Abstract #2077

Evidence for axonal beading and loss in traumatic brain injury using ultra-high gradient ex vivo diffusion MRI

Dongsuk Sung¹, Hong-Hsi Lee¹, Kwok-Shing Chan¹, Gabriel Ramos-Llorden¹, Alina Müller², Boris Keil^2,3, C. Dirk Keene⁴, Amber Nolan⁴, Brian L. Edlow^1,5, Cristine L. Mac Donald⁶, Kristen Dams-O’Connor^7,8, Bruce Fischl¹, Andre van der Kouwe¹, and Susie Y. Huang¹

¹Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States, ²Institute of Medical Physics and Radiation Protection, TH-Mittelhessen University of Applied Sciences, Giessen, Germany, ³LOEWE Research Cluster for Advanced Medical Physics in Imaging and Therapy (ADMIT), TH-Mittelhessen University of Applied Sciences, Giessen, Germany, ⁴University of Washington, Seattle, WA, United States, ⁵Department of Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁶Department of Neurological Surgery, University of Washington, Seattle, WA, United States, ⁷Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁸Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Synopsis

Keywords: Traumatic Brain Injury, Ex-Vivo Applications, traumatic brain injury, ultra-high gradient diffusion MRI, microstructure

Motivation: Understanding the impact of traumatic brain injury (TBI) on axonal microstructure can elucidate neurodegenerative mechanisms and inform novel therapeutics.

Goal(s): To investigate post-TBI alterations in axonal microstructure using high-resolution, ultra-high b-value ex vivo diffusion MRI in postmortem human whole-brain specimens.

Approach: Four postmortem brains from TBI patients were scanned using 3D diffusion-weighted multi-shot EPI on the Connectome 2.0 MRI scanner. Diffusion data were fitted to the AxCaliber-SMT model to estimate axon diameter, intra-axonal diffusivity, and intra-axonal fraction.

Results: Axon diameter and intra-axonal fraction were reduced in focal white matter near cortical contusions, aligning with histopathologically observed features such as axonal beading and loss.

Impact: This study leverages the high-performance gradients of the Connectome 2.0 scanner and a state-of-the-art RF coil for ex vivo imaging to create a platform for histopathologic-imaging correlation and elucidate the mechanisms of post-traumatic neurodegeneration.

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