Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesi...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12634 |
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| author | Marije J. D. Huitema Eva M. M. Strijbis Antonio Luchicchi John G. J. M. Bol Jason R. Plemel Jeroen J. G. Geurts Geert J. Schenk |
| author_facet | Marije J. D. Huitema Eva M. M. Strijbis Antonio Luchicchi John G. J. M. Bol Jason R. Plemel Jeroen J. G. Geurts Geert J. Schenk |
| author_sort | Marije J. D. Huitema |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to present and validate a novel standardized method for myelin quantification in progressive MS brains to study myelin content more precisely. Fifty-five MS lesions in 32 tissue blocks from 14 progressive MS cases and five tissue blocks from 5 non-neurological controls were sampled. MS lesions were selected by macroscopic investigation of WM by standard histopathological methods. Tissue sections were stained for myelin with luxol fast blue (LFB) and histological assessment of de- or remyelination was performed by light microscopy. The myelin quantity was estimated with a novel myelin quantification method (MQM) in ImageJ. Three independent raters applied the MQM and the inter-rater reliability was calculated. We extended the method to diffusely appearing white matter (DAWM) and encephalitis to test potential wider applicability of the method. Inter-rater agreement was excellent (ICC = 0.96) and there was a high reliability with a lower- and upper limit of agreement up to −5.93% to 18.43% variation in myelin quantity. This study builds on the established concepts of histopathological semi-quantitative assessment of myelin and adds a novel, reliable and accurate quantitative measurement tool for the assessment of myelination in human post-mortem samples. |
| first_indexed | 2024-03-10T04:53:47Z |
| format | Article |
| id | doaj.art-f07d33eac83f4e9891790b06aca0a9e2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:47Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f07d33eac83f4e9891790b06aca0a9e22023-11-23T02:25:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231263410.3390/ijms222312634Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying RemyelinationMarije J. D. Huitema0Eva M. M. Strijbis1Antonio Luchicchi2John G. J. M. Bol3Jason R. Plemel4Jeroen J. G. Geurts5Geert J. Schenk6Department of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1108, 1081 HV Amsterdam, The NetherlandsDepartment of Neurology, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, 1081 HZ Amsterdam, The NetherlandsDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1108, 1081 HV Amsterdam, The NetherlandsDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1108, 1081 HV Amsterdam, The NetherlandsDepartment of Medicine, Division of Neurology, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2S2, CanadaDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1108, 1081 HV Amsterdam, The NetherlandsDepartment of Anatomy and Neurosciences, Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, VU University Medical Center, De Boelelaan 1108, 1081 HV Amsterdam, The NetherlandsMultiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system (CNS). Repair through remyelination can be extensive, but quantification of remyelination remains challenging. To date, no method for standardized digital quantification of remyelination of MS lesions exists. This methodological study aims to present and validate a novel standardized method for myelin quantification in progressive MS brains to study myelin content more precisely. Fifty-five MS lesions in 32 tissue blocks from 14 progressive MS cases and five tissue blocks from 5 non-neurological controls were sampled. MS lesions were selected by macroscopic investigation of WM by standard histopathological methods. Tissue sections were stained for myelin with luxol fast blue (LFB) and histological assessment of de- or remyelination was performed by light microscopy. The myelin quantity was estimated with a novel myelin quantification method (MQM) in ImageJ. Three independent raters applied the MQM and the inter-rater reliability was calculated. We extended the method to diffusely appearing white matter (DAWM) and encephalitis to test potential wider applicability of the method. Inter-rater agreement was excellent (ICC = 0.96) and there was a high reliability with a lower- and upper limit of agreement up to −5.93% to 18.43% variation in myelin quantity. This study builds on the established concepts of histopathological semi-quantitative assessment of myelin and adds a novel, reliable and accurate quantitative measurement tool for the assessment of myelination in human post-mortem samples.https://www.mdpi.com/1422-0067/22/23/12634multiple sclerosisremyelinationdemyelinationmyelin quantificationrepair |
| spellingShingle | Marije J. D. Huitema Eva M. M. Strijbis Antonio Luchicchi John G. J. M. Bol Jason R. Plemel Jeroen J. G. Geurts Geert J. Schenk Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination International Journal of Molecular Sciences multiple sclerosis remyelination demyelination myelin quantification repair |
| title | Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination |
| title_full | Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination |
| title_fullStr | Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination |
| title_full_unstemmed | Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination |
| title_short | Myelin Quantification in White Matter Pathology of Progressive Multiple Sclerosis Post-Mortem Brain Samples: A New Approach for Quantifying Remyelination |
| title_sort | myelin quantification in white matter pathology of progressive multiple sclerosis post mortem brain samples a new approach for quantifying remyelination |
| topic | multiple sclerosis remyelination demyelination myelin quantification repair |
| url | https://www.mdpi.com/1422-0067/22/23/12634 |
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