Highly precise measurements from fully automated techniques are required to quantify brain atrophy in individual multiple sclerosis (MS) patients. We developed a novel approach to reliably estimate brain atrophy in MS that combines two techniques applied to different image contrasts and incorporates inter-scanner calibrations. We validated this approach using data acquired in a scan-rescan study. Mean coefficient of variation (CV) for the new brain parenchymal fraction measurement was 0.18%, which was lower than the CV attained for the individual techniques. This new metric will next be integrated into the radiology workflow in MS PATHS institutions for further testing.