Specialized MRI sensor can detect light deep within tissues

Using a specialized MRI sensor, MIT researchers have shown they can detect light deep in tissues such as the brain.

Imaging light in deep tissues is extremely difficult because as light travels into the tissue, much of it is either absorbed or scattered. The MIT team overcame that hurdle by designing a sensor that converts light into a magnetic signal that can be detected by MRI (magnetic resonance imaging).

This type of sensor could be used to map the light emitted by optical fibers implanted in the brain, such as the fibers used to stimulate neurons during optogenetic experiments. With further development, it could also prove useful for monitoring patients receiving light therapies for cancer, the researchers said.

We can visualize the distribution of light in the tissue, and that’s important because people who use light to stimulate tissue or take measurements from tissue often don’t know where the light is going, where it’s stimulating, or where the light is coming from. Our tool can be used to solve those unknowns.”


Alan Jasanoff, MIT professor of biological engineering, brain and cognitive science, and nuclear science and engineering

Jasanoff, who is also a research associate at MIT’s McGovern Institute for Brain Research, is senior author of the study, which appears today in Natural Biomedical Engineering. Jacob Simon PhD ’21 and MIT postdoc Miriam Schvalm are the lead authors of the paper, and Johannes Morstein and Dirk Trauner of New York University are also authors of the paper.

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A light-sensitive probe

Scientists have been using light to study living cells for hundreds of years, ever since the late 1500s, when the light microscope was invented. This type of microscopy allows researchers to peer into cells and thin slices of tissue, but not deep into the organism.

“One of the persistent problems with using light, especially in the life sciences, is that it doesn’t do a very good job of penetrating many materials,” says Jasanoff. “Biological materials absorb light and scatter light, and the combination of those things prevents us from using most types of optical imaging for anything that involves focusing into deep tissue.”

To overcome that limitation, Jasanoff and his students decided to design a sensor that could transform light into a magnetic signal.

“We wanted to make a magnetic sensor that responds to light locally, and is therefore not subject to absorption or scattering. Then this light detector can be imaged with MRI,” he says.

Jasanoff’s lab has previously developed MRI probes that can interact with various molecules in the brain, including dopamine and calcium. When these probes bind to their targets, it affects the sensor’s magnetic interactions with the surrounding tissue, dimming or brightening the MRI signal.

To create a light-sensitive MRI probe, the researchers decided to coat the magnetic particles in a nanoparticle called a liposome. The liposomes used in this study were made from specialized light-sensitive lipids previously developed by Trauner. When these lipids are exposed to a certain wavelength of light, the liposomes become more permeable to water, or “permeable.” This allows the magnetic particles inside to interact with the water and generate a signal that can be detected by MRI.

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The particles, which the researchers called liposomal nanoparticle reporters (LisNRs), can be switched from permeable to impervious depending on the type of light they are exposed to. In this study, the researchers created particles that are transparent when exposed to ultraviolet light and then become opaque again when exposed to blue light. The researchers also showed that the particles can respond to other wavelengths of light.

“This work demonstrates a new sensor that enables photon detection with MRI through the brain. This illuminating work opens a new path for bridging photon- and proton-guided neuroimaging studies,” says Xin Yu, assistant professor of radiology at Harvard Medical School, who was not involved in the study.

Light mapping

Researchers tested sensors in the brains of rats -; specifically, in a part of the brain called the striatum, which is involved in planning movements and responding to reward. After injecting the particles through the striatum, the researchers were able to map the distribution of light from an optical fiber implanted nearby.

The fibers they used are similar to those used for optogenetic stimulation, so this type of sensing could be useful for researchers performing optogenetic experiments in the brain, Jasanoff says.

“We don’t expect everyone doing optogenetics to use this for every experiment—it’s more something you would do every once in a while, to see if the paradigm you’re using is actually producing the light profile you think it should be,” Jasanoff says. .

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In the future, this type of sensor could also be useful for monitoring patients receiving treatments that involve light, such as photodynamic therapy, which uses light from a laser or LED to kill cancer cells.

Researchers are now working on similar probes that could be used to detect the light emitted by luciferases, a family of light-emitting proteins often used in biological experiments. These proteins can be used to detect whether a particular gene is activated or not, but currently they can only be imaged in surface tissue or cells grown in a lab dish.

Jasanoff also hopes to use the strategy used for the LisNR sensor to design MRI probes that can detect stimuli other than light, such as neurochemicals or other molecules found in the brain.

“We think the principle we use to construct these sensors is quite broad and can be used for other purposes as well,” he says.

The research was funded by the National Institutes of Health, Foundation G. Harold and Leila I. Mathers, Friends of the McGovern Fellowship from the McGovern Institute for Brain Research, the MIT Neurobiological Engineering Training Program and a Marie Curie Individual Fellowship from the European Commission.

Source:

Massachusetts Institute of Technology

Journal reference:

Simon, J., e t al. (2022) Mapping light distribution in tissue using MRI-detectable photosensitive liposomes. Natural Biomedical Engineering. doi.org/10.1038/s41551-022-00982-3.

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