Assessing myelin loss in the white matter near to and distant from chronic black holes in multiple sclerosis. (304)

Objective: 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. Background: 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. Design/Methods: 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. Results: 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. Conclusions: 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. Disclosure: Dr. Lakhani has nothing to disclose. Dr. Wen has nothing to disclose. Dr. Gao has nothing to disclose. Dr. Ciccone has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Xu has nothing to disclose. Dr. Dortch has nothing to disclose. Dr. Bagnato has nothing to disclose.