Abstract Details

Title Characterization of Whole Brain Axonal Pathology in Multiple Sclerosis Using High-Gradient Diffusion MRI

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-001

Objective To expand axon diameter/density estimation to whole brain white matter in people with multiple sclerosis (MS) compared to healthy controls (HC) using high-gradient diffusion MRI (dMRI) and spherical averaging.

Background Axonal damage is considered the substrate of disability in MS but lacks a specific imaging biomarker. Advances in dMRI hardware and modeling have enabled axon diameter/density estimation in single fiber bundles without crossings. Previous analysis by our group in MS was restricted to the corpus callosum where axons largely course in one direction.

Design/Methods Twenty-six people with MS [twenty relapsing-remitting MS (RRMS); six progressive MS (PMS)] and twenty-four HC were scanned on the dedicated high-gradient 3T Connectome MRI scanner with 300 mT/m maximum gradient strength. An optimized multi-shell protocol was used to image across the whole brain of MS and HC subjects using a maximum b-value of 17,800 s/mm². Multicompartment modeling was adapted for spherically averaged signal to map axon diameter/density throughout the brain. dMRI metrics between groups were compared using Student’s t-test, correcting for multiple comparisons using the false discovery rate.

Results Axon diameter was significantly larger in normal appearing white matter (NAWM) of MS versus HC (5.25 vs 4.98 um, p=0.03). The volume fraction of intra-axonal water was significantly lower than in HC (0.38 vs 0.40, p=0.01), with similar trends observed in RRMS versus PMS. Axon density was significantly reduced in MS NAWM versus HC (3.07 vs 3.49 x 10¹⁰/m², p=0.004). Lesions showed significantly larger axon diameter (6.13 vs 5.25 um, p<0.001), and reduced axon density versus NAWM (1.72 vs 3.07 x 10¹⁰/m², p<0.00001).

Conclusions Widespread alterations in axon diameter/density were observed throughout MS NAWM and lesions, in agreement with histopathological findings and previous results restricted to the corpus callosum, suggesting this approach is robust to characterizing axonal pathology throughout the whole brain, independent of fiber crossings.

Authors/Disclosures
Susie Y. Huang, MD, PhD (Massachusetts General Hospital, Harvard Medical School) PRESENTER	Dr. Huang has received personal compensation in the range of $0-$499 for serving as a Consultant for Siemens Healthineers. The institution of Dr. Huang has received research support from Siemens Healthineers. The institution of Dr. Huang has received research support from Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School.
	No disclosure on file
Natalya Machado	No disclosure on file
Andrew Russo	Andrew Russo has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Eric Klawiter, MD, F�鶹��ýӳ�� (Massachusetts General Hospital)	Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Galen/Atlantica. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Klawiter has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for OM1. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Klawiter has received research support from Biogen. The institution of Dr. Klawiter has received research support from Abbvie. The institution of Dr. Klawiter has received research support from Genentech.

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