Wavefront Shaping for Deep-Tissue Therapeutic Light Delivery: From Optical Focusing to Precision Photomedicine

To systematically evaluate wavefront shaping (WFS) as a strategy for deep-tissue phototherapy, assessing progress and translational readiness across four clinically relevant dimensions.

Narrative review of three mainstream WFS strategies-feedback iterative optimization, transmission matrix (TM) measurement, and optical phase conjugation (OPC)-evaluated against the core requirements of phototherapy: penetration depth, energy deposition accuracy, dynamic stability, and clinical translation.

Time-reversal of ultrasound-encoded (TRUE)-based WFS has achieved TRUE-based WFS has demonstrated focusing through approximately 2 mm of living brain tissue, substantially exceeding the approximately 1 mm limit of conventional optics. Peak-to-background ratios (PBR) exceeding 400 have been demonstrated with natural gradient optimization algorithms, and millisecond-scale system response times have been achieved with digital optical phase conjugation. However, no study has simultaneously demonstrated millisecond-scale correction and sustained, therapeutically effective, and safe light-dose delivery in a living model, and only one study has established a quantitative relationship between WFS optical optimization and a biophysical therapeutic endpoint.

WFS demonstrates compelling optical capabilities that directly address the physical barriers limiting conventional phototherapy. Clinical translation requires a shift from optical demonstration to therapeutic validation, incorporating standardized preclinical protocols, absolute light-dose measurement at the target, and multidimensional biological endpoint assessment.