Photoacoustic imaging (PAI) has many interesting advantages, such as deep imaging depth, high image resolution, and high contrast to intrinsic and extrinsic chromophores, enabling morphological, functional, and molecular imaging of living subjects. Photoacoustic microscopy (PAM) is one form of the PAI inheriting its characteristics and is useful in both preclinical and clinical research. Over the years, PAM systems have been evolved in several forms and each form has its relative advantages and disadvantages. Thus, to maximize the benefits of PAM for a specific application, it is important to configure the PAM system optimally by targeting a specific application. In this review, we provide practical methods for implementing a PAM system to improve the resolution, signal-to-noise ratio (SNR), and imaging speed. In addition, we review the preclinical and the clinical applications of PAM and discuss the current challenges and the scope for future developments.
Photoacoustic microscopy (PAM) has become a premier microscopy tool that can provide the anatomical, functional, and molecular information of animals and humans in vivo. However, conventional PAM systems suffer from limited temporal and/or spatial resolution. Here, we present a fast PAM system and an agent-free localization method based on a stable and commercial galvanometer scanner with a custom-made scanning mirror (L-PAM-GS). This novel hardware implementation enhances the temporal resolution significantly while maintaining a high signal-to-noise ratio (SNR). These improvements allow us to photoacoustically and noninvasively observe the microvasculatures of small animals and humans in vivo. Furthermore, the functional hemodynamics, namely, the blood flow rate in the microvasculature, is successfully monitored and quantified in vivo. More importantly, thanks to the high SNR and fast B-mode rate (500 Hz), by localizing photoacoustic signals from captured red blood cells without any contrast agent, unresolved microvessels are clearly distinguished, and the spatial resolution is improved by a factor of 2.5 in vivo. L-PAM-GS has great potential in various fields, such as neurology, oncology, and pathology.
During cancer resection surgeries, intraoperative histopathologic examination of the surgical specimen is crucial for tumor margin identification. A conventional frozen‐section analysis requires complex tissue processing, which prolongs surgery and potentially introduces interpretation errors. Here, as a novel approach to label‐free intraoperative histopathology, a high‐speed reflection‐mode ultraviolet photoacoustic microscopy (UV‐PAM) system employing a waterproof 1‐axis microelectromechanical systems scanner is demonstrated. Label‐free nuclear imaging is photoacoustically verified using tissue sections excised from mice and humans. Moreover, by imaging clinical specimens from cancer patients and numerically quantifying the histopathologic results, it is successfully demonstrated that the proposed UV‐PAM system has great potential as an alternative intraoperative histopathology method with minimal tissue preparation processes.
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