Publications

2017

Ariel D Stock, Sivan Gelb, Ofer Pasternak, Ayal Ben-Zvi, and Chaim Putterman. 2017. The Blood Brain Barrier and Neuropsychiatric Lupus: New Perspectives in Light of Advances in Understanding the Neuroimmune Interface. Autoimmun Rev, 16, 6, Pp. 612-9.
Experts have previously postulated a linkage between lupus associated vascular pathology and abnormal brain barriers in the immunopathogenesis of neuropsychiatric lupus. Nevertheless, there are some discrepancies between the experimental evidence, or its interpretation, and the working hypotheses prevalent in this field; specifically, that a primary contributor to neuropsychiatric disease in lupus is permeabilization of the blood brain barrier. In this commonly held view, any contribution of the other known brain barriers, including the blood-cerebrospinal fluid and meningeal barriers, is mostly excluded from the discussion. In this review we will shed light on some of the blood brain barrier hypotheses and try to trace their roots. In addition, we will suggest new research directions to allow for confirmation of alternative interpretations of the experimental evidence linking the pathology of intra-cerebral vasculature to the pathogenesis of neuropsychiatric lupus.
Roxana G Burciu, Edward Ofori, Derek B Archer, Samuel S Wu, Ofer Pasternak, Nikolaus R McFarland, Michael S Okun, and David E Vaillancourt. 2017. Progression Marker of Parkinson’s Disease: A 4-year Multi-site Imaging Study. Brain, 140, 8, Pp. 2183-92.
Progression markers of Parkinson’s disease are crucial for successful therapeutic development. Recently, a diffusion magnetic resonance imaging analysis technique using a bitensor model was introduced allowing the estimation of the fractional volume of free water within a voxel, which is expected to increase in neurodegenerative disorders such as Parkinson’s disease. Prior work demonstrated that free water in the posterior substantia nigra was elevated in Parkinson’s disease compared to controls across single- and multi-site cohorts, and increased over 1 year in Parkinson’s disease but not in controls at a single site. Here, the goal was to validate free water in the posterior substantia nigra as a progression marker in Parkinson’s disease, and describe the pattern of progression of free water in patients with a 4-year follow-up tested in a multicentre international longitudinal study of de novo Parkinson’s disease (http://www.ppmi-info.org/). The analyses examined: (i) 1-year changes in free water in 103 de novo patients with Parkinson’s disease and 49 controls; (ii) 2- and 4-year changes in free water in a subset of 46 patients with Parkinson’s disease imaged at baseline, 12, 24, and 48 months; (iii) whether 1- and 2-year changes in free water predict 4-year changes in the Hoehn and Yahr scale; and (iv) the relationship between 4-year changes in free water and striatal binding ratio in a subgroup of Parkinson’s disease who had undergone both diffusion and dopamine transporter imaging. Results demonstrated that: (i) free water level in the posterior substantia nigra increased over 1 year in de novo Parkinson’s disease but not in controls; (ii) free water kept increasing over 4 years in Parkinson’s disease; (iii) sex and baseline free water predicted 4-year changes in free water; (iv) free water increases over 1 and 2 years were related to worsening on the Hoehn and Yahr scale over 4 years; and (v) the 4-year increase in free water was associated with the 4-year decrease in striatal binding ratio in the putamen. Importantly, all longitudinal results were consistent across sites. In summary, this study demonstrates an increase over 1 year in free water in the posterior substantia nigra in a large cohort of de novo patients with Parkinson’s disease from a multi-site cohort study and no change in healthy controls, and further demonstrates an increase of free water in Parkinson’s disease over the course of 4 years. A key finding was that results are consistent across sites and the 1-year and 2-year increase in free water in the posterior substantia nigra predicts subsequent long-term progression on the Hoehn and Yahr staging system. Collectively, these findings demonstrate that free water in the posterior substantia nigra is a valid, progression imaging marker of Parkinson’s disease, which may be used in clinical trials of disease-modifying therapies.
Sarah Parisot, Ben Glocker, Sofia Ira Ktena, Salim Arslan, Markus D Schirmer, and Daniel Rueckert. 2017. A Flexible Graphical Model for Multi-modal Parcellation of the Cortex. Neuroimage, 162, Pp. 226-48.
Advances in neuroimaging have provided a tremendous amount of in-vivo information on the brain’s organisation. Its anatomy and cortical organisation can be investigated from the point of view of several imaging modalities, many of which have been studied for mapping functionally specialised cortical areas. There is strong evidence that a single modality is not sufficient to fully identify the brain’s cortical organisation. Combining multiple modalities in the same parcellation task has the potential to provide more accurate and robust subdivisions of the cortex. Nonetheless, existing brain parcellation methods are typically developed and tested on single modalities using a specific type of information. In this paper, we propose Graph-based Multi-modal Parcellation (GraMPa), an iterative framework designed to handle the large variety of available input modalities to tackle the multi-modal parcellation task. At each iteration, we compute a set of parcellations from different modalities and fuse them based on their local reliabilities. The fused parcellation is used to initialise the next iteration, forcing the parcellations to converge towards a set of mutually informed modality specific parcellations, where correspondences are established. We explore two different multi-modal configurations for group-wise parcellation using resting-state fMRI, diffusion MRI tractography, myelin maps and task fMRI. Quantitative and qualitative results on the Human Connectome Project database show that integrating multi-modal information yields a stronger agreement with well established atlases and more robust connectivity networks that provide a better representation of the population.
Lena Maier-Hein, Swaroop S Vedula, Stefanie Speidel, Nassir Navab, Ron Kikinis, Adrian Park, Matthias Eisenmann, Hubertus Feussner, Germain Forestier, Stamatia Giannarou, Makoto Hashizume, Darko Katic, Hannes Kenngott, Michael Kranzfelder, Anand Malpani, Keno März, Thomas Neumuth, Nicolas Padoy, Carla Pugh, Nicolai Schoch, Danail Stoyanov, Russell Taylor, Martin Wagner, Gregory D Hager, and Pierre Jannin. 2017. Surgical data science for next-generation interventions. Nat Biomed Eng, 1, 9, Pp. 691-696.
Joost J M van Griethuysen, Andriy Fedorov, Chintan Parmar, Ahmed Hosny, Nicole Aucoin, Vivek Narayan, Regina G H Beets-Tan, Jean-Christophe Fillion-Robin, Steve Pieper, and Hugo J W L Aerts. 2017. Computational Radiomics System to Decode the Radiographic Phenotype. Cancer Res, 77, 21, Pp. e104-e107.
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 , a flexible open-source platform capable of extracting a large panel of engineered features from medical images. is implemented in Python and can be used standalone or using 3D Slicer. Here, we discuss the workflow and architecture of and demonstrate its application in characterizing lung lesions. Source code, documentation, and examples are publicly available at www.radiomics.io 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. .

2016

Miaomiao Zhang and Polina Golland. 2016. Statistical Shape Analysis: From Landmarks to Diffeomorphisms. Med Image Anal, 33, Pp. 155-8.

We offer a blazingly brief review of evolution of shape analysis methods in medical imaging. As the representations and the statistical models grew more sophisticated, the problem of shape analysis has been gradually redefined to accept images rather than binary segmentations as a starting point. This transformation enabled shape analysis to take its rightful place in the arsenal of tools for extracting and understanding patterns in large clinical image sets. We speculate on the future developments in shape analysis and potential applications that would bring this mathematically rich area to bear on clinical practice.

Demian Wassermann, Nikos Makris, Yogesh Rathi, Martha Shenton, Ron Kikinis, Marek Kubicki, and Carl-Fredrik Westin. 2016. The White Matter Query Language: A Novel Approach for Describing Human White Matter Anatomy. Brain Struct Funct, 221, 9, Pp. 4705-4721.

We have developed a novel method to describe human white matter anatomy using an approach that is both intuitive and simple to use, and which automatically extracts white matter tracts from diffusion MRI volumes. Further, our method simplifies the quantification and statistical analysis of white matter tracts on large diffusion MRI databases. This work reflects the careful syntactical definition of major white matter fiber tracts in the human brain based on a neuroanatomist’s expert knowledge. The framework is based on a novel query language with a near-to-English textual syntax. This query language makes it possible to construct a dictionary of anatomical definitions that describe white matter tracts. The definitions include adjacent gray and white matter regions, and rules for spatial relations. This novel method makes it possible to automatically label white matter anatomy across subjects. After describing this method, we provide an example of its implementation where we encode anatomical knowledge in human white matter for ten association and 15 projection tracts per hemisphere, along with seven commissural tracts. Importantly, this novel method is comparable in accuracy to manual labeling. Finally, we present results applying this method to create a white matter atlas from 77 healthy subjects, and we use this atlas in a small proof-of-concept study to detect changes in association tracts that characterize schizophrenia.

Nematollah K Batmanghelich, Adrian Dalca, Gerald Quon, Mert Sabuncu, and Polina Golland. 2016. Probabilistic Modeling of Imaging, Genetics and Diagnosis. IEEE Trans Med Imaging, 35, 7, Pp. 1765-79.

We propose a unified Bayesian framework for detecting genetic variants associated with disease by exploiting image-based features as an intermediate phenotype. The use of imaging data for examining genetic associations promises new directions of analysis, but currently the most widely used methods make sub-optimal use of the richness that these data types can offer. Currently, image features are most commonly selected based on their relevance to the disease phenotype. Then, in a separate step, a set of genetic variants is identified to explain the selected features. In contrast, our method performs these tasks simultaneously in order to jointly exploit information in both data types. The analysis yields probabilistic measures of clinical relevance for both imaging and genetic markers. We derive an efficient approximate inference algorithm that handles the high dimensionality of image and genetic data. We evaluate the algorithm on synthetic data and demonstrate that it outperforms traditional models. We also illustrate our method on Alzheimer’s Disease Neuroimaging Initiative data.

Carl-Fredrik Westin, Hans Knutsson, Ofer Pasternak, Filip Szczepankiewicz, Evren Özarslan, Danielle van Westen, Cecilia Mattisson, Mats Bogren, Lauren J O Donnell, Marek Kubicki, Daniel Topgaard, and Markus Nilsson. 2016. Q-space Trajectory Imaging for Multidimensional Diffusion MRI of the Human Brain. Neuroimage, 135, Pp. 345-62.

This work describes a new diffusion MR framework for imaging and modeling of microstructure that we call q-space trajectory imaging (QTI). The QTI framework consists of two parts: encoding and modeling. First we propose q-space trajectory encoding, which uses time-varying gradients to probe a trajectory in q-space, in contrast to traditional pulsed field gradient sequences that attempt to probe a point in q-space. Then we propose a microstructure model, the diffusion tensor distribution (DTD) model, which takes advantage of additional information provided by QTI to estimate a distributional model over diffusion tensors. We show that the QTI framework enables microstructure modeling that is not possible with the traditional pulsed gradient encoding as introduced by Stejskal and Tanner. In our analysis of QTI, we find that the well-known scalar b-value naturally extends to a tensor-valued entity, i.e., a diffusion measurement tensor, which we call the b-tensor. We show that b-tensors of rank 2 or 3 enable estimation of the mean and covariance of the DTD model in terms of a second order tensor (the diffusion tensor) and a fourth order tensor. The QTI framework has been designed to improve discrimination of the sizes, shapes, and orientations of diffusion microenvironments within tissue. We derive rotationally invariant scalar quantities describing intuitive microstructural features including size, shape, and orientation coherence measures. To demonstrate the feasibility of QTI on a clinical scanner, we performed a small pilot study comparing a group of five healthy controls with five patients with schizophrenia. The parameter maps derived from QTI were compared between the groups, and 9 out of the 14 parameters investigated showed differences between groups. The ability to measure and model the distribution of diffusion tensors, rather than a quantity that has already been averaged within a voxel, has the potential to provide a powerful paradigm for the study of complex tissue architecture.

Tina Kapur, Steve Pieper, Andriy Fedorov, J-C Fillion-Robin, Michael Halle, Lauren O Donnell, Andras Lasso, Tamas Ungi, Csaba Pinter, Julien Finet, Sonia Pujol, Jayender Jagadeesan, Junichi Tokuda, Isaiah Norton, Raul San Jose Estepar, David Gering, Hugo J W L Aerts, Marianna Jakab, Nobuhiko Hata, Luiz Ibanez, Daniel Blezek, Jim Miller, Stephen Aylward, W, Gabor Fichtinger, William M Wells, William E Lorensen, Will Schroeder, and Ron Kikinis. 2016. Increasing the Impact of Medical Image Computing using Community-based Open-access Hackathons: The NA-MIC and 3D Slicer Experience. Med Image Anal, 33, Pp. 176-80.

The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004 with the goal of investigating and developing an open source software infrastructure for the extraction of information and knowledge from medical images using computational methods. Several leading research and engineering groups participated in this effort that was funded by the US National Institutes of Health through a variety of infrastructure grants. This effort transformed 3D Slicer from an internal, Boston-based, academic research software application into a professionally maintained, robust, open source platform with an international leadership and developer and user communities. Critical improvements to the widely used underlying open source libraries and tools-VTK, ITK, CMake, CDash, DCMTK-were an additional consequence of this effort. This project has contributed to close to a thousand peer-reviewed publications and a growing portfolio of US and international funded efforts expanding the use of these tools in new medical computing applications every year. In this editorial, we discuss what we believe are gaps in the way medical image computing is pursued today; how a well-executed research platform can enable discovery, innovation and reproducible science ("Open Science"); and how our quest to build such a software platform has evolved into a productive and rewarding social engineering exercise in building an open-access community with a shared vision.