{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T15:59:28Z","timestamp":1782748768823,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Hypoperfusion and tissue hypoxia have been implicated as contributory mechanisms in the neuropathology of multiple sclerosis (MS). Our objective has been to study cortical oxygenation <jats:italic>in vivo<\/jats:italic> in patients with MS and age\u2010matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A custom, multiwavelength time\u2010domain near\u2010infrared spectroscopy system was developed for assessing tissue hypoxia from the prefrontal cortex. A cross\u2010sectional case\u2013control study was undertaken assessing patients with secondary progressive MS (SPMS) and age\u2010matched controls. Co\u2010registered magnetic resonance imaging was used to verify the location from which near\u2010infrared spectroscopy data were obtained through Monte Carlo simulations of photon propagation. Additional clinical assessments of MS disease severity were carried out by trained neurologists. Linear mixed effect models were used to compare cortical oxygenation between cases and controls, and against measures of MS severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010three patients with secondary progressive MS (median expanded disability status scale 6 [IQR: 5\u20136.5]; median age 53.0 [IQR: 49\u201358]) and 20 age\u2010matched controls were recruited. Modeling of photon propagation confirmed spectroscopy data were obtained from the prefrontal cortex. Patients with SPMS had significantly lower cortical hemoglobin oxygenation compared with controls (\u22126.0% [95% CI: \u221210.0 to \u22121.9], <jats:italic>P<\/jats:italic>\u2009=\u20090.004). There were no significant associations between cortical oxygenation and MS severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Using an advanced, multiwavelength time\u2010domain near\u2010infrared spectroscopy system, we demonstrate that patients with SPMS have lower cortical oxygenation compared with controls.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52150","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T13:08:55Z","timestamp":1721653735000},"page":"2372-2381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating cortical hypoxia in multiple sclerosis via time\u2010domain near\u2010infrared spectroscopy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-0177","authenticated-orcid":false,"given":"Thomas","family":"Williams","sequence":"first","affiliation":[{"name":"UCL Queen Square 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