Photoacoustic Imaging for Liver Disease: The Systems and the Molecules.

Liver disease represents a significant global health burden, and its effective management relies on early, accurate diagnosis. Established assessments for liver diseases, ranging from invasive biopsies to conventional noninvasive imaging (e.g., ultrasound, MRI, and CT), are often limited by inadequate specificity, potential safety risks, or unsuitability for dynamic tracking. Photoacoustic imaging (PAI), a hybrid modality that combines optical absorption contrast with deep ultrasonic detection, offers an attractive solution for noninvasive, high-sensitivity, and high-specificity imaging in deep organs such as the liver. This review summarizes recent advances in photoacoustic imaging for liver pathophysiology, beginning with the evolution of imaging systems and extending to the diverse molecules employed for preclinical studies and early clinical trials. Specifically, novel reconstruction algorithms improved the spatial resolution and acquisition speed by up to threefold, Monte Carlo-based fluence compensation increased the deep-tissue signal-to-background ratio by approximately 50%, and a 7-azaindole-modified probe exhibited one-magnitude-higher superoxide-triggered activation than conventional hemicyanine dyes. Furthermore, we discuss key challenges and future perspectives, highlighting the translational potential of PAI as an emerging liver imaging modality.