Gray matter blood-brain barrier water exchange dynamics are reduced in progressive multiple sclerosis

Background and purpose: To compare transcapillary wall water exchange, a putative marker of cerebral metabolic health, in brain T₂ white matter (WM) lesions and normal appearing white and gray matter (NAWM and NAGM, respectively) in individuals with progressive multiple sclerosis (PMS) and healthy controls (HC).

Methods: Dynamic-contrast-enhanced 7T MRI data were obtained from 19 HC and 23 PMS participants. High-resolution pharmacokinetic parametric maps representing tissue microvascular and microstructural properties were created by shutter-speed (SS) paradigm modeling to obtain estimates of blood volume fraction (v_b ), water molecule capillary efflux rate constant (k_po ), and the water capillary wall permeability surface area product (P_w S ≡ v_b *k_po ). Linear regression models were used to investigate differences in (i) k_po and P_w S between groups in NAWM and NAGM, and (ii) between WM lesions and NAWM in PMS.

Results: High-resolution parametric maps were produced to visualize tissue classes and resolve individual WM lesions. Normal-appearing gray matter k_po and P_w S were significantly decreased in PMS compared to HC (p ≤ .01). Twenty-one T₂ WM lesions were analyzed in 10 participants with PMS. k_po was significantly decreased in WM lesions compared to PMS NAWM (p < .0001).

Conclusions: Transcapillary water exchange is reduced in PMS NAGM compared to HC and is further reduced in PMS WM lesions, suggesting pathologically impaired brain metabolism. k_po provides a sensitive measure of cerebral metabolic activity and/or coupling, and can be mapped at higher spatial resolution than conventional imaging techniques assessing metabolic activity.