24 May 2022
Hardware innovations plus machine learning create fastest photoacoustic imaging tool available.Duke University has made a further advance in the application of photoacoustic microscopy (PAM) to neural imaging, creating "the fastest photoacoustic imaging tool available."
The breakthrough allows the scanning and imaging of blood flow and oxygen levels inside a mouse brain in real-time, with sufficient resolution to view the activity of both individual vessels and the entire brain at once.
As described in Light: Science & Applications, the findings "break speed and resolution barriers in brain imaging technologies and could uncover new insights into neurovascular diseases like stroke, dementia and even acute brain injury."
Recent progress in photoacoustic platforms has involved modifications tailored to specific applications. In 2021 PAM pioneer Lihong Wang of Caltech described the different requirements of imaging blood vessels around breast cancer tumors and the functional imaging of the brain - the latter being more than an order of magnitude harder to measure.
Hardware advances in polygon scanners, in which a rotating multi-sided polygon mirror creates a scanning laser beam at constant linear velocity, have made them attractive for PAM applications, and the Duke project incorporated a 12-facet water-immersible polygon scanner in its new ultrafast functional photoacoustic microscopy (UFF-PAM) device.
The platform also included an automatic image registration method to overcome the misalignment of the polygon facets due to water damping, and a deep-learning approach to mitigate spatial undersampling inherent in the faster imaging speed and substantially improve the image quality.
Overall UFF-PAM achieved a volumetric imaging rate of 2 Hz over a field of view of 11×7.5×1.5 millimeters, with a high spatial resolution of around 10 microns.
"The resulting images looked as detailed as the high-resolution images we would usually get if we went at a much slower speed, and we didn’t need to sacrifice a full field of view,” said Junjie Yao of Duke University.
Long-standing roadblocks addressed
The Duke instrument quantifies the relative concentrations of oxy- and deoxy-hemoglobin from the PA signals generated by the pair of laser pulses at 532 and 558 nanometers, and the project applied its platform to the in vivo imaging of hemodynamic responses in mouse brains to hypoxia, hypotension and stroke.
UFF-PAM revealed new details in each instance, showing for example that immediately after a stroke the constriction of blood vessels in the affected area causes neighboring vessels to also constrict in a phenomenon called a spreading depolarization wave. The findings allowed the team to precisely pinpoint the wave's starting position and track its movement as it propagated throughout the brain.
For its next steps, the team aims to use UFF-PAM to explore additional brain disease models, like dementia, Alzheimer’s disease or even long Covid-19. It also plans to expand the tool's use outside of the brain to image organs like the heart, liver and placenta. These organs have traditionally been challenging to image because they are always in motion, so imaging tools need to operate at a faster speed.
"There is a lot that we can do with this technology now that we have addressed these long-standing roadblocks," said Yao. "We're trying to pick the most challenging projects to work on, to maximize the impact of this technology."