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Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis

BACKGROUND: Multiple Sclerosis (MS) lesions are pathologically heterogeneous and the temporal behavior in terms of growth and myelination status of individual lesions is highly variable, especially in the early phase of the disease. Thus, monitoring the development of individual lesion myelination b...

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Autores principales: Kitzler, Hagen H., Wahl, Hannes, Kuntke, Paul, Deoni, Sean C.L., Ziemssen, Tjalf, Linn, Jennifer, Köhler, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668603/
https://www.ncbi.nlm.nih.gov/pubmed/36162236
http://dx.doi.org/10.1016/j.nicl.2022.103192
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author Kitzler, Hagen H.
Wahl, Hannes
Kuntke, Paul
Deoni, Sean C.L.
Ziemssen, Tjalf
Linn, Jennifer
Köhler, Caroline
author_facet Kitzler, Hagen H.
Wahl, Hannes
Kuntke, Paul
Deoni, Sean C.L.
Ziemssen, Tjalf
Linn, Jennifer
Köhler, Caroline
author_sort Kitzler, Hagen H.
collection PubMed
description BACKGROUND: Multiple Sclerosis (MS) lesions are pathologically heterogeneous and the temporal behavior in terms of growth and myelination status of individual lesions is highly variable, especially in the early phase of the disease. Thus, monitoring the development of individual lesion myelination by using quantitative magnetic resonance myelin water imaging (MWI) could be valuable to capture the variability of disease pathology and get an individual insight into the subclinical disease activity. OBJECTIVE: The goal of this work was (1) to observe the variation and longitudinal change of in vivo lesion myelination by means of MWI and its parameter Myelin Water Fraction (MWF), and, (2) to identify individual lesion myelination patterns in early MS. METHODS: In this study n = 12 patients obtained conventional MRI and quantitative MWI derived from multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) within four weeks after presenting a clinically isolated syndrome and remained within the study if clinically definitive MS was diagnosed within the 12 months study period. Four MRI sessions were acquired at baseline, 3, 6, and 12 months. The short-term and long-term variability of MWF maps was evaluated by scan-rescan measures and the coefficient of variation was determined in four healthy controls. Tracking of individual lesions was performed using the Automatic Follow-up of Individual Lesions (AFIL) algorithm. Lesion volume and MWF were evaluated for every individual lesion in all patients. Median lesion MWF change was used to define lesion categories as decreasing, varying, increasing and invariant for MWF variation. RESULTS: In total n = 386 T2 lesions were detected with a subset of n = 225 permanent lesions present at all four time-points. Among those, a heterogeneous lesion MWF reduction was found, with the majority of lesions bearing only mild MWF reduction, approximately a third with an intermediate MWF decrease and highest MWF reduction in acute-inflammatory active lesions. A moderate negative correlation was determined between individual lesion volumes and median MWF consistent across all time-points. Permanent lesions featured variable temporal dynamics with the majority of varying MWF (58 %), however decreasing (16 %), increasing (15 %) and invariant (11 %) subgroups could be identified resembling demyelinating activity and post-demyelinating inactivity known from histopathology studies. Inflammatory-active enhancing lesions showed a distinct pattern of MWF reduction followed by partial recovery after 3 months. This was similar in new enhancing lesions and those with a non-enhancing precursor lesion. CONCLUSION: This work provides in vivo evidence for an individual evolution of early demyelinated MS lesions measured by means of MWF imaging. Our results support the hypothesis, that MS lesions undergo multiple demyelination and remyelination episodes in the early acute phase. The in vivo MRI surrogate of myelin turnover bears capacity as a novel biomarker to select and potentially monitor personalized MS treatment.
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spelling pubmed-96686032022-11-17 Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis Kitzler, Hagen H. Wahl, Hannes Kuntke, Paul Deoni, Sean C.L. Ziemssen, Tjalf Linn, Jennifer Köhler, Caroline Neuroimage Clin Regular Article BACKGROUND: Multiple Sclerosis (MS) lesions are pathologically heterogeneous and the temporal behavior in terms of growth and myelination status of individual lesions is highly variable, especially in the early phase of the disease. Thus, monitoring the development of individual lesion myelination by using quantitative magnetic resonance myelin water imaging (MWI) could be valuable to capture the variability of disease pathology and get an individual insight into the subclinical disease activity. OBJECTIVE: The goal of this work was (1) to observe the variation and longitudinal change of in vivo lesion myelination by means of MWI and its parameter Myelin Water Fraction (MWF), and, (2) to identify individual lesion myelination patterns in early MS. METHODS: In this study n = 12 patients obtained conventional MRI and quantitative MWI derived from multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) within four weeks after presenting a clinically isolated syndrome and remained within the study if clinically definitive MS was diagnosed within the 12 months study period. Four MRI sessions were acquired at baseline, 3, 6, and 12 months. The short-term and long-term variability of MWF maps was evaluated by scan-rescan measures and the coefficient of variation was determined in four healthy controls. Tracking of individual lesions was performed using the Automatic Follow-up of Individual Lesions (AFIL) algorithm. Lesion volume and MWF were evaluated for every individual lesion in all patients. Median lesion MWF change was used to define lesion categories as decreasing, varying, increasing and invariant for MWF variation. RESULTS: In total n = 386 T2 lesions were detected with a subset of n = 225 permanent lesions present at all four time-points. Among those, a heterogeneous lesion MWF reduction was found, with the majority of lesions bearing only mild MWF reduction, approximately a third with an intermediate MWF decrease and highest MWF reduction in acute-inflammatory active lesions. A moderate negative correlation was determined between individual lesion volumes and median MWF consistent across all time-points. Permanent lesions featured variable temporal dynamics with the majority of varying MWF (58 %), however decreasing (16 %), increasing (15 %) and invariant (11 %) subgroups could be identified resembling demyelinating activity and post-demyelinating inactivity known from histopathology studies. Inflammatory-active enhancing lesions showed a distinct pattern of MWF reduction followed by partial recovery after 3 months. This was similar in new enhancing lesions and those with a non-enhancing precursor lesion. CONCLUSION: This work provides in vivo evidence for an individual evolution of early demyelinated MS lesions measured by means of MWF imaging. Our results support the hypothesis, that MS lesions undergo multiple demyelination and remyelination episodes in the early acute phase. The in vivo MRI surrogate of myelin turnover bears capacity as a novel biomarker to select and potentially monitor personalized MS treatment. Elsevier 2022-09-15 /pmc/articles/PMC9668603/ /pubmed/36162236 http://dx.doi.org/10.1016/j.nicl.2022.103192 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Kitzler, Hagen H.
Wahl, Hannes
Kuntke, Paul
Deoni, Sean C.L.
Ziemssen, Tjalf
Linn, Jennifer
Köhler, Caroline
Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title_full Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title_fullStr Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title_full_unstemmed Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title_short Exploring in vivo lesion myelination dynamics: Longitudinal Myelin Water Imaging in early Multiple Sclerosis
title_sort exploring in vivo lesion myelination dynamics: longitudinal myelin water imaging in early multiple sclerosis
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668603/
https://www.ncbi.nlm.nih.gov/pubmed/36162236
http://dx.doi.org/10.1016/j.nicl.2022.103192
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