The Development of a Resonant Scanning MMM system for high resolution 3D CNS imaging

PROJECT SUMMARY Central Nervous System disorders have proven to be among the most difficult of diseases to treat and have placed an enormous burden on societyA major contributing factor to this situation is that currently we often cannot distinguish between normal and pathological states since we do not possess even a basicground truthmap of how neurons and other cells are arranged at the nanoscale level for representative pieces of neuronal tissueExtensive efforts are underway to build these fine scale structural maps of mammalian brains with the hope that these will lead to an understanding of the how brain ultimately functions and how best to target therapeuticsHowever the problem is immense as a single cubic mm of brain tissue contains aboutneurons and roughly a billion synaptic connectionsThe overwhelming majority of these structural details are too small to be resolved with even the best optical microscopes and current super resolution approaches lack the necessary throughputWe propose to meet this challenge by developing an ultra high speed Serial Two Photon Tomography system that combines high speed resonant scanning with TissueVision s novel multi focal microscopy and which will be able to quickly imageD volumes of neuronal tissue with sub micron resolutionWith our collaborators at MIT in the Ed Boyden groupwe will apply this system to study the CNS cytoarchitecture at the nanoscopic level by using a new technique the Boyden lab has developed called Expansion MicroscopyExMthat physically expands tissue up tofold to provide an effective nanoscalenmview into the structure of macroscopic portions of the CNSFor this projectwe have put together a world class team of experts from TissueVision and MIT who have deep expertise with optics and neuroscience as well as a successful track record of commercializing biomedical imaging systems for the neuroscience marketWhile our focus here is on nanoscale imaging of CNS tissuesthe device we will develop will represent a major tool for a variety of brain mapping efforts including whole brain neuronal circuit analysis and mesoscale mapping efforts