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Aguirre Bueno, J. ; Gasteiger, C. ; Hindelang, B. ; Seeger, M. ; Berezhnoi, A. ; Weidenfeld, I. ; Darsow, U.* ; Stiel, A.-C. ; Steimle-Grauer, S.A.* ; Posch, C.* ; Biedermann, T.* ; Ntziachristos, V.

Non-invasive characterization of melanoma depth at single-cell resolution.

J. Eur. Acad. Dermatol. Venereol., DOI: 10.1111/jdv.20811 (2025)
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BACKGROUND: Efficient staging and management of cutaneous melanoma, one of today's deadliest skin cancers, requires non-invasive determination of tumour depth (Breslow depth). However, current imaging technologies lack the necessary contrast or penetration to measure Breslow depth. OBJECTIVES: To determine if raster-scanning optoacoustic mesoscopy (RSOM) can fill this gap in dermatology. METHODS: We used phantoms to optimize RSOM for melanoma imaging and demonstrated its capability to image melanocytes at single-cell resolution in deep tissue. We then compared RSOM's ability to measure Breslow depth against the clinical standard in a pilot study. For the phantoms studies, we compared the ability of an optimized RSOM system to measure the concentration and diameter of single melanoma cells against gold-standard microscopy methods. For the pilot clinical study, we used linear regression to compare RSOM's Breslow depth against the clinical standard, obtaining the goodness of fit (R2) and the p-value. For the pilot clinical study, we imaged nine lesions: 7 superficially spreading melanomas, 1 benign dysplastic nevus and 1 blue nevus. The average age of the patients was 56.2 ± 12.5 years. We also imaged 10 non-lesional skin areas from healthy volunteers. RESULTS: By utilizing ultra-wideband frequency detection and optimized illumination wavelength, we show that RSOM achieves non-invasive imaging of melanoma at the resolution of single melanocytes, penetrating more than 3 mm into the skin. The agreement between RSOM and the standard-of-care histological assessment was R2 = 0.886 (p = 0.0002) for Breslow depth determination. CONCLUSIONS: RSOM provides non-invasive imaging performance that correlates with the Breslow depth determination. Further work is needed to confirm these findings and to test RSOM against other non-invasive methods.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cells ; Imaging ; Melanoma ; Melanoma Classification; Reflectance Confocal Microscopy; High-frequency Ultrasound; Malignant-melanoma; Cutaneous Melanoma; Thickness
ISSN (print) / ISBN 0926-9959
e-ISSN 1468-3083
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Grants HORIZON EUROPE European Innovation Council