Interpreting therapeutic effect in multiple sclerosis via MRI contrast enhancing lesions: now you see them, now you don’t

Gadolinium (Gd) enhancement of multiple sclerosis (MS) lesions on MRI scans is a commonly used outcome measure in therapeutic trials. However, enhancement depends on MRI acquisition parameters that might significantly alter detectability. We investigated how the difference in blood–brain barrier (BBB) permeability threshold between MRI protocols affects lesion detection and apparent enhancement time using dynamic-contrast-enhanced (DCE) MRI. We examined fourty-four relapsing-remitting MS patients with two MRI protocols: ‘standard sensitivity’ (SS) (1.5 T, single-dose Gd) and ‘high sensitivity’ (HS) (3 T, triple-dose Gd, delayed acquisition). Eleven patients had at least one enhancing lesion and completed the 1-month follow-up. We acquired DCE-MRI during the HS protocol and calculated BBB permeability. Sixty-five lesions were enhanced with the SS vs. 135 with the HS protocol. The detection threshold of the HS was significantly lower than that of the SS protocol (K trans = 2.64 vs. 4.00E−3 min−1, p < 0.01). Most lesions (74 %) were in the recovery phase; none were in the onset phase and 26 % were at the peak of enhancement. The estimated duration of detectability with the HS protocol was significantly longer than for the SS protocol (6–12 weeks vs. 3 weeks). Our observations on the protocol-dependent threshold for detection and time-course help explain discrepancies in the observed effects of anti-inflammatory therapies on MS lesions.