The Neuropathology Core
The Neuropathology Core is an advanced, state-of-the-art academic and research-oriented facility that collects, processes, and assesses postmortem human and animal brain tissues to advance traumatic brain injury (TBI) research. The Neuropathology Core has a team of expertly trained staff that offer assistance with neuropathological and neurohistological protocol development, study design, data acquisition, analysis and interpretation, and clinical-pathological correlations.
The Core’s primary goal is to provide the proper collection, preservation, and characterization of human brains donated to its Brain Tissue Repository (BTR). The BTR is the only brain bank facility in the world that is exclusively dedicated to collecting, assessing, classifying, analyzing, and storing brains from individuals who have served in the military. These tissues are available to qualified researchers and scientist upon request and approval through appropriate mechanisms from the Core’s Steering Committee. These selfless and invaluable donations enable scientists to use innovative approaches to better understand the pathophysiological mechanisms underlying military-related TBI. To learn more about the BTR, please visit its website at www.researchbraininjury.org.
Donations to the BTR have already led to pivotal findings. Dr. Daniel Perl, the Director of the BTR, discovered a unique pattern of interface astroglial scarring in cases of deceased Service Members who sustained blast-related TBIs. The Neuropathology Core participates in collaborative research efforts with various institutions such as the Uniformed Services University; University of California, San Francisco; Harvard University; and University of Washington. It also collaborates with other federally funded research projects such as Chronic Effects of Neurotrauma Consortium (CENC) and Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI).
Iacono, D., Lee, P., Edlow, B. L., Gray, N., Fischl, B., Kenney, K., … Perl, D. P. (2019). Early-Onset Dementia in War Veterans: Brain Polypathology and Clinicopathologic Complexity. Journal of Neuropathology & Experimental Neurology, 79(2), 144–162. doi: 10.1093/jnen/nlz122
Edlow, B. L., Keene, C. D., Perl, D. P., Iacono, D., . . . Dams-O’Connor, K. (2018). Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project. Journal of Neurotrauma, 35, 1604-1619. doi:10.1089/neu.2017.5457
The Neuropathology-Neuroradiology Integration Core
The Neuropathology Core recently partnered with Dr. Peter Basser’s Section on Quantitative Imaging and Tissue Sciences (SQITS) at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), to form the Neuropathology-Neuroradiology Integration Core. The Neuropathology Core and SQITS will work together to develop and test novel magnetic resonance imaging (MRI) approaches that could potentially identify TBI-related structural abnormalities in vivo, which currently can only be identified ex vivo using neuropathological methods. To date, there have been no reliable and reproducible neuroradiological methods developed to detect TBI tissue damage in vivo.
The Neuropathological-Neuroradiological Integration Core represents a novel union of two complementary but distinct fields: neuroradiology and neuropathology. An interdisciplinary team is now working together to try to discover and develop actionable in vivo quantitative imaging biomarkers to make “invisible” TBI tissue damage “visible.” MRI methods sensitive to TBI-related damage could improve diagnoses and could be used to refine inclusion criteria in future clinical trials of candidate therapeutics. A limitation of current TBI clinical trials, especially those involving “concussive” or “mild TBI”, is that the inclusion criteria is based on subjective rather than objective assessments.
Establishing correlations between neuroradiology image data and neuropathology-based histological data could facilitate advances in both fields. Neuroradiological methods can accelerate neuropathology assessments by identifying salient areas of high scientific and/or clinical value prior to highly labor intensive sectioning and subsequent histological analysis. Neuropathological methods can provide detailed image data at the cellular and subcellular level that can inform the development of new MR imaging “contrasts” and “stains.”
The first step in establishing bidirectional correlations between these fields is to develop and test various MRI stains and contrasts on control and injured tissue specimens. The team is evaluating whether various novel MRI contrasts can help distinguish differences among fixed brain tissue specimen and be able to detect sequelae of damage or injury. They are also assessing the robustness and reproducibility of these methods to ensure their suitability for more routine use.
The second step in this collaborative initiative is to robustly and reliably fuse MRI data with images of the same tissue that has later been histologically sectioned and stained. Blinded and de-identified tissues are scanned via MRI and, then, returned to the Neuropathology Core. The Neuropathological data is processed, scanned, and returned to Dr. Basser’s lab. The neuroimaging and neuropathological data are then coregistered and correlated.
The third step, which is aspirational, is to discover, if possible, one or more potential quantitative MRI biomarkers that can effectively detect sequelae of TBI. If the Neuropathology Core achieves this milestone, a future goal is to use objective MR imaging methods that are based on solid neuropathological validation to advance TBI diagnosis, clinical trial inclusion, and treatment guidance, in order to improve clinical outcomes.
Benjamini, D., & Basser, P. J. (2019). Water mobility spectral imaging of the spinal cord: Parametrization of model-free Laplace MRI. Magnetic Resonance Imaging,56, 187-193. doi:10.1016/j.mri.2018.12.001
Benjamini, D., & Basser, P. J. (2018). Towards clinically feasible relaxation-diffusion correlation MRI using MADCO. Microporous and Mesoporous Materials,269, 93-96. doi:10.1016/j.micromeso.2017.02.001
Cai, T. X., Benjamini, D., Komlosh, M. E., Basser, P. J., & Williamson, N. H. (2018). Rapid detection of the presence of diffusion exchange. Journal of Magnetic Resonance,297, 17-22. doi:10.1016/j.jmr.2018.10.004
Komlosh, M. E., Benjamini, D., Hutchinson, E. B., King, S., Haber, M., Avram, A. V., . . . Basser, P. J. (2018). Using double pulsed-field gradient MRI to study tissue microstructure in traumatic brain injury (TBI). Microporous and Mesoporous Materials,269, 156-159. doi:10.1016/j.micromeso.2017.05.030
Benjamini, D., & Basser, P. J. (2017). Magnetic resonance microdynamic imaging reveals distinct tissue microenvironments. NeuroImage,163, 183-196. doi:10.1016/j.neuroimage.2017.09.033