Intrinsic, widefield optical imaging of hemodynamics in rodent models of Alzheimer's disease and neurological injury.

The complex cerebrovascular network is critical to controlling local cerebral blood flow (CBF) and maintaining brain homeostasis. Alzheimer's disease (AD) and neurological injury can result in impaired CBF regulation, blood-brain barrier breakdown, neurovascular dysregulation, and ultimately impaired brain homeostasis. Measuring cortical hemodynamic changes in rodents can help elucidate the complex physiological dynamics that occur in AD and neurological injury. Widefield optical imaging approaches can measure hemodynamic information, such as CBF and oxygenation. These measurements can be performed over fields of view that range from millimeters to centimeters and probe up to the first few millimeters of rodent brain tissue. We discuss the principles and applications of three widefield optical imaging approaches that can measure cerebral hemodynamics: (1) optical intrinsic signal imaging, (2) laser speckle imaging, and (3) spatial frequency domain imaging. Future work in advancing widefield optical imaging approaches and employing multimodal instrumentation can enrich hemodynamic information content and help elucidate cerebrovascular mechanisms that lead to the development of therapeutic agents for AD and neurological injury.