2012 Progress Report DBP TBI
2.4. Roadmap Project: Traumatic Brain Injury
Key Investigators Jack Van Horn, PI, UCLA Andrei Irimia, DBP Engineer, UCLA Guido Gerig, NA-MIC Algorithms, Utah and SCI Institute Stephen Aylward, NA-MIC Engineering, Kitware Host Institution: UCLA 3D Slicer as a Tool for Longitudinal Neuroimaging of TBI
Sample MR images for three TBI cases labeled as Patient 1 (Part A), Patient 2 (Part B), and Patient 3 (Part C). Images are displayed in radiological convention. The sequence types shown include T2, GRE T2, and FLAIR. Red, green and blue arrows identify the locations of three different insults.
Throughout the past year, progress on this grant has been excellent. One of our important achievements is that we have developed a patient-tailored framework which makes use of 3D Slicer methodologies to allow mapping and characterization of TBI-related structural damage to the brain via multimodal neuroimaging and personalized connectomics. Specifically, we have introduced 3D Slicer workflows for the assessment of trauma-related atrophy of white matter (WM) connections between cortical structures, with relevance to the quantification of TBI chronic case evolution. Our workflows allow one to use 3D Slicer in order to inform the formulation of graphical neurophysiological and neuropsychological TBI profiles based on the particular structural deficits of the affected patient. In addition, they allow us to relate the findings supplied by our workflow to the existing body of research that focuses on the functional roles of the cortical structures being targeted. Our work is relevant for the purpose of using 3D Slicer to investigate TBI patient status, which makes the 3D Slicer platform appreciably more appealing to TBI clinicians.
Figure 2. Three-dimensional models of automatically segmented TBI pathology superposed on transparent models of the brain for each patient. Edema and hemorrhage are shown in green and red, respectively. To guide the eye in localizing three distinct lesions in the 3D models, color-coded (red, green and blue) arrows are provided to identify the locations of the insults indicated in Figure 1 using corresponding colors. Our patient-tailored approaches to the graphical representation of WM change over time offer the ability to use 3D Slicer in order to produce detailed noninvasive characterization of TBI-related GM/WM abnormality and atrophy in vivo. This allows the visualization of brain connections affected by pathology as obviated by MRI and to relate patient injury profiles to the existing body of scientific and clinical knowledge on affected cortical structure function. These methods, which make use of VTK/ITK functionality, provide the ability to quantify the neural atrophy of WM tracts for personalized connectomics. Consequently, they allow one to integrate neuroimaging knowledge with other clinical case information so as to inform clinicians on specific neuroplasticity and neurodegeneration patterns that occur in the TBI brain. Using this approach, we hope to contribute to the clinical care of TBI patients, maximizing the utility of modern neuroimaging technologies, and having possible implications for the improvement of outcome in this important clinical population.
VTK/ITK methods for DTI-based structural connectivity in TBI
One of our notable efforts as part of our collaboration within the NA-MIC consortium has involved the development and implementation of DTI-based workflows for the analysis of structural connectivity. Specifically, we have developed ITK/VTK modules for computing inter-region brain connectivity in both TBI and healthy adults. To accomplish this, we have developed methods that allow the location of fiber tract extremities to be identified and then associated with appropriately parcellated gyral and sulcal structures in the brain. This has allowed us to generate brain connectivity matrices of the brain in both health as well as TBI. Because they make use of VTK/ITK functionality, these workflows are integrated with 3D Slicer tools and, consequently, they can significantly aid the investigation of connectivity using this environment.
In our approach, appropriate connectivity matrix entries can be updated as necessary to reflect fiber count increments. To validate the accuracy of algorithm results, connectivity results as produced using our VTK/ITK software can be reproduced by individually counting all fibers in 3D Slicer that connect any two brain regions. For each pair of cortical regions, our VTK/ITK modules allow the change Δ in the fiber density D between times t1 and t2 to be computed as a percentage of the fiber count at acute baseline based on the multimodal imaging data acquired at the two time points. Fibers can also be thresholded by the user, who can specify either more conservative or more liberal values for the purpose of data exploration or for reasons related to statistical significance criteria.
Development of 3D Slicer Workflows for TBI pathology identification
Throughout the past year, we have continued and expanded the collaboration with our clinical colleagues in the Neurointensive Care Unit of the UCLA Ronald Reagan Medical Center. Specifically, we have continued to acquire and process TBI MR data using a newly implemented, state-of-the-art neuroimaging protocol. This protocol includes T1-weighted MP-RAGE imaging, fast spin echo (FSE) T2–weighted imaging, gradient recalled echo (GRE) T2, fluid attenuated inversion recovery (FLAIR) and 32-direction diffusion tensor imaging (DTI). Scanning sessions are held both one day (acute baseline) as well as 6 months (chronic follow-up) after TBI, and the same scanner and sequence parameters are used for both acute and chronic time in our patients.
In the past year, we have greatly extended and perfected our TBI image processing methodologies. Specifically, we have greatly advanced and streamlined the process whereby we perform pathology identification from MR images. The context of our perfected workflow is a desire to maximally utilize the multimodal information contained in the MR sequences used by our colleagues at the UCLA Neurointensive Care Unit, as well as our collaboration with the algorithm core members at the University of Utah.
In our approach, non-hemorrhagic lesions are coded as hyperintensities on FLAIR, and segmentation quality is confirmed using GRE imaging as well as TSE T2-weighted volumes. Non-hemorrhagic shearing lesions are defined as hyperintense lesions visible on T2-weighted or FLAIR images. Hemorrhagic lesions are defined as hypointense foci that are not compatible with vascular, bone, or artifactual structures on conventional GRE images. WM, GM and pathology are classified using 3D Slicer (slicer.org), and Atlas Based Classification (ABC), the latter having been developed by our colleagues at the University of Utah. Our use of 3D Slicer to provide TBI processing solutions for neurointensivists includes multimodal MR volume registration followed by tissue classification, lesion segmentation using outlier detection and by physical model estimation. Co-registration of MR volumes, intensity normalization within and between scans are applied in 3D Slicer. Our segmentation results in Slicer have been favorably compared to manual segmentations by a human expert. Another area of progress involves the integration of DTI data with structural imaging in 3D Slicer for the purpose of TBI neuroimaging. In this approach, diffusion tensors are computed from DWI images and rotationally re-oriented at each voxel. Tensor-valued images were linearly realigned based on trilinear interpolation of log-transformed tensors and resampled to isotropic voxel resolution.
3D Slicer Solutions for Clinically Driven TBI Rehabilitation Strategies
Rehabilitation of TBI is an exceedingly important public health goal not only because neurotrauma-related activity limitations can have significant impact upon life roles, but also because it affects interpersonal communication, as well as social participation in personal activities of daily living. In this context, our results and methodology hold implications for the systematic mapping of human neural impairment caused by this condition. Firstly, our 3D Slicer and VTK/ITK work is of potential clinical relevance to the study of neural atrophy changes. Aside from identifying and describing connectomic patient profiles, our methodologies can be used to generate suggestions for informing and guiding clinical interventions designed to ameliorate recuperation. Rapidly visualizing the longitudinal evolution of individual TBI cases using our 3D Slicer tools can reveal how deficit patterns are influenced by lesion site, by relative sparing and redundancy within the distributed cortical system under scrutiny, as well as by the neural plastic changes that can occur with recovery.
Because of the high level of TBI neuroanatomic information that is made available through the use of 3D Slicer, our visualization workflows can be exploited to quickly delineate the function of specific WM fibers or cortical (sub-)regions. Thus, in addition to their relevance to the clinical field, our methods have potential applications to the formulation, validation or information of basic science theories concerning perceptual learning and neural plasticity. They could also complement and extend information already gained from previous animal and human lesion studies. The detailed level of structural impairment description afforded by our techniques can be used to construct more effective patient interventions. Such strategies can be used to explain occupational performance difficulties as well as to shed light upon existing or emerging compensatory rehabilitation techniques.
The potential for recovery from TBI depends on the patient’s ability for regeneration of structures and on his/her capacity for neural plasticity. Consequently, the ability to provide TBI researchers and rehabilitation professionals with information regarding the longitudinal atrophy/regeneration profile of patients using VTK/ITK and 3D Slicer is an important advantage of our work throughout the past year. Firstly, our techniques for rapidly visualizing structural WM connectivity in 3D Slicer may allow clinicians to compare changes in cortical regions and in connectivity with metrics of patient case evolution. Secondly, these tools can be applied to individual patients as well as used to visualize brain morphometric and connectomics on a population level, as well. Thirdly, the use of our framework to the study of atrophy profiles may be useful in the context of personalized rehabilitation treatments by informing qualified personnel on recovery prospects and by providing guidance in the process of evaluating the need for long-term care.
Outreach and Dissemination Events
Our TBI research was honored with the Mazziotta Prize of the Department of Neurology at UCLA for best postdoctoral research in the field of neurology. In addition, it received the First Prize and the Fine Science Award from the Brain Research Institute at UCLA, and the first Prize in the Annual Tutorial Contest of NA-MIC in Boston, MA. Our work was also acknowledged with several postdoctoral travel awards to various conferences, including Dynamics Days 2012 in Baltimore, MD and the Annual Meeting of the Society for Neuroscience in Washington, DC. Our research was selected for a postdoctoral travel award as well as a plenary session presentation that was made at the Keystone Symposium on Chronic Traumatic Encephalopathies. A member of our team was also selected to the Faculty of the Keystone Symposium Continuing Medical Education Program on account of our emerging expertise in the field.
Publications that Acknowledge NA-MIC
Peer-reviewed journal articles
 Andrei Irimia, Micah C. Chambers, Carinna M. Torgerson and John D. Van Horn (2012) Circular representation of human cortical networks for subject and population-level connectomic visualization NeuroImage volume 60, pages 1340-1351  Andrei Irimia, Micah C. Chambers, Carinna M. Torgerson, Maria Filippou, David A. Hovda, Jeffry R. Alger, Guido Gerig, Arthur W. Toga, Paul M. Vespa, Ron Kikinis and John D. Van Horn (2012) Patient-tailored connectomics visualization for the assessment of white matter atrophy in traumatic brain injury Frontiers in Neurology, volume 3, 21 pages
Peer-reviewed conference proceedings
 Bo Wang, Marcel W. Prastawa, Andrei Irimia, Micah C. Chambers, Paul M. Vespa, John D. Van Horn and Guido Gerig (2012) Segmentation of MRI presenting pathology and inconsistent multimodal information Proceedings of the Fifteenth International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2012), October 1-5, 2012, Nice, France.  Bo Wang, Marcel W. Prastawa, Suyash P. Awate, Andrei Irimia, Micah C. Chambers, Paul M. Vespa, John D. Van Horn and Guido Gerig (2012) Segmentation of serial MRI of TBI patients using personalized atlas construction and topological change estimation Proceedings of the Tenth International Symposium on Biomedical Imaging (ISBI 2012), May 2-5, 2012, Barcelona, Catalonia, Spain  Bo Wang, Marcel W. Prastawa, Andrei Irimia, Micah C. Chambers, Paul M. Vespa, John D. Van Horn and Guido Gerig (2012) A patient-specific segmentation framework for longitudinal MR images of traumatic brain injury Proceedings of the Twenty-Fifth International Conference of the International Society for Optical Engineering (SPIE 2012), February 4-9, 2012, San Diego, California, USA  Marc Niethammer, Gabriel L. Hart, Danielle F. Pace, Micah C. Chambers, Andrei Irimia, John D. Van Horn and Stephen R. Aylward (2011) Geometric metamorphosis Proceedings of the Fourteenth International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2011), September 18-22, 2011, Toronto, Ontario, Canada. Also published in Lecture Notes in Computer Science, volume 6891, pages 617-624
Peer-reviewed conference abstracts
 Andrei Irimia, John D. Van Horn, Micah C. Chambers, Marcel W. Prastawa, Silvain Gouttard, Paul M. Vespa, David A. Hovda, Jeffry R. Algers, Sonia M. A. Pujol, Guido Gerig, Stephen R. Aylward, Arthur W. Toga and Ron Kikinis (2011) Connectome-level evaluation of neurodegeneration caused by traumatic brain injury Proceedings of the Eighteenth Annual Meeting of the Organization on Human Brain Mapping (OHBM 2012), June 10-14, 2012, Beijing, China  Andrei Irimia, SY Matthew Goh, Carinna M. Torgerson, Micah C. Chambers, Jeffry R. Alger, David A. Hovda, Paul M. Vespa, Arthur W. Toga, Ron Kikinis and John D. Van Horn (2012) Connectome-level quantification of longitudinal changes in brain circuitry: a study of human neurodegeneration caused by traumatic brain injury Accepted for publication in the Proceedings of the Annual Keystone Conference on Synapses and Circuits: From Formation to Disease, April 1-6, 2012, Steamboat Resort, Steamboat Springs, Colorado, USA  Andrei Irimia, Micah C. Chambers, Jeffry R. Alger, David A. Hovda, Paul M. Vespa, Arthur W. Toga, Ron Kikinis and John D. Van Horn (2012) Patient-tailored longitudinal quantification of brain atrophy in chronic traumatic encephalopathy using multimodal neuroimaging Proceedings of the Annual Keystone Conference on the Clinical and Molecular Biology of Acute and Chronic Traumatic Encephalopathies, February 26-March 2, 2012, Keystone Resort, Keystone, Colorado, USA  Andrei Irimia, Micah C. Chambers, Maria Filippou, Paul M. Vespa, Jeffry R. Alger, David A. Hovda, Arthur W. Toga, Ron Kikinis, John D. Van Horn (2012) Impact of traumatic brain injury upon the architecture and longitudinal dynamics of cortical networks Proceedings of the Thirtieth Annual International Conference on Chaos and Nonlinear Dynamics (Dynamics Days 2012), January 4-7, 2012, Baltimore, Maryland, USA  Andrei Irimia, Micah C. Chambers, Maria Filippou, Jeffry R. Alger, Marcel W. Prastawa, Bo Wang, Silvain Gouttard, Sonia M. A. Pujol, Stephen R. Aylward, David A. Hovda, Guido Gerig, Arthur W. Toga, Ron Kikinis, Paul M. Vespa and John D. Van Horn (2011) Quantification of morphometric and volumetric changes associated with recovery from traumatic brain injury using clinical atrophy measures Neuroscience Poster Session, Brain Research Institute, Ackerman Student Union Grand Ballroom, University of California, Los Angeles, November 29, 2011, Los Angeles, California, USA  Andrei Irimia, Micah C. Chambers, Maria Filippou, Jeffry R. Alger, Marcel W. Prastawa, Bo Wang, Silvain Gouttard, Sonia M. A. Pujol, Stephen R. Aylward, David A. Hovda, Guido Gerig, Arthur W. Toga, Ron Kikinis, Paul M. Vespa and John D. Van Horn (2011) Three‐dimensional calculation and quantification of morphometric and volumetric cortical atrophy indices of widespread clinical use from MRI volumes of traumatic brain injury using 3D Slicer Proceedings of the Forty-First Annual Meeting of the Society for Neuroscience (SfN 2011), November 12-16, 2011, Washington, District of Columbia, USA  Andrei Irimia, Micah C. Chambers, Paul M. Vespa, Arthur W. Toga and John D. Van Horn (2011) Cortical network visualization and analysis in traumatic brain injury using multimodal neuroimaging Proceedings of the Eighteenth Joint Symposium on Neural Computation, June 4, 2011, Institute of Neural Computation, University of California, San Diego, La Jolla, California, USA  Andrei Irimia, John D. Van Horn, Micah C. Chambers, Marcel W. Prastawa, Silvain Gouttard, Paul M. Vespa, David A. Hovda, Jeffry R. Algers, Sonia M. A. Pujol, Guido Gerig, Stephen R. Aylward, Arthur W. Toga and Ron Kikinis (2011) Automatic multimodal MR image segmentation for the clinical assessment of traumatic brain injury in 3D Slicer Proceedings of the Seventeenth Annual Meeting of the Organization on Human Brain Mapping (OHBM 2011), June 26-30, 2011, Quebec City, Canada  John D. Van Horn, Andrei Irimia, , Micah C. Chambers, Marcel W. Prastawa, Silvain Gouttard, Paul M. Vespa, David A. Hovda, Jeffry R. Algers, Sonia M. A. Pujol, Guido Gerig, Stephen R. Aylward, Arthur W. Toga and Ron Kikinis (2011) National Alliance for Medical Image Computing (NA-MIC) All Hands Meeting, Salt Lake City Utah, January 15th, 2012.  John D. Van Horn, Andrei Irimia, , Micah C. Chambers, Marcel W. Prastawa, Silvain Gouttard, Paul M. Vespa, David A. Hovda, Jeffry R. Algers, Sonia M. A. Pujol, Guido Gerig, Stephen R. Aylward, Arthur W. Toga and Ron Kikinis (2011) 2nd Annual Traumatic Brain Injury Conference, Alexandria, Virginia, February 2nd, 2012.