overview: Researchers have developed a new specialized MRI sensor that detects light deep within brain tissue.
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 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. People who use light to stimulate tissue or to take measurements from tissue can see where the light is going, where it is stimulating, This is important because we often don’t know where the light is coming from. Our tools can be used to address these unknown problems,” says Bioengineering, Brain and Cognitive Science, Nuclear says Alan Jasanoff, Massachusetts Institute of Technology (MIT) professor of science and engineering.
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 of the deepest problems with using light, especially in the life sciences, is that it doesn’t work well through many materials,” says Jasanoff. “Biomaterials absorb light and scatter light. These combinations make most types of optical imaging unusable for those that involve 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 create a magnetic sensor that is immune to absorption and scattering because it responds to light locally. 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 demonstrates 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,” said Harvard. Xin Yu, assistant professor of radiology at the university’s medical school, said he was not involved in the research.
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 make sure the paradigm you’re using really produces the light profile you think it is.” It’s something you do once in a while for the sake of it, and 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.
Funding: 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.
About this Neurotech Research News
author: Anne Trafton
contact: Ann Trafton – MIT
image: Image credited to MIT
Original research: closed access.
“Mapping light distribution in tissues using MRI-detectable photosensitive liposomes” by Alan Jasanoff et al. Nature Biomedical Engineering
Mapping light distribution in tissues using MRI-detectable photosensitive liposomes
Characterizing the source and target of illumination in living tissue is difficult. Here we show that magnetic resonance imaging (MRI) can be used in the presence of photosensitive nanoparticle probes to map the spatial distribution of light in tissue.
Each probe consists of a reservoir of paramagnetic molecules surrounded by a liposomal membrane that incorporates photosensitive lipids. Incident light causes photoisomerization of lipids, altering hydrodynamic exchange across the membrane, thereby affecting longitudinal relaxation-weighted contrast in MRI.
We injected nanoparticles into the brains of living rats and used MRI to map responses to lighting profiles that are hallmarks of the widely used applications of photostimulation, photometry, and phototherapy.
The response deviates from a simple photon propagation model and reveals light scattering and nonlinear response features. Paramagnetic liposomal nanoparticles have the potential to map a wide range of optical phenomena in deep tissue and other opaque environments with MRI.