Imaging chronic active lesions in multiple sclerosis: a consensus statement

Author:

Bagnato Francesca12ORCID,Sati Pascal3,Hemond Christopher C4,Elliott Colm5ORCID,Gauthier Susan A6ORCID,Harrison Daniel M78,Mainero Caterina9,Oh Jiwon10,Pitt David11,Shinohara Russell T1213,Smith Seth A14,Trapp Bruce15,Azevedo Christina J16,Calabresi Peter A17ORCID,Henry Roland G18,Laule Cornelia19202122,Ontaneda Daniel23ORCID,Rooney William D24,Sicotte Nancy L25,Reich Daniel S26ORCID,Absinta Martina1727ORCID

Affiliation:

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. Department of Neurology, 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 , New York, 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. Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, 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 and 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 and 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, Division of Neuroscience, Institute of Experimental Neurology, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute , Milan, 20132 , Italy

Abstract

Abstract Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and T2-weighted 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.

Funder

Conrad N. Hilton Foundation

Cariplo Foundation

Fondazione Regionale per la Ricerca Biomedica Early Career Award

NMSS Society

International Progressive MS Alliance

National MS Society

National Institutes of Health

Veterans Health Administration

Voros Innovation Impact Funds

Principia

Myelin Repair Foundation

NIH-NINDS

Department of Defense

National Center for Advancing Translational Sciences

Atara

Natural Sciences and Engineering Research Council of Canada

Craig H. Neilsen Foundation

International Collaboration on Repair Discoveries

Roche-Genentech

MS Society of Canada

Brain Canada

Patient Centered Outcomes Research Institute

Intramural Research Program of NIH-NINDS

Erwin Rautenberg Foundation

Publisher

Oxford University Press (OUP)

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