New Microscope peers Deep into Brain Tissue Using Sound
For both research and medical purposes, scientists have spent decades improving microscopy to get deeper and sharper images of brain activity, not just in the cortex but also in areas underneath like the hippocampus. Now, a team of MIT scientists and engineers has created a new microscope system that can see exceptionally deep into brain tissues and detect the molecular activity of individual cells using sound.
“The major advance here is that we can now image deeper at single-cell resolution,” said neuroscientist Mriganka Sur,a corresponding author along with mechanical engineering Professor Peter So and principal research scientist Brian Anthony. Sur is the Paul and Lilah Newton Professor in The Picower Institute for Learning and Memory and the Department of Brain and Cognitive Sciences at MIT.
In the journal Light: Science and Applications, the team showed they could detect NAD(P)H – a molecule closely linked to cell metabolism and electrical activity in neurons – all the way through samples like a 1.1 mm “cerebral organoid” (a 3D, mini brain-like tissue grown from human stem cells) and a 0.7 mm thick slice of mouse brain tissue.
In fact, co-lead author and mechanical engineering postdoc W. David Lee, who designed the microscope, said the system could have peered even deeper, but the test samples weren’t large enough to prove it.
“That’s when we hit the glass on the other side. I think we’re pretty confident about going deeper.”
W. David Lee, co-lead author and mechanical engineering postdoc
Reaching a depth of 1.1 mm is more than five times deeper than other microscope technologies can resolve NAD(P)H within dense brain tissue. The new system achieved this depth and clarity by combining several advanced technologies to precisely and efficiently excite the molecule and then detect the resulting energy, all without needing to add external labels – either chemicals or genetically engineered fluorescence.
Rather of focusing the required NAD(P)H excitation energy…