Using a specialized MRI sensor, MIT researchers have demonstrated that they can detect light deep within tissues such as the brain.
Imaging light in deep tissues is extremely difficult because much of the light travels into, is absorbed, or is scattered by the tissue. 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 can be used to map 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-based treatments 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 to measure from tissue often don’t really know where the light is going, where they’re stimulating, or where the light is coming from. Our tools can be used to address these unknowns,” said Alan Jasanoff, MIT professor of biological engineering, brain and cognitive science, and nuclear science and engineering.
Jasanoff, who is also an associate investigator at MIT’s McGovern Institute for Brain Research, is senior author of the study, which appears today in Nature Biomedical Engineering. Jacob Simon PhD ’21 and MIT postdoc Miriam Schwalm are the paper’s lead authors, and Johannes Morstein and Dirk Trauner of 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 scientists to look into cells and thin slices of tissue, but not deep inside an 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,” Jasanoff says. “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 focusing in deep tissue.”
To overcome that limitation, Jasanoff and his students decided to design a sensor that could convert light into a magnetic signal.
“We wanted to create a magnetic sensor that responds to light locally, and is therefore not subject to absorbance or scattering. Then this light detector can be imaged using 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, dampening or brightening the MRI signal.
To make a light-sensitive MRI probe, the researchers decided to enclose magnetic particles in a nanoparticle called a liposome. The liposomes used in this study are made from specialized 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 “leaky.” This allows the magnetic particles inside to interact with water and generate a signal that can be detected by MRI.
The particles, which the researchers called liposomal nanoparticle reporters (LisNRs), can switch from permeable to impermeable depending on the type of light they are exposed to. In this study, the researchers created particles that become leaky when exposed to ultraviolet light, then become impermeable again when exposed to blue light. The researchers also showed that the particles could respond to other wavelengths of light.
“This paper demonstrates a new sensor to enable photon detection with MRI through the brain. This enlightening work introduces a new way to bridge photon- and proton-driven neuroimaging studies,” said Xin Yu, assistant professor of radiology at Harvard Medical School, who was not involved in the study.
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 movement and responding to reward. After injecting the particles throughout the striatum, the researchers were able to map the distribution of light from an optical fiber implanted nearby.
The fiber they used is similar to those used for optogenetic stimulation, so this type of sensing could be useful for researchers conducting optogenetic experiments in the brain, Jasanoff said.
“We don’t expect everyone doing optogenetics to use this for every experiment – it’s more something that you would do once in a while, to see if a paradigm that you’re using really produces the profile of light 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 photodynamic therapy, which uses light from a laser or LED to kill cancer cells.
The researchers are now working on similar probes that can be used to detect light emitted by luciferases, a family of glowing proteins often used in biological experiments. These proteins can be used to reveal whether a particular gene is activated or not, but currently they can only be imaged in superficial 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 believe that the principle that 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, 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.