Lampinen B, Lätt J, Wasselius J, van Westen D, Nilsson M. Time Dependence in Diffusion MRI Predicts Tissue Outcome in Ischemic Stroke Patients. Magn Reson Med. 2021;86(2):754–64.

PURPOSE: Reperfusion therapy enables effective treatment of ischemic stroke presenting within 4-6 hours. However, tissue progression from ischemia to infarction is variable, and some patients benefit from treatment up until 24 hours. Improved imaging techniques are needed to identify these patients. Here, it was hypothesized that time dependence in diffusion MRI may predict tissue outcome in ischemic stroke. METHODS: Diffusion MRI data were acquired with multiple diffusion times in five non-reperfused patients at 2, 9, and 100 days after stroke onset. Maps of "rate of kurtosis change" (k), mean kurtosis, ADC, and fractional anisotropy were derived. The ADC maps defined lesions, normal-appearing tissue, and the lesion tissue that would either be infarcted or remain viable by day 100. Diffusion parameters were compared (1) between lesions and normal-appearing tissue, and (2) between lesion tissue that would be infarcted or remain viable. RESULTS: Positive values of k were observed within stroke lesions on day 2 (P = .001) and on day 9 (P = .023), indicating diffusional exchange. On day 100, high ADC values indicated infarction of 50 ± 20% of the lesion volumes. Tissue infarction was predicted by high k values both on day 2 (P = .026) and on day 9 (P = .046), by low mean kurtosis values on day 2 (P = .043), and by low fractional anisotropy values on day 9 (P = .029), but not by low ADC values. CONCLUSIONS: Diffusion time dependence predicted tissue outcome in ischemic stroke more accurately than the ADC, and may be useful for predicting reperfusion benefit.

Sedghi A, Donnell LJO, Kapur T, Learned-Miller E, Mousavi P, Wells WM. Image Registration: Maximum Likelihood, Minimum Entropy and Deep Learning. Med Image Anal. 2021;69:101939.

In this work, we propose a theoretical framework based on maximum profile likelihood for pairwise and groupwise registration. By an asymptotic analysis, we demonstrate that maximum profile likelihood registration minimizes an upper bound on the joint entropy of the distribution that generates the joint image data. Further, we derive the congealing method for groupwise registration by optimizing the profile likelihood in closed form, and using coordinate ascent, or iterative model refinement. We also describe a method for feature based registration in the same framework and demonstrate it on groupwise tractographic registration. In the second part of the article, we propose an approach to deep metric registration that implements maximum likelihood registration using deep discriminative classifiers. We show further that this approach can be used for maximum profile likelihood registration to discharge the need for well-registered training data, using iterative model refinement. We demonstrate that the method succeeds on a challenging registration problem where the standard mutual information approach does not perform well.

Ning L, Szczepankiewicz F, Nilsson M, Rathi Y, Westin CF. Probing Tissue Microstructure by Diffusion Skewness Tensor Imaging. Sci Rep. 2021;11(1):135.

Probing the cellular structure of in vivo biological tissue is a fundamental problem in biomedical imaging and medical science. This work introduces an approach for analyzing diffusion magnetic resonance imaging data acquired by the novel tensor-valued encoding technique for characterizing tissue microstructure. Our approach first uses a signal model to estimate the variance and skewness of the distribution of apparent diffusion tensors modeling the underlying tissue. Then several novel imaging indices, such as weighted microscopic anisotropy and microscopic skewness, are derived to characterize different ensembles of diffusion processes that are indistinguishable by existing techniques. The contributions of this work also include a theoretical proof that shows that, to estimate the skewness of a diffusion tensor distribution, the encoding protocol needs to include full-rank tensor diffusion encoding. This proof provides a guideline for the application of this technique. The properties of the proposed indices are illustrated using both synthetic data and in vivo data acquired from a human brain.

Beers A, Brown J, Chang K, Hoebel K, Patel J, Ly I, Tolaney SM, Brastianos P, Rosen B, Gerstner ER, Kalpathy-Cramer J. DeepNeuro: An Open-Source Deep Learning Toolbox for Neuroimaging. Neuroinformatics. 2021;19(1):127–40.
Translating deep learning research from theory into clinical practice has unique challenges, specifically in the field of neuroimaging. In this paper, we present DeepNeuro, a Python-based deep learning framework that puts deep neural networks for neuroimaging into practical usage with a minimum of friction during implementation. We show how this framework can be used to design deep learning pipelines that can load and preprocess data, design and train various neural network architectures, and evaluate and visualize the results of trained networks on evaluation data. We present a way of reproducibly packaging data pre- and postprocessing functions common in the neuroimaging community, which facilitates consistent performance of networks across variable users, institutions, and scanners. We show how deep learning pipelines created with DeepNeuro can be concisely packaged into shareable Docker and Singularity containers with user-friendly command-line interfaces.
Nitsch J, Sack J, Halle MW, Moltz JH, Wall A, Rutherford AE, Kikinis R, Meine H. MRI-Based Radiomic Feature Analysis of End-Stage Liver Disease for Severity Stratification. Int J Comput Assist Radiol Surg. 2021;16(3):457–66.
PURPOSE: We aimed to develop a predictive model of disease severity for cirrhosis using MRI-derived radiomic features of the liver and spleen and compared it to the existing disease severity metrics of MELD score and clinical decompensation. The MELD score is compiled solely by blood parameters, and so far, it was not investigated if extracted image-based features have the potential to reflect severity to potentially complement the calculated score. METHODS: This was a retrospective study of eligible patients with cirrhosis ([Formula: see text]) who underwent a contrast-enhanced MR screening protocol for hepatocellular carcinoma (HCC) screening at a tertiary academic center from 2015 to 2018. Radiomic feature analyses were used to train four prediction models for assessing the patient’s condition at time of scan: MELD score, MELD score [Formula: see text] 9 (median score of the cohort), MELD score [Formula: see text] 15 (the inflection between the risk and benefit of transplant), and clinical decompensation. Liver and spleen segmentations were used for feature extraction, followed by cross-validated random forest classification. RESULTS: Radiomic features of the liver and spleen were most predictive of clinical decompensation (AUC 0.84), which the MELD score could predict with an AUC of 0.78. Using liver or spleen features alone had slightly lower discrimination ability (AUC of 0.82 for liver and AUC of 0.78 for spleen features only), although this was not statistically significant on our cohort. When radiomic prediction models were trained to predict continuous MELD scores, there was poor correlation. When stratifying risk by splitting our cohort at the median MELD 9 or at MELD 15, our models achieved AUCs of 0.78 or 0.66, respectively. CONCLUSIONS: We demonstrated that MRI-based radiomic features of the liver and spleen have the potential to predict the severity of liver cirrhosis, using decompensation or MELD status as imperfect surrogate measures for disease severity.
Wu C, Diao B, Ungi T, Sedghi A, Kikinis R, Mousavi P, Fichtinger G. Development of an Open-Source System for Prostate Biopsy Training in Senegal. SPIE Medical Imaging. 2021;.
PURPOSE: Prostate cancer is the second most common cancer diagnosed in men. The rate is disproportionately high among men in sub-Saharan Africa where, unlike in North America and Western Europe, the screening process for prostate cancer has historically not been routine. Currently, as awareness regarding prostate health increases, more patients in this region are being referred to trans-rectal ultrasound guided prostate biopsy, a diagnosis procedure which requires a strong understanding of prostate zonal anatomy. To aid in the instruction of this procedure, prostate biopsy training programs need to be implemented. Unfortunately, current TRUS-guided training tools are not ideal for reproducibility in these Western African countries. To answer this challenge, we are developing an affordable and open-source training simulator for TRUS-guided prostate biopsy, for use in Senegal.  In this paper, we present the implementation of the training simulator’s virtual interface, highlighting the generation and evaluation of the critical training component of zonal anatomy overlaid on TRUS. METHODS: For the simulator’s dataset, we registered TRUS and MRI volumes together to obtain the zonal segmentation from the MRI volumes. After generating ten pairings of TRUS overlaid with zonal segmentation, we designed and implemented a virtual TRUS training system, developed in open-source software. The objective of our simulator is to teach trainees to accurately identify the prostate’s anatomical zones in TRUS. To confirm the system’s usability for training zonal identification, we conducted a two-part survey on the quality of the zonal overlays with 7 urology experts. In the first part, they assessed the zonal overlay for visual correctness by rating 10 images from one patient’s TRUS with registered overlay on a 5-point Likert scale. For the second part, they labelled 10 plain TRUS volumes with zonal anatomy and the labels were compared to the labels of our overlay. RESULTS: On average, experts rated the zonal overlay’s visual accuracy at 4 out of 5. Furthermore, 7 out of 7 experts labelled the peripheral, anterior, and transitional zones in the same regions we overlaid them, and 5 out of 7 labelled the central zone in the same region we overlaid it. CONCLUSION: We created the prototype of a TRUS imaging simulator in open-source software. A vital training component, zonal overlay, was generated using publicly accessible data and validated by expert urologists for prostate zone identification, confirming the concept.
Steinmann S, Lyall AE, Langhein M, Nägele FL, Rauh J, Cetin-Karayumak S, Zhang F, Mussmann M, Billah T, Makris N, Pasternak O, Donnell LJO, Rathi Y, Kubicki M, Leicht G, Shenton ME, Mulert C. Sex-Related Differences in White Matter Asymmetry and Its Implications for Verbal Working Memory in Psychosis High-Risk State. Front Psychiatry. 2021;12:686967.
Objective: Sexual dimorphism has been investigated in schizophrenia, although sex-specific differences among individuals who are at clinical high-risk (CHR) for developing psychosis have been inconclusive. This study aims to characterize sexual dimorphism of language areas in the brain by investigating the asymmetry of four white matter tracts relevant to verbal working memory in CHR patients compared to healthy controls (HC). HC typically show a leftward asymmetry of these tracts. Moreover, structural abnormalities in asymmetry and verbal working memory dysfunctions have been associated with neurodevelopmental abnormalities and are considered core features of schizophrenia. Methods: Twenty-nine subjects with CHR (17 female/12 male) for developing psychosis and twenty-one HC (11 female/10 male) matched for age, sex, and education were included in the study. Two-tensor unscented Kalman filter tractography, followed by an automated, atlas-guided fiber clustering approach, were used to identify four fiber tracts related to verbal working memory: the superior longitudinal fasciculi (SLF) I, II and III, and the superior occipitofrontal fasciculus (SOFF). Using fractional anisotropy (FA) of tissue as the primary measure, we calculated the laterality index for each tract. Results: There was a significantly greater right>left asymmetry of the SLF-III in CHR females compared to HC females, but no hemispheric difference between CHR vs. HC males. Moreover, the laterality index of SLF-III for CHR females correlated negatively with Backward Digit Span performance, suggesting a greater rightward asymmetry was associated with poorer working memory functioning. Conclusion: This study suggests increased rightward asymmetry of the SLF-III in CHR females. This finding of sexual dimorphism in white matter asymmetry in a language-related area of the brain in CHR highlights the need for a deeper understanding of the role of sex in the high-risk state. Future work investigating early sex-specific pathophysiological mechanisms, may lead to the development of novel personalized treatment strategies aimed at preventing transition to a more chronic and difficult-to-treat disorder.
Fichtinger G, Mousavi P, Ungi T, Fenster A, Abolmaesumi P, Kronreif G, Ruiz-Alzola J, Ndoye A, Diao B, Kikinis R. Design of an Ultrasound-Navigated Prostate Cancer Biopsy System for Nationwide Implementation in Senegal. J Imaging. 2021;7(8):154.
This paper presents the design of NaviPBx, an ultrasound-navigated prostate cancer biopsy system. NaviPBx is designed to support an affordable and sustainable national healthcare program in Senegal. It uses spatiotemporal navigation and multiparametric transrectal ultrasound to guide biopsies. NaviPBx integrates concepts and methods that have been independently validated previously in clinical feasibility studies and deploys them together in a practical prostate cancer biopsy system. NaviPBx is based entirely on free open-source software and will be shared as a free open-source program with no restriction on its use. NaviPBx is set to be deployed and sustained nationwide through the Senegalese Military Health Service. This paper reports on the results of the design process of NaviPBx. Our approach concentrates on "frugal technology", intended to be affordable for low-middle income (LMIC) countries. Our project promises the wide-scale application of prostate biopsy and will foster time-efficient development and programmatic implementation of ultrasound-guided diagnostic and therapeutic interventions in Senegal and beyond.
Ye Y, Barapatre S, Davis MK, Elliston KO, Davatzikos C, Fedorov A, Fillion-Robin JC, Foster I, Gilbertson JR, Lasso A, Miller J V, Morgan M, Pieper S, Raumann BE, Sarachan BD, Savova G, Silverstein JC, Taylor DP, Zelnis JB, Zhang GQ, Cuticchia J, Becich MJ. Open-source Software Sustainability Models: Initial White Paper From the Informatics Technology for Cancer Research Sustainability and Industry Partnership Working Group. J Med Internet Res. 2021;23(12):e20028.
BACKGROUND: The National Cancer Institute Informatics Technology for Cancer Research (ITCR) program provides a series of funding mechanisms to create an ecosystem of open-source software (OSS) that serves the needs of cancer research. As the ITCR ecosystem substantially grows, it faces the challenge of the long-term sustainability of the software being developed by ITCR grantees. To address this challenge, the ITCR sustainability and industry partnership working group (SIP-WG) was convened in 2019. OBJECTIVE: The charter of the SIP-WG is to investigate options to enhance the long-term sustainability of the OSS being developed by ITCR, in part by developing a collection of business model archetypes that can serve as sustainability plans for ITCR OSS development initiatives. The working group assembled models from the ITCR program, from other studies, and from the engagement of its extensive network of relationships with other organizations (eg, Chan Zuckerberg Initiative, Open Source Initiative, and Software Sustainability Institute) in support of this objective. METHODS: This paper reviews the existing sustainability models and describes 10 OSS use cases disseminated by the SIP-WG and others, including 3D Slicer, Bioconductor, Cytoscape, Globus, i2b2 (Informatics for Integrating Biology and the Bedside) and tranSMART, Insight Toolkit, Linux, Observational Health Data Sciences and Informatics tools, R, and REDCap (Research Electronic Data Capture), in 10 sustainability aspects: governance, documentation, code quality, support, ecosystem collaboration, security, legal, finance, marketing, and dependency hygiene. RESULTS: Information available to the public reveals that all 10 OSS have effective governance, comprehensive documentation, high code quality, reliable dependency hygiene, strong user and developer support, and active marketing. These OSS include a variety of licensing models (eg, general public license version 2, general public license version 3, Berkeley Software Distribution, and Apache 3) and financial models (eg, federal research funding, industry and membership support, and commercial support). However, detailed information on ecosystem collaboration and security is not publicly provided by most OSS. CONCLUSIONS: We recommend 6 essential attributes for research software: alignment with unmet scientific needs, a dedicated development team, a vibrant user community, a feasible licensing model, a sustainable financial model, and effective product management. We also stress important actions to be considered in future ITCR activities that involve the discussion of the sustainability and licensing models for ITCR OSS, the establishment of a central library, the allocation of consulting resources to code quality control, ecosystem collaboration, security, and dependency hygiene.
Schilling KG, Rheault F, Petit L, Hansen CB, Nath V, Yeh FC, Girard G, Barakovic M, Rafael-Patino J, Yu T, Fischi-Gomez E, Pizzolato M, Ocampo-Pineda M, Schiavi S, Canales-Rodríguez EJ, Daducci A, Granziera C, Innocenti G, Thiran JP, Mancini L, Wastling S, Cocozza S, Petracca M, Pontillo G, Mancini M, Vos SB, Vakharia VN, Duncan JS, Melero H, Manzanedo L, Sanz-Morales E, Peña-Melián Ángel, Calamante F, Attyé A, Cabeen RP, Korobova L, Toga AW, Vijayakumari AA, Parker D, Verma R, Radwan A, Sunaert S, Emsell L, De Luca A, Leemans A, Bajada CJ, Haroon H, Azadbakht H, Chamberland M, Genc S, Tax CMW, Yeh PH, Srikanchana R, Mcknight CD, Yang JYM, Chen J, Kelly CE, Yeh CH, Cochereau J, Maller JJ, Welton T, Almairac F, Seunarine KK, Clark CA, Zhang F, Makris N, Golby A, Rathi Y, Donnell LJO, Xia Y, Aydogan DB, Shi Y, Fernandes FG, Raemaekers M, Warrington S, Michielse S, Ramírez-Manzanares A, Concha L, Aranda R, Meraz MR, Lerma-Usabiaga G, Roitman L, Fekonja LS, Calarco N, Joseph M, Nakua H, Voineskos AN, Karan P, Grenier G, Legarreta JH, Adluru N, Nair VA, Prabhakaran V, Alexander AL, Kamagata K, Saito Y, Uchida W, Andica C, Abe M, Bayrak RG, Wheeler-Kingshott CAMG, Angelo ED, Palesi F, Savini G, Rolandi N, Guevara P, Houenou J, López-López N, Mangin JF, Poupon C, Román C, Vázquez A, Maffei C, Arantes M, Andrade JP, Silva SM, Calhoun VD, Caverzasi E, Sacco S, Lauricella M, Pestilli F, Bullock D, Zhan Y, Brignoni-Perez E, Lebel C, Reynolds JE, Nestrasil I, Labounek R, Lenglet C, Paulson A, Aulicka S, Heilbronner SR, Heuer K, Chandio BQ, Guaje J, Tang W, Garyfallidis E, Raja R, Anderson AW, Landman BA, Descoteaux M. Tractography Dissection Variability: What Happens When 42 Groups Dissect 14 White Matter Bundles on the Same Dataset?. Neuroimage. 2021;243:118502.
White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.