Affiliation:
1. Department of Biomedical Engineering City University of Hong Kong Hong Kong SAR 999077 China
2. Department of Chemistry and COSADAF (Centre of Super‐Diamond and Advanced Films) City University of Hong Kong Hong Kong SAR 999077 China
3. City University of Hong Kong Shenzhen Research Institute Shenzhen China 518057
Abstract
AbstractPhotoacoustic microscopy can image many biological molecules and nano‐agents in vivo via low‐scattering ultrasonic sensing. Insufficient sensitivity is a long‐standing obstacle for imaging low‐absorbing chromophores with less photobleaching or toxicity, reduced perturbation to delicate organs, and more choices of low‐power lasers. Here, the photoacoustic probe design is collaboratively optimized and a spectral‐spatial filter is implemented. A multi‐spectral super‐low‐dose photoacoustic microscopy (SLD‐PAM) is presented that improves the sensitivity by ≈33 times. SLD‐PAM can visualize microvessels and quantify oxygen saturation in vivo with ≈1% of the maximum permissible exposure, dramatically reducing potential phototoxicity or perturbation to normal tissue function, especially in imaging of delicate tissues, such as the eye and the brain. Capitalizing on the high sensitivity, direct imaging of deoxyhemoglobin concentration is achieved without spectral unmixing, avoiding wavelength‐dependent errors and computational noises. With reduced laser power, SLD‐PAM can reduce photobleaching by ≈85%. It is also demonstrated that SLD‐PAM achieves similar molecular imaging quality using 80% fewer contrast agents. Therefore, SLD‐PAM enables the use of a broader range of low‐absorbing nano‐agents, small molecules, and genetically encoded biomarkers, as well as more types of low‐power light sources in wide spectra. It is believed that SLD‐PAM offers a powerful tool for anatomical, functional, and molecular imaging.
Funder
National Natural Science Foundation of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)