{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T22:54:03Z","timestamp":1787352843602,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK Multiple Sclerosis Society","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"UK Multiple Sclerosis Society","award":["207495"],"award-info":[{"award-number":["207495"]}]},{"name":"Research Wales Innovation Fund","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"Research Wales Innovation Fund","award":["207495"],"award-info":[{"award-number":["207495"]}]},{"name":"Swansea University Research Excellence Scholarship (SURES)","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"Swansea University Research Excellence Scholarship (SURES)","award":["207495"],"award-info":[{"award-number":["207495"]}]},{"name":"BRAIN Unit Infrastructure Award","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"BRAIN Unit Infrastructure Award","award":["207495"],"award-info":[{"award-number":["207495"]}]},{"name":"Multiple Sclerosis Society of Great Britain","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"Multiple Sclerosis Society of Great Britain","award":["207495"],"award-info":[{"award-number":["207495"]}]},{"name":"Northern Ireland reg.charity","award":["UA05"],"award-info":[{"award-number":["UA05"]}]},{"name":"Northern Ireland reg.charity","award":["207495"],"award-info":[{"award-number":["207495"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. Aims: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropathological features in an autopsy cohort of progressive MS. Methods: Sequential sections of frontal, cingulate and occipital cortex, thalamus, brain stem (pons) and cerebellum including dentate nucleus (n = 35 progressive MS, females = 28, males = 7; age died = 53.5 years; range 38\u201398 years) were immunostained for myelin (anti-MOG), neurons (anti-HuC\/D) and microglia\/macrophages (anti-HLA). The extent of demyelination, neurodegeneration, the presence of active and\/or chronic active lesions and quantification of brain and leptomeningeal inflammation was captured by digital pathology. Results: Digital analysis of tissue sections revealed the variable extent of pathology that characterises progressive MS. Microglia\/macrophage activation, if found at a higher level in a single block, was typically elevated across all sampled blocks. Compartmentalised (perivascular\/leptomeningeal) inflammation was associated with age-related measures of disease severity and an earlier death. Conclusion: Digital pathology identified prognostically important clinicopathological correlations in MS. This methodology can be used to prioritise the principal pathological processes that need to be captured by future MS biomarkers.<\/jats:p>","DOI":"10.3390\/cells13121020","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T11:58:58Z","timestamp":1718107138000},"page":"1020","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes"],"prefix":"10.3390","volume":"13","author":[{"given":"Benjamin","family":"Cooze","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Neal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alka","family":"Vineed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4908-2360","authenticated-orcid":false,"given":"J. C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. H.","family":"Allen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-1368","authenticated-orcid":false,"given":"Kristen","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7118-7111","authenticated-orcid":false,"given":"Htoo","family":"Yadanar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisjanis","family":"Gerhards","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Farkas","sequence":"additional","affiliation":[{"name":"Division of Brain Sciences, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4622-4694","authenticated-orcid":false,"given":"Richard","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Division of Brain Sciences, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-9157","authenticated-orcid":false,"given":"Owain","family":"Howell","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Health & Life and Health Sciences, Swansea University, Swansea SA2 8PP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q","article-title":"Heterogeneity of Multiple Sclerosis Lesions: Implications for the Pathogenesis of Demyelination","volume":"47","author":"Lucchinetti","year":"2000","journal-title":"Ann. 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