A team of UCLA bioengineers, scientists and colleagues have built a new type of microscope that can make ultra-fast 3D videos inside living tissue. At 1,000 frames per second, the camera can track individual blood cells as they flow through tiny blood vessels. It can also see the electric spikes inside neurons of animals that are moving. A research study, published in Nature Methods, unveiled the camera’s design and results of experiments that showed its potential.
“The new capabilities can help scientists study how hearts pump, how brains process information during physical activity as well as how diseases can disrupt these processes,” said study leader Liang Gao, an associate professor of bioengineering at the UCLA Samueli School of Engineering.
The setup uses a standard scientific camera coupled with a custom array of prisms and accompanying lenslets and enhanced by computational techniques. The camera essentially “squeezes” then rotates the light it’s capturing, resulting in simultaneous images from multiple angles that can be computational stitched together for 3D visualizations.
The researchers have described the system as squeezed light field microscopy, or SLIM. It can record over 1,000 3D frames per second across a 0.5mm diameter field of view and 0.3 mm depth. can resolve objects as small as 3.6 micrometers (0.0036 mm), powerful enough to make out individual cells.
They demonstrated the system in several experiments showing its potential in cardiovascular and neurological studies. This included:
- Tracking individual blood cells as they are pumped through a zebrafish’s brain and tail as they swim. The experiments reveal flow speed differences between sections of the blood vessels network.
- They also used the camera to show the full detail of a beating zebrafish heart as it pumps blood.
- Observing electric pulses in neurons in the hippocampus region of the brain in mice.
- Observing electrical pulses inside leech nervous system cells as they swim.
“These results establish SLIM as a versatile and robust tool for high-speed volumetric microscopy across diverse biological systems,” said Gao, who directs the Intelligent Optical Laboratory at UCLA.
The system has advantages over scanning-based 3D optical microscopy techniques that tradeoff frame rates against higher resolution of images, the researchers said. It could be particularly beneficial in high-speed imaging where weak fluorescently tagged objects, like cells, are difficult to pick up, especially in living tissue. It could also be adapted into cameras with much higher speeds, up to hundreds of thousands of 3D frames per second.
The co-lead authors were Zhaoqiang Wang and Ruixuan Zhao, former and current UCLA bioengineering doctoral students advised by Gao. Other collaborators on the study include researchers from UCLA Bioengineering, the UCLA Geffen School of Medicine, Caltech and the University of Arizona.
Several videos from the experiments that used SLIM are available at the paper’s supplementary information section.
The research was supported by grants from the National Institutes of Health and the National Science Foundation.