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Abstract Details

Assessing myelin loss in the white matter near to and distant from chronic black holes in multiple sclerosis.
Multiple Sclerosis
P7 - Poster Session 7 (5:30 PM-6:30 PM)
9-012
We implement the macromolecular-to-free pool-size-ratio (PSR) and the longitudinal relaxation rate (R1f) derived from selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT), and intrinsic diffusivity (Dax) and intracellular volume fraction (Vax) derived from the multi-compartment microscopic diffusion magnetic resonance imaging (MRI) with the Spherical Mean Technique (SMT), to measure differences in myelin and axonal quantity among chronic black hole (cBHs), normal appearing white matter (NAWM) adjacent-to and contralateral-to cBHs in persons with multiple sclerosis (pwMS). Our ultimate goal is assessing anterograde and retrograde WM-degeneration and its impact on disability of pwMS. 
Histopathological evidence shows that following focal axonal degeneration, the axon undergo transection, followed by anterograde and retrograde degeneration. These degenerative changes include loss of myelin and axonal death. Experimental autoimmune encephalomyelitis animal model studies showed that these changes are largely preventable and axonal morphology can be restored with early intervention. Thus, quantifying and monitoring these changes will offer a tool to monitor disability progression before it becomes clinically overt and will allow personalizing treatments to prevent MS progression.
In this prospective case-control study nineteen pwMS underwent a 3T-MRI with clinical scans, SIR-qMT and SMT protocol. Region-of-interests on cBHs, NAWM adjacent-to-cBHs (referred as perilesional-NAWM) and contralateral-NAWM were manually delineated and PSR/R1f/Dax/Vax values were extracted. Mixed-effects regression model and bootstrapping 95% confidence interval (CI) were used to examine differences and correlations respectively.
Our preliminary analysis demonstrates that PSR, R1f and Vax were lower in cBHs (p≤0.001) compared to perilesional-NAWM and in perilesional-NAWM (p≤0.05) compared to contralateral-NAWM. We found significant associations between PSR-R1f (r=0.67,95%CI:0.17-0.92) and Vax-Dax (r=0.76,95%CI=0.42-0.93) in perilesional-NAWM. 
Our results indicate that perilesional-NAWM is characterized by lower myelin and axonal content compared to contralateral-NAWM, suggestive of degenerative changes extending outside lesions. We are further working on assessing the impact of lesional disease on distant degeneration and its effect on clinical outcome.
Authors/Disclosures
Dhairya Lakhani, MD (West Virginia Unversity)
PRESENTER 		Dr. Lakhani has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
Seth A. Smith, PhD (Vanderbilt University Institute of Imaging Science) Dr. Smith has nothing to disclose.
No disclosure on file
Richard D. Dortch, PhD Dr. Dortch has nothing to disclose.
Francesca Bagnato, MD (Vanderbilt University Medical Center) Dr. Bagnato has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Bagnato has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyne. Dr. Bagnato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Bagnato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jenseen. Dr. Bagnato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk-Serono.