In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis

Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis...

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Main Authors: Maxime Donadieu, Nathanael J Lee, María I Gaitán, Seung-Kwon Ha, Nicholas J Luciano, Snehashis Roy, Benjamin Ineichen, Emily C Leibovitch, Cecil C Yen, Dzung L Pham, Afonso C Silva, Mac Johnson, Steve Jacobson, Pascal Sati, Daniel S Reich
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-04-01
Series:eLife
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Online Access:https://elifesciences.org/articles/73786
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author Maxime Donadieu
Nathanael J Lee
María I Gaitán
Seung-Kwon Ha
Nicholas J Luciano
Snehashis Roy
Benjamin Ineichen
Emily C Leibovitch
Cecil C Yen
Dzung L Pham
Afonso C Silva
Mac Johnson
Steve Jacobson
Pascal Sati
Daniel S Reich
author_facet Maxime Donadieu
Nathanael J Lee
María I Gaitán
Seung-Kwon Ha
Nicholas J Luciano
Snehashis Roy
Benjamin Ineichen
Emily C Leibovitch
Cecil C Yen
Dzung L Pham
Afonso C Silva
Mac Johnson
Steve Jacobson
Pascal Sati
Daniel S Reich
author_sort Maxime Donadieu
collection DOAJ
description Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents.
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spelling doaj.art-82b3b20c13e342e28b70423fafd616cb2023-05-10T15:56:48ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.73786In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosisMaxime Donadieu0https://orcid.org/0009-0003-7349-1648Nathanael J Lee1María I Gaitán2Seung-Kwon Ha3Nicholas J Luciano4Snehashis Roy5Benjamin Ineichen6Emily C Leibovitch7Cecil C Yen8Dzung L Pham9Afonso C Silva10Mac Johnson11Steve Jacobson12https://orcid.org/0000-0003-3127-1287Pascal Sati13https://orcid.org/0000-0002-6763-0125Daniel S Reich14https://orcid.org/0000-0002-2628-4334Translational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States; Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States; Department of Neurobiology, University of Pittsburgh, Pittsburgh, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesSection on Neural Function, National Institute of Mental Health, National Institutes of Health, Bethesda, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States; Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Switzerland, SwitzerlandViral Immunology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesCerebral Microcirculation Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesDepartment of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, United StatesDepartment of Neurobiology, University of Pittsburgh, Pittsburgh, United States; Cerebral Microcirculation Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesVertex Pharmaceuticals Incorporated, Boston, United StatesViral Immunology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States; Neuroimaging Program, Department of Neurology, Cedars Sinai, Los Angeles, United StatesTranslational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United StatesRemyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents.https://elifesciences.org/articles/73786marmosetEAEMRIremyelinationprimatehistopathology
spellingShingle Maxime Donadieu
Nathanael J Lee
María I Gaitán
Seung-Kwon Ha
Nicholas J Luciano
Snehashis Roy
Benjamin Ineichen
Emily C Leibovitch
Cecil C Yen
Dzung L Pham
Afonso C Silva
Mac Johnson
Steve Jacobson
Pascal Sati
Daniel S Reich
In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
eLife
marmoset
EAE
MRI
remyelination
primate
histopathology
title In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
title_full In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
title_fullStr In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
title_full_unstemmed In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
title_short In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
title_sort in vivo mri is sensitive to remyelination in a nonhuman primate model of multiple sclerosis
topic marmoset
EAE
MRI
remyelination
primate
histopathology
url https://elifesciences.org/articles/73786
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