Quantification of blood-to-brain transfer rate in multiple sclerosis

Abstract

Blood–brain barrier (BBB) disruption visualized in lesions by MRI is a major biomarker of disease activity in multiple sclerosis (MS). However, in MS, destruction occurs to a variable extent in lesions as well as in gray matter (GM) and in the normal appearing white matter (NAWM). A method to quantify the BBB disruption in lesions as well as in non-lesion areas would be useful for assessment of MS progression and treatments. The objective of this study was to quantify the BBB transfer rate (Ki) in WM lesions, in the NAWM, and in the full-brain of MS patients. Thirteen MS patients with active lesions and 10 healthy controls with age and gender matching were recruited for full-brain and WM Ki studies. Dynamic contrast-enhanced MRI (DCEMRI) scans were conducted using T1 mapping with partial inversion recovery (TAPIR), a fast T1 mapping technique, following administration of a quarter-dose of the contrast agent Gadolinium-DTPA (Gd-DTPA). The Patlak modeling technique was used to derive a voxel-based map of Ki. In all patients contrast-enhanced lesions, quantified by Ki maps, were observed. Compared with controls, patients with MS exhibited an increase in mean Ki of the full-brain (P-value<0.05) but no significant difference in mean Ki of NAWM. The identified increase in full-brain Ki of MS patients suggests a global vascular involvement associated with MS disease. The lack of observed significant decrease in Ki in NAWM suggests lower involvement of WM vasculature than full-brain vasculature in MS. Ki maps constructed from time series data acquired by DCEMRI provide additional information about BBB that could be used for evaluation of vascular involvement in MS and monitoring treatment effectiveness.