Imaging chronic active lesions in multiple sclerosis: a consensus statement

Francesca Bagnato; Pascal Sati; Christopher C Hemond; Colm Elliott; Susan A Gauthier; Daniel M Harrison; Caterina Mainero; Jiwon Oh; David Pitt; Russell T Shinohara; Seth A Smith; Bruce Trapp; Christina J Azevedo; Peter A Calabresi; Roland G Henry; Cornelia Laule; Daniel Ontaneda; William D Rooney; Nancy L Sicotte; Daniel S Reich; Martina Absinta

doi:10.1093/brain/awae013

Imaging chronic active lesions in multiple sclerosis: a consensus statement

Brain. 2024 Jan 16:awae013. doi: 10.1093/brain/awae013. Online ahead of print.

Authors

Francesca Bagnato^{1

2}, Pascal Sati³, Christopher C Hemond⁴, Colm Elliott⁵, Susan A Gauthier⁶, Daniel M Harrison^{7

8}, Caterina Mainero⁹, Jiwon Oh¹⁰, David Pitt¹¹, Russell T Shinohara^{12

13}, Seth A Smith¹⁴, Bruce Trapp¹⁵, Christina J Azevedo¹⁶, Peter A Calabresi¹⁷, Roland G Henry¹⁸, Cornelia Laule^{19

20

21

22}, Daniel Ontaneda²³, William D Rooney²⁴, Nancy L Sicotte²⁵, Daniel S Reich²⁶, Martina Absinta^{17

27}

Affiliations

¹ Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
² Department of Neurology, Nashville VA Medical Center, Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
³ Neuroimaging Program, Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048 USA.
⁴ University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
⁵ NeuroRx Research, Montréal, QC, H2X 3P9 Canada.
⁶ Department of Neurology, Weill Cornell Medicine, NYC, NY 10021, USA.
⁷ Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
⁸ Department of Neurology, Baltimore VA Medical Center, VA Maryland Healthcare System; Baltimore, MD 21201, USA.
⁹ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁰ Division of Neurology, St. Michael's Hospital, University of Toronto, Toronto, ON M5S, Canada.
¹¹ Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA.
¹² Penn Statistics in Imaging and Visualization Endeavor, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹³ Center for Biomedical Image Computing and Analytics, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁴ Vanderbilt University Institute of Imaging Science, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37235, USA.
¹⁵ Department on Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
¹⁶ Department of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90007, USA.
¹⁷ Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
¹⁸ Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA 94158, USA.
¹⁹ Department of Radiology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
²⁰ Department of Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
²¹ Department of Physics & Astronomy, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
²² International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
²³ Mellen Center for Multiple Sclerosis, Cleveland Clinic, Cleveland, OH 44195, USA.
²⁴ Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR 97239, USA.
²⁵ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
²⁶ Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
²⁷ Translational Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, Vita-Salute San Raffaele University and Hospital, Milan, 20132, Italy.

PMID: 38226694
DOI: 10.1093/brain/awae013

Abstract

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted (T1-w) and T2-w scans, and 18-kDa translocator protein-positive lesions on PET are promising candidate biomarkers of CAL. While partially overlapping, these biomarkers do not have equivalent sensitivity and specificity to histopathological CAL. Standardization in the use of available imaging measures for CAL identification, quantification, and monitoring is lacking. To fast-forward clinical translation of CAL, the North American Imaging in Multiple Sclerosis Cooperative developed a Consensus Statement, which provides guidance for the radiological definition and measurement of CAL. The proposed manuscript presents this Consensus Statement, summarizes the multistep process leading to it, and identifies the remaining major gaps in knowledge.

Keywords: MRI-defined slowly evolving lesions; chronic active lesions; iron; microglia; multiple sclerosis; paramagnetic rim lesions.

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