We explore new optical microscopic methods to look deeper into the living brain and see disease progression. We have built optical microscopes that form cellular-scale images at record depths in the mouse brain, over one millimeter in depth, without removing the skull. Such microscopes enabled three-dimensional neuropathology of Alzheimer’s disease deep in the living mouse neocortex, without requiring slicing or staining of the tissue. We are currently improving the signal-to-noise ratio and resolution while adding additional functional contrast.

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