Opening a window to skin biomarkers for diabetes stage with optoacoustic mesoscopy

Being the largest and most accessible organ of the human body, the skin could offer a window to diabetes-related complications on the microvasculature. However, skin microvasculature is typically assessed by histological analysis, which is not suited for applications to large populations or longitudinal studies. We introduce ultra-wideband raster-scan optoacoustic mesoscopy (RSOM) for precise, non-invasive assessment of diabetes-related changes in the dermal microvasculature and skin micro-anatomy, resolved with unprecedented sensitivity and detail without the need for contrast agents. Providing unique imaging contrast, we explored a possible role for RSOM as an investigational tool in diabetes healthcare and offer the first comprehensive study investigating the relationship between different diabetes complications and microvascular features in vivo. We applied RSOM to scan the pretibial area of 95 participants with diabetes mellitus and 48 age-matched volunteers without diabetes, grouped according to disease complications, and extracted six label-free optoacoustic biomarkers of human skin, including dermal microvasculature density and epidermal parameters, based on a novel image-processing pipeline. We then correlated these biomarkers to disease severity and found statistically significant effects on microvasculature parameters as a function of diabetes complications. We discuss how label-free RSOM biomarkers can lead to a quantitative assessment of the systemic effects of diabetes and its complications, complementing the qualitative assessment allowed by current clinical metrics, possibly leading to a precise scoring system that captures the gradual evolution of the disease.