Scientists at MIT say they made a finding in optical physics that could enable a new bioimaging method that’s faster and higher-resolution than existing technology. They discovered that, under the right conditions, laser light clutter can spontaneously self-organize into a highly focused “pencil beam.”
Using this self-organized pencil beam, the team captured 3D images of the human blood-brain barrier 25 times faster than the gold-standard method, while maintaining comparable resolution, according to the scientists.
By showing individual cells absorbing drugs in real-time, this technology could help scientists test whether new drugs for neurodegenerative disease like Alzheimer’s or ALS reach their targets in the brain, with greater speed and resolution, they add.
“The common belief in the field is that if you crank up the power in this type of laser, the light will inevitably become chaotic. But we proved that this is not the case. We followed the evidence, embraced the uncertainty, and found a way to let the light organize itself into a novel solution for bioimaging,” says Sixian You, PhD, assistant professor in the MIT department of electrical engineering and computer science (EECS), a member of the research laboratory for electronics.
You is senior author of a paper “Self-localized ultrafast pencil beam for volumetric multiphoton imaging” on this imaging technique in Nature Medicine.
A better beam
When the researchers performed characterization experiments of this pencil beam, it was more stable and high-resolution than many similar beams. Other beams often suffer from “sidelobes,” blurry halos of light that can distort images.
Their beam was more pristine and tightly focused, according to You. Building on those experiments, the researchers demonstrated the use of this pencil-beam in biomedical imaging of the human blood-brain barrier.
Scientists and clinicians often want to see how drugs flow inside the vasculature of the blood-brain barrier and whether they reach their targets within the brain. But with standard optical settings, the best one can do is capture one 2D section of the vasculature at a time, and then repeat the process multiple times to generate a fuller image, You explains.
Using this new technique, the researchers created an ultrafast, high-precision pencil beam that enabled them to dynamically track how cells absorb proteins in real-time.
“The pharmaceutical industry is especially interested in using human-based models to screen for drugs that effectively cross the barrier, as animal models often fail to predict what happens in humans. That this new method doesn’t require the cells to have a fluorescent tag is a game-changer,” notes Roger Kamm, PhD, the Cecil and Ida Green Distinguished Professor of Biological Science and Mechanical Engineering.
“For the first time, we can now visualize the time-dependent entry of drugs into the brain and even identify the rate at which specific cell types internalize the drug.”
“Importantly, however, this approach is not limited to the blood-brain barrier but enables time-resolved tracking of diverse compounds and molecular targets across engineered tissue models, providing a powerful tool for biological engineering,” points out postdoctoral fellow Sarah Spitz, PhD.
The team reports that it captured cellular-level 3D images that were higher quality than with other methods, and generated these images about 25 times faster.
“Usually, you have a tradeoff between image resolution and depth of focus—you can only probe so far at a time. But with our method, we can overcome this tradeoff by creating a pencil-beam with both high resolution and a large depth of focus,” You says.
In the future, the researchers want to better understand the fundamental physics of the pencil-beam and the mechanisms behind its self-organization. They also plan to apply the technique to other scenarios, such as imaging neurons in the brain, and work toward commercializing the technology.
