Detection of collagen content evolution modulated by cancer-associated fibroblasts using photoacoustic spectral analysis

Noninvasive in vivo measurements of collagen can promote studying the mechanism of tumor microenvironment (TME) change modulated by cancer-associated fibroblasts (CAFs). This study investigated the effectiveness of photoacoustic spectral analysis (PASA) for detecting the collagen evolution affected by CAFs based on numerical simulations and in vivo experiments. The development of collagen was simulated via histopathological images of the maximum cross-sections of mouse tumor models. A total of 21 mice bearing breast cancer under the administration of 3 levels of CAFs were established and tested using a pulsed laser from 1200 nm to 1700 nm. The results revealed that the relative collagen contents within the slices of cancers were highly correlated with the PA parameter "relative area of power spectrum density (APSD)" (R≈0.97). The tumors subjected to a sufficient dose (3×10 ⁵ ) of CAFs exhibited significantly increased relative APSDs (*p<0.05). The method proposed in this study proves that PASA is promising for the clinical research of CAF-targeted cancer theranostics.