by Using a special MRI sensor, MIT researchers have shown they can detect light deep within tissues such as the brain.
Imaging light in deep tissues is extremely difficult because much of it is either absorbed or scattered as light penetrates tissue. The MIT team overcame this obstacle by developing 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 image light emitted from optical fibers implanted in the brain, such as B. the fibers used to stimulate neurons during optogenetic experiments. As it evolves, it could also prove useful for monitoring patients receiving light-based therapies for cancer, the researchers say.
“We can image the distribution of light in tissue, and that’s important because people who use light to stimulate tissue or measure tissue often don’t know exactly where the light is going, where they are stimulating, or where the light is ours.” Tool can be used to address these unknowns,” says Alan Jasanoff, MIT Professor of Bioengineering, Brain and Cognitive Sciences, and Nuclear Science and Engineering.
Jasanoff, who is also an Associate Investigator at MIT’s McGovern Institute for Brain Research, is the senior author of the study, which appears in today’s Nature Biomedical Engineering. Jacob Simon PhD ’21 and MIT postdoc Miriam Schwalm are the lead authors of the paper, and Johannes Morstein and Dirk Trauner from New York University are also authors of the paper.
A light-sensitive probe
Scientists have used light to study living cells for hundreds of years, dating back to the late 16th century when the light microscope was invented. This type of microscopy allows researchers to look inside cells and thin sections of tissue, but not deep into an organism.
“One of the ongoing problems with using light, particularly in the life sciences, is that it doesn’t penetrate many materials very well,” says Jasanoff. “Biological materials absorb light and scatter light, and the combination of these things prevents us from using most types of optical imaging for anything that involves deep tissue focusing.”
To overcome this limitation, Jasanoff and his students decided to develop a sensor that could convert light into a magnetic signal.
“We wanted to create a magnetic sensor that reacts 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 a variety of molecules in the brain, including dopamine and calcium. When these probes bind to their targets, it affects the sensors’ magnetic interactions with the surrounding tissue, causing the MRI signal to dim or brighten.
To create a light-sensitive MRI probe, the researchers decided to encapsulate magnetic particles in a nanoparticle called a liposome. The liposomes used in this study are made from special light-sensitive lipids that Trauner had previously developed. When these lipids are exposed to a certain wavelength of light, the liposomes become more permeable to water, or “leak”. This allows the magnetic particles inside to interact with water and generate a signal detectable by MRI.
The particles, which the researchers dubbed liposomal nanoparticle reporters (LisNR), can switch from transparent to opaque depending on the type of light they are exposed to. In this study, the researchers made particles that leak in ultraviolet light and become opaque again in blue light. The researchers also showed that the particles could respond to other wavelengths of light.
“This paper demonstrates a novel sensor that enables photon detection by the brain using MRI. This insightful work opens up a new avenue to bridge photon- and proton-driven neuroimaging studies,” says Xin Yu, assistant professor of radiology at Harvard Medical School not involved in the study.
map light
The researchers tested the 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 rewards. After the particles were injected through the striatum, the researchers were able to map the light distribution from an optical fiber implanted nearby.
The fiber they used is similar to the one used for optogenetic stimulation, so this type of sensing could be useful for researchers conducting optogenetic experiments in the brain, says Jasanoff.
“We don’t expect everyone who studies optogenetics to use this for every experiment – it’s rather something you would do every once in a while to see if a paradigm you’re using is really producing the light profile, that you think it should be,” says Jasanoff.
In the future, this type of sensor could also be useful for monitoring patients receiving treatments that involve light, such as B. 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 light emitted by luciferases, a family of glowing proteins commonly used in biological experiments. These proteins can be used to show whether or not a particular gene is activated, but currently they can only be imaged in superficial tissue or cells grown in a laboratory dish.
Jasanoff also hopes to use the strategy used for the LisNR sensor to develop MRI probes that can detect stimuli other than light, such as B. neurochemicals or other molecules found in the brain.
“We think the principle we’re using to construct these sensors is pretty broad and can be used for other purposes as well,” he says.
The research was funded by the National Institutes of Health, the G. Harold and Leyla Y. Mathers Foundation, a 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 .
