Imaging Chronic Active Lesions in Multiple Sclerosis: a Consensus Statement from the North America Imaging in Multiple Sclerosis Cooperative
Francesca Bagnato1, Pascal Sati2, Christopher Hemond3, Colm Elliott4, Susan Gauthier5, Daniel Harrison6, Caterina Mainero7, Jiwon Oh8, David Pitt9, Russell Shinohara10, Seth Smith11, Trapp Bruce12, Christina Azevedo13, Peter Calabresi14, Roland Henry15, Cornelia Laule16, Daniel Ontaneda12, William Rooney17, Nancy Sicotte2, Daniel Reich18, Martina Absinta19
1Vanderbilt University Medical Center, 2Cedars-Sinai Medical Center, 3University of Massachusetts Memorial Medical Center, 4NeuroRx Research, 5Weill Cornell Medicine, 6University of Maryland School of Medicine, 7Massachusettes General Hosptial, 8St. Michael’s Hospital, University of Toronto, 9Yale School of Medicine, 10University Of Pennsylvania, 11Vanderbilt University Institute of Imaging Science, 12Cleveland Clinic, 13University of Southern California, 14Johns Hopkins University, 15University of California, San Francisco, 16University of British Columbia, 17Oregon Health & Science University, 18National Institutes of Health, Neuroimmunology Branch, NINDS, 19St. Raffaele Hospital
Objective:
To develop a consensus statement for the radiological definition and measurement of chronic active lesions (CAL) and assessment of their role as disease prognosticators in multiple sclerosis (MS).
Background:
CAL are an important manifestation of chronic inflammation in MS and have implications for non-relapsing biological progression. Promising biomarkers of CAL include paramagnetic rim lesions (PRL) identified on susceptibility-sensitive magnetic resonance imaging (MRI), MRI-defined slowly expanding lesions (SEL) identified on serial T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein (TSPO)-positive lesions on positron emission tomography PET. However, standardization in the use of these biomarkers is lacking.
Design/Methods:
Via a multistep process including a day-long workshop and multiple experts’ participations, the North American Imaging in Multiple Sclerosis Cooperative (NAIMS) identified and discussed: (1) the role of PRL as surrogate measures of CAL; (2) SEL and their accuracy in reflecting CAL and PRL; and (3) PET and its ability to identify CAL and PRL. The relationships among these biomarkers and disease outcome were also reviewed.
Results:
A consensus was reached on all the proposed topics, including recommendations for image acquisition and interpretation. The experts agreed that while partially overlapping, PRL, SEL, and TSPO-positive lesions do not have equivalent sensitivity and specificity to histopathologic CAL and should not be considered interchangeable. PRL is the biomarker with the most robust histopathological substantiation. PRL and SEL are associated with physical and cognitive disability, but their prognostic value is yet to be determined.
Conclusions:
We propose a standardized approach to identify CAL in vivo using MRI and PET and provide expert opinion on the role of PRL, SEL and TSPO-positive lesions as prognosticators of disease outcome. More research is needed to validate our proposed definitions, but the current consensus statement provides a common ground for harmonizing future efforts.