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

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Abstract

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.

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Acknowledgments

We would like to thank Rozalia Arnaoutelis for her invaluable help in patient recruitment and booking. This work was supported by the Multiple Sclerosis Society of Canada.

Conflicts of interest

Dr. Arnold has served on advisory boards, received speaker honoraria, served as a consultant or received research support from Bayer, Biogen Idec, Coronado Biosciences, Consortium of Multiple Sclerosis Centers, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, MS Forum, NeuroRx Research, Novartis, Opexa Therapeutics, Roche, Merck Serono, S.A., Serono Symposia International Foundation, Teva, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada; and holds stock in NeuroRx Research. Dr. Narayanan has received personal compensation from NeuroRx Research, Teva Neurosciences Canada and Biogen Idec Canada for consulting services. Dr. Giacomini has received personal compensation from NeuroRx Research, Allergan, Bayer, Biogen Idec, Genzyme, Novartis, EMD Serono and Teva Neuroscience for speaking, advisory board participation or consulting services.

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Correspondence to Ilana R. Leppert.

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Leppert, I.R., Narayanan, S., Araújo, D. et al. Interpreting therapeutic effect in multiple sclerosis via MRI contrast enhancing lesions: now you see them, now you don’t. J Neurol 261, 809–816 (2014). https://doi.org/10.1007/s00415-014-7284-0

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  • DOI: https://doi.org/10.1007/s00415-014-7284-0

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