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New photoacoustic system breaks microscopy limits


Comparison of the in vivo results of (a) Traditional-PAM, (b) SLD-PAM at super-low pulse energy with a green-light source, and (c) oxygen saturation image SLD-PAM acquired via dual-wavelength spectrum unmixing. (Image: Zhang, Y. et al.)

A new microscopy system has been developed that is 33 times more sensitive than traditional options, researchers say, and which could lead to new biomedical applications. 

The multi-spectral, super-low-dose photoacoustic microscopy system (SLD-PAM), developed by researchers from the City University of Hong Kong (CityU), breaks the sensitivity limit of traditional photoacoustic microscopy, according to the team. 

Optical-resolution photoacoustic microscopy is used to study diseases such as cancer, diabetes and stroke but insufficient sensitivity has hindered the technology’s wider application, CityU says.

“High sensitivity is important for high-quality imaging and it helps detect chromophores (molecules that confer colour on materials by absorbing particular wavelengths of visible light) that do not strongly absorb light,” says Professor Wang Lidai, Associate Professor in the Department of Biomedical Engineering at 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 researchers say they have now overcome the sensitivity challenge with the SLD-PAM system, which breaks through the sensitivity limit of traditional photoacoustic microscopy, improving sensitivity by about 33 times.

Lidai says: “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.” 

He adds: “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.”

Photoacoustic microscopy combines ultrasound detection and laser-induced photoacoustic signals to create detailed images of biological tissue. When biological tissue is irradiated with a pulsed laser, it generates ultrasonic waves, which are then detected and converted into electric signals for imaging. 

The SLD-PAM was developed using a 4D spectral-spatial filter algorithm and a high-numerical-aperture acoustic lens, which optimised the optical and acoustic beam combiner, and improved the optical and acoustic alignment, CityU says. The device also features a low-cost multi-wavelength pulsed laser that provides 11 wavelengths – ranging from green to red light – and operates at a repetition frequency up to megahertz, with a spectral switching time in the sub-microseconds.

After demonstrating the device via in vivo animal imaging at super-low pulse energy with green-light and red-light sources, the team found that the SLD-PAM enabled high-quality in vivo anatomical and functional imaging, while the super-low laser power and high sensitivity reduced perturbations in eye and brain imaging. The SLD-PAM also reduced photobleaching by about 85% using laser power without compromising image quality, the team says, and enabled the use of a broader range of molecular and nano-probes. 


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