Acoustic-resolution-based spectroscopic photoacoustic endoscopy towards molecular imaging in deep tissues

Due to many technical difficulties, the study of molecular photoacoustic endoscopic (PAE) imaging in deep tissues is limited. In this work, we have set up a multimodal acoustic-resolution-based PAE (AR-PAE) system to image the rabbit rectum and preliminarily explored the potential of molecular PAE for deep-seated targets in proof-of-concept. We developed an improved back-projection (IBP) algorithm for focused detection over the centimeter-scale imaging depth. We also developed a deep-learning-based algorithm to remove the electrical noise from the step motor to prevent data averaging for reduced scanning time. We injected a dose of indocyanine green (ICG) near the rabbit rectum and compared 2D and 3D photoacoustic/ultrasound (PA/US) images at different wavelengths. We proposed incorporating a small camera to guide the slow PA/US endoscopic scan. Results show that this system has achieved a lateral resolution of about 0.77/0.65 mm for PA/US images with a signal-to-noise ratio (SNR) of 25/38 dB at an imaging depth of 1.4 cm. We found that the rectum wall and the ICG can be well distinguished spectroscopically. Results also show that the PA images at 532 nm have higher signal intensity and reflection artifacts from pelvic tendons and bones than those at longer wavelengths such as 800 nm. The proposed methods and the intuitive findings in this work may guide and promote the development of high-penetration molecular PAE.