Fast volumetric imaging of neural activity in deep brain

Che Pin Jonathan Chang, Timothy E. Holy

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

1 Scopus citations


Calcium imaging is a widely-used technique for recording neuronal activity. For deep-brain imaging, light scattering degrades image acquisition. To avoid imaging through thick tissue, one common approach is to implant a small lens system (a microendoscope) into the brain. But there is no technique to achieve fast volumetric imaging through such lenses, and this lack forces a choice between abandoning optical sectioning or sampling with risk of confusion from overlaps (when labeling is dense) or being limited to modest neural population size (when labeling is sparse). To address these limitations, we designed a novel imaging technique, RE-imaging Axial Light-sheet Microscopy (REALM), suitable for fast three-dimensional imaging through a microendoscope. REALM images via a tilted light-sheet, illuminating and collecting fluorescence emission with single objective. The first-stage “Maxwell theorem” microscope employs a matching pair of objectives to reimage sample volume onto a sawtooth mirror, which consists of a series of sub-micrometer scale angled surfaces. The sawtooth mirror redirects the light horizontally into the second-stage microscope, forming a crisp image of the illuminated near-axial plane. The whole second microscope system collects over 40% of light reflected by the sawtooth mirror, compared to previous studies 28% of light collection efficiency at numerical apertures that are unavailable for microendoscopy. This microscope will combine the speed and resolution advantages of light-sheet microscopy with the capabilities of microendoscopes for deep-brain imaging, providing the ability to perform fast three-dimensional imaging in deep tissue.

Original languageEnglish
Title of host publicationOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics
EditorsV. X. D. Yang, Q. M. Luo, S. K. Mohanty, J. Ding, A. W. Roe, J. M. Kainerstorfer, L. Fu, S. Shoham
ISBN (Electronic)9781510640931
StatePublished - 2021
EventOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics 2021 - Virtual, Online, United States
Duration: Mar 6 2021Mar 11 2021

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
ISSN (Print)1605-7422


ConferenceOptical Techniques in Neurosurgery, Neurophotonics, and Optogenetics 2021
Country/TerritoryUnited States
CityVirtual, Online


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