Ultra Wide-field Acoustic-resolution Photoacoustic Microscopy

Photoacoustic microscopy ( PAM) is able to represent the light energy absorption of specific biological molecules ( hemoglobin, melanin, DNA/RNA, lipid etc.) without the contrast agents. Especially, AR-PAM can overcome the optical diffusion limit and achieve much greater penetration depth up to a quasi-diffusive regime with low acoustic scattering. Therefore, AR-PAM has been significantly investigated in various applications for morphological, physiological, and molecular information. However, previously developed AR-PAM systems have limited field-of-view ( FOV) and imaging speed. These barriers preclude AR-PAM systems from their application to exploratory preclinical and clinical trials. In this work, we introduce an ultra-wide-field AR-PAM system. We fabricated a water-proof microelectromechanical systems ( MEMS) scanner for high-speed imaging integrated with two stepper-motors for wide-field scanning ( 30 x 80 mm(2)). Finally, we performed in-vivo experiments for preclinical and clinical applications to validate the developed AR-PAM system. For the preclinical experiment with mice, we visualized ventral, sagittal, and dorsal anatomical microstructures including vascular layers and inner organs non-invasively using one wavelength. An entire 3D volume data was acquired with the developed system and depth-encoded along the skin surface up to 2.3 mm. Subcutaneous multi-layers were differentiated on each layer according to distinct microstructures such as recognizable vasculatures and organs ( mammary vessels, caudal vessels, popliteal vessels, intestine, heart, spline, etc.). Moreover, we have successfully obtained the distinct microstructures and microvascular networks of human fingers, palm and forearm in-vivo.