Abnormal blood-brain barrier water exchange in chronic multiple sclerosis lesions: A preliminary study

Abstract

Relapsing-remitting multiple sclerosis (RRMS) is associated with persistent blood-brain barrier (BBB) dysfunction. The impact of this persistent dysfunction in both active and chronic MS lesions has yet to be investigated due to technological challenges associated with invasive assessment of BBB water transportation (e.g. 15O-PET). The purpose of this study was to test if persistent BBB dysfunction in RRMS manifests as lower BBB water exchange in chronic lesions using a recently developed noninvasive MRI paradigm. Patients with relapsing-remitting MS and healthy subjects were recruited for this prospective study. The novel Intrinsic Diffusivity Encoding of Arterial Labeled Spins (IDEALS) MRI method was used to map BBB water extraction fraction (Ew) and water permeability surface area product (PSw), as well as cerebral blood flow (CBF). Regional differences in BBB water exchange were evaluated between MS patients (normal appearing white matter [NAWM] and normal appearing gray matter [NAGM]) and healthy subjects (white matter [WM] and gray matter [GM]) and within MS subjects in non gadolinium-based contrast-agent (GBCA) enhancing chronic lesions, perilesional areas, and NAWM. Significantly lower PSw and Ew were observed in NAWM compared to WM (ΔPSw: −11.9 mL/100 g/min, p < .05; ΔEw: −4.3%, p < .01). Significantly lower Ew was observed in NAGM compared to GM (ΔEw: −12.1%, p < .01). Significantly lower PSw and CBF were observed in non-GBCA contrast enhancing lesions compared to NAWM (ΔPSw = −11.5 mL/100 g/min, p < .05; ΔCBF = −8.1 mL/100 g/min, p < .05). Ew was significantly higher in non-GBCA enhancing chronic MS lesions compared to NAWM (ΔEw = 1.6%, p < .05). The lower BBB water exchange in chronic MS lesions is consistent with previously reported observations and may demonstrate metabolic changes associated with MS.