High-resolution label-free ultraviolet photoacoustic microscopy via an ultraviolet-transparent ultrasound transducer

Ultraviolet photoacoustic microscopy (UV-PAM) has emerged as a promising medical imaging technique for alternative histopathology, relying on the inherent optical absorption of DNA/RNA. However, traditional UV-PAM faces resolution challenges compared to clinical histological methods, limiting the observation of cellular structures. This limitation stems from the constraints of conventional reflection-mode UV-PAM systems, utilizing opto-ultrasound beam combiners or ring-shaped ultrasound transducers. These components impose constraints on numerical apertures (NA), thereby limiting spatial resolution. On the flip side, transmission-mode UV-PAM encounters difficulties in imaging thick specimens due to signal attenuation. In this study, we introduce an innovative solution – the development of an ultraviolet-transparent ultrasound transducer (UV-TUT) – overcoming these limitations and enabling high-resolution UV-PAM system. The UV-TUT significantly enhances both NA and lateral resolution, outperforming previous reflection-mode UV-PAM systems. With an impressive light transmission efficiency in the UV region and sensitivity four times greater than traditional ring-shaped ultrasound transducers, the UV-TUT lays the foundation for improved imaging capabilities. Leveraging the capabilities of the UV-TUT, we exploited a UV-PAM system, showcasing superior performance for imaging mouse brain tissue sections compared to conventional opto-ultrasound beam combiner-based UV-PAM. Furthermore, our application of photoacoustic histopathology on uterine cancer tissue sections demonstrated image quality comparable to microscopy images, providing valuable insights for accurate histopathological analysis. This work signifies a significant advancement in UV-PAM system, holding the promise to enhance the clinical utility of alternative histopathology with unprecedented resolution and imaging capabilities.