Using a specialized MRI sensor, MIT researchers have shown that they will detect light deep inside tissues equivalent to the brain.

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

One of these sensor might be used to map light emitted by optical fibers implanted within the brain, equivalent to the fibers used to stimulate neurons during optogenetic experiments. With further development, it could also prove useful for monitoring patients who receive light-based therapies for cancer, the researchers say.

We are able to image the distribution of sunshine in tissue, and that is vital because individuals who use light to stimulate tissue or to measure from tissue often don’t quite know where the sunshine goes, where they’re stimulating, or where the sunshine is coming from. Our tool might be used to deal with those unknowns.”

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

Jasanoff, who can also be an associate investigator at MIT’s McGovern Institute for Brain Research, is the senior creator 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 Recent York University are also authors of the paper.

A light-weight-sensitive probe

Scientists have been using light to review living cells for a whole bunch of years, dating back to the late 1500s, when the sunshine microscope was invented. This type of microscopy allows researchers to see inside cells and thin slices of tissue, but not deep inside an organism.

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

To beat that limitation, Jasanoff and his students decided to design a sensor that might transform light right into a magnetic signal.

“We desired to create a magnetic sensor that responds to light locally, and subsequently will not be subject to absorbance or scattering. Then this light detector might be imaged using MRI,” he says.

Jasanoff’s lab has previously developed MRI probes that may interact with quite a lot of molecules within the brain, including dopamine and calcium. When these probes bind to their targets, it affects the sensors’ magnetic interactions with the encompassing tissue, dimming or brightening the MRI signal.

To make a light-sensitive MRI probe, the researchers decided to encase magnetic particles in a nanoparticle called a liposome. The liposomes utilized in this study are made out of specialized light-sensitive lipids that Trauner had previously developed. When these lipids are exposed to a certain wavelength of sunshine, the liposomes grow to be more permeable to water, or “leaky.” This enables the magnetic particles inside to interact with water and generate a signal detectable by MRI.

The particles, which the researchers called liposomal nanoparticle reporters (LisNR), can switch from permeable to impermeable depending on the form of light they’re exposed to. On this study, the researchers created particles that grow to be leaky when exposed to ultraviolet light, after which grow to be impermeable again when exposed to blue light. The researchers also showed that the particles could reply to other wavelengths of sunshine.

“This paper shows a novel sensor to enable photon detection with MRI through the brain. This illuminating work introduces a recent avenue to bridge photon and proton-driven neuroimaging studies,” says Xin Yu, an assistant professor radiology at Harvard Medical School, who was not involved within the study.

Mapping light

The researchers tested the sensors within the brains of rats -; specifically, in an element 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 in a position to map the distribution of sunshine from an optical fiber implanted nearby.

The fiber they used is comparable to those used for optogenetic stimulation, so this type of sensing might be useful to researchers who perform optogenetic experiments within the brain, Jasanoff says.

“We do not expect that everyone doing optogenetics will use this for each experiment -; it’s more something that you simply would do from time to time, to see whether a paradigm that you simply’re using is admittedly producing the profile of sunshine that you’re thinking that it needs to be,” Jasanoff says.

In the long run, this kind of sensor may be useful for monitoring patients receiving treatments that involve light, equivalent to photodynamic therapy, which uses light from a laser or LED to kill cancer cells.

The researchers at the moment are working on similar probes that might be used to detect light emitted by luciferases, a family of glowing proteins which can be often utilized in biological experiments. These proteins might be used to disclose whether a specific gene is activated or not, but currently they will only be imaged in superficial tissue or cells grown in a lab dish.

Jasanoff also hopes to make use of the strategy used for the LisNR sensor to design MRI probes that may detect stimuli aside from light, equivalent to neurochemicals or other molecules present in the brain.

“We expect that the principle that we use to construct these sensors is sort of broad and might be used for other purposes too,” 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.

Source:

Massachusetts Institute of Technology

Journal reference:

Simon, J., et al. (2022) Mapping light distribution in tissue through the use of MRI-detectable photosensitive liposomes. Nature Biomedical Engineering. doi.org/10.1038/s41551-022-00982-3.