Using specialized MRI sensors, MIT researchers have shown that light can be detected deep in tissues such as the brain.
Imaging deep tissue light is very difficult. This is because when light reaches tissue, much of it is absorbed or scattered. An MIT team overcame this obstacle by designing a sensor that converts light into magnetic signals that his MRI (magnetic resonance imaging) can detect.
This type of sensor can 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, the researchers say, it could also help monitor patients undergoing light-based cancer treatments.
“We can image the distribution of light in tissue, which is important. Our tools can be used to address these unknowns,” said Massachusetts Institute of Technology’s Bioengineering, Brain and Alan Jasanoff, professor of cognitive science, nuclear science and engineering, said.
Jasanoff, also an Associate Fellow at MIT’s McGovern Institute for Brain Research, was the lead author of the study and today Nature Biomedical EngineeringJacob Simon PhD ’21 and MIT postdoc Miriam Schwalm are lead authors of the paper, as are Johannes Morstein and Dirk Trauner of New York University.
light sensitive probe
Scientists have used light to study living cells for hundreds of years, dating back to the late 1500s when the light microscope was invented. This type of microscopy allows researchers to peer inside thin slices of cells and tissue, but not the depths of living organisms.
“One persistent problem with using light, especially in the life sciences, is that many materials do not penetrate well,” says Jasanoff. “Biomaterial absorbs light and scatters light. These combinations preclude the use of most types of optical imaging, including focusing on deep tissue.”
To overcome that limitation, Jasanoff and his students decided to design a sensor that could convert light into magnetic signals.
“We wanted to make a magnetic sensor that reacts to light locally, so it is not affected by absorption or scattering. This photodetector can then be imaged using MRI,” he says.
Jasanoff’s lab has previously developed MRI probes that can interact with various molecules in the brain, such as dopamine and calcium. When these probes bind to their targets, they affect the magnetic interaction between the sensor and surrounding tissue, dimming or brightening the MRI signal.
To create light-sensitive MRI probes, researchers decided to encase magnetic particles in nanoparticles called liposomes. The liposomes used in this study are made from special photosensitive lipids previously developed by Trauner. When these lipids are exposed to certain wavelengths of light, the liposomes become highly permeable to water and become ‘leaky’. This allows the magnetic particles inside to interact with the water and produce a signal detectable 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, researchers created particles that became leaky when exposed to ultraviolet light and became impermeable again when exposed to blue light. Researchers have also shown that the particles can respond to other wavelengths of light.
“This paper presents a new sensor that enables photon detection by MRI through the brain. This bright study opens up new avenues for bridging photon- and proton-driven neuroimaging studies.” not involved in
mapping light
The researchers tested the sensor in rat brains, specifically a part of the brain called the striatum. The striatum is involved in planning movements and responding to rewards. After injecting particles throughout the striatum, researchers were able to map the distribution of light from nearby-embedded optical fibers.
The fibers they used are similar to those used for optogenetic stimulation, so this type of sensing could be useful for researchers doing optogenetic experiments in the brain, says Jasanoff. Says.
“I don’t expect everyone doing optogenetics to use this for every experiment. Just to see if the paradigm you’re using really produces the light profile you think it is. , is something you do once in a while, it should be,” Jasanov says.
In the future, this type of sensor could also help monitor patients undergoing light-based treatments, such as photodynamic therapy, which uses light from lasers or LEDs to kill cancer cells.
Researchers are now working on similar probes that could be used to detect light emitted by luciferases, a family of photoproteins commonly used in biological experiments. These proteins can be used to reveal whether a particular gene is activated, but currently can only be imaged on surface tissue or cells grown in laboratory dishes.
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 and other molecules found in the brain.
“I think the principles we use to build these sensors are very broad and can be used for other purposes,” he says.
This work was funded by the National Institutes of Health, the G. Harold and Leila Y. Mathers Foundation, the McGovern Brain Institute Friends of the McGovern Fellowship, the MIT Neurobiology Training Program, and the Marie Curie Individual Fellowship. European Commission.
