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The method was validated by dermatologist\u2010approved confident delineations of only definitely affected and definitely unaffected areas in photographs. A prototype hyperspectral imaging system acquired a 2.5\u2009\u00d7\u20093.5\u2009cm<jats:sup>2<\/jats:sup> area of skin at 120 wavelengths in the 450\u2013850\u2009nm range. Unsupervised extraction of unknown absorbers by endmember analysis achieved a comparable accuracy to that of supervised extraction of known absorbers (melanin, hemoglobin) by chromophore mapping: 0.78 (IQR: 0.39\u20130.85) vs. 0.83 (0.53\u20130.91) to delineate erythema and 0.74 (0.57\u20130.87) vs. 0.73 (0.52\u20130.84) to delineate hyperpigmentation. Both algorithms achieved higher specificity than sensitivity. Whereas a trained human confidently marked a median of 7% of image pixels, unsupervised and supervised algorithms delineated a median of 14% and 27% pixels. Hyperspectral imaging could overcome a fundamental practice gap of distinguishing active from inactive manifestations of inflammatory skin disease.<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio202300009-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.202300009","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T08:18:48Z","timestamp":1679386728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hyperspectral imaging to accurately segment skin erythema and hyperpigmentation in cutaneous chronic graft\u2010versus\u2010host disease"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-5485","authenticated-orcid":false,"given":"Inga","family":"Saknite","sequence":"first","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Biophotonics Laboratory, Institute of Atomic Physics and Spectroscopy, University of Latvia  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinwho","family":"Kwun","sequence":"additional","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Hood","sequence":"additional","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9609-5731","authenticated-orcid":false,"given":"Fuyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Kangas","sequence":"additional","affiliation":[{"name":"Revenio Group  Vantaa Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirjo","family":"Kortteisto","sequence":"additional","affiliation":[{"name":"Revenio Group  Vantaa Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Kukkonen","sequence":"additional","affiliation":[{"name":"Revenio Group  Vantaa Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3000-4486","authenticated-orcid":false,"given":"Janis","family":"Spigulis","sequence":"additional","affiliation":[{"name":"Biophotonics Laboratory, Institute of Atomic Physics and Spectroscopy, University of Latvia  Riga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-4740","authenticated-orcid":false,"given":"Eric R.","family":"Tkaczyk","sequence":"additional","affiliation":[{"name":"Vanderbilt Dermatology Translational Research Clinic, Department of Dermatology Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"},{"name":"Vanderbilt\u2010Ingram Cancer Center  Nashville Tennessee USA"},{"name":"Dermatology Service and Research Service, Department of Veterans Affairs Tennessee Valley Healthcare System  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-31485-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000323274"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2019.0977"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18730"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(83)70131-3"},{"key":"e_1_2_8_7_1","first-page":"187","volume":"8","author":"Fistarol S. 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