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Ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) offers unprecedented non-invasive visualization of tissue microvasculature, achieving three-dimensional (3D) resolution in the 10\u201330 micrometer range (axial, lateral). Nevertheless, the lack of availability of suitable multi-wavelength illumination sources has generally limited RSOM to single-wavelength studies of microvasculature morphology. Herein, we present a dual-wavelength ultra-wideband RSOM (DW RSOM) system for dynamic mapping of cutaneous microvascular oxygenation by integrating two diode-pumped solid-state lasers at 515\u2009nm and 532\u2009nm. The system was evaluated on healthy volunteers during post-occlusive reactive hyperemia (PORH) tests on the forearm and proximal nailfold (DRKS00037749 registered on 26th August 2025 on the German Clinical Trials Register). The system recorded 3D oxygenation changes, including ischemic decline, hyperemic overshoot, and recovery, consistent with invasive blood gas analyzer (BGA) measurements. Extracted parameters, such as oxygenation gradients and recovery times, correlated with expected vascular reactivity metrics. These findings validate DW RSOM as a portable prototype for the in vivo assessment of microvascular oxygenation in humans at a single microvessel level. By providing quantitative, layer-resolved imaging of skin microcirculation, DW RSOM offers a promising platform for extending single-wavelength RSOM to studying microvascular dysfunction and supports future clinical translation of optoacoustic technologies toward bedside vascular diagnostics.<\/jats:p>","DOI":"10.1038\/s44303-026-00184-5","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T06:25:31Z","timestamp":1783664731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recording skin oxygenation by dual-wavelength ultra-wideband optoacoustic mesoscopy"],"prefix":"10.1038","volume":"4","author":[{"given":"Juan","family":"Aguirre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Berezhnoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Hindelang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Gasteiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Darsow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilo","family":"Biedermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Ntziachristos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"184_CR1","doi-asserted-by":"publisher","first-page":"e12673","DOI":"10.1111\/micc.12673","volume":"28","author":"TK Roy","year":"2021","unstructured":"Roy, T. 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V.N. serves as a Guest Editor for the collection \u201cAdvances in Optoacoustic Imaging\u201d in npj Imaging, but was not involved in the journal\u2019s review of, or decisions related to, this manuscript. The other authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"51"}}