Acoustic-resolution photoacoustic microscopy (AR-PAM) is an emerging biomedical imaging modality that combines superior optical sensitivity and fine ultrasonic resolution in an optical quasi-diffusive regime (∼1-3 mm in tissues). AR-PAM has been explored for anatomical, functional, and molecular information in biological tissues. Heretofore, AR-PAM systems have suffered from a limited field-of-view (FOV) and/or slow imaging speed, which have precluded them from routine preclinical and clinical applications. Here, we demonstrate an advanced AR-PAM system that overcomes both limitations of previous AR-PAM systems. The new AR-PAM system demonstrates a super wide-field scanning that utilized a 1-axis water-proofing microelectromechanical systems (MEMS) scanner integrated with two linear stepper motor stages. We achieved an extended FOV of 36 × 80mm2 by mosaicking multiple volumetric images of 36 × 2.5 mm2 with a total acquisition time of 224 seconds. For one volumetric data (i.e., 36 × 2.5 mm2), the B-scan imaging speed over the short axis (i.e., 2.5 mm) was 83 Hz in humans. The 3D volumetric image was also provided by using MEMS mirror scanning along the X-axis and stepper-motor scanning along the Y-axis. The super-wide FOV mosaic image was realized by registering and merging all individual volumetric images. Finally, we obtained multi-plane whole-body in-vivo PA images of small animals, illustrating distinct multi-layered structures including microvascular networks and internal organs. Importantly, we also visualized microvascular networks in human fingers, palm, and forearm successfully. This advanced MEMS-AR-PAM system could potentially enable hitherto not possible wide preclinical and clinical applications.

Functional imaging of microvascular dynamics in extremities delivers intuitive information for early detection, diagnosis, and prognosis of vascular diseases. High-resolution and high-speed photoacoustic microscopy (PAM) visualizes and measures multiparametric information of microvessel networks in vivo such as morphology, flow, oxygen saturation, and metabolic rate. Here, we demonstrate high-resolution photoacoustic monitoring of vascular dynamics in human fingers. We photoacoustically monitored the position displacement of blood vessels associated with arterial pulsation in human fingers. Then, during and after arterial occlusion, we photoacoustically quantified oxygen consumption and blood perfusion in the fingertips. The results demonstrate that high-resolution functional PAM could be a vital tool in peripheral vascular examination for measuring heart rate, oxygen consumption, and/or blood perfusion.

Photoacoustic microscopy (PAM) is used to visualize blood vessels and to monitor their time-dependent changes. Photoplethysmography (PPG) measures hemodynamic time-series changes such as heart rate. However, PPG’s limited visual access to the dynamic changes of blood vessels has prohibited further understanding of hemodynamics. Here, we propose a novel, fully integrated PAM and photoplethysmography (PAM-PPG) system to understand hemodynamic features in detail. Using the PAM-PPG system, we simultaneously acquire vascular images (by PAM) and changes in the blood volume (by PPG) from human fingers. Next, we determine the heart rate from changes in the PA signals, which match well with the PPG signals. These changes can be measured if the blood flow is not blocked. From the results, we believe that PAM-PPG could be a useful clinical tool in various clinical fields such as cardiology and endocrinology.

Photoacoustic imaging (PAI) is a new biomedical imaging technology currently in the spotlight providing a hybrid contrast mechanism and excellent spatial resolution in the biological tissues. It has been extensively studied for preclinical and clinical applications taking advantage of its ability to provide anatomical and functional information of live bodies noninvasively. Recently, microelectromechanical systems (MEMS) technologies, particularly actuators and sensors, have contributed to improving the PAI system performance, further expanding the research fields. This review introduces cutting-edge MEMS technologies for PAI and summarizes the recent advances of scanning mirrors and detectors in MEMS.

Vascular damage is one of the therapeutic mechanisms of photodynamic therapy (PDT). In particular, short-term PDT treatments can effectively destroy malignant lesions while minimizing damage to nonmalignant tissue. In this study, we investigate the feasibility of label-free quantitative photoacoustic microscopy (PAM) for monitoring the vasculature changes under the effect of PDT in mouse ear melanoma tumors. In particular, quantitative vasculature evaluation was conducted based on Hessian filter segmentation. Three-dimensional morphological PAM and depth-resolved images before and after PDT treatment were acquired. In addition, five quantitative vasculature parameters, including the PA signal, vessel diameter, vessel density, perfused vessel density, and vessel complexity, were analyzed to evaluate the influence of PDT on four different areas: Two melanoma tumors, and control and normal vessel areas. The quantitative and qualitative results successfully demonstrated the potential of the proposed PAM-based quantitative approach to evaluate the effectiveness of the PDT method.