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).
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 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. Currently, these structural abnormalities can only be identified ex vivo using neuropathological methods. There are currently no reliable and reproducible neuroradiological methods to detect TBI tissue damage in vivo.
The Neuropathological-Neuroradiological Integration Core is a novel union of two complementary but distinct fields of neuroradiology and neuropathology. An interdisciplinary team is 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 as 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 advancements in both fields. Neuroradiological methods can accelerate neuropathology assessments by identifying areas of high scientific and/or clinical value prior to highly labor intensive sectioning and subsequent histological analysis. Neuropathological methods provide detailed image data on the cellular and subcellular level that can inform the development of new 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 MRI contrasts can help distinguish differences among fixed brain tissue specimen and 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 is to fuse MRI data with images of the same tissue that has later been histologically stained. Blinded and de-identified tissues are scanned 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 final step is to discover, if possible, one or more potential quantitative MRI biomarkers that can effectively detect TBI sequelae. The future goal is to use objective imaging methods that are based on solid neuropathological validation to advance TBI diagnosis, clinical trial inclusion, and treatment guidance.