Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions
Colm Elliott, Jerry S Wolinsky, Stephen L Hauser, Ludwig Kappos, Frederik Barkhof, Corrado Bernasconi, Wei Wei, Shibeshih Belachew, Douglas L Arnold, Colm Elliott, Jerry S Wolinsky, Stephen L Hauser, Ludwig Kappos, Frederik Barkhof, Corrado Bernasconi, Wei Wei, Shibeshih Belachew, Douglas L Arnold
Abstract
Background: Chronic lesion activity driven by smoldering inflammation is a pathological hallmark of progressive forms of multiple sclerosis (MS).
Objective: To develop a method for automatic detection of slowly expanding/evolving lesions (SELs) on conventional brain magnetic resonance imaging (MRI) and characterize such SELs in primary progressive MS (PPMS) and relapsing MS (RMS) populations.
Methods: We defined SELs as contiguous regions of existing T2 lesions showing local expansion assessed by the Jacobian determinant of the deformation between reference and follow-up scans. SEL candidates were assigned a heuristic score based on concentricity and constancy of change in T2- and T1-weighted MRIs. SELs were examined in 1334 RMS patients and 555 PPMS patients.
Results: Compared with RMS patients, PPMS patients had higher numbers of SELs (p = 0.002) and higher T2 volumes of SELs (p < 0.001). SELs were devoid of gadolinium enhancement. Compared with areas of T2 lesions not classified as SEL, SELs had significantly lower T1 intensity at baseline and larger decrease in T1 intensity over time.
Conclusion: We suggest that SELs reflect chronic tissue loss in the absence of ongoing acute inflammation. SELs may represent a conventional brain MRI correlate of chronic active MS lesions and a candidate biomarker for smoldering inflammation in MS.
Keywords: Chronic active lesions; progressive multiple sclerosis; relapsing multiple sclerosis; slowly expanding/evolving lesions; smoldering plaques.
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.E. is an employee of NeuroRx Research and has served on an advisory board for F. Hoffmann-La Roche Ltd. J.S.W. has served on advisory boards, data monitoring or steering committees, and has consulting agreements from the following entities: AbbVie, Actelion, Alkermes, Bayer HealthCare Pharmaceuticals, Biogen, BioNEST, Celgene, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, GeNeuro SA, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, and Teva Pharmaceuticals; royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation. S.L.H. serves on the board of trustees for Neurona and on scientific advisory boards for Annexon, Bionure, and Symbiotix, and has received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd for CD20-related meetings and presentations. L.K.’s institution, the University Hospital Basel, has received research support and payments that were used exclusively for research support for L.K.’s activities as principal investigator and member or chair of planning and steering committees or advisory boards for trials sponsored by Actelion, Addex, Almirall, Bayer HealthCare Pharmaceuticals, CSL Behring, F. Hoffmann-La Roche Ltd and Genentech, Inc., GeNeuro SA, Genzyme, Merck Serono, Mitsubishi Pharma, Novartis, Octapharma, Ono Pharmaceutical, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and XenoPort; has received license fees for Neurostatus products; and has received research grants from the European Union, Gianni Rubatto Foundation, Novartis Research Foundation, Roche Research Foundation, Swiss Multiple Sclerosis Society, and Swiss National Research Foundation. F.B. is an editorial board member for the publications Brain, European Radiology, Multiple Sclerosis Journal, Neurology, and Radiology; has received consultancy fees from Bayer Schering, Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Janssen Research, Merck Serono, Novartis, Synthon, and Teva; has received grants from the Dutch MS Society (EU-FP7/Horizon 2020); has received payments for developing educational presentations, including service on speaker bureaus, for Biogen and IXICO; and was supported by the NIHR UCLH Biomedical Research Centre. C.B. is a contractor for F. Hoffmann-La Roche Ltd. W.W. is an employee and shareholder of F. Hoffmann-La Roche Ltd. S.B. is an employee and shareholder of F. Hoffmann-La Roche Ltd. D.L.A. has received personal fees for consulting from Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedImmune, Mitsubishi, Novartis, Receptos, and Sanofi-Aventis; grants from Biogen and Novartis; and an equity interest in NeuroRx Research.
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Source: PubMed