Wide-Field Optical Imaging in Mouse Models of Ischemic Stroke

Abstract

Functional neuroimaging is a powerful tool for evaluating how local and global brain circuits evolve after focal ischemia and how these changes relate to functional recovery. For example, acutely after stroke, changes in functional brain organization relate to initial deficit and are predictive of recovery potential. During recovery, the reemergence and restoration of connections lost due to stroke correlate with recovery of function. Thus, information gleaned from functional neuroimaging can be used as a proxy for behavior and inform on the efficacy of interventional strategies designed to affect plasticity mechanisms after injury. And because these findings are consistently observed across species, bridge measurements can be made in animal models to enrich findings in human stroke populations. In mice, genetic engineering techniques have provided several new opportunities for extending optical neuroimaging methods to more direct measures of neuronal activity. These developments are especially useful in the context of stroke where neurovascular coupling can be altered, potentially limiting imaging measures based on hemodynamic activity alone. This chapter is designed to give an overview of functional wide-field optical imaging (WFOI) for applications in rodent models of stroke, primarily in the mouse. The goal is to provide a protocol for laboratories that want to incorporate an affordable functional neuroimaging assay into their current research thrusts, but perhaps lack the background knowledge or equipment for developing a new arm of research in their lab. Within, we offer a comprehensive guide developing and applying WFOI technology with the hope of facilitating accessibility of neuroimaging technology to other researchers in the stroke field.

Keywords: BOLD; GECI; Genetically encoded calcium indicator; ISA; Infra-slow activity; OISI; Optical intrinsic optical imaging; RS-FC; Resting-state functional connectivity; WFOI; Wide-field optical imaging; blood oxygen level dependent.