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With the Clustering for Anatomical Quantification and Evaluation (CAQE) framework, quantitative MRI measures can be used to classify tissue based only on microstructural features with no spatial enforcement, and pathological changes in disease can be evaluated. In this study, maps of whole-brain myelin water fraction, microscopic fractional anisotropy, and tissue heterogeneity were used to classify brain tissue in 25 healthy participants. CAQE was then applied to 25 participants with multiple sclerosis (MS), where tissue classifications indicated areas of increased demyelination and axonal injury in white matter compared with a healthy average tissue classification. Severity scores were derived from tissue classifications to quantify diffuse white matter damage, and correlated significantly with cognitive ability in MS. The CAQE framework can be adapted for other applications and extended to use different quantitative MRI measures.<\/jats:p>","DOI":"10.1162\/imag_a_00526","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T20:01:13Z","timestamp":1742328073000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":2,"title":["Microstructure-informed brain tissue classification using clustering of quantitative MRI measures"],"prefix":"10.1162","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-8488","authenticated-orcid":false,"given":"Sharada","family":"Balaji","sequence":"first","affiliation":[{"name":"Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Obajtek","sequence":"additional","affiliation":[{"name":"Physics and Astronomy, University of British Columbia, 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