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

Abstract

Melanoma is associated with angiogenesis and vascular changes that may extend through the entire skin depth. Three-dimensional imaging of vascular characteristics in skin lesions could therefore allow diagnostic insights not available by conventional visual inspection. Raster-scan optoacoustic mesoscopy (RSOM) images microvasculature through the entire skin depth with resolutions of tens of micrometers; however, current RSOM implementations are too slow to overcome the strong breathing motions on the upper torso where melanoma lesions commonly occur. To enable high-resolution imaging of melanoma vasculature in humans, we accelerate RSOM scanning using an illumination scheme that is coaxial with a high-sensitivity ultrasound detector path, yielding 15 s single-breath-hold scans that minimize motion artifacts. We apply this Fast RSOM to image 10 melanomas and 10 benign nevi in vivo, showing marked differences between malignant and benign lesions, supporting the possibility to use biomarkers extracted from RSOM imaging of vasculature for lesion characterization to improve diagnostics.

Optoacoustic Endoscopy of the Gastrointestinal Tract

“…The top row shows cross-sectional RSOM images, while the second and third rows show the corresponding MIP (maximum intensity projection) images of the epidermis (EP) and dermis (DR) layers in the coronal views. Adapted with permission from ref . Copyright 2022 Springer Nature /.…”

“…Relying on spectral unmixing methods, the patterns of oxygenation, vasculature, and perfusion in breast cancer animal models were resolved across the entire tumor mass, showcasing different levels of structural and functional organization . Operating at even higher frequencies and bandwidths in the range of 10–200 MHz, raster-scan OA mesoscopy (RSOM) achieves resolutions ranging from less than 10 to a few tens of micrometers at penetration depths of several millimeters, depending on the illumination wavelength employed. ,− ,− RSOM has been applied to a variety of noninvasive applications, such as visualizing microvasculature oxygenation and hypoxia in tissues or tumors, microvascular dynamics in response to vascular-targeted therapy, distinct vascular patterns in melanomas (Figure e), and quantitatively analyzing skin morphology and vascular patterns in psoriasis patients demonstrating the computation of biomarkers associated with inflammatory burden or treatment efficacy. ,, Wavelength selection in a range spanning the visible and short-wavelength infrared (SWIR) has further enabled the resolution of sebaceous glands, hair, and the distributions of lipids, hemoglobin, melanin, and water in human skin in vivo (Figure f) . Due to the availability of spatial contrast, spectral contrast, and time-dependent imaging, RSOM enables the assessment of anatomical, functional, and molecular features in high-resolution at depths of a few millimeters or even deeper, making it a highly capable tool for GI lumen inspection. , Therefore, adaptation of the technology from hand-held to endoscopic implementations became the scope of several research investigations as described in the following.…”

“…33 Operating at even higher frequencies and bandwidths in the range of 10−200 MHz, raster-scan OA mesoscopy (RSOM) achieves resolutions ranging from less than 10 to a few tens of micrometers at penetration depths of several millimeters, depending on the illumination wavelength employed. 11,15−17,34−36 RSOM has been applied to a variety of noninvasive applications, such as visualizing microvasculature oxygenation and hypoxia in tissues or tumors, microvascular dynamics in response to vasculartargeted therapy, 37 distinct vascular patterns in melanomas (Figure 1e), 17 and quantitatively analyzing skin morphology and vascular patterns in psoriasis patients demonstrating the computation of biomarkers associated with inflammatory burden or treatment efficacy. 15,16,35 Wavelength selection in a range spanning the visible and short-wavelength infrared (SWIR) has further enabled the resolution of sebaceous glands, hair, and the distributions of lipids, hemoglobin, melanin, and water in human skin in vivo (Figure 1f).…”

“…Illumination at multiple wavelengths further allows imaging of oxygenation and hypoxia using spectral unmixing techniques . These abilities have been employed for dermatological applications, including imaging of cancer or inflammatory disease and treatment. ,− …”

Transrectal Absorber Guide Raster‐Scanning Optoacoustic Mesoscopy for Label‐Free In Vivo Assessment of Colitis

“…[17] In early clinical studies, RSOM has been used to image superficial human skin pathologies. [18] Moreover, RSOM technology is now being deployed in endoscopic systems. [5c,19] We therefore hypothesized that RSOM vascular biomarkers could be applied for precise assessment of IBD through deeptissue imaging of inflammatory biomarkers.…”