Quantitative magnetic resonance imaging reflects different levels of histologically determined myelin densities in multiple sclerosis, including remyelination in inactive multiple sclerosis lesions.
MRI
MTR
histopathology
iron
multiple sclerosis
remyelination
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
05
05
2022
accepted:
16
11
2022
medline:
23
10
2023
pubmed:
1
2
2023
entrez:
31
1
2023
Statut:
ppublish
Résumé
Magnetic resonance imaging (MRI) of focal or diffuse myelin damage or remyelination may provide important insights into disease progression and potential treatment efficacy in multiple sclerosis (MS). We performed post-mortem MRI and histopathological myelin measurements in seven progressive MS cases to evaluate the ability of three myelin-sensitive MRI scans to distinguish different stages of MS pathology, particularly chronic demyelinated and remyelinated lesions. At 3 Tesla, we acquired two different myelin water imaging (MWI) scans and magnetisation transfer ratio (MTR) data. Histopathology included histochemical stainings for myelin phospholipids (LFB) and iron as well as immunohistochemistry for myelin proteolipid protein (PLP), CD68 (phagocytosing microglia/macrophages) and BCAS1 (remyelinating oligodendrocytes). Mixed-effects modelling determined which histopathological metric best predicted MWF and MTR in normal-appearing and diffusely abnormal white matter, active/inactive, inactive, remyelinated and ischemic lesions. Both MWI measures correlated well with each other and histology across regions, reflecting the different stages of MS pathology. MTR data showed a considerable influence of components other than myelin and a strong dependency on tissue storage duration. Both MRI and histology revealed increased myelin densities in inactive compared with active/inactive lesions. Chronic inactive lesions harboured single scattered myelin fibres indicative of low-level remyelination. Mixed-effects modelling showed that smaller differences between white matter areas were linked to PLP densities and only to a small extent confounded by iron. MWI reflects differences in myelin lipids and proteins across various levels of myelin densities encountered in MS, including low-level remyelination in chronic inactive lesions.
Identifiants
pubmed: 36720269
doi: 10.1111/bpa.13150
pmc: PMC10580011
doi:
Substances chimiques
Iron
E1UOL152H7
BCAS1 protein, human
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13150Subventions
Organisme : CIHR
ID : RN382474-418628
Pays : Canada
Informations de copyright
© 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
Références
Neuroimage. 2017 Feb 15;147:253-261
pubmed: 27986605
Magn Reson Med. 2000 Nov;44(5):799-802
pubmed: 11064415
Magn Reson Med. 1997 Jan;37(1):34-43
pubmed: 8978630
Ann Neurol. 2022 Sep;92(3):486-502
pubmed: 35713309
Acta Neuropathol. 2020 Nov;140(5):715-736
pubmed: 32894330
Hum Brain Mapp. 2017 Apr;38(4):1780-1790
pubmed: 28009069
J Med Imaging (Bellingham). 2014 Jul;1(2):024003
pubmed: 26158035
PLoS One. 2018 Mar 21;13(3):e0193839
pubmed: 29561895
Neurology. 2019 Mar 12;92(11):519-533
pubmed: 30787160
J Magn Reson Imaging. 2011 Mar;33(3):713-8
pubmed: 21563257
Magn Reson Med. 2015 Jan;73(1):70-81
pubmed: 24604728
Neuroimage. 2018 Nov 15;182:511-521
pubmed: 28025129
Magn Reson Med. 2017 Jul;78(1):49-57
pubmed: 27416957
J Clin Invest. 2016 Jul 1;126(7):2597-609
pubmed: 27270171
Neuroimage. 2019 Jul 15;195:78-88
pubmed: 30930311
Front Neurol. 2021 Dec 21;12:632749
pubmed: 34992573
AJNR Am J Neuroradiol. 2003 Nov-Dec;24(10):1935-40
pubmed: 14625213
Ann Neurol. 2020 May;87(5):710-724
pubmed: 32057118
Magn Reson Med. 2012 Jun;67(6):1803-14
pubmed: 22012743
Arch Histol Cytol. 2008 Dec;71(4):205-22
pubmed: 19359804
J Neuroimaging. 2021 Nov;31(6):1119-1125
pubmed: 34310789
Neuroimage. 2012 Oct 15;63(1):533-9
pubmed: 22776448
Brain. 2006 Dec;129(Pt 12):3165-72
pubmed: 16921173
AJNR Am J Neuroradiol. 2018 Apr;39(4):634-641
pubmed: 29472299
Neurology. 2021 Aug 10;97(6):e543-e553
pubmed: 34088875
Magn Reson Med. 2008 Feb;59(2):268-77
pubmed: 18228601
Acta Neuropathol. 2017 Jan;133(1):25-42
pubmed: 27796537
Magn Reson Med. 2012 Mar;67(3):614-21
pubmed: 22344579
Magn Reson Med. 1994 Jun;31(6):673-7
pubmed: 8057820
Brain Pathol. 2023 Nov;33(6):e13150
pubmed: 36720269
Nature. 2019 Feb;566(7745):538-542
pubmed: 30675058
NMR Biomed. 2020 Dec;33(12):e4277
pubmed: 32124505
NMR Biomed. 2017 Apr;30(4):
pubmed: 27060968
NMR Biomed. 2016 Apr;29(4):458-65
pubmed: 26835664
Neuroimage. 2007 Jul 15;36(4):1152-8
pubmed: 17543541
Magn Reson Med. 2015 Nov;74(5):1327-35
pubmed: 25399771
Magn Reson Med. 2010 Jul;64(1):177-85
pubmed: 20572139
Magn Reson Med. 2020 Sep;84(3):1264-1279
pubmed: 32065474
Sci Transl Med. 2017 Dec 6;9(419):
pubmed: 29212715
J Neuropathol Exp Neurol. 2013 Jan;72(1):42-52
pubmed: 23242281
AJNR Am J Neuroradiol. 2020 Mar;41(3):461-463
pubmed: 32139431
Brain. 2017 Jul 1;140(7):1900-1913
pubmed: 28541408
Ann Neurol. 2012 Dec;72(6):918-26
pubmed: 23076662
Ann Neurol. 2013 Dec;74(6):848-61
pubmed: 23868451
Neuroimage. 2019 Oct 1;199:545-552
pubmed: 31108214
Acta Neuropathol. 2020 Sep;140(3):359-375
pubmed: 32710244
Mult Scler. 2006 Dec;12(6):747-53
pubmed: 17263002
Radiology. 1996 Apr;199(1):219-26
pubmed: 8633148
Neuroimage. 2017 Jun;153:122-130
pubmed: 28377211
J Magn Reson Imaging. 2007 Jul;26(1):41-51
pubmed: 17659567
Neuroimage. 2002 Oct;17(2):825-41
pubmed: 12377157
Neuroimage. 2020 Oct 15;220:117080
pubmed: 32585344
Ann Neurol. 2004 Sep;56(3):407-15
pubmed: 15349868
Acta Neuropathol Commun. 2020 Jul 29;8(1):120
pubmed: 32727582
Magn Reson Med. 2009 Jul;62(1):106-15
pubmed: 19353659
J Magn Reson Imaging. 2000 Jun;11(6):586-95
pubmed: 10862056
Neurol Sci. 2001 Apr;22(2):141-4
pubmed: 11603615
Am J Pathol. 2000 Jul;157(1):267-76
pubmed: 10880396
Magn Reson Med. 2022 May;87(5):2329-2346
pubmed: 35001427
Neurology. 2009 Jun 2;72(22):1914-21
pubmed: 19487649
Neuroimage. 2012 Jan 16;59(2):1413-9
pubmed: 21893208
Neuroimage Clin. 2022;36:103177
pubmed: 36067611
Neuroimage. 2015 Oct 15;120:345-9
pubmed: 26172308
Curr Opin Neurol. 2016 Jun;29(3):286-92
pubmed: 27035897
Cell Stem Cell. 2019 Oct 3;25(4):473-485.e8
pubmed: 31585093
Brain. 2021 Apr 12;144(3):833-847
pubmed: 33484118
Brain. 2011 Dec;134(Pt 12):3602-15
pubmed: 22171355
Magn Reson Med. 2008 Dec;60(6):1396-407
pubmed: 19025906
AJNR Am J Neuroradiol. 2018 Feb;39(2):303-310
pubmed: 29242359