image analysis software (Version 3.6.3)."


  • SAF2014-54070-JIN/Secretaría de Estado de Investigación, Desarrollo e Innovación/United States
Normalized PET images of [18F] VUIIS1008 and displacements by VUIIS1008 and DPA-714. PET images (ID%/cc) of the coronal and horizontal planes at the level of the lesion from left to right. Summed images of [18F] VUIIS1008 before displacement (0 to 20 min) and after displacement (40 to 60 min) by VUIIS1008 (upper row) and by DPA-714 (lower row). PET images were co-registered with a rat brain atlas for illustration of anatomical regions.]

3D Printed Pathological Sectioning Boxes to Facilitate Radiological-Pathological Correlation in Hepatectomy Cases

Publication: J Clin Pathol. 2017 Nov;70(11):984-7. PMID: 28596154

Authors: Trout AT, Batie MR, Gupta A, Sheridan RM, Tiao GM, Towbin AJ.

Institution: Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract: Radiogenomics promises to identify tumour imaging features indicative of genomic or proteomic aberrations that can be therapeutically targeted allowing precision personalised therapy. An accurate radiological-pathological correlation is critical to the process of radiogenomic characterisation of tumours. An accurate correlation, however, is difficult to achieve with current pathological sectioning techniques which result in sectioning in non-standard planes. The purpose of this work is to present a technique to standardise hepatic sectioning to facilitateradiological-pathological correlation. We describe a process in which three-dimensional (3D)-printed specimen boxes based on preoperative cross-sectional imaging (CT and MRI) can be used to facilitate pathological sectioning in standard planes immediately on hepatic resection enabling improved tumour mapping. We have applied this process in 13 patients undergoing hepatectomy and have observed close correlation between imaging and gross pathology in patients with both unifocal and multifocal tumours. Following image review, a clinical engineering specialist (MRB) digitally isolates the liver from the cross-sectional imaging study using open-source software 3D Slicer.

The Functional Anatomy of Nerves Innervating the Ventral Grooved Blubber of Fin Whales (Balaenoptera Physalus)

Publication: Anat Rec. 2017 Nov;300(11):1963-72. PMID: 28971627 | PDF

Authors: Vogl W, Petersen H, Adams A, Lillie MA, Shadwick RE.

Institution: Department of Cellular and Physiological Sciences, Life Sciences Centre, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.


Nerves that supply the floor of the oral cavity in rorqual whales are extensible to accommodate the dramatic changes in tissue dimensions that occur during "lunge feeding" in this group. We report here that the large nerves innervating the muscle component of the ventral grooved blubber (VGB) in fin whales are branches of cranial nerve VII (facial nerve). Therefore, the muscles of the VGB are homologous to second branchial arch derived muscles, which in humans include the muscles of "facial expression." We speculate, based on the presence of numerous foramina on the dorsolateral surface of the mandibular bones, that general sensation from the VGB likely is carried by branches of the mandibular division (V3) of cranial nerve V (trigeminal nerve), and that these small branches travel in the lipid-rich layer directly underlying the skin. We show that intercostal and phrenic nerves, which are not extensible, have a different wall and nerve core morphology than the large VGB nerves that are branches of VII. Although these VGB nerves are known to have two levels of waviness, the intercostal and phrenic nerves have only one in which the nerve fascicles in the nerve core are moderately wavy. In addition, the VGB nerves have inner and outer parts to their walls with numerous large elastin fibers in the outer part, whereas intercostal and phrenic nerves have single walls formed predominantly of collagen. Our results illustrate that overall nerve morphology depends greatly on location and the forces to which the structures are exposed.

"The relevant anatomy was reconstructed using 3D Slicer software."

Retrospective Evaluation and SEEG Trajectory Analysis for Interactive Multi-trajectory Planner Assistant

Publication: Int J Comput Assist Radiol Surg. 2017 Oct;12(10):1727-38. PMID: 28710548

Authors: Scorza D, De Momi E, Plaino L, Amoroso G, Arnulfo G, Narizzano M, Kabongo L, Cardinale F.

Institution: e-Health and Biomedical Applications Department, Vicomtech-IK4, Donostia-San Sebastián, Spain.


Purpose: Focal epilepsy is a neurological disease that can be surgically treated by removing area of the brain generating the seizures. The stereotactic electroencephalography (SEEG) procedure allows patient brain activity to be recorded in order to localize the onset of seizures through the placement of intracranial electrodes. The planning phase can be cumbersome and very time consuming, and no quantitative information is provided to neurosurgeons regarding the safety and efficacy of their trajectories. In this work, we present a novel architecture specifically designed to ease the SEEG trajectory planning using the 3D Slicer platform as a basis.

Methods: Trajectories are automatically optimized following criteria like vessel distance and insertion angle. Multi-trajectory optimization and conflict resolution are optimized through a selective brute force approach based on a conflict graph construction. Additionally, electrode-specific optimization constraints can be defined, and an advanced verification module allows neurosurgeons to evaluate the feasibility of the trajectory.

Results: A retrospective evaluation was performed using manually planned trajectories on 20 patients: the planning algorithm optimized and improved trajectories in 98% of cases. We were able to resolve and optimize the remaining 2% by applying electrode-specific constraints based on manual planning values. In addition, we found that the global parameters used discards 68% of the manual planned trajectories, even when they represent a safe clinical choice.

Conclusions: Our approach improved manual planned trajectories in 98% of cases in terms of quantitative indexes, even when applying more conservative criteria with respect to actual clinical practice. The improved multi-trajectory strategy overcomes the previous work limitations and allows electrode optimization within a tolerable time span.

AAV-mediated Direct in vivo CRISPR Screen Identifies Functional Suppressors in Glioblastoma

Publication: Nat Neurosci. 2017 Oct;20(10):1329-41. PMID: 28805815 | PDF

Authors: Chow RD, Guzman CD, Wang G, Schmidt F, Youngblood MW, Ye L, Errami Y, Dong MB, Martinez MA, Zhang S, Renauer P, Bilguvar K, Gunel M, Sharp PA, Zhang F, Platt RJ, Chen S.

Institution: Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.


A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts. Co-mutation analysis identified co-occurring driver combinations such as B2m-Nf1, Mll3-Nf1 and Zc3h13-Rb1, which were subsequently validated using AAV minipools. Distinct from Nf1-mutant tumors, Rb1-mutant tumors are undifferentiated and aberrantly express homeobox gene clusters. The addition of Zc3h13 or Pten mutations altered the gene expression profiles of Rb1 mutants, rendering them more resistant to temozolomide. Our study provides a functional landscape of gliomagenesis suppressors in vivo.

"Raw image stacks were processed using Osirix or 3D Slicer tools. Rendering and quantification were performed using 3D Slicer."


  • U54 CA209992/CA/NCI NIH HHS/United States
  • R01 MH110049/MH/NIMH NIH HHS/United States
  • R01 CA133404/CA/NCI NIH HHS/United States
  • DP1 MH100706/MH/NIMH NIH HHS/United States
  • R01 GM034277/GM/NIGMS NIH HHS/United States
  • T32 GM007205/GM/NIGMS NIH HHS/United States
  • T32 GM007499/GM/NIGMS NIH HHS/United States
Autochthonous brain tumorigenesis induced by an AAV-mediated CRISPR library. (a) Schematics of direct in vivo AAV-CRISPR GBM screen design. Top: AAV-mTSG library design, synthesis and production. Bottom: stereotaxic injection of AAV library and subsequent analysis. HPF, hippocampus; LV, lateral ventricle. (b) MRI sections show brain tumors in AAV-mTSG injected mice but not in PBS- or AAV-vector-injected mice. Matching sections are shown. Arrowheads indicate brain tumors. Scale bar, 5 mm. (c) MRI-based volumetric quantification of time-matched tumor size ± s.e.m. Two-tailed Welch’s t test, t17 = 2.62, P = 0.018, mTSG vs. vector or PBS (PBS, n = 2 mice; vector, n = 6; mTSG, n = 18). (d) Kaplan-Meier curves for overall survival (OS) of mice injected with PBS (n = 5), AAV-vector (n = 24) or AAV-mTSG library (n = 56). OS for PBS and vector groups are both 100%; the curves are dashed and slightly offset for visibility; dpi, days postinjection. Log-rank (LR) test, P < 2.20 × 10−16, mTSG vs. vector or PBS.

Presurgical Planning for Supratentorial Lesions with Free 3D Slicer Software and Sina App

Publication: World Neurosurg. 2017 Oct;106:193-7. PMID: 28673889

Authors: Chen JG, Han KW, Zhang DF, Li ZX, Li YM, Hou LJ.

Institution: Department of Neurosurgery, Shanghai Neurosurgical Institute, Changzheng Hospital, Shanghai, China.


Background: Neuronavigation system is widely used in the localization of intracranial lesions with satisfactory accuracy. However, it's expensive and difficult to learn. Therefore, simple and practical augmented reality (AR) system using mobile devices might be an alternative technique.

Objective: We aim to introduce a mobile AR system for the localization of supratentorial lesions. Its practicability and accuracy were examined by clinical application in patients and comparison with standard neuronavigation system.

Methods: Three-dimensional (3D) model including lesions is created using 3D Slicer. 2D image of this 3D model was obtained and overlapped on patients' head using Sina app. Registration was conducted with the assistance of anatomical landmarks and fiducial markers. Center of lesion projected on scalp was identified with our mobile AR system and standard neuronavigation system, respectively. Distance difference between centers identified by these two systems was measured.

Result: Our mobile AR system was simple and accurate in the localization of supratentorial lesions with a mean distance difference of 4.4 ± 1.1 mm. Registration added on an average of 141.7 ± 39 seconds to operation time. There was no statistically significant difference for the required time among three registrations (P=0.646).

Conclusion: The mobile AR system presents an alternative technology for image-guided neurosurgery and proves to be practical and reliable. The technique contributes to optimal presurgical planning for supratentorial lesions, especially in the absence of neuronavigation system.

Canal Transportation, Unprepared Areas, and Dentin Removal after Preparation with BT-RaCe and ProTaper Next Systems

Publication: J Endod. 2017 Oct;43(10):1683-7. PMID: 28712638

Authors: Brasil SC, Marceliano-Alves MF, Marques ML, Grillo JP, Lacerda MFLS, Alves FRF, Siqueira JF Jr, Provenzano JC.

Institution: Department of Endodontics, Faculty of Dentistry, Estácio de Sá University, Rio de Janeiro, Brazil.


Background: This study compared the shaping ability of ProTaper Next (Dentsply Sirona, Tulsa, OK) and BT-RaCe (FKG Dentaire, La Chaux-de-Fonds, Switzerland) instrument systems in the mesial canals of mandibular molars using micro-computed tomographic (micro-CT) imaging.

Methods: A total of 17 type IV mesial roots of extracted first mandibular molars were scanned using micro-CT imaging before and after root canal preparation with the 2 instrument systems. Both systems were used in the same root but alternating the mesial canals from root to root. The following parameters were analyzed: root canal volume, surface area, unprepared surface areas, transportation, canal/root width ratio, and preparation time.

Results: There were no statistically significant differences between the 2 systems for all evaluated parameters (P > .05). The unprepared surface areas for the full canal length and the apical 5-mm segment were 33% and 14% for BT-RaCe and 31% and 14% for ProTaper Next, respectively. After preparation, all root canals had a diameter that was not larger than 35% of the root diameter at the coronal and middle segments.

Conclusions: The 2 systems showed no differences in any of the evaluated shaping parameters. None of the tested systems put the roots at risk of fracture because of excessive dentin removal.

Three-Dimensional Volume Rendering of Pelvic Models and Paraurethral Masses Based on MRI Cross-Sectional Images

Publication: Int Urogynecol J. 2017 Oct;28(10):1579-87. PMID: 28352953

Authors: Doumouchtsis SK, Nazarian DA, Gauthaman N, Durnea CM, Munneke G.

Institution: Department of Obstetrics & Gynecology, Epsom and St. Helier University Hospital NHS Trust, Epsom, UK.


Aims: Our aim was to assess the feasibility of rendering 3D pelvic models using magnetic resonance imaging (MRI) scans of patients with vaginal, urethral and paraurethral lesions and obtain additional information previously unavailable through 2D imaging modalities.

Methods: A purposive sample of five female patients 26-40 years old undergoing investigations for vaginal or paraurethral mass was obtained in a tertiary teaching hospital. 3D volume renderings of the bladder, urethra and paraurethral masses were constructed using 3D Slicer v.3.4.0. Spatial dimensions were determined and compared with findings from clinical, MRI, surgical and histopathological reports. The quality of information regarding size and location of paraurethral masses obtained from 3D models was compared with information from cross-sectional MRI and review of clinical, surgical and histopathological findings.

Results: The analysis of rendered 3D models yielded detailed anatomical dimensions and provided information that was in agreement and in higher detail than information based on clinical examination, cross-sectional 2D MRI analysis and histopathological reports. High-quality pelvic 3D models were rendered with the characteristics and resolution to allow identification and detailed viewing of the spatial relationship between anatomical structures.

Conclusions: To our knowledge, this is the first preliminary study to evaluate the role of MRI-based 3D pelvic models for investigating paraurethral masses. This is a feasible technique and may prove a useful addition to conventional 2D MRI. Further prospective studies are required to evaluate this modality for investigating such lesions and planning appropriate management.

Comparison of Diffusion-Weighted MRI Reconstruction methods for Visualization of Cranial Nerves in Posterior Fossa Surgery

Publication: Front Neurosci. 2017 Oct 9;11:554. PMID: 29062268 | PDF

Authors: Behan B, Chen DQ, Sammartino F, DeSouza DD, Wharton-Shukster E, Hodaie M.

Institution: Division of Brain, Imaging and Behaviour - Systems Neuroscience, Krembil Institute, University Health Network, Toronto, ON, Canada.


Diffusion-weighted imaging (DWI)-based tractography has gained increasing popularity as a method for detailed visualization of white matter (WM) tracts. Different imaging techniques, and more novel, advanced imaging methods provide significant WM structural detail. While there has been greater focus on improving tract visualization for larger WM pathways, the relative value of each method for cranial nerve reconstruction and how this methodology can assist surgical decision-making is still understudied. Images from 10 patients with posterior fossa tumors (4 male, mean age: 63.5), affecting either the trigeminal nerve (CN V) or the facial/vestibular complex (CN VII/VIII), were employed. Three distinct reconstruction methods [two tensor-based methods: single diffusion tensor tractography (SDT) 3D Slicer, eXtended streamline tractography (XST), and one fiber orientation distribution (FOD)-based method: streamline tractography using constrained spherical deconvolution (CSD)-derived estimates (MRtrix3)], were compared to determine which of these was best suited for use in a neurosurgical setting in terms of processing speed, anatomical accuracy, and accurate depiction of the relationship between the tumor and affected CN. Computation of the tensor map was faster when compared to the implementation of CSD to provide estimates of FOD. Both XST and CSD-based reconstruction methods tended to give more detailed representations of the projections of CN V and CN VII/VIII compared to SDT. These reconstruction methods were able to more accurately delineate the course of CN V and CN VII/VIII, differentiate CN V from the cerebellar peduncle, and delineate compression of CN VII/VIII in situations where SDT could not. However, CSD-based reconstruction methods tended to generate more invalid streamlines. XST offers the best combination of anatomical accuracy and speed of reconstruction of cranial nerves within this patient population. Given the possible anatomical limitations of single tensor models, supplementation with more advanced tensor-based reconstruction methods might be beneficial.

Reconstruction methods differ in how they represent underlying diffusion processes. (1) Axial view of a sample tensor map displaying CN V entry into the brainstem, (2) Tensors visible as glyphs displaying CN V entry into the brainstem, (3) results from single diffusion tensor tractography (SDT) after placing region-of-interest (ROI) seeds on anterior portions of CN V bilaterally. Generated streamlines do not show their projections to brainstem nuclei, (4) results from EXtended Streamline Tractography (XST) after placing ROI seeds on anterior portions of CN V bilaterally. Streamlines projecting to the area of the nuclei of the trigeminal nerves can be seen, (5) Axial view of sample fiber orientation distribution (FOD) map displaying CN V entry into the brainstem, (6) results from streamline tractography on FODs derived from constrained spherical deconvolution (CSD) after placing ROI seeds on anterior portions of CN V bilaterally. Streamlines projecting to the area of the nuclei of the trigeminal nerves can be seen.

Nerve Atrophy in Trigeminal Neuralgia Due to Neurovascular Compression and its Association with Surgical Outcomes after Microvascular Decompression

Publication: Acta Neurochir (Wien). 2017 Sep;159(9):1699-1705. PMID: 28638946

Authors: Cheng J, Meng J, Liu W, Zhang H, Hui X, Lei D.

Institution: Department of Neurosurgery, West China Hospital, Sichuan University, Sichuan, China.


Background: Idiopathic trigeminal neuralgia (TN) is caused by neurovascular compression and is often related to morphological changes in the trigeminal nerve. The aim of this study was to quantitatively measure atrophic changes of trigeminal nerves in patients with TN, and to further investigate whether nerve atrophy affected the efficacy of microvascular decompression (MVD).

Methods: We conducted a prospective case-control study of 60 consecutive patients with TN and 30 sex- and age-matched healthy controls. All subjects underwent high-resolution three-dimensional MRI. The volume of the cisternal segment of trigeminal nerves was measured and compared using 3D Slicer software. Patients with TN underwent primary MVD and regular follow-up for at least 2 years. Associations of nerve atrophy with patient characteristics and operative outcomes were analyzed.

Results: The mean volume of the affected trigeminal nerve was significantly reduced in comparison to that of the nonaffected side (65.8 ± 21.1 versus 77.9 ± 19.3 mm3, P = 0.001) and controls (65.8 ± 21.1 versus 74.7 ± 16.5 mm3, P = 0.003). Fifty-two patients (86.7%) achieved complete pain relief without medication immediately after surgery, and 77.6% of patients were complete pain relief at the 2-year follow-up. The Spearman correlation test showed that there was a positive correlation (r = 0.46, P = 0.018) between the degree of trigeminal nerve indentation and nerve atrophy. In multivariate logistic regression analysis, two factors, indentation on nerve root (OR = 2.968, P = 0.022) and degree of nerve atrophy (OR = 1.18, P = 0.035), were associated with the long-term outcome.

Conclusions: TN is associated with atrophy on the affected nerve. Furthermore, greater nerve atrophy is associated with more severe trigeminal nerve indentation and better long-term outcome following MVD.

A Comparative Study of Irrigation Versus no Irrigation during Burr Hole Craniostomy to Treat Chronic Subdural Hematoma

Publication: BMC Surg. 2017 Sep 11;17(1):99. PMID: 28893217 | PDF

Authors: Wang QP, Yuan Y, Guan JW, Jiang XB.

Institution: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.


Background: Burr hole craniostomy is a widely used method for the evacuation of CSDH. However it is not clear whether the irrigation during operation improves the prognosis or gives rise to additional complications instead. This retrospective cohort study was conducted to determine this issue.

Methods: Patients attending two medical centers in China who underwent burr hole drainage with irrigation (BHDI) or burr hole drainage without irrigation (BHD) for unilateral CSDH during January 2013 to December 2016 were included in this study. The patients' clinical information and follow-up data were retrospectively reviewed, and the radiologic findings were processed using the 3D Slicer software. The differences in outcomes were identified using t-test, chi-square test, or Fisher's exact test.

Results: A total of 151 patients comprising 63 patients in the BHD group and 88 patients in the BHDI group were included. Patients in the BHDI group had a higher volume of pneumocrania on the first postoperative day than that of patients in the BHD group (p < 0.05). No significant differences were observed between the two approaches in rates of rebleeding, recurrence and other complications (p > 0.05).

Conclusions: Irrigation had no improvement in the long-term curative effect on CSDH, but it increased the risk of short-term complication in terms of pneumocrania. Therefore, this study suggests that irrigation is not an obligatory procedure during burr hole drainage.

CT scans of two typical patients undergoing BHD and BHDI. a and b are the preoperative and first postoperative day images of a patient receiving BHDI, respectively. c and d are the preoperative and first postoperative day images of a patient receiving BHD, respectively. Obvious pneumocrania can be observed in image b. This image is from the preliminary report of the present study, which was published in West China Medicine Journal [27]. The authors have got the permission to republish this image.

A New Genus of Hell Ants from the Cretaceous (Hymenoptera: Formicidae: Haidomyrmecini) with a Novel Head Structure

Publication: Systematic Entomology. 2017 Sep 4;42(4):837-46.

Authors: Barden, Phillip A., Herhold, Hollister W., Grimaldi, David A.

Institutions: Department of Biological Sciences, New Jersey Institute of Technology, Newark, NJ, USA.


An unusual Cretaceous trap jaw ant is described from Burmese amber dated to the Late Cretaceous. Linguamyrmex vladi gen.n. sp.n. is distinguished by an unusual suite of morphological characters indicating specialized predatory behaviour and an adaptive strategy no longer found among modern ant lineages. The clypeus, highly modified as in other closely related haidomyrmecine hell ants, is equipped with a paddle-like projection similar to Ceratomyrmex. X-ray imaging reveals that this clypeal paddle is reinforced, most probably with sequestered metals. Presumably this fortified clypeal structure was utilized in tandem with scythe-like mandibles to pin and potentially puncture soft-bodied prey. This unique taxon, which stresses the diversity of stem-group ants, is discussed in the context of modern and other Cretaceous trap jaw ant species.

Slicer: Mid-way through the analysis and post-processing of the specimen, we switched from a different CT application to 3D Slicer. The toolset provided, combined with the active community, enabled rapid, high-quality visualizations.

Three-dimensional reconstruction and two-dimensional X-ray ‘slices’ of Linguamyrmex vladi. (A) Three-dimensional reconstruction of specimen BuPH-01 in lateral view. Some elements are irrecoverable in X-ray imaging due to the similar attenuation properties of both amber and thin cuticle. Scale bar, 0.75 mm. (B) Lateral view of head capsule, mandibles and clypeal paddle. Planes C and D correspond with panels C and D, respectively. Scale bar, 0.2 mm. (C) Cross-section of clypeal paddle from oblique dorsal view. Labels demonstrate approximate pixel ‘grey values’ for each fossil material, which in turn represent relative X-ray attenuation levels. (D) Cross-section of clypeal paddle from frontal view. Scale bar, 0.08 mm in each cross-section.

Improvement of Pyramidal Tract Side Effect Prediction using a Data-Driven Method in Subthalamic Stimulation

Publication: IEEE Trans Biomed Eng. 2017 Sep;64(9):2134-41. PMID: 27959795

Authors: Baumgarten C, Zhao Y, Sauleau P, Malrain C, Jannin P, Haegelen C.

Institution: Signal and Image Processing Laboratory, Department LTSI , University of Rennes, France.


Objective: Subthalamic nucleus deep brain stimulation (STN DBS) is limited by the occurrence of a pyramidal tract side effect (PTSE) induced by electrical activation of the pyramidal tract. Predictive models are needed to assist the surgeon during the electrode trajectory preplanning. The objective of the study was to compare two methods of PTSE prediction based on clinical assessment of PTSE induced by STN DBS in patients with Parkinson's disease.

Methods: Two clinicians assessed PTSE postoperatively in 20 patients implanted for at least three months in the STN. The resulting dataset of electroclinical tests was used to evaluate two methods of PTSE prediction. The first method was based on the volume of tissue activated (VTA) modeling and the second one was a data-driven-based method named Pyramidal tract side effect Model based on Artificial Neural network (PyMAN) developed in our laboratory. This method was based on the nonlinear correlation between the PTSE current threshold and the 3-D electrode coordinates. PTSE prediction from both methods was compared using Mann-Whitney U test.

Results: 1696 electroclinical tests were used to design and compare the two methods. Sensitivity, specificity, positive- and negative-predictive values were significantly higher with the PyMAN method than with the VTA-based method (P < 0.05).

Conclusion: The PyMAN method was more effective than the VTA-based method to predict PTSE.

Significance: This data-driven tool could help the neurosurgeon in predicting adverse side effects induced by DBS during the electrode trajectory preplanning.

Pre-operative registration between the ParkMedAtlis atlas and the patient’s T1 and T2 weighted MRI. Top left: axial view; top right: antero-superior left three-dimensional view of the cerebral sulci and the segmented basal ganglia, down left; parasagittal view; down right: coronal view. The red dot and line are the preplanned trajectory few days before the surgery to implant an electrode in the left subthalamic nucleus. A: anterior; P: posterior; L: left; R: right; S: superior; I: inferior. Amygdala (light pink), hippocampus (dark pink), putamen (violet), medial pallidum (orange), lateral pallidum (green), caudate nucleus (light blue), thalami (yellow), substantia nigra (grey), subthalamic nucleus (light orange), red nucleus (red), ventricles (dark blue).

High Expression of Glypican-1 Predicts Dissemination and Poor Prognosis in Glioblastomas

Publication: World Neurosurg. 2017 Sep;105:282-8. PMID: 28602885

Authors:Saito T, Sugiyama K, Hama S, Yamasaki F, Takayasu T, Nosaka R, Onishi S, Muragaki Y, Kawamata T, Kurisu K.

Institution: Department of Neurosurgery, Hiroshima University, Graduate School of Biomedical and Health Science, Hiroshima, Japan.


Objective: Glioblastoma (GBM) relapses locally or in a disseminated pattern, and is highly resistant to chemo-radiotherapy. Although dissemination is associated with poor prognosis for GBM patients, the clinico-pathological factors that promote dissemination have not been elucidated. Glypican-1 (GPC-1) is a heparin sulfate proteoglycan that is attached to the extracytoplasmic surface of the cell membrane and regulates cell motility. The aim of this study was to determine whether GPC-1 expression correlated with GBM dissemination and patient prognosis.

Methods: GPC-1 expression was examined by immunohistochemistry in 53 patients with GBM who received radiotherapy and temozolomide (TMZ) treatment. We assessed the relationship between dissemination and clinico-pathological factors, including GPC-1 expression. Additionally, we evaluated the relationship between GPC-1 expression and overall survival (OS) by uni- and multivariate analyses of a range of clinico-pathological factors, including age, Karnofsky Performance Status (KPS), extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) status. To evaluate the extent of resection by 13 semi-automatic volumetry, we used 3D Slicer, version 4.0 software.

Results: Logistic regression analysis revealed that GPC-1 expression correlated with dissemination (P = 0.0116). Log-rank tests revealed that age, KPS, extent of resection, MGMT status, dissemination (P = 0.0008) and GPC-1 expression (P = 0.0011) were significantly correlated with OS. Multivariate analysis indicated that age, MGMT status, and GPC-1 expression were significantly correlated with OS. GPC-1 expression had the highest hazard ratio (2.392) among all regressors.

Conclusions: GPC-1 expression significantly correlated with OS in GBM patients who received radiotherapy and TMZ treatment. GPC-1 expression can help predict the occurrence of dissemination and shorter OS in GBM patients.

Factors Affecting the Visual Outcome of Pituitary Adenoma Patients Treated with Endoscopic Transsphenoidal Surgery

Publication: World Neurosurg. 2017 Sep;105:422-31. PMID: 28583452

Authors: Luomaranta T, Raappana A, Saarela V, Liinamaa MJ.

Institution: Department of Ophthalmology, Oulu University Hospital, Oulu, Finland.


Objective: To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenomas' (PAs') suprasellar extension (SSE), volume and the patients' age.

Methods: Medical records of 47 PA patients operated with ETS were evaluated. VA, VF and visual impairment score (VIS) were determined pre- (VISpre) and postoperatively (VISpost). The PA's SSE, volume and chiasmal contact and their correlation with visual function was pre- and postoperatively assessed. Each PA was preoperatively manually segmented from (typically from T1-weighted, contrast-enhanced, coronal) MRI planes of the patient using 3D Slicer, a modelling software, which also reported the volume of the modeled PA.

Results: The final cohort included 47 patients. VA improved in 54/76 eyes (71.0 %) after ETS and 69/76 eyes (90.7 %) gained normal VA. Postoperative VF recovery occurred in 32/37 (86.5 %) of the eyes. The mean VISchange was 12.0 (95% CI 7.7-16.3) and improved in all patients with tumor-related visual impairment (n=25). However, visual outcome was poorer when VISpre>40. When VISpre was 21-40, age linearly correlated with VIS improvement (p=0.03); younger patients had satisfactory and older poorer visual outcome. The mean SSE in patients with VF defects (n=20) was 16.6 mm (95% CI 13.3-19.9) and in patients with no VF defects (n=23) 6.6 mm (95% CI 4.9-8.3, p<0.001) and cut-off value for visual perturbations was 9.5 mm for SSE and 8.6 ml for PA volume (p<0.001 for both).

Conclusions: The visual outcome after ETS for PAs was excellent and significant complications rare. Severe preoperative visual impairment resulted poorer postoperative visual outcome. The SSE of PA was the most important predictor of visual outcome after ETS.

Retrospective Validation of a Computer-Assisted Quantification Model of Intracerebral Hemorrhage Volume on Accuracy, Precision, and Acquisition Time, Compared with Standard ABC/2 Manual Volume Calculation

Publication: AJNR Am J Neuroradiol. 2017 Aug;38(8):1536-42. PMID: 28596188

Authors: Xue W, Vegunta S, Zwart CM, Aguilar MI, Patel AC, Hoxworth JM, Demaerschalk BM, Mitchell JR.

Institution: Department of Biomedical Informatics, Arizona State University, Scottsdale, AZ, USA.


Purpose: Intracerebral hemorrhage accounts for 6.5%-19.6% of all acute strokes. Initial intracerebral hemorrhage volume and expansion are both independent predictors of clinical outcomes and mortality. Therefore, a rapid, unbiased, and precise measurement of intracerebral hemorrhage volume is a key component of clinical management. The most commonly used method, ABC/2, results in overestimation. We developed an interactive segmentation program, SegTool, using a novel graphic processing unit, level set algorithm. Until now, the speed, bias, and precision of SegTool had not been validated.

Materials and Methods: In a single stroke academic center, 2 vascular neurologists and 2 neuroradiologists independently performed a test-retest experiment that involved repeat measurements of static, unchanging intracerebral hemorrhage volumes on CT from 76 intracerebral hemorrhage cases. Measurements were made with SegTool and ABC/2. True intracerebral hemorrhage volumes were estimated from a consensus of repeat manual tracings by 2 operators. These data allowed us to estimate measurement bias, precision, and speed. Computer-assisted measurements were made with an intensity-threshold algorithm in 3D Slicer.

Results: The measurements with SegTool were not significantly different from the true intracerebral hemorrhage volumes, while ABC/2 overestimated volume by 45%. The interrater measurement variability with SegTool was 50% less than that with ABC/2. The average measurement times for ABC/2 and SegTool were 35.7 and 44.6 seconds, respectively.

Conclusions: SegTool appears to have attributes superior to ABC/2 in terms of accuracy and interrater reliability with a 9-second delay in measurement time (on average); hence, it could be useful in clinical trials and practice.

ROS-IGTL-Bridge: An Open Network Interface for Image-guided Therapy using the ROS Environment

Publication: Int J Comput Assist Radiol Surg. 2017 Aug;12(8):1451-60. PMID: 28567563

Authors: Frank T, Krieger A, Leonard S, Patel NA, Tokuda J.

Institution: Institute of Mechatronic Systems, Gottfried Wilhelm Leibniz University, Hannover, Germany.


Purpose: With the growing interest in advanced image-guidance for surgical robot systems, rapid integration and testing of robotic devices and medical image computing software are becoming essential in the research and development. Maximizing the use of existing engineering resources built on widely accepted platforms in different fields, such as robot operating system (ROS) in robotics and 3D Slicer in medical image computing could simplify these tasks. We propose a new open network bridge interface integrated in ROS to ensure seamless cross-platform data sharing.

Methods: A ROS node named ROS-IGTL-Bridge was implemented. It establishes a TCP/IP network connection between the ROS environment and external medical image computing software using the OpenIGTLink protocol. The node exports ROS messages to the external software over the network and vice versa simultaneously, allowing seamless and transparent data sharing between the ROS-based devices and the medical image computing platforms.

Results: Performance tests demonstrated that the bridge could stream transforms, strings, points, and images at 30 fps in both directions successfully. The data transfer latency was <1.2 ms for transforms, strings and points, and 25.2 ms for color VGA images. A separate test also demonstrated that the bridge could achieve 900 fps for transforms. Additionally, the bridge was demonstrated in two representative systems: a mock image-guided surgical robot setup consisting of 3D Slicer, and Lego Mindstorms with ROS as a prototyping and educational platform for IGT research; and the smart tissue autonomous robot surgical setup with 3D Slicer.

Conclusion: The study demonstrated that the bridge enabled cross-platform data sharing between ROS and medical image computing software. This will allow rapid and seamless integration of advanced image-based planning/navigation offered by the medical image computing software such as 3D Slicer into ROS-based surgical robot systems.


  • P41 EB015898/EB/NIBIB NIH HHS/United States
  • R01 CA111288/CA/NCI NIH HHS/United States
  • R01 EB020610/EB/NIBIB NIH HHS/United States
  • R01 EB020667/EB/NIBIB NIH HHS/United States

Automated Catheter Navigation with Electromagnetic Image Guidance

Publication: IEEE Trans Biomed Eng. 2017 Aug;64(8):1972-9. PMID: 28362578

Authors: Jaeger HA, Nardelli P, O'Shea C, Tugwell J, Khan KA, Power T, O'Shea M, Kennedy MP, Cantillon-Murphy P.

Institution: School of Engineering, University College Cork, Cork, Ireland.


This paper describes a novel method of controlling an endoscopic catheter using an automated catheter tensioning system with the objective of providing clinicians with improved manipulation capabilities within the patient. Catheters are used in many clinical procedures to provide access to the cardiopulmonary system. Control of such catheters is performed manually by the clinicians using a handle, typically actuating a single or opposing set of pull-wires. Such catheters are generally actuated in a single plane, requiring the clinician to rotate the catheter handle to navigate the system. The automation system described here allows closed-loop control of a custom bronchial catheter in tandem with an electromagnetic tracking of the catheter tip and image guidance using 3D Slicer. An electromechanical drive train applies tension to four pull-wires to steer the catheter tip, with the applied force constantly monitored though force sensing load-cells. The applied tension is controlled through a PC connected joystick. An electromagnetic sensor embedded in the catheter tip enables constant real-time position tracking while a working channel provides a route for endoscopic instruments. The system is demonstrated and tested in both a breathing lung model and a preclinical animal study. Navigation to predefined targets in the subject's airways using the joystick while using virtual image guidance and electromagnetic tracking was demonstrated. Average targeting times were 24 seconds and 10 seconds respectively for the breathing lung and live animal studies. This paper presents the first reported remote controlled bronchial working channel catheter utilizing electromagnetic tracking and has many implications for future development in endoscopic and catheter based procedures.

Exercise Decreases Marrow Adipose Tissue Through ß-Oxidation in Obese Running Mice

Publication: J Bone Miner Res. 2017 Aug;32(8):1692-1702. PMID: 28436105 | PDF

Authors: Styner M, Pagnotti GM, McGrath C, Wu X, Sen B, Uzer G, Xie Z, Zong X, Styner MA, Rubin CT, Rubin J.

Institution: Department of Medicine, Division of Endocrinology and Metabolism, University of North Carolina, Chapel Hill, NC, USA.

Abstract: The relationship between marrow adipose tissue (MAT) and bone health is poorly understood. We used running exercise to ask whether obesity-associated MAT can be attenuated via exercise and whether this correlates with gains in bone quantity and quality. C57BL/6 mice were divided into diet-induced obesity (DIO, n = 14) versus low-fat diet (LFD, n = 14). After 3 months, 16-week-old mice were allocated to an exercise intervention (LFD-E, DIO-E) or a control group (LFD, DIO) for 6 weeks (4 groups, n = 7/group). Marrow adipocyte area was 44% higher with obesity (p < 0.0001) and after exercise 33% lower in LFD (p < 0.0001) and 39% lower in DIO (p < 0.0001). In LFD, exercise did not affect adipocyte number; however, in DIO, the adipocyte number was 56% lower (p < 0.0001). MAT was 44% higher in DIO measured by osmium-μCT, whereas exercise associated with reduced MAT (-23% in LFD, -48% in DIO, p < 0.05). MAT was additionally quantified by 9.4TMRI, and correlated with osmium-µCT (r = 0.645; p < 0.01). Consistent with higher lipid beta oxidation, perilipin 3 (PLIN3) rose with exercise in tibial mRNA (+92% in LFD, +60% in DIO, p < 0.05). Tibial µCT-derived trabecular bone volume (BV/TV) was not influenced by DIO but responded to exercise with an increase of 19% (p < 0.001). DIO was associated with higher cortical periosteal and endosteal volumes of 15% (p = 0.012) and 35% (p < 0.01), respectively, but Ct.Ar/Tt.Ar was lower by 2.4% (p < 0.05). There was a trend for higher stiffness (N/m) in DIO, and exercise augmented this further. In conclusion, obesity associated with increases in marrow lipid-measured by osmium-μCT and MRI-and partially due to an increase in adipocyte size, suggesting increased lipid uptake into preexisting adipocytes. Exercise associated with smaller adipocytes and less bone lipid, likely invoking increased ß-oxidation and basal lipolysis as evidenced by higher levels of PLIN3. © 2017 American Society for Bone and Mineral Research.


  • P20 GM109095/GM/NIGMS NIH HHS/United States
  • R01 EB014351/EB/NIBIB NIH HHS/United States
  • P30 DK056350/DK/NIDDK NIH HHS/United States
  • K08 AR062097/AR/NIAMS NIH HHS/United States
  • R01 AR066616/AR/NIAMS NIH HHS/United States

Three‐Dimensional Printing: An Aid to Epidural Access for Neuromodulation

Publication: Neuromodulation. 2017 Aug;20(6):622-6. PMID: 28425137

Authors: Taverner MG, Monagle JP.

Institution: Frankston Pain Management, Victoria, Australia.


Objective: The case report details to use of three-dimensional (3D) printing as an aid to neuromodulation.

Methods: A patient is described in whom previous attempts at spinal neuromodulation had failed due to lack of epidural or intrathecal access, and the use of a 3D printed model allowed for improved planning and ultimately, success. Thin-slices (0.625 mm) of a high-resolution CT scan of the patient's thoracolumbar spine and iliac crests was used to create a CAD model on 3D Slicer software (Surgical Planning Laboratory, Boston, MA

Results: Successful spinal cord stimulation was achieved with the plan developed by access to a 3D model of the patient's spine.

Conclusion: Neuromodulation techniques can provide the optimal analgesic techniques for individual patients. At times these can fail due to lack of access to the site for intervention, in this case epidural access. 3D printing may provide additional information to improve the likelihood of access when anatomy is distorted and standard approaches prove difficult.

Quantitative CT ventriculography for Assessment and Monitoring of Hydrocephalus: a Pilot Study and Description of method in Subarachnoid Hemorrhage (SAH)

Publication: World Neurosurg. 2017 Aug;104:136-41. PMID: 28456742

Authors: Multani JS, Oermann EK, Titano J, Mascitelli J, Nicol K, Feng R, Skovrlj B, Pain M, Mocco JD, Bederson JB, Costa A, Shrivastava R.

Institution: Department of Neurological Surgery, Mount Sinai Health System, New York, NY, USA.


Background: There is no facile quantitative method for monitoring hydrocephalus (HCP).

Objective: We propose quantitative CT ventriculography (qCTV) as a novel computer vision tool for empirically assessing HCP in patients with subarachnoid hemorrhage (SAH).

Methods: Twenty patients with SAH who were evaluated for ventriculoperitoneal shunt (VPS) placement were selected for inclusion. Ten patients with normal CT head (CTH) were analyzed as negative controls. CTH scans were segmented both manually and automatically (qCTV) to generate measures of ventricular volume.

Results: Median manually calculated ventricular volume was 36.1cm3(IQR 30-115cm3), which was similar to a median qCTV measured volume of 37.5cm3 (IQR 32-118cm3) (p=0.796). Patients undergoing VPS placement demonstrated an increase in ventricular volume on qCTV from 21cm3 to 40cm3 on Day T-2, and 51cm3 by Day 0, a change of 144%. This contrasts with patients who did not require shunting whose ventricular volumes decreased from 16 to 14cm3 on Day T-2, and 13cm3 by Day 0, with an average overall decrease in volume of 19% (p=0.001). Average change in ventricular volume predicted which patients would require VPS placement, successfully identifying 7/10 patients (p=0.004). using an optimized cutoff of change in ventricular volume of 2.5cm3 identified all patients who went on to require VPS placement (10/10, p=0.011).

Conclusions: qCTV is a reliable means of quantifying ventricular volume and hydrocephalus. This technique offers a new tool for monitoring neurosurgical patients for hydrocephalus, and may be beneficial for use in future research studies as well as the routine care of patients with hydrocephalus.

What are the True Volumes of SEGA Tumors? Reliability of Planimetric and Popular Semi-automated Image Segmentation Methods

Publication: MAGMA. 2017 Aug;30(4):397-405. PMID: 28321524

Authors: Stawiski K, Trelińska J, Baranska D, Dachowska I, Kotulska K, Jóźwiak S, Fendler W, Młynarski W.

Institution: Department of Biostatistics and Translational Medicine, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.


Objective: To evaluate the reliability of the standard planimetric methodology of volumetric analysis and three different open-source semi-automated approaches of brain tumor segmentation.

Materials and Methods: The volumes of subependymal giant cell astrocytomas (SEGA) examined by 30 MRI studies of 10 patients from a previous everolimus-related trial (EMINENTS study) were estimated using four methods planimetric method (modified MacDonald ellipsoid method), ITK-Snap (pixel clustering, geodesic active contours, region competition methods), 3D Slicer (level-set thresholding), and NIRFast (k-means clustering, Markov random fields). The methods were compared, and a trial simulation was performed to determine how the choice of approach could influence the final decision about progression or response.

Results: Intraclass correlation coefficient was high (0.95; 95% CI 0.91-0.98). The planimetric Method: always overestimated the size of the tumor, while virtually no mean difference was found between ITK-Snap and 3D Slicer (P = 0.99). NIRFast underestimated the volume and presented a proportional bias. During the trial simulation, a moderate level of agreement between all the methods (kappa 0.57-0.71, P < 0.002) was noted.

Conclusion: Semi-automated segmentation can ease oncological follow-up but the moderate level of agreement between segmentation methods suggests that the reference standard volumetric method for SEGA tumors should be revised and chosen carefully, as the selection of volumetry tool may influence the conclusion about tumor progression or response.

MRI Visible Fe3O4 Polypropylene Mesh: 3D Reconstruction of Spatial Relation to Bony Pelvis and Neurovascular Structures

Publication: Int Urogynecol J. 2017 Aug;28(8):1131-8. PMID: 28124074

Authors: Chen L, Lenz F, Alt CD, Sohn C, De Lancey JO, Brocker KA.

Institution: Pelvic Floor Research Group, Biomedical Engineering Department, University of Michigan, Ann Arbor, MI, USA.


Introduction and Hypothesis: To demonstrate mesh magnetic resonance imaging (MRI) visibility in living women, the feasibility of reconstructing the full mesh course in 3D, and to document its spatial relationship to pelvic anatomical structures.

Methods: This is a proof of concept study of three patients from a prospective multi-center trial evaluating women with anterior vaginal mesh repair using a MRI-visible Fe3O4 polypropylene implant for pelvic floor reconstruction. High-resolution sagittal T2-weighted (T2w) sequences, transverse T1-weighted (T1w) FLASH 2D, and transverse T1w FLASH 3D sequences were performed to evaluate Fe3O4 polypropylene mesh MRI visibility and overall post-surgical pelvic anatomy 3 months after reconstructive surgery. Full mesh course in addition to important pelvic structures were reconstructed using the 3D Slicer software program based on T1w and T2w MRI.

Results: Three women with POP-Q grade III cystoceles were successfully treated with a partially absorbable MRI-visible anterior vaginal mesh with six fixation arms and showed no recurrent cystocele at the 3-month follow-up examination. The course of mesh in the pelvis was visible on MRI in all three women. The mesh body and arms could be reconstructed allowing visualization of the full course of the mesh in relationship to important pelvic structures such as the obturator or pudendal vessel nerve bundles in 3D.

Conclusions: The use of MRI-visible Fe3O4 polypropylene meshes in combination with post-surgical 3D reconstruction of the mesh and adjacent structures is feasible suggesting that it might be a useful tool for evaluating mesh complications more precisely and a valuable interactive feedback tool for surgeons and mesh design engineers.

Three-Dimensional Printing of X-ray Computed Tomography Datasets with Multiple Materials using Open-source Data Processing

Publication: Anat Sci Educ. 2017 Jul;10(4):383-91. PMID: 28231405

Authors: Sander IM, McGoldrick MT, Helms MN, Betts A, van Avermaete A, Owers E, Doney E, Liepert T, Niebur G, Liepert D, Leevy WM.

Institution: Department of Biological Sciences, College of Science, University of Notre Dame, Notre Dame, IN, USA.


Advances in three-dimensional (3D) printing allow for digital files to be turned into a "printed" physical product. For example, complex anatomical models derived from clinical or pre-clinical X-ray computed tomography (CT) data of patients or research specimens can be constructed using various printable materials. Although 3D printing has the potential to advance learning, many academic programs have been slow to adopt its use in the classroom despite increased availability of the equipment and digital databases already established for educational use. Herein, a protocol is reported for the production of enlarged bone core and accurate representation of human sinus passages in a 3D printed format using entirely consumer-grade printers and a combination of free-software platforms. The comparative resolutions of three surface rendering programs were also determined using the sinuses, a human body, and a human wrist data files to compare the abilities of different software available for surface map generation of biomedical data. Data shows that 3D Slicer provided highest compatibility and surface resolution for anatomical 3D printing. Generated surface maps were then 3D printed via fused deposition modeling (FDM printing). In conclusion, a methodological approach that explains the production of anatomical models using entirely consumer-grade, fused deposition modeling machines, and a combination of free software platforms is presented in this report. The methods outlined will facilitate the incorporation of 3D printed anatomical models in the classroom.

3D Print of the Maxillary Sinus for Morphological Study

Publication: Int. J. Morphol. 2017 Jul; 35(3):1102-6. PDF

Authors: Araneda N, Parra M, Valdivia Osorio J, Olate S.

Institutions: Division of Oral and Maxillofacial Surgery, Temuco, Chile.


The maxillary sinus (MS) is described as a pyramid-shaped cavity of the maxilla. Knowledge of its morphology makes it possible to define normality and abnormality so that its three-dimensional analysis can be a valuable preoperative tool during surgery in this anatomical area. The aim of this study is to present a strategy of morphological analysis of the MS using 3D printing acquired through computed cone beam tomography (CBCT) images. A cross-sectional descriptive study was conducted, including 15 subjects (8 women and 7 men). The 3D virtual reconstruction and modeling was done on the MSs bilaterally, and 30 physical models were produced on a 3D printer. The results revealed that the MSs obtained exhibited various morphologies. An individual analysis of each MS allowed the tripod nature of the MS to be defined. We also were able to observe anatomical repairs such as the MS ostium, as well as complex areas affecting important surgical decisions. This method for creating 3D models of MSs provides a new approach to understanding the precise anatomical characteristics in these structures, which cannot be assessed in the same way on a 2D screen. It may be concluded that 3D printouts of the MS are a suitable method of preoperative analysis that can be useful in educating the patient, however, less time-consuming strategies should be explored.

Direct work on the 3D Slicer software to determine the areas of the maxillary sinus in 2D images; the image segmentation obtains the image of the maxillary sinus in the different spatial directions.

MultiXplore: Visual Exploration Platform for Multimodal Neuroimaging Data

Publication: J Neurosci Methods. 2017 Jul 13;290:1-12. PMID: 28712912

Authors: Bakhshmand SM, Khan AR, de Ribaupierre S, Eagleson R.

Institution: Biomedical Engineering Graduate Program, University of Western Ontario, London, ON, Canada.


Background: Construction of brain functional and structural networks by neuroimaging methods facilitates inter-modal studies. These type of studies often demand exploration tools to carry out functional-structural discoveries and answer questions regarding the anatomical basis of brain networks.

New Method: This paper describes the design and development of a software module for interactive visualization and exploration of dual-modal brain networks. Our objective was to equip the user with a research tool to investigate brain connectivity matrices while visualizing relevant anatomical landmarks within a 3D volumetric view. In order to create this view, MultiXplore was designed to load data from both structural and diffusion MRI and connectivity matrices.

Results: Once user starts to select desired cells through an interactive matrix unit, associated axonal fiber pathways and grey matter regions are generated and displayed. Integration and visualization of functional and structural networks in this 3D interactive framework was successfully implemented and tested.

Comparison with Existing Method(s): MultiXplore contributes to the transition of connectivity visualization techniques from node-link format to an anatomically more realistic graphical form and assists scientists in relating connectivity matrices to their anatomical correlates. This module also benefits from additional novel functionalities to annotate and differentiate fibers in a large bundle. Unlike traditional graph displays, interactive functionality helps in the inspection and visualization of relevant structures without cluttering the scene with excessive items.

Conclusion: This module was designed and developed as a plugin to 3D Slicer imaging platform and is accessible for neuroimaging researchers through NITRC.

Shape, Septa and Scalloping of the Maxillary Sinus

Publication: Int. J. Morphol. 2017 July; 35(3):970-8. PDF

Authors: Rennie C, Haffajee MR, Satyapal KS.

Institutions: Department of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences College of Health Sciences University of KwaZulu-Natal, Durban, South Africa.


The maxillary sinus varies according to age, however there are limited studies that have illustrated its 3D form over time. This study aimed to classify the maxillary sinus by the shape, number of septa and scallops in a 1 to 25 year age group, utilising computerized tomography (CT) scans and 3D reconstruction. CT scans (n=480) were reviewed from the picture archiving and communication system (PACS) of the state and private hospitals in Pietermaritzburg and Durban KwaZulu- Natal (KZN), South Africa. The sample consisted of 276 males and 204 females, 1-25 years and of two population groups, black African and white. 3D Slicer was utilised in order to reconstruct a 3D model of the sinus. Morphological traits such as the presence of the sinus, scalloping and septa within the sinuses were categorised. In addition, the shape of the 3D model of the sinus was analysed anteriorly (coronal) and laterally (sagittal) adapting the classifications by Kim (1962) and Kim et al. (2002). The maxillary sinus was present bilaterally in n=477 individuals (99.4 %). Five different anterior shapes viz. Type 1 (triangular), Type 2 (upside down triangle), Type 3 (square), Type 4 (irregular) and Type 5 (rectangular) were identified in the anterior view. This shape was associated with age and population groups (p<0.05). In the lateral view, the maxillary sinus appeared to be quadrilateral with differences noted along the inferior wall. Intrasinus maxillary septa were more evident in the anterior region of the maxillary sinus (27.9 % right; 28.5 % left). The maxillary septa were commoner in females (37.9 % right; 39.4 % left) than in males (28.5 % right; 30.3 % left). They were also more commonly observed in the white cohort (63.8 % right; 68.1 % left) than in the black African cohort (29.1 % right; 30.5 % left). Scalloping in the axial plane from above along its anterior margin was also observed. An in-depth classification of the morphology of the 3D form of the maxillary sinus according to age (1 to 25 years) was established. Five different shapes in both the anterior and lateral view of the 3D model were observed. Anteriorly, it was noted that the main shape was Type 2 (upside down triangle). The shape of the sinus changed in the form according to age. Laterally, the shape was related to the development of the teeth, as the inferior wall of the sinus was classified. Maxillary septa and scalloping of the sinus were reported in all age groups. Surgically, the sinus morphology is essential for dental procedures such as sinus augmentation or dental implants, and anthropologically, in forensic identification.

A. Intrasinus septa ­ anterior region. (outline indicates maxillary septum). B. Maxillary air sinus- scallops (bracket indicating scallops along the anterior margin).

Optimization of a Novel Large Field of View Distortion Phantom for MR-only Treatment Planning

Publication: J Appl Clin Med Phys. 2017 Jul;18(4):51-61. PMID: 28497476 | PDF

Authors: Price RG, Knight RA, Hwang KP, Bayram E, Nejad-Davarani SP, Glide-Hurst CK.

Institution: Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA.


Purpose: MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution.

Method and Materials: To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform.

Results: All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer's plugin framework and results agreed with the literature.

Conclusion: The design and implementation of a modular, extendable distortion phantom was optimized for several bore configurations. The phantom and analysis software will be available for multi-institutional collaborations and cross-validation trials to support MR-only planning.


  • R01 CA204189/CA/NCI NIH HHS/United States
3D Slicer distortion module graphic user interface for 3D gradient nonlinear distortion assessment

Validation of a method for "Dose of the Day" Calculation in Head-neck Tomotherapy by using Planning CT-to-MVCT Deformable Image Registration

Publication: Phys Med. 2017 Jul;39:73-9. PMID: 28619289

Authors: Branchini M, Fiorino C, Dell'Oca I, Belli ML, Perna L, Di Muzio N, Calandrino R, Broggi S.

Institution: Medical Physics Department, San Raffaele Scientific Institute, Milano, Italy.


Purpose: The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT).

Methods: For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D Slicer.

Results: On average, 87.9%±1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6%±0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8%±0.8% of body's voxels.

Conclusions: This study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.

Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation

Publication: Mol Cancer Ther. 2017 Jul;16(7):1279-1289. PMID: 28500233 | PDF

Authors: van de Ven AL, Tangutoori S, Baldwin P, Qiao J, Gharagouzloo C, Seitzer N, Clohessy JG, Makrigiorgos GM, Cormack R, Pandolfi PP, Sridhar S.

Institution: Department of Physics, Northeastern University, Boston, MA, USA.

Abstract: The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Here we show that radiation-resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of advanced prostate cancer are rendered radiation sensitive following treatment with NanoOlaparib, a lipid-based injectable nanoformulation of olaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and is specific to NanoOlaparib alone. In animals, twice-weekly intravenous administration of NanoOlaparib results in significant tumor growth inhibition, whereas previous studies of oral olaparib as monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered prior to radiation, a single dose of radiation is sufficient to triple the median mouse survival time compared to radiation only controls. Half of mice treated with NanoOlaparib + radiation achieved a complete response over the 13-week study duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed that NanoOlaparib enhances the intratumoral accumulation of systemically administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold higher nanoparticle accumulation compared to untreated and radiation-only controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated by its ability to enhance its own accumulation. Together, these data suggest that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCA mutations, such as those with PTEN and TP53 deletions.


  • R01 CA082328/CA/NCI NIH HHS/United States
  • U54 CA151881/CA/NCI NIH HHS/United States
Ferumoxytol delivery and accumulation in FKO1 tumors. (A) Timeline for longitudinal MRI experiments involving multiple boluses of ferumoxytol. (B) Representative negative- and positive-contrast MRI image slices of a single tumor before ferumoxytol injection (left), 24hr after ferumoxytol injection with 4hr vehicle pre-treatment (middle), and 24hr after ferumoxytol injection with 4hr NanoOlaparib pre-treatment (right). Ferumoxytol accumulation appeared as a darkening in the T1 and T2 images and a brightening of the UTE image. This tumor received 1 × 10Gy radiation 3 weeks prior to MRI study. (C) Histogram of the UTE signal intensity for all voxels within the tumor volume following each treatment. (D) The fold-increase in voxel number as a function of signal intensity between the first and second rounds of ferumoxytol accumulation. (E) The percentage of tumor volume with significant nanoparticle accumulation (as measured from the UTE signal intensity) following a single ferumoxytol injection in 11 different tumors pre-treated with NanoOlaparib, radiation, or no treatment. Statistically significant differences (P<0.01) were observed between the average of the indicated groups (*). (F) 2-D maximum intensity projections of ferumoxytol accumulation in all 11 different tumors. "T1, T2, and UTE signal intensity images were transformed and rendered using 3D Slicer v4.4."

SLIDE: Automatic Spine Level Identification System using a Deep Convolutional Neural Network

Publication: Int J Comput Assist Radiol Surg. 2017 Jul;12(7):1189-98. PMID: 28361323

Authors: Hetherington J, Lessoway V, Gunka V, Abolmaesumi P, Rohling R.

Institution: Department of Electrical and Computer Engineering, The University of British Columbia, Vancouver, Canada.


Purpose: Percutaneous spinal needle insertion procedures often require proper identification of the vertebral level to effectively and safely deliver analgesic agents. The current clinical Method: involves "blind" identification of the vertebral level through manual palpation of the spine, which has only 30% reported accuracy. Therefore, there is a need for better anatomical identification prior to needle insertion.

Methods: A real-time system was developed to identify the vertebral level from a sequence of ultrasound images, following a clinical imaging protocol. The system uses a deep convolutional neural network (CNN) to classify transverse images of the lower spine. Several existing CNN architectures were implemented, utilizing transfer learning, and compared for adequacy in a real-time system. In the system, the CNN output is processed, using a novel state machine, to automatically identify vertebral levels as the transducer moves up the spine. Additionally, a graphical display was developed and integrated within 3D Slicer. Finally, an augmented reality display, projecting the level onto the patient's back, was also designed. A small feasibility study [Formula: see text] evaluated performance.

Results: The proposed CNN successfully discriminates ultrasound images of the sacrum, intervertebral gaps, and vertebral bones, achieving 88% 20-fold cross-validation accuracy. Seventeen of 20 test ultrasound scans had successful identification of all vertebral levels, processed at real-time speed (40 frames/s).

Conclusion: A machine learning system is presented that successfully identifies lumbar vertebral levels. The small study on human subjects demonstrated real-time performance. A projection-based augmented reality display was used to show the vertebral level directly on the subject adjacent to the puncture site.

A New Approach for Radiosynoviorthesis: A Dose-Optimized Planning Method: Based on Monte Carlo Simulation and Synovial Measurement using 3D Slicer and MRI

Publication: Med Phys. 2017 Jul;44(7):3821-9. PMID: 28419533

Authors: Torres Berdeguez MB, Thomas S, Rafful P, Arruda Sanchez T, Medeiros Oliveira Ramos S, Albernaz MS, Vasconcellos de Sá L, Lopes de Souza SA, Mas Milian F, Xavier da Silva A.

Institution: Department of Nuclear Engineering, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.


Purpose: Recently, there has been a growing interest in a methodology for dose planning in radiosynoviorthesis to substitute fixed activity. Clinical practice based on fixed activity frequently does not embrace radiopharmaceutical dose optimization in patients. The aim of this paper is to propose and discuss a dose planning methodology considering the radiological findings of interest obtained by three-dimensional magnetic resonance imaging combined with Monte Carlo simulation in radiosynoviorthesis treatment applied to hemophilic arthropathy.

Method: The parameters analyzed were: surface area of the synovial membrane (synovial size), synovial thickness and joint effusion obtained by 3D MRI of nine knees from nine patients on a SIEMENS AVANTO 1.5 T scanner using a knee coil. The 3D Slicer software performed both the semiautomatic segmentation and quantification of these radiological findings. A Lucite phantom 3D MRI validated the quantification methodology. The study used Monte Carlo N-Particle eXtended code version 2.6 for calculating the S-values required to set up the injected activity to deliver a 100 Gy absorbed dose at a determined synovial thickness. The radionuclides assessed were: 90Y, 32P, 188Re, 186Re, 153Sm, and 177Lu, and the present study shows their effective treatment ranges.

Result: The quantification methodology was successfully tested, with an error below 5% for different materials. S-values calculated could provide data on the activity to be injected into the joint, considering no extra-articular leakage from joint cavity. Calculation of effective treatment range could assist with the therapeutic decision, with an optimized protocol for dose prescription in RSO.

Conclusion: Using 3D Slicer software, this study focused on segmentation and quantification of radiological features such as joint effusion, synovial size and thickness, all obtained by 3D MRI in patients knees with hemophilic arthropathy. The combination of synovial size and thickness with the parameters obtained by Monte Carlo simulation such as effective treatment range and S-value, from which is calculated the injected activity, could be used for treatment planning in RSO. Data from this methodology could be a potential aid to clinical decision making by selecting the most suitable radionuclide; justifying the procedure, fractioning the dose and the calculated injected activity for children and adolescents, considering both the synovial size and thickness.

Device-specific Evaluation of Intraventricular Left Ventricular Assist Device Position by Quantitative Coaxiality Analysis

Publication: J Surg Res. 2017 Jun 1;213:110-4. PMID: 28601303

Authors: Anselmi A, Collin S, Haigron P, Verhoye JP, Flecher E.

Institution: INSERM U1099, Rennes, France.


Background: Patient-specific anatomy may influence the final intraventricular positioning of inflow cannula in left ventricular assist device (LVAD) recipients. An association exists between such positioning and clinical outcomes (specifically, orientation toward the interventricular septum has negative prognostic implications). Alternative commercially available LVADs are characterized by markedly different design, with potential consequences on intrathoracic fitting among individual patients.

Material and Methods: A cohort of 13 LVAD recipients (either HeartMate II-group A or Jarvik 2000 Flowmaker-group B) was evaluated. On postoperative computed tomography scans, we reconstructed the implanted LVAD (semiautomatic segmentation), defined the target mitral orifice (3D Slicer software), and built a coordinate system to quantify the coaxiality of the cannula with the mitral valve axis (angles φ and θ, expressed as percentage variation from the ideal value φ = θ = 0°).

Results: Group A presented significantly greater average percentage variation of the φ angle (significantly greater orientation of the intraventricular cannula toward the interventricular septum; 33.2% ± 32.1% versus 1.9% ± 0.9%, P = 0.001). Group A presented significantly greater average percentage variation of the θ angle (52.7% ± 23.6% versus 14.5% ± 6.3%, P = 0.013).

Conclusions: The device assessed in group B showed in the present series better average coaxiality with the mitral orifice. Such finding is related with its design (total intraventricular placement) and interaction with thoracic structures. The present method is being integrated in the development of LVAD virtual implantation tools and may help physicians in patient-specific selection among alternative devices.

Anser EMT: The First Open-Source Electromagnetic Tracking Platform for Image-Guided Interventions

Publication: Int J Comput Assist Radiol Surg. 2017 Jun;12(6):1059-67. PMID: 28357627

Authors: Jaeger HA, Franz AM, O'Donoghue K, Seitel A, Trauzettel F, Maier-Hein L, Cantillon-Murphy P.

Institution: Institute of Image Guided Surgery, Strasbourg, France.


Purpose: Electromagnetic tracking is the gold standard for instrument tracking and navigation in the clinical setting without line of sight. Whilst clinical platforms exist for interventional bronchoscopy and neurosurgical navigation, the limited flexibility and high costs of electromagnetic tracking (EMT) systems for research investigations mitigate against a better understanding of the technology's characterization and limitations. The Anser project provides an open-source implementation for EMT with particular application to image-guided interventions.

Methods: This work provides implementation schematics for our previously reported EMT system which relies on low-cost acquisition and demodulation techniques using both National Instruments and Arduino hardware alongside MATLAB support code. The system performance is objectively compared to other commercial tracking platforms using the Hummel assessment protocol.

Results: Positional accuracy of 1.14 mm and angular rotation accuracy of [Formula: see text] are reported. Like other EMT platforms, Anser is susceptible to tracking errors due to eddy current and ferromagnetic distortion. The system is compatible with commercially available EMT sensors as well as the Open Network Interface for image-guided therapy (OpenIGTLink) for easy communication with visualization and medical imaging toolkits such as MITK and 3D Slicer.

Conclusions: By providing an open-source platform for research investigations, we believe that novel and collaborative approaches can overcome the limitations of current EMT technology.

The Effects of Iterative Reconstruction and Kernel Selection on Quantitative Computed Tomography Measures of Lung Density

Publication: Med Phys. 2017 Jun;44(6):2267-80. PMID: 28376262

Authors: Rodriguez A, Ranallo FN, Judy PF, Fain SB.

Institution: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.


Purpose: To determine the effects of iterative reconstruction (IR) and high frequency kernels on quantitative computed tomography (qCT) density measures at reduced X-ray dose.

Materials and Methods: The COPDGene 2 Phantom (CTP 698, The Phantom Laboratory, Salem, NY) with four embedded lung mimicking foam densities (12lb, 20lb, and 4lb), as well as water, air, and acrylic reference inserts was imaged using a GE 64 slice CT750 HD scanner in helical mode with four current-time products ranging from 12-100 mAs. The raw acquired data was reconstructed using standard (STD - low frequency) and Bone (high frequency) kernels with filtered back projection (FBP), 100% ASIR, and Veo reconstruction algorithms. The reference density inserts were manually segmented using 3D Slicer and the mean, standard deviation, and histograms of the segmented regions were generated using Fiji for each reconstruction. Measurements of threshold values placed on the cumulative frequency distribution of voxels determined by these measured histograms at 5%, PD5phant , and 15%, PD15phant , (analogous to the relative area below -950 HU (RA950) and percent density 15 (PD15) in human lung emphysema quantification, respectively), were also performed.

Results: The use of high-resolution kernels in conjunction with ASIR, and Veo did not significantly affect the mean Hounsfield units (HU) of each of the density standards (<4 HU deviation) and current-time products within the phantom when compared with the STD+FBP reconstruction conventionally used in clinical applications. A truncation of the scanner reported HU values at -1024 that shifts the mean towards more positive values was found to cause a systematic error in lower attenuating regions. Use of IR drove convergence toward the mean of measured histograms (~100-137% increase in the number measured voxels at the mean of the histogram) while the combination of Bone+ASIR preserved the standard deviation of HU values about the mean compared to STD+FBP, with the added effect of improved spatial resolution and accuracy in airway measures. PD5phant and PD15phant were most similar between the Bone+ASIR and STD+FBP in all regions except those affected by the -1024 truncation artifact.

Conclusions: Extension of the scanner reportable HU values below the present limit of -1024 will mitigate discrepancies found in qCT lung densitometry in low-density regions. The density histogram became more sharply peaked and standard deviation was reduced for IR, directly effecting density thresholds, PD5phant and PD15phant, placed on the cumulative frequency distribution of each region in the phantom, which serve as analogs to RA950 and PD15 typically used in lung density quantitation. The combination of high frequency kernels (Bone) with ASIR mitigates this effect and preserves density measures derived from the image histogram. Moreover, previous studies have shown improved accuracy of qCT airway measures of wall thickness (WT) and wall area percentage (WA%) when using high frequency kernels in combination with ASIR to better represent airway walls. The results therefore suggest an IR approach for accurate assessment of airway and parenchymal density measures in the lungs.


  • HHSN268201300071C/EB/NIBIB NIH HHS/United States
  • U10 HL109168/HL/NHLBI NIH HHS/United States

Infantile Cranial Fasciitis: Case-based Review and Operative Technique

Publication: Childs Nerv Syst. 2017 Jun;33(6):899-908. PMID: 28451777

Authors: Flouty OE, Piscopo AJ, Holland MT, Abode-Iyamah K, Bruch L, Menezes AH, Dlouhy BJ.

Institution: Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.


Background: Cranial fasciitis (CF) is an uncommon benign primary lesion of the skull that typically affects the pediatric age group. Due to the rarity of CF, no prospective studies exist. Earliest description of this condition dates to 1980. The limited scientific and clinical literature regarding CF is dominated by case reports. For these reasons, questions pertaining to the true incidence, genetic risk factors, prognosis, and long-term outcome remain unanswered.

Discussion: Clinically, CF presents as a firm, painless, growing scalp mass that is typically not considered in the differential diagnosis. Preoperative pathognomonic signs and symptoms are absent, and imaging features are often nonspecific. Treatment is typically through complete surgical resection, at which time histopathological examination confirms the diagnosis of CF. Reconstruction of the skull defect in the child is critical. Autograft techniques help maintain a rigid construct that integrates with the native skull while preserving its continued ability to grow. Generally, a good outcome is observed with complete resection.

Exemplary Case: We report a case of CF in an infant with emphasis on operative nuances and early follow-up results.

Conclusion: CF is a rare fibroproliferative disease that has a poorly defined incidence and long-term follow-up. Due to its locally invasive nature and nonspecific presentation, CF is often difficult to differentiate from malignancies and infections. Complete surgical resection is the best approach for diagnosis and cure. Its occult clinical presentation often allows it to achieve considerable growth, leaving a sizeable skull defect following resection. Since CF presents in the pediatric population, allograft reconstruction is preferred over titanium mesh or other synthetic materials to allow osseous integration and continued uninterrupted skull growth.

Biomaterial Shell Bending with 3D-printed Templates in Vertical and Alveolar Ridge Augmentation: A Technical Note

Publication: Oral Surg Oral Med Oral Pathol Oral Radiol. 2017 Jun;123(6):651-60. PMID: 28215503

Authors: Draenert FG, Gebhart F, Mitov G, Neff A.

Institution: Oral & Maxillofacial Surgery, University of Marburg, Germany.


Objectives: Alveolar ridge and vertical augmentations are challenging procedures in dental implantology. Even material blocks with an interconnecting porous system are never completely resorbed. Shell techniques combined with autologous bone chips are therefore the gold standard. using biopolymers for these techniques is well documented. We applied three-dimensional (3-D) techniques to create an individualized bending model for the adjustment of a plane biopolymer membrane made of polylactide.

Study Design: Two cases with a vertical alveolar ridge defect in the maxilla were chosen. The cone beam computed tomography data were processed with a 3D Slicer and the Autodesk Meshmixer to generate data about the desired augmentation result. STL data were used to print a bending model. A 0.2-mm poly-D, L-lactic acid membrane (KLS Matin Inc., Tuttlingen, Germany) was bended accordingly and placed into the defect via a tunnel approach in both cases. A mesh graft of autologous bone chips and hydroxylapatite material was augmented beneath the shell, which was fixed with osteosynthesis screws.

Results: The operative procedure was fast and without peri- or postoperative complications or complaints. The panoramic x-ray showed correct fitting of the material in the location. Bone quality at the time of implant placement was type II, resulting in good primary stability.

Conclusions: A custom-made 3-D model for bending confectioned biomaterial pieces is an appropriate method for individualized adjustment in shell techniques. The advantages over direct printing of the biomaterial shell and products on the market, such as the Xyoss shell (Reoss Inc., Germany), include cost-efficiency and avoidance of regulatory issues.

Application of the 3D Slicer Chest Imaging Platform Segmentation Algorithm for Large Lung Nodule Delineation

Publication: PLoS One. 2017 Jun 8;12(6):e0178944. PMID: 28594880 | PDF

Authors: Yip SSF, Parmar C, Blezek D, Estepar RSJ, Pieper S, Kim J, Aerts HJWL.

Institution: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.


Purpose: Accurate segmentation of lung nodules is crucial in the development of imaging biomarkers for predicting malignancy of the nodules. Manual segmentation is time consuming and affected by inter-observer variability. We evaluated the robustness and accuracy of a publically available semiautomatic segmentation algorithm that is implemented in the 3D Slicer Chest Imaging Platform (CIP) and compared it with the performance of manual segmentation.

Methods: CT images of 354 manually segmented nodules were downloaded from the LIDC database. Four radiologists performed the manual segmentation and assessed various nodule characteristics. The semiautomatic CIP segmentation was initialized using the centroid of the manual segmentations, thereby generating four contours for each nodule. The robustness of both segmentation methods was assessed using the region of uncertainty (δ) and Dice similarity index (DSI). The robustness of the segmentation methods was compared using the Wilcoxon-signed rank test (pWilcoxon<0.05). The Dice similarity index (DSIAgree) between the manual and CIP segmentations was computed to estimate the accuracy of the semiautomatic contours.

Results: The median computational time of the CIP segmentation was 10 s. The median CIP and manually segmented volumes were 477 ml and 309 ml, respectively. CIP segmentations were significantly more robust than manual segmentations (median δCIP = 14ml, median dsiCIP = 99% vs. median δmanual = 222ml, median dsimanual = 82%) with pWilcoxon~10-16. The agreement between CIP and manual segmentations had a median DSIAgree of 60%. While 13% (47/354) of the nodules did not require any manual adjustment, minor to substantial manual adjustments were needed for 87% (305/354) of the nodules. CIP segmentations were observed to perform poorly (median DSIAgree≈50%) for non-/sub-solid nodules with subtle appearances and poorly defined boundaries.

Conclusion: Semi-automatic CIP segmentation can potentially reduce the physician workload for 13% of nodules owing to its computational efficiency and superior stability compared to manual segmentation. Although manual adjustment is needed for many cases, CIP segmentation provides a preliminary contour for physicians as a starting point.


  • U01 CA190234/CA/NCI NIH HHS/United States
  • U24 CA194354/CA/NCI NIH HHS/United States
  • R01 HL116931/HL/NHLBI NIH HHS/United States
Comparison of manual (left) and CIP-based (right) segmentation. Yellow shaded region indicated the disagreement (or region of uncertainty) between contours performed by four radiologists (bottom left) or different CIP-based seed locations (bottom right). In this example, the region of uncertainty for manual segmentation was 3222 ml while the region was only 46 ml for the CIP-based segmentation. dsiCIP was ≈ 100%, while dsimanual was 88%.

Theoretical Observation on Diagnosis Maneuver for Benign Paroxysmal Positional Vertigo

Publication: Acta Otolaryngol. 2017 Jun;137(6):567-71. PMID: 28084876

Authors: Yang XK, Zheng YY, Yang XG.

Institution: Department of Neurology, Wenzhou People's Hospital, Wenzhou, Zhejiang, PR China.


Conclusion: To make a comprehensive analysis with a variety of diagnostic maneuvers is conducive to the correct diagnosis and classification of BPPV.

Objective: Based on the standard spatial coordinate-based semicircular canal model for theoretical observation on diagnostic maneuvers for benign paroxysmal positional vertigo (BPPV) to analyze the meaning and key point of each step of the maneuver.

Materials and Methods: This study started by building a standard model of semicircular canal with space orientation by segmentation of the inner ear done with the 3D Slicer software based on MRI scans, then gives a demonstration and observation of BPPV diagnostic maneuvers by using the model.

Results: The supine roll maneuver is mainly for diagnosis of lateral semicircular canal BPPV. The Modified Dix-Hallpike maneuver is more specific for the diagnosis of posterior semicircular canal BPPV. The side-lying bow maneuver designed here is theoretically suitable for diagnosis of anterior semicircular canal BPPV.

Clinical Outcomes of an Endoscopic Transclival and Transpetrosal Approach for Primary Skull Base Malignancies Involving the Clivus

Publication: J Neurosurg. 2017 Jun 2:1-9. PMID: 28574308 | PDF

Authors: Kim YH1, Jeon C, Se YB, Hong SD, Seol HJ, Lee JI, Park CK, Kim DG, Jung HW, Han DH, Nam DH, Kong DS.

Institution: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.


Objective: The endoscopic endonasal approach for treating primary skull base malignancies involving the clivus is a formidable task. The authors hypothesized that tumor involvement of nearby critical anatomical structures creates hurdles to endoscopic gross-total resection (GTR). The aim of this study was to retrospectively review the clinical outcomes of patients who underwent an endoscopic endonasal approach to treat primary malignancies involving the clivus and to analyze prognostic factors for GTR.

Methods: Between January 2009 and November 2015, 42 patients underwent the endoscopic endonasal approach for resection of primary skull base malignancies involving the clivus at 2 independent institutions. Clinical data; tumor locations within the clivus; and anatomical involvement of the cavernous or paraclival internal carotid artery, cisternal trigeminal nerve, hypoglossal canal, and dura mater were investigated to assess the extent of resection. Possible prognostic factors affecting GTR were also analyzed. The preoperative tumor volume was measured radiographically with 3D Slicer.

Results: Of the 42 patients, 37 were diagnosed with chordomas and 5 were diagnosed with chondrosarcomas. The mean (± SD) preoperative tumor volume was 25.2 ± 30.5 cm3 (range 0.8-166.7 cm3). GTR was achieved in 28 patients (66.7%) and subtotal resection in 14 patients (33.3%). All tumors were classified as upper (n = 17), middle (n = 17), or lower (n = 8) clival tumors based on clival involvement, and as central (24 [57.1%]) or paramedian (18 [42.9%]) based on laterality of the tumor. Univariate analysis identified the tumor laterality (OR 6.25, 95% CI 1.51-25.86; p = 0.011) as significantly predictive of GTR. In addition, the laterality of the tumor was found to be a statistically significant predictor in multivariate analysis (OR 41.16, 95% CI 1.12-1512.65; p = 0.043).

Conclusions: An endoscopic endonasal approach can provide favorable clinical and surgical outcomes. However, the tumor laterality should be considered as a potential obstacle to total removal.

1.5 T Augmented Reality Navigated Interventional MRI: Paravertebral Sympathetic Plexus Injections

Publication: Diagn Interv Radiol. 2017 May-Jun;23(3):227-32. PMID: 28420598 | PDF

Authors: Marker DR, U Thainual P, Ungi T, Flammang AJ, Fichtinger G, Iordachita II, Carrino JA, Fritz J.

Institution: Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.


Purpose: The high contrast resolution and absent ionizing radiation of interventional magnetic resonance imaging (MRI) can be advantageous for paravertebral sympathetic nerve plexus injections. We assessed the feasibility and technical performance of MRI-guided paravertebral sympathetic injections utilizing augmented reality navigation and 1.5 T MRI scanner.

Methods: A total of 23 bilateral injections of the thoracic (8/23, 35%), lumbar (8/23, 35%) and hypogastric (7/23, 30%) paravertebral sympathetic plexus were prospectively planned in twelve human cadavers using a 1.5 Tesla (T) MRI scanner and augmented reality navigation system. MRI-conditional needles were used. Gadolinium-DTPA-enhanced saline was injected. Outcome variables included the number of control magnetic resonance images, target error of the needle tip, punctures of critical nontarget structures, distribution of the injected fluid, and procedure length. The isotropic 3D MR images were transferred into the navigation module (PerkStation) of the 3D Slicer software for interactive 3D evaluation of the anatomy using its DICOM viewer function.

Results: Augmented-reality navigated MRI guidance at 1.5 T provided detailed anatomical visualization for successful targeting of the paravertebral space, needle placement, and perineural paravertebral injections in 46 of 46 targets (100%). A mean of 2 images (range, 1-5 images) were required to control needle placement. Changes of the needle trajectory occurred in 9 of 46 targets (20%) and changes of needle advancement occurred in 6 of 46 targets (13%), which were statistically not related to spinal regions (P = 0.728 and P = 0.86, respectively) and cadaver sizes (P = 0.893 and P 0.859, respectively). The mean error of the needle tip was 3.9±1.7 mm. There were no punctures of critical nontarget structures. The mean procedure length was 33±12 min.

Conclusion: 1.5 T augmented reality-navigated interventional MRI can provide accurate imaging guidance for perineural injections of the thoracic, lumbar, and hypogastric sympathetic plexus.


  • R01 CA118371/CA/NCI NIH HHS/United States
Procedural photograph demonstrating the operator’s augmented reality consisting of a hybrid view of MR image and underlying cadaver. The hybrid view is being created by the reflection of the target MR image (black arrow) from a semitransparent mirror (white arrow) into the line of sight of the operator, where it merges with the underlying cadaver (gray arrow). Location, size, and skin contour of MR image and cadaver are matched through co-registration by the image-overlay navigation system.

From Medical Imaging Data to 3D Printed Anatomical Models

Publication: PLoS One. 2017 May 31;12(5):e0178540. PMID: 28562693 | PDF

Authors: Bücking TM, Hill ER, Robertson JL, Maneas E, Plumb AA, Nikitichev DI.

Institution: Department of Medical Physics and Biomedical Engineering, University College London, London, UK.


Models are important training and teaching tools in the clinical environment and are routinely used in medical imaging research. Advances in segmentation algorithms and increased availability of three-dimensional (3D) printers have made it possible to create cost-efficient patient-specific models without expert knowledge. We introduce a general workflow that can be used to convert volumetric medical imaging data (as generated by Computer Tomography (CT)) to 3D printed physical models. This process is broken up into three steps: image segmentation, mesh refinement and 3D printing. To lower the barrier to entry and provide the best options when aiming to 3D print an anatomical model from medical images, we provide an overview of relevant free and open-source image segmentation tools as well as 3D printing technologies. We demonstrate the utility of this streamlined workflow by creating models of ribs, liver, and lung using a Fused Deposition Modelling 3D printer.

3D printed anatomical models generated from medical imaging data using 3D Slicer and Seg3D. Part of the ribcage (a), the liver (b), and the right lung (c).]

3D Printing and Modelling of Customized Implants and Surgical Guides for Non-human Primates

Publication: J Neurosci Methods. 2017 May 13;286:38-55. PMID: 28512008 | PDF

Authors: Chen X, Possel JK, Wacongne C, van Ham AF, Klink PC, Roelfsema PR.

Institution: Department of Vision & Cognition, Netherlands Institute for Neuroscience, Amsterdam, Netherlands.


Background: Primate neurobiologists use chronically implanted devices such as pedestals for head stabilization and chambers to gain access to the brain and study its activity. Such implants are skull-mounted, and made from a hard, durable material, such as titanium.

New Method: Here we present a low-cost method of creating customized 3D-printed cranial implants that are tailored to the anatomy of individual animals. We performed pre-surgical computed tomography (CT) and magnetic resonance (MR) scans to generate three-dimensional (3D) models of the skull and brain. We then used 3D modeling software to design implantable head posts, chambers, and a pedestal anchorage base, as well as craniotomy guides to aid us during surgery. Prototypes were made from plastic or resin, while implants were 3D-printed in titanium. The implants underwent post-processing and received a coating of osteocompatible material to promote bone integration.

Results: Their tailored fit greatly facilitated surgical implantation, and eliminated the gap between the implant and the bone. To date, our implants remain robust and well-integrated with the skull. Comparison with Existing Method: (s): Commercial-off-the-shelf solutions typically come with a uniform, flat base, preventing them from sitting flush against the curved surface of the skull. This leaves gaps for fluid and tissue ingress, increasing the risk of microbial infection and tissue inflammation, as well as implant loss.

Conclusions: The use of 3D printing technology enabled us to quickly and affordably create unique, complex designs, avoiding the constraints levied by traditional production methods, thereby boosting experimental success and improving the wellbeing of the animals.


  • 339490/European Research Council/International

Accuracy of Mobile Biplane X-ray Imaging in Measuring 6-Degree-of-Freedom Patellofemoral Kinematics during Overground Gait

Publication: J Biomech. 2017 May 24;57:152-6. PMID: 28454908

Authors: Gray HA, Guan S, Pandy MG.

Institution: Department of Mechanical Engineering, University of Melbourne, Victoria, Australia.


The aim of this study was to evaluate the accuracy with which mobile biplane X-ray imaging can be used to measure patellofemoral kinematics of the intact knee during overground gait. A unique mobile X-ray imaging system tracked and recorded biplane fluoroscopic images of two human cadaver knees during simulated overground walking at a speed of 0.7m/s. Six-degree-of-freedom patellofemoral kinematics were calculated using a bone volumetric model-based method and the results then compared against those derived from a gold-standard bead-based method. RMS errors for patellar anterior translation, superior translation and lateral shift were 0.19mm, 0.34mm and 0.37mm, respectively. RMS errors for patellar flexion, lateral tilt and lateral rotation were 1.08°, 1.15° and 1.46°, respectively. The maximum RMS error for patellofemoral translations was approximately one-half that reported previously for tibiofemoral translations using the same mobile X-ray imaging system while the maximum RMS error for patellofemoral rotations was nearly two times larger than corresponding errors reported for tibiofemoral rotations. The lower accuracy in measuring patellofemoral rotational motion is likely explained by the symmetric nature of the patellar geometry and the smaller size of the patella compared to the tibia.

Quality of Radiomic Features in Glioblastoma Multiforme: Impact of Semi-Automated Tumor Segmentation Software

Publication: Korean J Radiol. 2017 May-Jun;18(3):498-509. PMID: 28458602 | PDF

Authors: Lee M, Woo B, Kuo MD, Jamshidi N, Kim JH.

Institution: Center for Medical-IT Convergence Technology Research, Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Korea.


Objective: The purpose of this study was to evaluate the reliability and quality of radiomic features in glioblastoma multiforme (GBM) derived from tumor volumes obtained with semi-automated tumor segmentation software.

Materials and Methods: MR images of 45 GBM patients (29 males, 16 females) were downloaded from The Cancer Imaging Archive, in which post-contrast T1-weighted imaging and fluid-attenuated inversion recovery MR sequences were used. Two raters independently segmented the tumors using two semi-automated segmentation tools (TumorPrism3D and 3D Slicer). Regions of interest corresponding to contrast-enhancing lesion, necrotic portions, and non-enhancing T2 high signal intensity component were segmented for each tumor. A total of 180 imaging features were extracted, and their quality was evaluated in terms of stability, normalized dynamic range (NDR), and redundancy, using intra-class correlation coefficients, cluster consensus, and Rand Statistic.

Results: Our study results showed that most of the radiomic features in GBM were highly stable. Over 90% of 180 features showed good stability (intra-class correlation coefficient [ICC] ≥ 0.8), whereas only 7 features were of poor stability (ICC < 0.5). Most first order statistics and morphometric features showed moderate-to-high NDR (4 > NDR ≥1), while above 35% of the texture features showed poor NDR (< 1). Features were shown to cluster into only 5 groups, indicating that they were highly redundant.

Conclusion: The use of semi-automated software tools provided sufficiently reliable tumor segmentation and feature stability; thus helping to overcome the inherent inter-rater and intra-rater variability of user intervention. However, certain aspects of feature quality, including NDR and redundancy, need to be assessed for determination of representative signature features before further development of radiomics.

Example of segmentation results with two semi-automated software tools. Contrast-enhanced, necrotic, and non-enhancing T2 high signal intensity components are indicated by red, green, and blue color, respectively. A. Represents case in which similar segmentation results were produced. B. Represents case in which difference was observed in segmentation results. FLAIR = fluid-attenuated inversion recovery.

Axillary Lymph Node Evaluation Utilizing Convolutional Neural Networks Using MRI Dataset

Publication: J Digit Imaging. 2018 Apr 25. PMID: 29696472

Authors: Ha R, Chang P, Karcich J, Mutasa S, Fardanesh R, Wynn RT, Liu MZ, Jambawalikar S.

Institution: Department of Radiology, Columbia University, New York, NY, USA.

Abstract: The aim of this study is to evaluate the role of convolutional neural network (CNN) in predicting axillary lymph node metastasis, using a breast MRI dataset. An institutional review board (IRB)-approved retrospective review of our database from 1/2013 to 6/2016 identified 275 axillary lymph nodes for this study. Biopsy-proven 133 metastatic axillary lymph nodes and 142 negative control lymph nodes were identified based on benign biopsies (100) and from healthy MRI screening patients (42) with at least 3 years of negative follow-up. For each breast MRI, axillary lymph node was identified on first T1 post contrast dynamic images and underwent 3D segmentation using an open source software platform 3D Slicer. A 32 × 32 patch was then extracted from the center slice of the segmented tumor data. A CNN was designed for lymph node prediction based on each of these cropped images. The CNN consisted of seven convolutional layers and max-pooling layers with 50% dropout applied in the linear layer. In addition, data augmentation and L2 regularization were performed to limit overfitting. Training was implemented using the Adam optimizer, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. Code for this study was written in Python using the TensorFlow module (1.0.0). Experiments and CNN training were done on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Two class axillary lymph node metastasis prediction models were evaluated. For each lymph node, a final softmax score threshold of 0.5 was used for classification. Based on this, CNN achieved a mean five-fold cross-validation accuracy of 84.3%. It is feasible for current deep CNN architectures to be trained to predict likelihood of axillary lymph node metastasis. Larger dataset will likely improve our prediction model and can potentially be a non-invasive alternative to core needle biopsy and even sentinel lymph node evaluation.

Prognostic Implications of the Subcellular Localization of Survivin in Glioblastomas Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide

Publication: J Neurosurg. 2017 Apr 21:1-6. PMID: 28430038 | PDF

Authors: Saito T, Sugiyama K, Takeshima Y, Amatya VJ, Yamasaki F, Takayasu T, Nosaka R, Muragaki Y, Kawamata T, Kurisu K.

Institution: Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.


Objective: Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol.

Methods: The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment. The relationship between survivin localization and overall survival (OS) was assessed with uni- and multivariate analyses including other clinicopathological factors (age, sex, Karnofsky Performance Scale [KPS] score, extent of resection, the use of second-line bevacizumab, O6-methylguanine-DNA methyltransferase [MGMT] status, and MIB-1 labeling index).

Result: Log-rank tests revealed that patient age, KPS score, extent of resection, MGMT status, and survivin localization (p < 0.0001) significantly correlated with OS. Multivariate analysis indicated that patient age, MGMT status, and survivin localization significantly correlated with OS. Patients with nuclear localization of survivin had a significantly shorter OS than those in whom survivin expression was exclusively cytoplasmic (median OS 19.5 vs 31.7 months, respectively, HR 5.690, 95% CI 2.068-17.612, p = 0.0006). There was no significant difference in OS between patents whose survivin expression was exclusively nuclear or nuclear/cytoplasmic.

Conclusions: Nuclear expression of survivin is a factor for a poor prognosis in GBM patients. Subcellular localization of survivin can help to predict OS in GBM patients treated with the standard protocol.

An Ovine Model of Cerebral Catheter Venography for Implantation of an Endovascular Neural Interface

Publication: J Neurosurg. 2017 Apr 28:1-8. PMID: 28452616 | PDF

Authors: Oxley TJ, Opie NL, Rind GS, Liyanage K, John SE, Ronayne S, McDonald AJ, Dornom A, Lovell TJH, Mitchell PJ, Bennett I, Bauquier S, Warne LN, Steward C, Grayden DB, Desmond P, Davis SM, O'Brien TJ, May CN.

Institution: Vascular Bionics Laboratory, Department of Medicine, The Royal Melbourne Hospital, Melbourne, Australia.


Objective: Neural interface technology may enable the development of novel therapies to treat neurological conditions, including motor prostheses for spinal cord injury. Intracranial neural interfaces currently require a craniotomy to achieve implantation and may result in chronic tissue inflammation. Novel approaches are required that achieve less invasive implantation methods while maintaining high spatial resolution. An endovascular stent electrode array avoids direct brain trauma and is able to record electrocorticography in local cortical tissue from within the venous vasculature. The motor area in sheep runs in a parasagittal plane immediately adjacent to the superior sagittal sinus (SSS). The authors aimed to develop a sheep model of cerebral venography that would enable validation of an endovascular neural interface.

Methods: Cerebral catheter venography was performed in 39 consecutive sheep. Contrast-enhanced MRI of the brain was performed on 13 animals. Multiple telescoping coaxial catheter systems were assessed to determine the largest wide-bore delivery catheter that could be delivered into the anterior SSS. Measurements of SSS diameter and distance from the motor area were taken. The location of the motor area was determined in relation to lateral and superior projections of digital subtraction venography images and confirmed on MRI. Results: The venous pathway from the common jugular vein (7.4 mm) to the anterior SSS (1.2 mm) was technically challenging to selectively catheterize. The SSS coursed immediately adjacent to the motor cortex (< 1 mm) for a length of 40 mm, or the anterior half of the SSS. Attempted access with 5-Fr and 6-Fr delivery catheters was associated with longer procedure times and higher complication rates. A 4-Fr catheter (internal lumen diameter 1.1 mm) was successful in accessing the SSS in 100% of cases with no associated complications. Complications included procedure-related venous dissection in two major areas: the torcular herophili, and the anterior formation of the SSS. The bifurcation of the cruciate sulcal veins with the SSS was a reliable predictor of the commencement of the motor area. Conclusions: The ovine model for cerebral catheter venography has generalizability to the human cerebral venous system in relation to motor cortex location. This novel model may facilitate the development of the novel field of endovascular neural interfaces that may include preclinical investigations for cortical recording applications such as paralysis and epilepsy, as well as other potential applications in neuromodulation.

Effectiveness of Endoscopic Surgery for Supratentorial Hypertensive Intracerebral Hemorrhage: A Comparison with Craniotomy

Publication: J Neurosurg. 2017 Apr 7:1-7. PMID: 28387618 | PDF

Authors: Xu X, Chen X, Li F, Zheng X, Wang Q, Sun G, Zhang J, Xu B.

Institution: Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China.


Objective: The goal of this study was to investigate the effectiveness and practicality of endoscopic surgery for treatment of supratentorial hypertensive intracerebral hemorrhage (HICH) compared with traditional craniotomy.

Methods: The authors retrospectively analyzed 151 consecutive patients who were operated on for treatment of supratentorial HICH between January 2009 and June 2014 in the Department of Neurosurgery at Chinese PLA General Hospital. Patients were separated into an endoscopy group (82 cases) and a craniotomy group (69 cases), depending on the surgery they received. The hematoma evacuation rate was calculated using 3D Slicer software to measure the hematoma volume. Comparisons of operative time, intraoperative blood loss, Glasgow Coma Scale score 1 week after surgery, hospitalization time, and modified Rankin Scale score 6 months after surgery were also made between these groups.

Results: There was no statistically significant difference in preoperative data between the endoscopy group and the craniotomy group (p > 0.05). The hematoma evacuation rate was 90.5% ± 6.5% in the endoscopy group and 82.3% ± 8.6% in the craniotomy group, which was statistically significant (p < 0.01). The operative time was 1.6 ± 0.7 hours in the endoscopy group and 5.2 ± 1.8 hours in the craniotomy group (p < 0.01). The intraoperative blood loss was 91.4 ± 93.1 ml in the endoscopy group and 605.6 ± 602.3 ml in the craniotomy group (p < 0.01). The 1-week postoperative Glasgow Coma Scale score was 11.5 ± 2.9 in the endoscopy group and 8.3 ± 3.8 in the craniotomy group (p < 0.01). The hospital stay was 11.6 ± 6.9 days in the endoscopy group and 13.2 ± 7.9 days in the craniotomy group (p < 0.05). The mean modified Rankin Scale score 6 months after surgery was 3.2 ± 1.5 in the endoscopy group and 4.1 ± 1.9 in the craniotomy group (p < 0.01). Patients had better recovery in the endoscopy group than in the craniotomy group. Data are expressed as the mean ± SD.

Conclusions: Compared with traditional craniotomy, endoscopic surgery was more effective, less invasive, and may have improved the prognoses of patients with supratentorial HICH. Endoscopic surgery is a promising method for treatment of supratentorial HICH. With the development of endoscope technology, endoscopic evacuation will become more widely used in the clinic. Prospective randomized controlled trials are needed.

Asymmetry in Dentition and Shape of Pharyngeal Arches in the Clonal Fish Chrosomus Eos-neogaeus: Phenotypic Plasticity and Developmental Instability

Publication: PLoS One. 2017 Apr 5;12(4):e0174235. PMID: 28380079 | PDF

Authors: Leung C, Duclos KK, Grünbaum T, Cloutier R, Angers B.

Institution: Department of Biological Sciences, Université de Montréal, Montreal, Quebec, Canada.


The effect of the environment may result in different developmental outcomes. Extrinsic signals can modify developmental pathways and result in alternative phenotypes (phenotypic plasticity). The environment can also be interpreted as a stressor and increase developmental instability (developmental noise). Directional and fluctuating asymmetry provide a conceptual background to discriminate between these results. This study aims at assessing whether variation in dentition and shape of pharyngeal arches of the clonal fish Chrosomus eos-neogaeus results from developmental instability or environmentally induced changes. A total of 262 specimens of the Chrosomus eos-neogaeus complex from 12 natural sites were analysed. X-ray microcomputed tomography (X-ray micro-CT) was used to visualize the pharyngeal arches in situ with high resolution. Variation in the number of pharyngeal teeth is high in hybrids in contrast to the relative stability observed in both parental species. The basal dental formula is symmetric while the most frequent alternative dental formula is asymmetric. Within one lineage, large variation in the proportion of individuals bearing basal or alternative dental formulae was observed among sites in the absence of genetic difference. Both dentition and arch shape of this hybrid lineage were explained significantly by environmental differences. Only individuals bearing asymmetric dental formula displayed fluctuating asymmetry as well as directional left-right asymmetry for the arches. The hybrids appeared sensitive to environmental signals and intraspecific variation on pharyngeal teeth was not random but reflects phenotypic plasticity. Altogether, these results support the influence of the environment as a trigger for an alternative developmental pathway resulting in left-right asymmetry in dentition and shape of pharyngeal arches.

Dicom files were subsequently loaded within the open-source software 3D Slicer (Version 4.5 ). 3D models were rendered from dicom files using the editor module within 3D Slicer and the thresholding algorithm.

Scanning Laser Optical Tomography for in Toto Imaging of the Murine Cochlea

Publication: PLoS One. 2017 Apr 7;12(4):e0175431. PMID: 28388662 | PDF

Authors: Nolte L, Tinne N, Schulze J, Heinemann D, Antonopoulos GC, Meyer H, Nothwang HG, Lenarz T, Heisterkamp A, Warnecke A, Ripken T.

Institution: Industrial and Biomedical Optics Department, Laser Zentrum Hannover e.V., Hannover, Germany.


The mammalian cochlea is a complex macroscopic structure due to its helical shape and the microscopic arrangements of the individual layers of cells. To improve the outcomes of hearing restoration in deaf patients, it is important to understand the anatomic structure and composition of the cochlea ex vivo. Hitherto, only one histological technique based on confocal laser scanning microscopy and optical clearing has been developed for in toto optical imaging of the murine cochlea. However, with a growing size of the specimen, e.g., human cochlea, this technique reaches its limitations. Here, we demonstrate scanning laser optical tomography (SLOT) as a valuable imaging technique to visualize the murine cochlea in toto without any physical slicing. This technique can also be applied in larger specimens up to cm3 such as the human cochlea. Furthermore, immunolabeling allows visualization of inner hair cells (otoferlin) or spiral ganglion cells (neurofilament) within the whole cochlea. After image reconstruction, the 3D dataset was used for digital segmentation of the labeled region. As a result, quantitative analysis of position, length and curvature of the labeled region was possible. This is of high interest in order to understand the interaction of cochlear implants (CI) and cells in more detail.

To enable correct overlay of the two excitation channels, the general registration algorithm (BRAINS) from the open source software 3D Slicer was used.

Maximum intensity projections (MIP) were performed on the reconstructed data of samples 1 and 2. (A) MIP of sample 1. The labeled neurofilament appears as a helical shape inside the cochlea. (B) Higher magnification of the highlighted area in A. The dendrites of the spiral ganglions are visible. (C) Negative control (sample 2). Only autofluorescence and nonspecific binding shows the outer shape of the cochlea. (D) Higher magnification of the highlighted area in C.

Patient Education for Endoscopic Sinus Surgery: Preliminary Experience using 3D-Printed Clinical Imaging Data

Publication: J Funct Biomater. 2017 Apr 7;8(2). PMID: 28387702 | PDF

Authors: Sander IM, Liepert TT, Doney EL, Leevy WM, Liepert DR.

Institution: Department of Biological Sciences, University of Notre Dame, South Bend, IN, USA.


Within the Ear, Nose, and Throat (ENT) medical space, a relatively small fraction of patients follow through with elective surgeries to fix ailments such as a deviated septum or occluded sinus passage. Patient understanding of their diagnosis and treatment plan is integral to compliance, which ultimately yields improved medical outcomes and better quality of life. Here we report the usage of advanced, polyjet 3D printing methods to develop a multimaterial replica of human nasal sinus anatomy, derived from clinical X-ray computed tomography (CT) data, to be used as an educational aid during physician consultation. The final patient education model was developed over several iterations to optimize material properties, anatomical accuracy and overall display. A two-arm, single-center, randomized, prospective study was then performed in which 50 ENT surgical candidates (and an associated control group, n = 50) were given an explanation of their anatomy, disease state, and treatment options using the education model as an aid. Statistically significant improvements in patient ratings of their physician's explanation of their treatment options (p = 0.020), self-rated anatomical understanding (p = 0.043), self-rated understanding of disease state (p = 0.016), and effectiveness of the visualization (p = 0.007) were noted from the population that viewed the 3D education model, indicating it is an effective tool which ENT surgeons may use to educate and interact with patients.

All volumes outside of the volume of interest were masked at a value of −1000 Hounsfield Units (HU). The data was exported in Nifti (.nii) format and opened in 3D Slicer. A 3D surface map for bone was generated using the “Grayscale Modelmaker” tool within 3D Slicer at a threshold of 300 HU. A separate 3D surface map was generated for soft tissue using the same tool and process with a threshold level of −300 HU. Each surface map was exported from 3D Slicer as a .stl file.

Nasal cavity model generation and fabrication. (A) 3D surface maps generated from CT scan slices of patient nasal cavity used to generate a 3D-printed model; (B) 3D-printed, sliced model, printed with two distinct polymers to represent hard and soft tissues; (C) Single coronal model slice with specific anatomical details highlighted.

Comprehensive Evaluation of Ten Deformable Image Registration Algorithms for Contour Propagation between CT and Cone-beam CT Images in Adaptive Head & Neck Radiotherapy

Publication: PLoS One. 2017 Apr 17;12(4):e0175906. PMID: 28414799 | PDF

Authors: Li X, Zhang Y, Shi Y, Wu S, Xiao Y, Gu X, Zhen X, Zhou L.

Institution: Department of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, China.


Deformable image registration (DIR) is a critical technic in adaptive radiotherapy (ART) for propagating contours between planning computerized tomography (CT) images and treatment CT/cone-beam CT (CBCT) images to account for organ deformation for treatment re-planning. To validate the ability and accuracy of DIR algorithms in organ at risk (OAR) contour mapping, ten intensity-based DIR strategies, which were classified into four categories-optical flow-based, demons-based, level-set-based and spline-based-were tested on planning CT and fractional CBCT images acquired from twenty-one head & neck (H&N) cancer patients who underwent 6~7-week intensity-modulated radiation therapy (IMRT). Three similarity metrics, i.e., the Dice similarity coefficient (DSC), the percentage error (PE) and the Hausdorff distance (HD), were employed to measure the agreement between the propagated contours and the physician-delineated ground truths of four OARs, including the vertebra (VTB), the vertebral foramen (VF), the parotid gland (PG) and the submandibular gland (SMG). It was found that the evaluated DIRs in this work did not necessarily outperform rigid registration. DIR performed better for bony structures than soft-tissue organs, and the DIR performance tended to vary for different ROIs with different degrees of deformation as the treatment proceeded. Generally, the optical flow-based DIR performed best, while the demons-based DIR usually ranked last except for a modified demons-based DISC used for CT-CBCT DIR. These experimental results suggest that the choice of a specific DIR algorithm depends on the image modality, anatomic site, magnitude of deformation and application. Therefore, careful examinations and modifications are required before accepting the auto-propagated contours, especially for automatic re-planning ART systems.

Before performing the rigid and deformable registration, all the images were pre-processed using an open source software 3D Slicer.

Interactive Outlining of Pancreatic Cancer Liver Metastases in Ultrasound Images

Publication: Sci Rep. 2017 Apr 18;7(1):892. PMID: 28420871 | PDF

Authors: Egger J, Schmalstieg D, Chen X, Zoller WG, Hann A.

Institution: Institute for Computer Graphics and Vision, Graz University of Technology, Graz, Austria.


Ultrasound (US) is the most commonly used liver imaging modality worldwide. Due to its low cost, it is increasingly used in the follow-up of cancer patients with metastases localized in the liver. In this contribution, we present the results of an interactive segmentation approach for liver metastases in US acquisitions. A (semi-) automatic segmentation is still very challenging because of the low image quality and the low contrast between the metastasis and the surrounding liver tissue. Thus, the state of the art in clinical practice is still manual measurement and outlining of the metastases in the US images. We tackle the problem by providing an interactive segmentation approach providing real-time feedback of the segmentation results. The approach has been evaluated with typical US acquisitions from the clinical routine, and the datasets consisted of pancreatic cancer metastases. Even for difficult cases, satisfying segmentations results could be achieved because of the interactive real-time behavior of the approach. In total, 40 clinical images have been evaluated with our method by comparing the results against manual ground truth segmentations. This evaluation yielded to an average Dice Score of 85% and an average Hausdorff Distance of 13 pixels. We tested our data with the GrowCut implementation that is available in 3D Slicer.

GrowCut segmentation results for the two metastases from Fig. 9. The left images show the manual initialization of GrowCut: the metastases were initialized with green, and the backgrounds were initialized with yellow. The images in the middle show the segmentation results of GrowCut (green). The right images show a closer view of the segmentation results (green) with a lower opacity.

The Evolution of Cost-efficiency in Neural Networks during Recovery from Traumatic Brain Injury

Publication: PLoS One. 2017 Apr 19;12(4):e0170541. PMID: 28422992 | PDF

Authors: Roy A, Bernier RA, Wang J, Benson M, French JJ Jr, Good DC, Hillary FG.

Institution: Department of Psychology, The Pennsylvania State University, University Park, PA, USA.

Abstract: A somewhat perplexing finding in the systems neuroscience has been the observation that physical injury to neural systems may result in enhanced functional connectivity (i.e., hyperconnectivity) relative to the typical network response. The consequences of local or global enhancement of functional connectivity remain uncertain and this is particularly true for the overall metabolic cost of the network. We examine the hyperconnectivity hypothesis in a sample of 14 individuals with TBI with data collected at approximately 3, 6, and 12 months following moderate and severe TBI. As anticipated, individuals with TBI showed increased network strength and cost early after injury, but by one-year post injury hyperconnectivity was more circumscribed to frontal DMN and temporal-parietal attentional control regions. Cost in these subregions was a significant predictor of cognitive performance. Cost-efficiency analysis in the Power 264 data parcellation suggested that at 6 months post injury the network requires higher cost connections to achieve high efficiency as compared to the network 12 months post injury. These results demonstrate that networks self-organize to re-establish connectivity while balancing cost-efficiency trade-offs. To determine the influence of global pathology on brain networks, we created a 3-dimensional (3D) lesion model for each subject using 3D Slicer that utilizes information from multiple MR sequences, such as SWI, FLAIR, and T1 MPRAGE.

fMRI data preprocessing steps and the analytic pipeline.

Biomechanical Flow Amplification Arising From the Variable Deformation of the Subglottic Mucosa

Publication: J Voice. 2017 Apr 19. PMID: 28433346 | PDF

Authors: Goodyer E, Müller F, Hess M, Kandan K, Farukh F.

Institution: De Montfort University, Bio-Informatics Research Group, Leicester, UK.


Objective: This study mapped the variation in tissue elasticity of the subglottic mucosa, applied these data to provide initial models of the likely deformation of the mucosa during the myoelastic cycle, and hypothesized as to the impact on the process of phonation.

Study design: Six donor human larynges were dissected along the sagittal plane to expose the vocal folds and subglottic mucosa. A linear skin rheometer was used to apply a controlled shear force, and the resultant displacement was measured. These data provided a measure of the stress/strain characteristics of the tissue at each anatomic point. A series of measurements were taken at 2-mm interval inferior of the vocal folds, and the change in elasticity was determined. CT images of the excised larynges have been used to create 3D reconstructions with the help of an open-source medical imaging software, 3D Slicer.

Results: It was found that the elasticity of the mucosa in the subglottic region increased linearly with distance from the vocal folds in all 12 samples. A simple deformation model indicated that under low pressure conditions the subglottic mucosa will deform to form a cone, which could result in a higher velocity, thus amplifying the low pressure effect resulting from the Venturi principle, and could assist in maintaining laminar flow.

Conclusions: This study indicated that the deformation of the subglottic mucosa could play a significant role in the delivery of a low pressure airflow over the vocal folds. A large scale study will now be undertaken to secure more data to evaluate this hypothesis, and using computational fluid dynamics based on actual three-dimensional structure obtained from computed tomography scans the aerodynamics of this region will be investigated.

Three-dimensional (3D) model of a larynx constructed from a computed tomography scan images (A) showing the full 3D model. (B) and (C) Show the views of larynx looking down the arrow as indicated by the letter P and Q, respectively. CT images of the excised larynges have been used to create 3D reconstructions with the help of an open-source medical imaging software, 3D Slicer.

HTC Vive MeVisLab Integration via OpenVR for Medical Applications

Publication: PLoS One. 2017 Mar 21;12(3):e0173972. PMID: 28323840 | PDF

Authors: Egger J, Gall M, Wallner J, Boechat P, Hann A, Li X, Chen X, Schmalstieg D.

Institution: Institute of Computer Graphics and Vision, Graz University of Technology, Graz, Austria.


Virtual Reality, an immersive technology that replicates an environment via computer-simulated reality, gets a lot of attention in the entertainment industry. However, VR has also great potential in other areas, like the medical domain, Examples are intervention planning, training and simulation. This is especially of use in medical operations, where an aesthetic outcome is important, like for facial surgeries. Alas, importing medical data into Virtual Reality devices is not necessarily trivial, in particular, when a direct connection to a proprietary application is desired. Moreover, most researcher do not build their medical applications from scratch, but rather leverage platforms like MeVisLab, MITK, OsiriX or 3D Slicer. These platforms have in common that they use libraries like ITK and VTK, and provide a convenient graphical interface. However, ITK and VTK do not support Virtual Reality directly. In this study, the usage of a Virtual Reality device for medical data under the MeVisLab platform is presented. The OpenVR library is integrated into the MeVisLab platform, allowing a direct and uncomplicated usage of the head mounted display HTC Vive inside the MeVisLab platform. Medical data coming from other MeVisLab modules can directly be connected per drag-and-drop to the Virtual Reality module, rendering the data inside the HTC Vive for immersive virtual reality inspection.

Accessing Microfluidics through Feature-based Design Software for 3D Printing

Publication: PLoS One. 2018 Mar 29;13(3):e0192752. PMID: 29596418 | PDF

Authors: Shankles PG, Millet LJ, Aufrecht JA, Retterer ST.

Institution: The Bredesen Center for Interdisciplinary Research, The University of Tennessee, Knoxville, TN, USA.

Abstract: Additive manufacturing has been a cornerstone of the product development pipeline for decades, playing an essential role in the creation of both functional and cosmetic prototypes. In recent years, the prospects for distributed and open source manufacturing have grown tremendously. This growth has been enabled by an expanding library of printable materials, low-cost printers, and communities dedicated to platform development. The microfluidics community has embraced this opportunity to integrate 3D printing into the suite of manufacturing strategies used to create novel fluidic architectures. The rapid turnaround time and low cost to implement these strategies in the lab makes 3D printing an attractive alternative to conventional micro- and nanofabrication techniques. In this work, the production of multiple microfluidic architectures using a hybrid 3D printing-soft lithography approach is demonstrated and shown to enable rapid device fabrication with channel dimensions that take advantage of laminar flow characteristics. The fabrication process outlined here is underpinned by the implementation of custom design software with an integrated slicer program that replaces less intuitive computer aided design and 3D Slicer software tools. Devices are designed in the program by assembling parameterized microfluidic building blocks. The fabrication process and flow control within 3D printed devices were demonstrated with a gradient generator and two droplet generator designs. Precise control over the printing process allowed 3D microfluidics to be printed in a single step by extruding bridge structures to 'jump-over' channels in the same plane. This strategy was shown to integrate with conventional nanofabrication strategies to simplify the operation of a platform that incorporates both nanoscale features and 3D printed microfluidics.

Revealing Cancer Subtypes with Higher-Order Correlations Applied to Imaging and Omics Data

Publication: BMC Med Genomics. 2017 Mar 31;10(1):20. PMID: 28359308 | PDF

Authors: Graim K, Liu TT, Achrol AS, Paull EO, Newton Y, Chang SD, Harsh GR, Cordero SP, Rubin DL, Stuart JM.

Institution: Biomedical Engineering, University of California, Santa Cruz, CA, USA.


Background: Patient stratification to identify subtypes with different disease manifestations, severity, and expected survival time is a critical task in cancer diagnosis and treatment. While stratification approaches using various biomarkers (including high-throughput gene expression measurements) for patient-to-patient comparisons have been successful in elucidating previously unseen subtypes, there remains an untapped potential of incorporating various genotypic and phenotypic data to discover novel or improved groupings.

Methods: Here, we present HOCUS, a unified analytical framework for patient stratification that uses a community detection technique to extract subtypes out of sparse patient measurements. HOCUS constructs a patient-to-patient network from similarities in the data and iteratively groups and reconstructs the network into higher order clusters. We investigate the merits of using higher-order correlations to cluster samples of cancer patients in terms of their associations with survival outcomes.

Results: In an initial test of the method, the approach identifies cancer subtypes in mutation data of glioblastoma, ovarian, breast, prostate, and bladder cancers. In several cases, HOCUS provides an improvement over using the molecular features directly to compare samples. Application of HOCUS to glioblastoma images reveals a size and location classification of tumors that improves over human expert-based stratification.

Conclusions: Subtypes based on higher order features can reveal comparable or distinct groupings. The distinct solutions can provide biologically- and treatment-relevant solutions that are just as significant as solutions based on the original data.


  • U54 HG006097/HG/NHGRI NIH HHS/United States
  • U01 CA187947/CA/NCI NIH HHS/United States
  • R01 GM109031/GM/NIGMS NIH HHS/United States
  • U24 CA143858/CA/NCI NIH HHS/United States
  • R01 CA180778/CA/NCI NIH HHS/United States
  • U01 CA142555/CA/NCI NIH HHS/United States
  • U01 CA190214/CA/NCI NIH HHS/United States
  • U54 HL127365/HL/NHLBI NIH HHS/United States
  • U24 CA210990/CA/NCI NIH HHS/United States
HOCUS of GBM MR Images. a. P-values of survival separation (log-rank test) for each of the orders of clustering across a range of k clusters. b. Kaplan-Meier plot of the third-order HOCUS clusters. c. Images of tumors within each cluster projected onto the MNI brain atlas. Showing sagittal, coronal, axial views. Brightness of color indicates the number of patients with tumor at a given location. Generated using 3D Slicer. d. Violin plot showing tumor volumes within each third-order cluster. e. Molecular (gene expression based) subtypes within the clusters.

A Study of Volumetric Variations of Basal Nuclei in the Normal Human Brain by Magnetic Resonance Imaging

Publication: Clin Anat. 2017 Mar;30(2):175-82. PMID: 28078760

Authors: Elkattan A, Mahdy A, Eltomey M, Ismail R.

Institution: Department of Anatomy, Tanta University of Medical Sciences, Tanta, Egypt.


Knowledge of the effects of healthy aging on brain structures is necessary to identify abnormal changes due to diseases. Many studies have demonstrated age-related volume changes in the brain using MRI. 60 healthy individuals who had normal MRI aged from 20 years to 80 years were examined and classified into three groups: Group I: 21 persons; nine males and 12 females aging between 20-39 years old. Group II: 22 persons; 11 males and 11 females aging between 40-59 years old. Group III: 17 persons; eight males and nine females aging between 60-80 years old. Volumetric analysis was done to evaluate the effect of age, gender and hemispheric difference in the caudate and putamen by the 3D Slicer software using 3D T1-weighted images. Data were analyzed by student's unpaired t test, ANOVA and regression analysis. The volumes of the measured and corrected caudate nuclei and putamen significantly decreased with aging in males. There was a statistically insignificant relation between the age and the volume of the measured caudate nuclei and putamen in females but there was a statistically significant relation between the age and the corrected caudate nuclei and putamen. There was no significant difference on the caudate and putamen volumes between males and females. There was no significant difference between the right and left caudate nuclei volumes. There was a leftward asymmetry in the putamen volumes. The results can be considered as a base to track individual changes with time (aging and CNS diseases).

Linear Relationship Found by Magnetic Resonance Imaging between Cerebrospinal Fluid Volume and Body Weight in Dogs

Publication: Acta Vet Hung. 2017 Mar;65(1):1-12. PMID: 28244335

Authors: Reinitz LZ, Bajzik G, Garamvölgyi R, Benedek B, Petneházy Ö, Lassó A, Abonyi-Tóth Z, Lőrincz B, Sótonyi P.

Institution: Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary.


Despite numerous studies on cerebrospinal fluid (CSF) and its importance during hydrocephalus or myelography, no reliable values exist about its overall volume in dogs. In this study, our aim was to measure the intracranial (IC) volume of CSF in dogs and assess its possible relationship with body size and the symmetry of the lateral ventricles. We ran a 3D magnetic resonance imaging (MRI) sequence on the central nervous system of 12 healthy, male mongrel dogs between 3-5 years of age and 7.5-35.0 kg body weight. A validated semiautomatic segmentation protocol was implemented to segment the CSF and measure its volume. Values for the volume of the ventricular compartment were between 0.97 and 2.94 ml, with 62.1±11.7% in the lateral ventricles, 17.6±4.9% in the third ventricle, 4.9±1.6% in the aqueductus mesencephali and 15.5±6.6% in the fourth ventricle. In 11 cases a significant asymmetry was found between the lateral ventricles. The results suggest that it may be normal for a dog to have one of the lateral ventricles 1.5 times larger than the other. The correlation between body weight and CSF volume was linear, indicating that the current dosage protocols for myelography, based on a hypothetical proportional relationship with body weight, may have to be revised.

MITK-OpenIGTLink for Combining Open-Source Toolkits in Real-Time Computer-Assisted Interventions

Publication: Int J Comput Assist Radiol Surg. 2017 Mar;12(3):351-61. PMID: 27687984

Authors: Klemm M, Kirchner T, Gröhl J, Cheray D, Nolden M, Seitel A, Hoppe H, Maier-Hein L, Franz AM.

Institution: Laboratory for Computer-Assisted Medicine, Department of Electrical Engineering and Information Technology, Offenburg University, Offenburg, Germany.


Purpose: Due to rapid developments in the research areas of medical imaging, medical image processing and robotics, computer-assisted interventions (CAI) are becoming an integral part of modern patient care. From a software engineering point of view, these systems are highly complex and research can benefit greatly from reusing software components. This is supported by a number of open-source toolkits for medical imaging and CAI such as the medical imaging interaction toolkit (MITK), the public software library for ultrasound imaging research (PLUS) and 3D Slicer. An independent inter-toolkit communication such as the open image-guided therapy link (OpenIGTLink) can be used to combine the advantages of these toolkits and enable an easier realization of a clinical CAI workflow.

Methods: MITK-OpenIGTLink is presented as a network interface within MITK that allows easy to use, asynchronous two-way messaging between MITK and clinical devices or other toolkits. Performance and interoperability tests with MITK-OpenIGTLink were carried out considering the whole CAI workflow from data acquisition over processing to visualization.

Results: We present how MITK-OpenIGTLink can be applied in different usage scenarios. In performance tests, tracking data were transmitted with a frame rate of up to 1000 Hz and a latency of 2.81 ms. Transmission of images with typical ultrasound (US) and greyscale high-definition (HD) resolutions of [Formula: see text] and [Formula: see text] is possible at up to 512 and 128 Hz, respectively.

Conclusion: With the integration of OpenIGTLink into MITK, this protocol is now supported by all established open-source toolkits in the field. This eases interoperability between MITK and toolkits such as PLUS or 3D Slicer and facilitates cross-toolkit research collaborations. MITK and its submodule MITK-OpenIGTLink are provided open source under a BSD-style license (

Increased Cerebellar Gray Matter Volume in Head Chefs

Publication: PLoS One. 2017 Feb 9;12(2):e0171457. PMID: 28182712 | PDF

Authors: Cerasa A, Sarica A, Martino I, Fabbricatore C, Tomaiuolo F, Rocca F, Caracciolo M, Quattrone A.

Institution: Institute of Bioimaging and Molecular Physiology, National Research Council, Catanzaro, Italy.


Objective: Chefs exert expert motor and cognitive performances on a daily basis. Neuroimaging has clearly shown that that long-term skill learning (i.e., athletes, musicians, chess player or sommeliers) induces plastic changes in the brain thus enabling tasks to be performed faster and more accurately. How a chef's expertise is embodied in a specific neural network has never been investigated.

Methods: Eleven Italian head chefs with long-term brigade management expertise and 11 demographically-/ psychologically- matched non-experts underwent morphological evaluations.

Results: Voxel-based analysis performed with SUIT, as well as, automated volumetric measurement assessed with Freesurfer, revealed increased gray matter volume in the cerebellum in chefs compared to non-experts. The most significant changes were detected in the anterior vermis and the posterior cerebellar lobule. The magnitude of the brigade staff and the higher performance in the Tower of London test correlated with these specific gray matter increases, respectively.

Conclusions: We found that chefs are characterized by an anatomical variability involving the cerebellum. This confirms the role of this region in the development of similar expert brains characterized by learning dexterous skills, such as pianists, rock climbers and basketball players. However, the nature of the cellular events underlying the detected morphological differences remains an open question.

Sample color-coded automated brain segmentation results. A 3D surface image (created with 3D Slicer v 4.6) showing typical automated subcortical segmentation of the cerebellum performed by FreeSurfer (v 5.3). Scatter plot of the mean normalized volumes of the left and right cerebellar cortex for each single subject has been plotted. Advanced neuroimaging analysis reveals bilateral cerebellar volumetric increase in the chef group with respect to non-expert individuals.

Tumor Heterogeneity Assessed by Texture Analysis on Contrast-Enhanced CT in Lung Adenocarcinoma: Association with Pathologic Grade

Publication: Oncotarget. 2017 Feb 16;8(32):53664-74. PMID: 28881840 | PDF

Authors: Liu Y, Liu S, Qu F, Li Q, Cheng R, Ye Z.

Institution: Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.


Objectives: To investigate whether texture features on contrast-enhanced computed tomography (CECT) images of lung adenocarcinoma have association with pathologic grade. Methods: A cohort of 148 patients with surgically operated adenocarcinoma was retrospectively reviewed. Fifty-four CT features of the primary lung tumor were extracted from CECT images using open-source 3D Slicer software; meanwhile, enhancement homogeneity was evaluated by two radiologists using visual assessment. Multivariate logistic regression analysis was performed to determine significant image indicator of pathologic grade.

Results: Tumors of intermediate grade were more likely to be never smokers (P=0.020). Enhancement heterogeneity by visual assessment showed no statistical difference between intermediate grade and high grade (P=0.671). Among those 54 features, 29 of them were significantly associated with pathologic grade. Multivariate logistic regression analyses identified F33 (Homogeneity 1) (P=0.005) and F38 (Inverse Variance) (P=0.032) as unique independent image indicators of pathologic grade, and the AUC calculated from this model (AUC=0.834) was higher than clinical model (AUC=0.615) (P=0.0001).Conclusions Our study revealed that texture analysis on CECT images could be helpful in predicting pathologic grade of lung adenocarcinoma.

Example of CT images showing segmentation of lung tumor. Semiautomatic tumor segmentation was done on every slice of the tumor using 3D Slicer (a), and the 3D view of the segmented tumor (b) which was shown in yellow.

SEEG Assistant: A 3D Slicer Extension to Support Epilepsy Surgery

Publication: BMC Bioinformatics. 2017 Feb 23;18(1):124. PMID: 28231759 | PDF

Authors: Narizzano M, Arnulfo G, Ricci S, Toselli B, Tisdall M, Canessa A, Fato MM, Cardinale F.

Institution: Department of Informatics, Bioengineering Robotics and System engineering (DIBRIS), University of Genoa, Genova, Italy.


Background: In the evaluation of Stereo-Electroencephalography (SEEG) signals, the physicist's workflow involves several operations, including determining the position of individual electrode contacts in terms of both relationship to grey or white matter and location in specific brain regions. These operations are (i) generally carried out manually by experts with limited computer support, (ii) hugely time consuming, and (iii) often inaccurate, incomplete, and prone to errors.

Results: In this paper we present SEEG Assistant, a set of tools integrated in a single 3D Slicer extension, which aims to assist neurosurgeons in the analysis of post-implant structural data and hence aid the neurophysiologist in the interpretation of SEEG data. SEEG Assistant consists of (i) a module to localize the electrode contact positions using imaging data from a thresholded post-implant CT, (ii) a module to determine the most probable cerebral location of the recorded activity, and (iii) a module to compute the Grey Matter Proximity Index, i.e. the distance of each contact from the cerebral cortex, in order to discriminate between white and grey matter location of contacts. Finally, exploiting 3D Slicer capabilities, SEEG Assistant offers a Graphical User Interface that simplifies the interaction between the user and the tools. SEEG Assistant has been tested on 40 patients segmenting 555 electrodes, and it has been used to identify the neuroanatomical loci and to compute the distance to the nearest cerebral cortex for 9626 contacts. We also performed manual segmentation and compared the results between the proposed tool and gold-standard clinical practice. As a result, the use of SEEG Assistant decreases the post implant processing time by more than 2 orders of magnitude, improves the quality of results and decreases, if not eliminates, errors in post implant processing.

Conclusions: The SEEG Assistant Framework for the first time supports physicists by providing a set of open-source tools for post-implant processing of SEEG data. Furthermore, SEEG Assistant has been integrated into 3D Slicer , a software platform for the analysis and visualization of medical images, overcoming limitations of command-line tools.

CPE out performs manual segmentation in complex and critical cases. a As an example of SEEG complexity, we show MRI and thresholded post-implant CT scans for one subject from our cohort. Contacts are shown as groups of white voxels. This case illustrates the complexity of SEEG implants with electrode shafts following non-planar directions (e.g. X), shafts targeting almost the same geometrical point (e.g. R and R’). b CPE segments all contacts (green spheres) belonging to each electrode from post-implant CT scans, represented here as red 3D meshes obtained tessellating the thresholded data to ease visualization. c Show the right pial surface with 3D post-implant thresholded-CT meshes and the cut plane used in panel d where the example of X and X’ electrodes are shown. Those examples represent the case of non-planar insertion trajectories which yielded an artefactually fused electrode. CPE integrating the knowledge of the electrode model can segment the contact positions more accurately than visual inspection.

Associations of Radiomic Data Extracted from Static and Respiratory-Gated CT Scans with Disease Recurrence in Lung Cancer Patients Treated with SBRT

Publication: PLoS One. 2017 Jan 3;12(1):e0169172. PMID: 28046060 | PDF

Authors: Huynh E, Coroller TP, Narayan V, Agrawal V, Romano J, Franco I, Parmar C, Hou Y, Mak RH, Aerts HJ.

Institution: Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.


Radiomics aims to quantitatively capture the complex tumor phenotype contained in medical images to associate them with clinical outcomes. This study investigates the impact of different types of computed tomography (CT) images on the prognostic performance of radiomic features for disease recurrence in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). 112 early stage NSCLC patients treated with SBRT that had static free breathing (FB) and average intensity projection (AIP) images were analyzed. Nineteen radiomic features were selected from each image type (FB or AIP) for analysis based on stability and variance. The selected FB and AIP radiomic feature sets had 6 common radiomic features between both image types and 13 unique features. The prognostic performances of the features for distant metastasis (DM) and locoregional recurrence (LRR) were evaluated using the concordance index (CI) and compared with two conventional features (tumor volume and maximum diameter). P-values were corrected for multiple testing using the false discovery rate procedure. None of the FB radiomic features were associated with DM, however, seven AIP radiomic features, that described tumor shape and heterogeneity, were (CI range: 0.638-0.676). Conventional features from FB images were not associated with DM, however, AIP conventional features were (CI range: 0.643-0.658). Radiomic and conventional multivariate models were compared between FB and AIP images using cross validation. The differences between the models were assessed using a permutation test. AIP radiomic multivariate models (median CI = 0.667) outperformed all other models (median CI range: 0.601-0.630) in predicting DM. None of the imaging features were prognostic of LRR. Therefore, image type impacts the performance of radiomic models in their association with disease recurrence. AIP images contained more information than FB images that were associated with disease recurrence in early stage NSCLC patients treated with SBRT, which suggests that AIP images may potentially be more optimal for the development of an imaging biomarker.


  • U01 CA190234/CA/NCI NIH HHS/United States
  • U24 CA194354/CA/NCI NIH HHS/United States
A) Examples of free breathing (FB) and average intensity projection (AIP) images, demonstrating the observable differences in tumor phenotype between each image type. AIP images were reconstructed from 4D computed tomography (CT) scans. B) Schematic representation of the radiomics workflow for FB and AIP images. I. CT images of the patient are acquired and the tumor is segmented. II. Imaging features (radiomic and conventional features) are extracted from the tumor volume. III. Radiomic features undergo a feature dimension reduction process to generate a low-dimensional feature set based on feature stability and variance. IV. Imaging features are then analyzed with clinical outcomes to evaluate their prognostic power. FB and AIP radiomics features are compared. A set of 644 radiomic features was extracted from tumor volumes isolated from FB or AIP images (Fig 1B) using an in-house Matlab 2013 toolbox and 3D Slicer 4.4.0 software

Early Experiences of Planning Stereotactic Radiosurgery using 3D Printed Models of Eyes with Uveal Melanomas

Publication: Clin Ophthalmol. 2017 Jan 31;11:267-71. PMID: 28203052 | PDF

Authors: Furdová A, Sramka M, Thurzo A, Furdová A.

Institution: Department of Ophthalmology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.


Objective: The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery.

Methods: The software for segmentation (3D Slicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D®) and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid.

Results: In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient's eye with intraocular tumor. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma) were treated. The median tumor volume was 0.5 cm3 (0.2-1.6 cm3). The radiation dose was 35.0 Gy by 99% of dose volume histogram.

Conclusion: The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures.

A) Virtual model of the eye, outer view; arrow indicates optic nerve. A virtual 3D model of eye globe with tumor based on tissue density was created from CT and MRI data by using the 3D Slicer software for segmentation.

Intra-rater Variability in Low-grade Glioma Segmentation

Publication: J Neurooncol. 2017 Jan;131(2):393-402. PMID: 27837437

Authors: Bø HK, Solheim O, Jakola AS, Kvistad KA, Reinertsen I, Berntsen EM.

Institution: Department of Radiology and Nuclear Medicine, St. Olavs University Hospital, Trondheim, Norway.


Assessment of size and growth are key radiological factors in low-grade gliomas (LGGs), both for prognostication and treatment evaluation, but the reliability of LGG-segmentation is scarcely studied. With a diffuse and invasive growth pattern, usually without contrast enhancement, these tumors can be difficult to delineate. The aim of this study was to investigate the intra-observer variability in LGG-segmentation for a radiologist without prior segmentation experience. Pre-operative 3D FLAIR images of 23 LGGs were segmented three times in the software 3D Slicer. Tumor volumes were calculated, together with the absolute and relative difference between the segmentations. To quantify the intra-rater variability, we used the Jaccard coefficient comparing both two (J2) and three (J3) segmentations as well as the Hausdorff Distance (HD). The variability measured with J2 improved significantly between the two last segmentations compared to the two first, going from 0.87 to 0.90 (p = 0.04). Between the last two segmentations, larger tumors showed a tendency towards smaller relative volume difference (p = 0.07), while tumors with well-defined borders had significantly less variability measured with both J2 (p = 0.04) and HD (p < 0.01). We found no significant relationship between variability and histological sub-types or Apparent Diffusion Coefficients (ADC). We found that the intra-rater variability can be considerable in serial LGG-segmentation, but the variability seems to decrease with experience and higher grade of border conspicuity. Our findings highlight that some criteria defining tumor borders and progression in 3D volumetric segmentation is needed, if moving from 2D to 3D assessment of size and growth of LGGs.

Hybrid Positron Emission Tomography Segmentation of Heterogeneous Lung Tumors using 3D Slicer: Improved Growcut Algorithm with Threshold Initialization

Publication: J. Med. Imag. 2017 Jan-Mar;4(1), 011009. PMID: 28149920 | PDF

Authors: Thomas HM, Devakumar D, Sasidharan B, Bowen SR, Heck DK, Jebaseelan J, Samuel E.

Institution: Department of Physics, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu, India.


This paper presents an improved GrowCut (IGC), a positron emission tomography-based segmentation algorithm, and tests its clinical applicability. Contrary to the traditional method that requires the user to provide the initial seeds, the IGC algorithm starts with a threshold-based estimate of the tumor and a three- dimensional morphologically grown shell around the tumor as the foreground and background seeds, respectively. The repeatability of IGC from the same observer at multiple time points was compared with the traditional GrowCut algorithm. The algorithm was tested in 11 nonsmall cell lung cancer lesions and validated against the clinician-defined manual contour and compared against the clinically used 25% of the maximum standardized uptake value [SUV-(max)], 40% SUVmax, and adaptive threshold methods. The time to edit IGC-defined functional volume to arrive at the gross tumor volume (GTV) was compared with that of manual contouring. The repeatability of the IGC algorithm was very high compared with the traditional GrowCut (p = 0.003) and demonstrated higher agreement with the manual contour with respect to threshold-based methods. Compared with manual contouring, editing the IGC achieved the GTV in significantly less time (p = 0.11). The IGC algorithm offers a highly repeatable functional volume and serves as an effective initial guess that can well minimize the time spent on labor-intensive manual contouring.

A) A representative example of the uncertainty volume observed with the 3D Slicer GrowCutMethod. (a) The lesion was delineated in three separate runs. There was variability with each run and the composite error in the variability calculated as the uncertainty volume is highlighted in green in (b).

Pre-clinical Validation of Virtual Bronchoscopy using 3D Slicer

Publication: Int J Comput Assist Radiol Surg. 2017 Jan;12(1):25-38. PMID: 27325238

Authors: Nardelli P, Jaeger A, O'Shea C, Khan KA, Kennedy MP, Cantillon-Murphy P.

Institution: School of Engineering, University College Cork, College Road, Cork, Ireland.


Purpose: Lung cancer still represents the leading cause of cancer-related death, and the long-term survival rate remains low. Computed tomography (CT) is currently the most common imaging modality for lung diseases recognition. The purpose of this work was to develop a simple and easily accessible virtual bronchoscopy system to be coupled with a customized electromagnetic (EM) tracking system for navigation in the lung and which requires as little user interaction as possible, while maintaining high usability.

Methods: The proposed method has been implemented as an extension to the open-source platform, 3D Slicer. It creates a virtual reconstruction of the airways starting from CT images for virtual navigation. It provides tools for pre-procedural planning and virtual navigation, and it has been optimized for use in combination with a [Formula: see text] of freedom EM tracking sensor. Performance of the algorithm has been evaluated in ex vivo and in vivo testing.

Results: During ex vivo testing, nine volunteer physicians tested the implemented algorithm to navigate three separate targets placed inside a breathing pig lung model. In general, the system proved easy to use and accurate in replicating the clinical setting and seemed to help choose the correct path without any previous experience or image analysis. Two separate animal studies confirmed technical feasibility and usability of the system.

Conclusions: This work describes an easily accessible virtual bronchoscopy system for navigation in the lung. The system provides the user with a complete set of tools that facilitate navigation towards user-selected regions of interest. Results from ex vivo and in vivo studies showed that the system opens the way for potential future work with virtual navigation for safe and reliable airway disease diagnosis.

Anatomical Study and Locating Nasolacrimal Duct on Computed Topographic Image

Publication: J Craniofac Surg. 2017 Jan;28(1):275-9. PMID: 27977487

Authors: Zhang S, Cheng Y, Xie J, Wang Z, Zhang F, Chen L, Feng Y, Wang G.

Institution: Department of Endocrinology, First Hospital of Jilin University, Changchun, China.


Background: We performed a novel anatomical and radiological investigation to understand the structure of nasolacrimal duct (NLD) and to provide data to help surgeons locate the openings of NLD efficiently based on landmarks.

Materials and Methods: We examined the NLD region using computed tomography images of 133 individuals and 6 dry skull specimens. Multiplanar reconstruction of the computed tomography images was performed, and the anatomical features of the NLD were studied in the coronal, sagittal, and axial planes. The long and short diameters of NLD were measured along its cross-section. The position of NLD was localized using the nostril, concha nasalis media, and medial orbital corner as landmarks. The free and open source software, 3D Slicer, was used for the segmentation of the NLD and 3D visualization of the superior and inferior openings of the NLD.

Results: The length, angle, and diameter of NLD were significantly influenced by the age in females compared to those in males. The inferior opening of the NLD could be located efficiently using the nostril and the midsagittal line while the superior opening of NLD could be located using the medial orbital corner. Third, 3D Slicer enabled us to measure the distance between the skin and the bony structure in the image.

Conclusion: Our study indicates that the sex and age of the patient should be considered while selecting the optimal NLD stent for a patient, and that the precise location of NLD in reference to landmarks can simplify the surgical difficulties and reduce the risk of injury during the transnasal operation.

Open Wedge High Tibial Osteotomy using Three-Dimensional Printed Models: Experimental Analysis using Porcine Bone

Publication: Knee. 2017 Jan;24(1):16-22. PMID: 27876267

Authors: Kwun JD, Kim HJ, Park J, Park IH, Kyung HS.

Institution: Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.


Background: The purpose of this study was to evaluate the usefulness of three-dimensional (3D) printed models for open wedge high tibial osteotomy (HTO) in porcine bone.

Methods: Computed tomography (CT) images were obtained from 10 porcine knees and 3D imaging was planned using the 3D Slicer program. The osteotomy line was drawn from the three centimeters below the medial tibial plateau to the proximal end of the fibular head. Then the osteotomy gap was opened until the mechanical axis line was 62.5% from the medial border along the width of the tibial plateau, maintaining the posterior tibial slope angle. The wedge-shaped 3D-printed model was designed with the measured angle and osteotomy section and was produced by the 3D printer. The open wedge HTO surgery was reproduced in porcine bone using the 3D-printed model and the osteotomy site was fixed with a plate. Accuracy of osteotomy and posterior tibial slope was evaluated after the osteotomy.

Results: The mean mechanical axis line on the tibial plateau was 61.8±1.5% from the medial tibia. There was no statistically significant difference (P=0.160). The planned and post-osteotomy correction wedge angles were 11.5±3.2° and 11.4±3.3°, and the posterior tibial slope angle was 11.2±2.2° pre-osteotomy and 11.4±2.5° post-osteotomy. There were no significant differences (P=0.854 and P=0.429, respectively).

Conclusion: This study showed that good results could be obtained in high tibial osteotomy by using 3D printed models of porcine legs.