Dual-wavelength OR-PAM with compressed sensing for cell tracking in a 3D cell culture system

Monitoring dynamic interactions of T cells migrating toward tumor is beneficial to understand how cancer immunotherapy works. Optical-resolution photoacoustic microscope (OR-PAM) can provide not only high spatial resolution but also deeper penetration than conventional optical microscopy. With the aid of exogenous contrast agents, the dual-wavelength OR-PAM can be applied to map the distribution of CD8+ cytotoxic T lymphocytes (CTLs) with gold nanospheres (AuNS) under 523nm laser irradiation and Hepta1-6 tumor spheres with indocyanine green (ICG) under 800nm irradiation. However, at 1K laser PRF, it takes approximately 20 minutes to obtain a full sample volume of 160 × 160 × 150 μm3 . To increase the imaging rate, we propose a random non-uniform sparse sampling mechanism to achieve fast sparse photoacoustic data acquisition. The image recovery process is formulated as a low-rank matrix recovery (LRMR) based on compressed sensing (CS) theory. We show that it could be stably recovered via nuclear-norm minimization optimization problem to maintain image quality from a significantly fewer measurement. In this study, we use the dual-wavelength OR-PAM with CS to visualize T cell trafficking in a 3D culture system with higher temporal resolution. Data acquisition time is reduced by 40% in such sample volume where sampling density is 0.5. The imaging system reveals the potential to understand the dynamic cellular process for preclinical screening of anti-cancer drugs.