Optical Biopsy of Melanoma and Basal Cell Carcinoma Progression by Noncontact Photoacoustic and Optical Coherence Tomography: In Vivo Multi-Parametric Characterizing Tumor Microenvironment.

Abstract

Measuring the structural and functional status of tumor microenvironment for malignant melanoma (MM) and basal cell carcinoma (BCC) is of profound significance in understanding dermatological condition for biopsy. However, conventional optical imaging techniques are limited to visualize superficial skin features and parameter information is deficient to depict pathophysiology correlations of skin diseases. Here, we demonstrate a preclinical device, all-optically integrated photoacoustic and optical coherence tomography (AOPA/OCT), that, for the first time, can simultaneously provide label-free biomarkers of vascular patterns, temporal and spatial heterogeneity of blood flow, and tissue micro-structure changes during tumor growth with pathophysiological correlations in mice models. We found that tumor microenvironment of MM and BCC led to the alternation in spatial-temporal heterogeneity that affected morphological and functional parameters, performing the AOPA/OCT quantitative metrics. A robust correlation between imaging biomarkers derived from this in vivo technique and histopathology validation ex vivo in distinguishing benign from malignant is also presented. In receiver operating characteristics (ROC) analysis, multi-parametric AOPA/OCT yields improved diagnostic accuracy of 98.4% and 95.8% for MM and BCC respectively, which indicate that AOPA/OCT represents a high-performance and clinically translatable technique for accurate diagnosis and therapy monitoring in dermatology.