Miniaturized optical neuroimaging in unrestrained animals

Abstract

The confluence of technological advances in optics, miniaturized electronic components and the availability of ever increasing and affordable computational power have ushered in a new era in functional neuroimaging. Namely, an era in which neuroimaging of cortical function in unrestrained and unanesthetized rodents has become a reality. Traditional optical neuroimaging required animals to be anesthetized and restrained. This greatly limited the kinds of experiments that could be performed in vivo. Now one can assess blood flow and oxygenation changes resulting from functional activity, image functional response in disease models such as stroke and seizure, and even conduct long-term imaging of tumor physiology, all without the confounding effects of anesthetics or animal restraints. These advances are shedding new light on mammalian brain organization and function, and helping to elucidate loss of this organization or ‘dysfunction’ in a wide array of central nervous system disease models. In this review, we highlight recent advances in the fabrication, characterization and application of miniaturized head-mounted optical neuroimaging systems pioneered by innovative investigators from a wide array of disciplines. We broadly classify these systems into those based on exogenous contrast agents, such as single- and two-photon microscopy systems; and those based on endogenous contrast mechanisms, such as multispectral or laser speckle contrast imaging systems. Finally, we conclude with a discussion of the strengths and weaknesses of these approaches along with a perspective on the future of this exciting new frontier in neuroimaging.

Transcranial Functional Ultrasound Imaging in Freely Moving Awake Mice and Anesthetized Young Rats without Contrast Agent

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Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain

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Two-photon probes for in vivo multicolor microscopy of the structure and signals of brain cells

“…New kinds of detectors like GaAsP photomultipliers or hybrid avalanche photodiodes allow detection of dimmer signals. Also, promising advances in the miniaturization of two-photon microscopes are enabling simultaneous recordings of neural circuit activity in freely moving animals (Yu et al 2015; Zong et al 2017) while avoiding the side effects associated with the use of anesthetics (Tran and Gordon 2015; Santisakultarm et al 2016). …”