Neuropathological and Neuroradiological Research

Neuropathological and Neuroradiological Research

The Neuropathology-Neuroradiology Integration Core

The Neuropathology-Neuroradiology Integration Core is a novel union and synthesis of two complementary but distinct fields: neuropathology and neuroradiology.

It includes Dr. Daniel Perl's Neuropathology Research Division and Dr. Peter Basser’s Section on Quantitative Imaging and Tissue Sciences, who work together to develop and test novel magnetic resonance imaging (MRI) approaches that could potentially identify traumatic brain injury (TBI)-related structural abnormalities in vivo. Currently, these abnormalities can only be identified ex vivo using laborious neuropathological methods. To date, there have been no reliable, robust, and reproducible neuroradiological methods developed to detect TBI tissue damage in vivo. This team is attempting to change this.

MRI methods sensitive to TBI-related damage could improve diagnoses and 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 (mTBI), is that the inclusion criteria is based on subjective and not objective assessments.

Establishing relationships between neuroradiology image data and neuropathology-based histological data could also facilitate advances in both fields. New neuroradiological methods could accelerate neuropathology assessments by identifying areas of high scientific and/or clinical value prior to performing labor intensive sectioning and subsequent histological analyses. Conversely, neuropathological methods can provide detailed “ground truth” image data at the cellular and subcellular levels that can inform the development of new MR imaging contrasts and stains.

The first step in establishing bi-directional correlations between these fields is to develop and test various MRI stains and contrasts using controlled (non-injured) and well-characterized injured tissue specimens. This team evaluates whether various novel MRI contrasts can help detect sequelae of injury. They also assess the robustness and reproducibility of these MRI 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 specimens that are later histologically sectioned and stained. Blinded and de-identified tissues are scanned via MRI and then returned to the Neuropathology Research Division where they are processed and scanned using state-of-the-art histological techniques. 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 and confirm sequelae of TBI found by neuropathological methods. If the team achieves this milestone, a subsequent 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 service members.

Core-related Publications

Benjamini, D., & Basser, P. J. (2020). Multidimensional correlation MRINMR in biomedicine33(12), e4226.

Pas, K., Komlosh, M. E., Perl, D. P., Basser, P. J., & Benjamini, D. (2020). Retaining information from multidimensional correlation MRI using a spectral regions of interest generatorScientific reports10(1), 3246.

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