Detection of weak optical absorption by optical-resolution photoacoustic microscopy

Optical-resolution photoacoustic microscopy (OR-PAM) is one of the major implementations of photoacoustic (PA) imaging. With tightly focused optical illumination and high-frequency ultrasound detection, OR-PAM provides micrometer-level resolutions as well as high sensitivity to optical absorption contrast. Traditionally, it is assumed that the detected PA signal in OR-PAM has a linear dependence on the target's optical absorption coefficient, which is the basis for quantitative functional and molecular PA imaging. In this paper, we demonstrate that, due to the limited detection bandwidth and detection view, OR-PAM can have a strong nonlinear dependence on the optical absorption, especially for weak optical absorption (<10 cm^-1). We have investigated the nonlinear dependence in OR-PAM using numerical simulations, analyzed the underlining mechanisms, proposed potential solutions, and experimentally confirmed the results on phantoms. This work may correct a traditional misunderstanding of the OR-PAM signals and improve quantitative accuracy for functional and molecular applications.