Label-free photoacoustic microscopy for biomedical and point-of-care applications

Photoacoustic tomography (PAT) is a promising imaging technique which utilizes ultrasonic waves induced by pulse light energy absorbed by intrinsic biomolecules, such as DNA/RNA and hemoglobin, to reconstruct images. Taking the advantage of endogenous optical absorption contrast, PAT can provide label-free structural, histological, functional, and metabolic images for clinical applications and basic studies. In this thesis, we propose several techniques to improve the performance of PAT and promote its applications in biomedical and point-of-care fields. With the high optical absorption of DNA/RNA at 266 nm, ultraviolet photoacoustic microscopy (UV-PAM) has been developed for cellular imaging, providing histological information for revealing organ structures and disease diagnosis. However, the cellular contrast might be low because of the high UV absorption of lipids and pigments into tissues, affecting the microstructure analysis and degrading the diagnostic accuracy. To improve the cellular contrast of UV-PAM, we first develop a tissue clearing-enhanced UV-PAM to remove lipids and pigments, reducing the background signals. The image contrast has been significantly improved and multilayers of cell nuclei can be obtained after tissue clearing. Then, we further develop a dual-modality imaging system with UV-PA and auto-fluorescence microscopy (uvPA-AFM) to achieve cellular contrast improvement without any tissue processing, promoting the clinical applications of UV-PAM in histological examination of various tissues. High-quality histological images can even be obtained by our system under low excitation energy and high pulse-to-pulse energy fluctuation.