Medical Design Briefs - October 2023 - 56

Ultra-Sensitive Photoacoustic Microscopy Enables New
Biomedical Applications
City University of Hong Kong
Hong Kong
O
ptical-resolution photoacoustic
microscopy is
an up-and-coming biomedical
imaging technique for
studying a broad range of
diseases, such as cancer,
diabetes, and stroke. But
its insufficient sensitivity
has been a longstanding
obstacle for its wider application.
Recently, a research
team from City University
of Hong Kong (CityU) developed
a multi-spectral,
super-l ow-dose photoacoustic
microscopy system with a
significant improvement in
the system sensitivity limit,
enabling new biomedical applications and
clinical translation in the future.
Photoacoustic microscopy is a biomedical
imaging technique that 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.
This attention-getting technique can
achieve up to capillary-level or subcellular
resolution at greater depths than
traditional optical microscopy methods.
However, insufficient sensitivity
has hindered the technology's wider
application.
(a)
Traditional PAM (532 nm)
1 nJ
400 µm
min
Total hemoglobin concentration
max 0SO2
1
Image 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 SLD-PAM acquired via dual-wavelength
spectrum unmixing. (Credit: Zhang, Y. et al., https://onlinelibrary.wiley.com/
doi/10.1002/advs.202302486)
monitoring of pharmacokinetics or blood
flow requires low-dose imaging to alleviate
perturbation to tissue functions, he adds.
To overcome the sensitivity challenge,
Wang and his research team recently developed
a multi-spectral, super-low-dose
photoacoustic microscopy (SLD-PAM)
system, which breaks through the sensitivity
limit of traditional photoacoustic
microscopy, significantly improving sensitivity
by about 33 times.
" 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, "
says Prof. Wang Lidai, associate professor
in the department of biomedical engineering
at CityU.
For instance, in an ophthalmic examination,
a low-power laser is preferred
for more safety and comfort. Long-term
56
They achieved the breakthrough
by combining improvement in the
photoacoustic sensor design and innovation
of a 4D spectral-spatial filter
algorithm for computation. They
improved the sensor design by using
a lab- customized high-numerical-aperture
acoustic lens, optimizing the
optical and acoustic beam combiner,
and improving the optical and acoustic
alignment.
The SLD-PAM also utilizes a low-cost
multi-wavelength pulsed laser, providing
11 wavelengths, ranging from green
to red light. The laser operates at a repetition
frequency up to megahertz, and
the spectral switching time is in submicroseconds.
To
demonstrate the significance and
novelty of SLD-PAM, the team tested it
thoroughly via in vivo animal imaging at
super-low pulse energy with green-light
and red-light sources, resulting in remarkable
findings.
www.medicaldesignbriefs.com
(b)
Vein
Artery
(c)
SLD-PAM (532 nm)SLD-PAM (532&558 nm)
First, SLD-PAM enabled
high-quality in vivo anatomical
and functional imaging.
The super-low laser
power and high sensitivity
significantly reduced perturbations
in eye and brain
imaging, paving an avenue
for clinical translation. Second,
without compromising
image quality, SLD-PAM reduced
photobleaching by
about 85 percent, using lower
laser power, and enabled
the use of a much broader
range of molecular and
nano- probes. In addition,
the system cost is significantly
lower, making it more affordable for research
laboratories and clinics.
" SLD-PAM enables noninvasive imaging
of biological tissue with minimal
damage to the subjects, offering a powerful
and promising tool for anatomical,
functional, and molecular imaging, " says
Wang. " 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. "
Next, Wang and his research team will
test a broader range of small molecules
and genetically encoded biomarkers in
biological imaging using the SLD-PAM
system. They also plan to adopt more
types of low-power light sources in a wider
spectra to develop wearable or portable
microscopy.
The findings were published in the
journal Advanced Science. The first coauthors
are Dr. Zhang Yachao and
Dr. Chen Jiangbo; the corresponding
author is Prof. Wang Lidai. The coauthors
are Prof. Sun Hongyan, Dr.
Zhang Jie, Dr. Liu Chao, and PhD student
Zhu Jingyi. All are from the CityU.
The research was funded by the Hong
Kong Research Grants Council and the
National Natural Science Foundation
of China.
For more information, visit www.cityu.
edu.hk. Contact: Prof. Wang Lidai,
lidawang@cityu.edu.hk or +852 3442-6157.
Medical Design Briefs, October 2023

https://onlinelibrary.wiley.com/doi/10.1002/advs.202302486 https://onlinelibrary.wiley.com/doi/10.1002/advs.202302486 http://www.cityu.edu.hk http://www.cityu.edu.hk http://www.medicaldesignbriefs.com

Medical Design Briefs - October 2023

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