CityU low-dose photoacoustic system boosts technique's sensitivity

05 Sep 2023

Improved sensor design and spectral filter could offer new avenue for clinical translation.

Photoacoustic microscopy (PAM) continues to make inroads into biomedical imaging, thanks to its potential for capillary-level or sub-cellular resolution at greater depths than traditional optical microscopy methods.

Recent advances have included its use in monitoring hemoglobin for disease diagnosis, and studying brain activity as a way to understand neurovascular diseases.

The technique's inherent sensitivity limits have remained a hurdle, however, potentially limiting the wider applicability of PAM in clinical use.

A project at City University of Hong Kong (CityU) has now developed a multi-spectral low-dose photoacoustic microscopy system with a significant improvement in the system sensitivity limit, and published its findings in Advanced Science.

"High sensitivity is important for high-quality imaging, and it helps detect chromophores that do not strongly absorb light," commented Wang Lidai from CityU. "It also helps lessen photobleaching and phototoxicity, reduce perturbation to the biological tissues of delicate organs, and broaden the choices of low-cost, low-power lasers in a wide spectrum."

The CityU solution involved a dual-track approach of optimizing the photoacoustic probe employed and developing a bespoke spectral-spatial filter algorithm, to create a modified process christened super-low-dose photoacoustic microscopy (SLD-PAM).

These changes allowed the overall optical/acoustic design to collect three times more photoacoustic signals than CityU's previous PAM technique, according to the project, and to "break through the sensitivity limit of traditional photoacoustic microscopy, significantly improving sensitivity by about 33 times."

Broader range of applications at lower costs

The project's high sensitivity PAM probe uses a lab-customized high-numerical-aperture acoustic lens, optimizing the alignment of the optical and acoustic beams, according to the team, while the new spectral-spatial filter algorithm is designed to de-noise the 3D multi-wavelength data and further improve the signal-to-noise performance.

Photoacoustic imaging using just the modified probe can outperform traditional PAM imaging detail for the same laser pulse energy, according to CityU's published paper, with the new algorithm filter adding further to the improvement. The combination was found to make SLD-PAM between 6 and 33-times more sensitive than a traditional platform, and require super low-dose excitation for in vivo use.

In trials imaging the vasculature of mice, SLD-PAM significantly reduced perturbations in eye and brain imaging, and reduce sample photobleaching by 85 percent through the use of lower laser power. Both improvements indicate a possible smoother path towards clinical translation

They should also allow the use of a broader range of molecular and nano-probes in PAM applications, according to the project, while reducing the costs for laboratories and clinics.

"SLD-PAM enables non-invasive imaging of biological tissue with minimal damage to the subjects, offering a powerful and promising tool for anatomical, functional and molecular imaging,” said Wang Lidai. "We believe that SLD-PAM can help advance the applications of photoacoustic imaging, enable numerous new biomedical applications, and pave a new avenue for clinical translation."