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 T-2 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 (PwS equivalent to v(b)*k(po)). Linear regression models were used to investigate differences in (i) k(po) and PwS 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 PwS were significantly decreased in PMS compared to HC (p <= .01). Twenty-one T-2 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.