Noninvasive imaging method can penetrate deeper into living tissue

But light scatters when it hits biological tissue, limiting its penetration depth and affecting the resolution of captured images.

Now, MIT researchers have developed a new technique that can more than double the usual depth limits of metabolic imaging. Their method also increases imaging speed, producing richer, more detailed images.

The new technique does not require pre-processing of the tissue, such as cutting or staining it with dyes. Instead, a specialized laser shines deep into the tissue, causing certain intrinsic molecules within the cells and tissue to glow. This eliminates the need to alter the organization, providing a more natural and accurate representation of its structure and function.

Researchers achieve this goal by adapting and customizing lasers for deep tissue. Using a recently developed fiber shaper, a device controlled by bending, they can adjust the color and pulse of light to minimize scatter and maximize signal as the light penetrates deeper into tissue. This allows them to peer deeper into living tissue and capture clearer images.

Greater penetration depth, faster speed and higher resolution make this method particularly suitable for demanding imaging applications such as cancer research, tissue engineering, drug discovery and immune response studies.

“This work shows a significant improvement in deep penetration of label-free metabolic imaging. It opens up new ways to study and explore metabolic dynamics deep in living biological systems,” said You Sixian, assistant professor in the Department of Electrical Engineering and Computer Science (EECS ), a member of the Research Laboratory of Electronics and senior author of a paper on this imaging technology.

The main author of the paper, EECS graduate student Kunzan Liu, also participated in the writing of the paper. Tong Qiu, postdoctoral researcher at MIT; Honghao Cao, graduate student at EECS; Fan Wang, professor of brain and cognitive sciences; Roger Kamm, Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering; Linda Griffith, bioengineering, School of Engineering Department Teaching Innovation Professor; and other MIT colleagues. The research will appear in scientific progress.

laser focus

The new method falls under label-free imaging, meaning the tissue is not stained beforehand. The contrast produced by the staining helps clinical biologists better visualize cell nuclei and proteins. But staining often requires biologists to section the sample, a process that often kills the tissue and makes it impossible to study dynamic processes in living cells.

In label-free imaging, researchers use lasers to illuminate specific molecules within cells, causing them to emit different colors of light, revealing various molecular contents and cellular structures. However, generating the ideal laser with specific wavelengths and high-quality pulses for deep tissue imaging has been challenging.

Researchers have developed a new method to overcome this limitation. They used multimode fiber, a fiber that can carry large amounts of power, and coupled it to a compact device called a “fiber shaper.” This shaper allows them to precisely modulate light propagation by adaptively changing the shape of the fiber. Bending the fiber changes the color and intensity of the laser.

Building on previous work, the researchers modified the first version of the fiber former to perform deeper multimodal metabolic imaging.

“We want to convert all this energy into the color we need with the pulse characteristics we need. This gives us higher generation efficiency and clearer images, even deep within tissue,” Cao said.

Once the controllable mechanism was established, they developed an imaging platform that uses a powerful laser light source to generate longer wavelength light, which is critical for deeper penetration into biological tissue.

“We believe this technology has the potential to significantly advance biological research. By making it affordable and accessible to biological laboratories, we hope to provide scientists with a powerful discovery tool,” Liu said.

dynamic application

When the researchers tested their imaging device, light was able to penetrate more than 700 microns through biological samples, while the best existing technology could only penetrate about 200 microns.

“With this new type of depth imaging, we hope to look at biological samples and see things we’ve never seen before,” Liu added.

Deep imaging technology allows them to see cells at multiple levels within living systems, which can help researchers study the metabolic changes that occur at different depths. In addition, faster imaging speeds allowed them to collect more detailed information about how a cell’s metabolism affects the speed and direction of its movement.

This new imaging method could facilitate research into organoids, which are cells engineered to grow to mimic the structure and function of an organ. Researchers in the Kamm and Griffith laboratories have pioneered the development of brain and endometrial organoids that can be grown like organs for disease and treatment evaluation.

However, it is challenging to accurately observe internal development without cutting or staining the tissue, which would kill the sample.

This new imaging technique allows researchers to non-invasively monitor the metabolic state inside living organoids as they continue to grow.

With these and other biomedical applications in mind, the researchers plan to target higher-resolution imaging. At the same time, they are working to create low-noise laser light sources, which can achieve deeper imaging with less light dose.

They are also developing algorithms that respond to images to reconstruct the complete 3D structure of biological samples at high resolution.

In the long term, they hope to apply this technology to the real world, helping biologists to monitor drug responses in real time to aid the development of new drugs.

“By enabling multimodal metabolic imaging deep into tissue, we provide scientists with an unprecedented ability to observe opaque biological systems in their natural state. We are excited to collaborate with clinicians, biologists and bioengineers to push the boundaries in this field. limit.

This research was funded in part by an MIT Startup Grant, a National Science Foundation CAREER Award, an MIT Irving Jacobs and Joan Klein Presidential Fellowship, and an MIT Kailas Fellowship .