Longitudinal in Vivo Imaging Study of Watershed Brain Lesions due to Multiple Sclerosis
Marc Graham1, Ahmad Toubasi1, Eric Brian1, Victoria Lim1, Caroline Gheen1, Taegan Vinarsky1, Chaoyang Jin2, Stephanie Taylor1, James Eaton1, Richard Dortch3, Manus Donahue1, Junzhong Xu1, Francesca Bagnato1
1Department of Neurology, 2Department of Radiology, Vanderbilt University Medical Center, 3Department of Neurology, Barrow Neurological Institute
Objective:
To compare the longitudinal changes in WMLs volume and degree of microstructural injury among ws, non-watershed (nws), and mixed (m) regions of the brain over one-year duration.
Background:
Watershed (ws) white matter (WM) regions of the brain are more vulnerable to lesion formation in multiple sclerosis (MS). However, the longitudinal evolution of WM lesions (WMLs) located in different vascular territories has not been assessed.
Design/Methods:
Methods
In this prospective study, 31 treatment-naïve subjects with early clinical and pre-clinical MS underwent a baseline and year-one magnetic resonance imaging (MRI) inclusive of T2-weighted fluid attenuated inversion recovery (FLAIR), T1-weighted turbo spin echo, selective inversion recovery quantitative magnetization transfer (SIR-qMT) and multi-compartment diffusion with spherical mean technique (SMT). Changes in SIR-qMT-derived pool size ratio (PSR) and SMT-derived volume axonal fraction (Vax) were assessed using generalized linear mixed model (β). Spearman's correlation coefficients (r) were calculated to assess the relationships between baseline MRI metrics (volume, PSR, Vax) and neurocognitive outcomes at year-one.
Results:
No differences were observed in WMLs volume changes among the groups. However, PSR (β= -11.58; 95%CI= -22.37- -1.27; p=0.029) and Vax (β= -5.10; 95%CI= -9.95- -0.23; p=0.041) percentage changes were lower in ws-WMLs than in nws-WMLs, with no differences between ws- and m-ones which is consistent with lower improvement in myelin and axonal integrity of the tissue. Ws-WMLs Vax at baseline was correlated with nine-hole peg test of the dominant (r=-0.478, p=0.012) and non-dominant hand (r=-0.513, p=0.010), and California verbal learning test (r=0.508, p=0.044) at year-one while Ws-WMLs volume was correlated with timed 25-foot walk test (r=-0.800, p=0.010). No correlations were found between nws-WMLs metrics and neurocognitive outcomes.
Conclusions:
WMLs in ws-areas show a smaller degree of myelin and axonal repair, relative to those located in nws-zones. Our data underscores that the arterial vascularization of the brain may impact tissue recovery in MS.
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