Deficits in prefrontal function play a crucial role in compulsive cocaine use, which is a hallmark of addiction.
Dysfunction of the prefrontal cortex might result from effects of cocaine on neurons as well as from disruption of
cerebral blood vessels. However, the mechanisms underlying cocaine’s neurotoxic effects are not fully understood,
partially due to technical limitations of current imaging techniques (e.g., PET, fMRI) to differentiate vascular from
neuronal effects at sufficiently high temporal and spatial resolutions. We have recently developed a multimodal imaging
platform which can simultaneously characterize the changes in cerebrovascular hemodynamics, hemoglobin oxygenation
and intracellular calcium fluorescence for monitoring the effects of cocaine on the brain. Such a multimodality imaging
technique (OFI) provides several uniquely important merits, including: 1) a large field-of-view, 2) high spatiotemporal
resolutions, 3) quantitative 3D imaging of the cerebral blood flow (CBF) networks, 4) label-free imaging of
hemodynamic changes, 5) separation of vascular compartments (e.g., arterial and venous vessels) and monitoring of
cortical brain metabolic changes, 6) discrimination of cellular (neuronal) from vascular responses. These imaging
features have been further advanced in combination with microprobes to form micro-OFI that allows quantification of
drug effects on subcortical brain. In addition, our ultrahigh-resolution ODT (μODT) enables 3D microangiography and
quantitative imaging of capillary CBF networks. These optical strategies have been used to investigate the effects of
cocaine on brain physiology to facilitate the studies of brain functional changes induced by addictive substance to
provide new insights into neurobiological effects of the drug on the brain.