An international research team has developed a new bioimaging technology that overturns conventional optical wisdom. They confirmed that under specific conditions, a strong laser beam transforms into a very thin, sharp, pencil-shaped beam, enabling 3D imaging of the human blood-brain barrier about 25 times faster than the standard method while maintaining a comparable level of resolution.
Researchers at the Massachusetts Institute of Technology (MIT) published the findings in the international journal Nature Methods on the 27th.
The discovery came as the team tested the limits of multimode optical fibers. Multimode optical fibers allow light to travel simultaneously along multiple paths and can deliver a large amount of light. However, due to subtle internal imperfections, light tends to spread and mix along different paths.
However, the researchers found that when they increased the laser power close to the level that could damage the fiber, the light focused into a needle-thin, sharp beam. This resulted from raising the laser power until the light interacted with the glass forming the fiber, with the laser incident on the fiber at exactly a 0-degree angle.
They then applied the pencil-shaped beam to imaging the human blood-brain barrier. The blood-brain barrier is a kind of checkpoint that protects the brain. It blocks toxic substances in the blood from entering the brain, but at the same time makes it difficult for treatments for degenerative brain diseases such as Alzheimer's disease or Lou Gehrig's disease to reach the brain. Therefore, when developing brain disease treatments, it is crucial to verify whether a drug can cross this barrier.
Using the pencil-shaped beam, they were able to track in real time how blood-brain barrier cells absorb proteins. They obtained cell-level 3D images about 25 times faster than the standard method, while maintaining comparable image quality.
Conventional optical imaging typically captures thin 2D sections one by one and stacks them to create a 3D image. While precise, this approach takes a long time. It also has limitations for observing, in real time, how cells absorb drugs.
Another reason the newly developed technology is drawing attention is that it enables observation without fluorescent labeling. In bioimaging research, fluorescent tags are often attached to visualize specific cells or substances. While fluorescent labeling makes targets glow and easier to see, the process is complex and can cause cell or drug behavior to differ from what occurs in the body.
The researchers said, "This technology can be used not only for blood-brain barrier research but also to track the movement of specific substances over time in a variety of artificial tissue models," and noted, "We will further elucidate the fundamental physical principles behind the formation of the 'pencil beam' and, in the long term, pursue commercialization of the technology."
References
Nature Methods (2026), DOI: https://doi.org/10.1038/s41592-026-03067-0