Dynamic models for ultrasound-switchable fluorescence

Objective.Near-infrared fluorescence imaging enables deep-tissue visualization but is limited to millimeter-scale resolution due to photon scattering. Ultrasound-switchable fluorescence (USF) improves resolution by thermally activating fluorophores within a focused ultrasound region. Although experimentally demonstrated, quantitative understanding of the coupled acoustic-thermal-fluorescence-optical processes governing USF signal formation remains limited. This work establishes a dynamic modeling framework to describe USF signal and velocity formation and to explore model-driven strategies for improving imaging performance.Approach.A physics-based framework integrating ultrasound pressure and heating, temperature-dependent fluorescence quantum yield, and photon diffusion was developed. Both analytical derivations and numerical simulations were performed to investigate the dynamic behavior of USF signal strength and velocity under different target configurations and optical source-detector geometries.Main results.The framework reproduces the dynamic evolution of USF signal strength and velocity. Analytical expressions were derived to estimate separation limits of adjacent targets within the ultrasound focal volume. Velocity-based analysis reveals structural information beyond conventional intensity-based imaging. A time-dependent sensitivity matrix was obtained, indicating improved spatial localization potential for tomographic reconstruction.Significance.This study provides a quantitative theoretical basis for dynamic USF imaging and highlights the additional structural information contained in signal velocity. The results suggest that velocity-based analysis may enable differentiation of otherwise indistinguishable features within the focal volume. The derived dynamic sensitivity matrix further supports tomographic reconstruction and may facilitate future deep-tissue super-resolution strategies.