Toward noninvasive precision oncology through optical clearing and real-time guided femtosecond laser ablation

Summary Laser ablation is a promising strategy for minimally invasive tumor removal due to its high precision and limited collateral damage. Among available modalities, femtosecond lasers provide ultrafast and spatially confined energy delivery, thereby minimizing thermal injury and enhancing tumor selectivity. However, their clinical translation remains constrained by limited penetration depth and the lack of real-time, high-precision imaging guidance. Recent advances offer new opportunities to address these challenges. Optical clearing of live tissues using refractive index-modulating dyes significantly improves laser energy transmission. Meanwhile, fluorescence lifetime imaging based on indocyanine green enables accurate discrimination between malignant and normal tissues. In this perspective, we discuss how the convergence of these approaches offers a potential route toward non-invasive, subcellular-resolution tumor removal. By enabling precise energy delivery through optically cleared tissues, this integration defines a new paradigm in precision oncology and lays the foundation for next-generation incision-free cancer therapies.