{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:54:38Z","timestamp":1784865278923,"version":"3.55.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01NS112161-01"],"award-info":[{"award-number":["1R01NS112161-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["428223038"],"award-info":[{"award-number":["428223038"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Conventional brain magnetic resonance imaging (MRI) produces image intensities that have an arbitrary scale, hampering quantification. Intensity scaling aims to overcome this shortfall. As neurodegenerative and inflammatory disorders may affect all brain compartments, reference regions within the brain may be misleading. Here we summarize approaches for intensity scaling of conventional T1-weighted (w) and T2w brain MRI avoiding reference regions within the brain.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Literature was searched in the databases of Scopus, PubMed, and Web of Science. We included only studies that avoided reference regions within the brain for intensity scaling and provided validating evidence, which we divided into four categories: 1) comparative variance reduction, 2) comparative correlation with clinical parameters, 3) relation to quantitative imaging, or 4) relation to histology.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of the 3825 studies screened, 24 fulfilled the inclusion criteria. Three studies used scaled T1w images, 2 scaled T2w images, and 21 T1w\/T2w-ratio calculation (with double counts). A robust reduction in variance was reported. Twenty studies investigated the relation of scaled intensities to different types of quantitative imaging. Statistically significant correlations with clinical or demographic data were reported in 8 studies. Four studies reporting the relation to histology gave no clear picture of the main signal driver of conventional T1w and T2w MRI sequences.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>T1w\/T2w-ratio calculation was applied most often. Variance reduction and correlations with other measures suggest a biologically meaningful signal harmonization. However, there are open methodological questions and uncertainty on its biological underpinning. Validation evidence on other scaling methods is even sparser.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0298642","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T17:26:13Z","timestamp":1710437173000},"page":"e0298642","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intensity scaling of conventional brain magnetic resonance images avoiding cerebral reference regions: A systematic review"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-3641","authenticated-orcid":true,"given":"Tun","family":"Wiltgen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuici","family":"Voon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koen","family":"Van Leemput","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Wiestler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"M\u00fchlau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"3","key":"pone.0298642.ref001","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.nic.2019.03.007","article-title":"MR Imaging of Normal Brain Development","volume":"29","author":"M. 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