Photoacoustic Microscopy for Multiscale Biological System Visualization and Clinical Translation

Photoacoustic microscopy (PAM) has emerged as a versatile modality in biomedical research, notable for its noninvasively, high spatial resolution, and superior optical contrast. Compared with pure optical imaging techniques, PAM leverages weakly scattered ultrasonic signals for image formation, thereby achieving high-resolution visualization of deep tissues. This review provides a comprehensive synthesis of recent advancements in PAM, encompassing technological innovations, organ-specific applications, and emerging pathways toward clinical translation. This discussion starts by exploring the fundamental physical principles of PAM and elaborates on the enhanced performance achieved through significant advancements in high-speed scanners, array transducers, artificial intelligence-enhanced algorithms, and molecular agents. Pioneering applications in single‑cell analysis, hepatic microcirculation characterization, renal clearance monitoring, tumor metastasis detection, and neuroscientific discovery are surveyed to demonstrate PAM's ability. Prospective clinical uses, including intraoperative guidance and point‑of‑care diagnostics, are considered alongside persistent limitations, notably limited penetration depth and multispectral imaging speed. Future advancements are expected to hinge on multimodal integration, deeper integration of artificial intelligence, and the development of standardized protocols to accelerate clinical implementation. Ultimately, this review offers a forward-looking perspective aimed at accelerating the translation of PAM from a laboratory tool to a clinical mainstay in the era of precision medicine.