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Enhancing Sensitivity in Photoacoustic Microscopy for Medical Advancements

Optical-resolution photoacoustic microscopy is a promising biomedical imaging technique for researching a wide range of diseases, like diabetes, cancer, and strokes. However, its inadequate sensitivity has been an age-old obstacle to its broader application.

Enhancing Sensitivity in Photoacoustic Microscopy for Medical Advancements

(a) SLD-PAM system and (b) sensitivity improvement from the probe and filter. Image Credit: Zhang, Y. et al., source:

Recently, a study group from the City University of Hong Kong (CityU) built a multi-spectral, super-low-dose photoacoustic microscopy system with an important enhancement in the system sensitivity limit, facilitating clinical translation and new biomedical applications in the future.

Photoacoustic microscopy, a biomedical imaging technique, integrates ultrasound detection and laser-induced photoacoustic signals to produce elaborate images of biological tissue. Upon irradiating biological tissue using a pulsed laser, it produces ultrasonic waves, which are then sensed and transformed into electric signals for imaging. This attention-gaining approach can gain up to sub-cellular or capillary-level resolution at higher depths than conventional optical microscopy approaches. Nevertheless, inadequate sensitivity has hampered the broader application of technology.

High sensitivity is important for high-quality imaging. And it helps detect chromophores (molecules that confer color on materials by absorbing particular wavelengths of visible light) that do not strongly absorb light. 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.

Professor Wang Lidai, Associate Professor, Department of Biomedical Engineering, City University of Hong Kong

For example, a low-power laser is favored in an ophthalmic assessment for more comfort and safety. Long-term tracking of pharmacokinetics or blood flow needs low-dose imaging to ease perturbation to tissue functions, he stated.

To win over the sensitivity challenge, Professor Wang and his study group developed a multi-spectral, super-low-dose photoacoustic microscopy (SLD-PAM) system now, breaking through the sensitivity limit of conventional photoacoustic microscopy, considerably enhancing sensitivity by around 33 times.

They attained the discovery by integrating enhancement in the photoacoustic sensor design and innovation of a 4D spectral-spatial filter algorithm for computation. By utilizing a lab-customized high-numerical-aperture acoustic lens, improving the optical and acoustic alignment, and optimizing the optical and acoustic beam combiner, they improved the sensor design. The SLD-PAM also uses a cheap multi-wavelength pulsed laser, offering 11 wavelengths, which range from green to red light. The laser functions at a repetition frequency up to megahertz, and the spectral switching time is in sub-microseconds.

At super-low pulse energy with green-light and red-light sources, the team assessed it completely through in vivo animal imaging, which led to notable results.

Firstly, SLD-PAM facilitated high-quality in vivo functional and anatomical imaging. The super-low laser power and high sensitivity considerably minimized perturbations in brain and eye imaging, setting the stage for an avenue for clinical translation. Secondly, with no compromise on image quality, SLD-PAM minimized photobleaching by approximated 85%, with the use of lower laser power, and facilitated the use of a much wider range of molecular and nano-probes. Additionally, the system price is considerably lower, making it cheaper for clinics and research laboratories.

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. 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.

Professor Wang Lidai, Associate Professor, Department of Biomedical Engineering, City University of Hong Kong

Then, Professor Wang and his research team will assess a wider range of tiny molecules and genetically encoded biomarkers in biological imaging with the use of the SLD-PAM system. They also think of adopting more kinds of low-power light sources in wider spectra to build portable or wearable microscopy.

The results were published in the scientific journal Advanced Science.

The first co-authors are Dr Zhang Yachao and Dr Chen Jiangbo; the corresponding author is Professor Wang. The co-authors are Professor Sun Hongyan, Dr. Zhang Jie, Dr. Liu Chao, and Ph.D. student Zhu Jingyi. Everyone is from the CityU. The study was financially supported by the Hong Kong Research Grants Council and the National Natural Science Foundation of China.

Journal Reference

Zhang, Y., et al. (2023). Super-Low-Dose Functional and Molecular Photoacoustic Microscopy. Advanced Science.


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