Chronic active lesions preferentially localize in watershed territories in multiple sclerosis

Abstract

Objective: Paramagnetic rim lesions (PRLs) are a biomarker of chronic active lesions (CALs), and an important driver of neurological disability in multiple sclerosis (MS). The reason subtending some acute lesions evolvement into CALs is not known. Here we ask whether a relatively lower oxygen content is linked to CALs.

Methods: In this prospective cross-sectional study, 64 people with multiple sclerosis (PwMS), clinically isolated syndrome and radiologically isolated syndrome underwent a 7.0 Tesla (7 T) brain magnetic resonance imaging (MRI). The scanning protocol included a T₂-w fluid-attenuated inversion recovery (FLAIR), and a single echo gradient echo from which susceptibility-weighted imaging (SWI) was derived. WM lesions were identified on the T₂-w-FLAIR whilst PRLs were identified on the SWI sequence. T₂-lesions were classified as PRLs and rimless lesions (PRLs-). We registered a universal vascular atlas to each subject's T₂-w-FLAIR and classified each T₂-lesions according to its location into watershed- (ws), non-watershed- (nws), and mixed-lesion (m). Ws-lesions were defined as lesions that were fully located in a region between the territories of two major arteries.

Results: Out of 1,975 T₂-lesions, 88 (4.5%) were PRLs. Ws-regions had a higher number (p = 0.005) and proportion (p < 0.001) of PRLs- compared to nws-regions. Ws-PRL- were larger compared to nws-ones (p = 0.009). The number (p = 0.043) and proportion (p < 0.001) of PRLs was higher in ws-regions compared to nws-ones. Ws-PRLs were not significantly larger than nws-ones (p = 0.195).

Interpretation: We propose the novel concept of a link between arterial vascularization and chronic activity in MS by demonstrating a preferential localization of CALs in ws-territories.

Figure 1

Anatomical and vascular maps. T₂‐weighted fluid‐attenuated inversion recovery showing four white matter T₂‐lesions, pointed by the arrows (A). The susceptibility‐weighted image in (B) shows that of the four lesions, one is a paramagnetic rim lesion (PRL, white arrow). In (C) one can see lesion localization relative to arterial vascularization with the blue arrows pointing toward the rimless‐T₂‐lesions (PRLs‐) and the white one pointing toward the PRL. Maps of arterial vascularization across different regions of the brain (D–F). In E, red and pink contours delineate watershed and non‐watershed areas, respectively. A and B indicate the right and left hemispheres; 1 = middle cerebral artery territory 2 = anterior cerebral artery territory and 3 = posterior cerebral artery territory. In this map, the red, pink, and dark red circles represent hypothetical lesions of watershed (ws), non‐watershed (nws), and mixed (m) zones, respectively.

Figure 2

Sizes of lesions located in different vascular territories. Mean lesions size of watershed (red), non‐watershed‐ (pink), and mixed‐lesions (dark red). The box represents the interquartile range, the horizontal lines inside the box represent the median, the vertical lines outside the box represent the 95% confidence interval, and the dots represent the lesions. We present rimless‐T₂‐lesions (PRLs‐) (A), non‐periventricular PRLs‐ (B), PRLs‐ in patients without comorbidities (C), paramagnetic rim lesions (D). *Signifies statistically significant results at p‐value <0.050.

Figure 3

The volume of paramagnetic rim lesions. We depict the mean size of non‐periventricular (nPV, light green box) and periventricular paramagnetic rim lesions (PV‐PRLs, dark green box) (A) and the mean size of nPV‐non‐watershed (PV‐nws, light blue), nPV‐watershsed (nPV‐ws, sky blue), PV‐ws (cornflower blue), nPV‐mixed (nPV‐m, dark blue), and PV‐m PRLs (midnight blue). The box represents the interquartile range, the horizontal lines inside the box represent the median, the vertical lines outside the box represent the 95% confidence interval, and the dots represent the lesions. *Signifies statistically significant results at p‐value <0.050.