Fast raster-scan optoacoustic mesoscopy enables assessment of human melanoma microvasculature in vivo

The development and progression of melanoma tumors is associated with angiogenesis, manifesting as changes in vessel density, morphology, and architecture that may extend through the entire skin depth. Three-dimensional imaging of vascular characteristics in skin lesions could allow diagnostic insights not available to the conventional visual inspection. Raster-scan optoacoustic mesoscopy (RSOM) has emerged as a unique modality to image microvasculature through the entire skin depth with resolutions of tens of micrometers, offering new possibilities to assess angiogenetic processes. However, current RSOM implementations are slow, exacerbating motion artifacts and reducing image quality, particularly when imaging melanoma lesions that often appear on the upper torso where breathing motion is strongest. To visualize for the first time melanoma vasculature in humans, in high-resolution, we accelerated RSOM scanning using an illumination scheme that is co-axial with a high-sensitivity ultrasound detector path, yielding 15 second single-breath-hold scans that minimize motion artifacts. Applied to 10 melanomas and 10 benign nevi in humans, we demonstrate visualization of microvasculature with performance never before shown in vivo. We show marked differences between malignant and benign lesions, supporting the possibility to use vasculature as a biomarker for lesion characterization. The study points to promising clinical potential for Fast-RSOM (FRSOM) as a three dimensional visualization method that can enable the complete assessment of microvascular parameters of melanoma and improve diagnostics.