Scientists at MIT have reached a new milestone in the quest to understand the intricacies of the brain. A freshly unveiled microscope system, promised to be a game-changer, allows researchers to view finely detailed images of the brain's activity down to individual cells, without introducing external markers. The technology adeptly navigates the depths of brain tissue with precision unheard of until now, a press release from MIT News reports.
According to the same source, MIT neuroscientist Mriganka Sur, teamed up with colleagues including mechanical engineering professor Peter So and principal research scientist Brian Anthony, has contributed to a study showcasing this scientific breakthrough. “The major advance here is to enable us to image deeper at single-cell resolution,” Sur said. Through the imaging of NAD(P)H, a molecule tied to cell metabolism and neurons' electrical activity, they've achieved views into brain tissue up to 1.1 millimeters deep, which significantly outpaces the capabilities of existing microscopy techniques. The team foresees that with this technology, the depths they can explore within the brain could extend well beyond their current samples.
The system achieves its depth by using a technique called "three-photon" excitation. This method, which employs a burst of light thrice the normal absorption wavelength of NAD(P)H, dives deep into tissue with minimal scattering, akin to the way fog lamps penetrate thick fog. Interestingly, the energy absorbed doesn't just trigger a fluorescent glow—most of it causes a localized thermal expansion that translates into sound waves. These are then picked up by a specialized ultrasound microphone, eventually converted into high-resolution images, explained co-lead author W. David Lee.
Combining their expertise, researchers including Tatsuya Osaki, Xiang Zhang, and Rebecca Zubajlo have taken this concept to demonstrate a label-free, multiphoton, photoacoustic microscopy (LF-MP-PAM). “We merged all these techniques — three-photon, label-free, photoacoustic detection,” Osaki noted on MIT News, setting the stage for a suite of neuroscience and clinical applications unmatched by previous methodologies. The third-harmonic generation imaging achieved alongside served to render cellular structures with precision.
Having already shown the potential of NAD(P)H imaging in wound care through Lee's founded, and sold company, Precision Healing, Inc., the next challenge for the team lies in in vivo application of the technology in living animals. In anticipation, Lee expressed confidence in achieving full imaging at 2 millimeters deep in live brains, an ambition that, if attained, might unlock new horizons in the diagnosis and treatment of brain conditions like Alzheimer's disease and epilepsy. This mission is backed by various funding sources, including the National Institutes of Health and The Picower Institute for Learning and Memory.
