Cocaine abuse can lead to cerebral strokes and hemorrhages secondary to cocaine’s cerebrovascular effects, which are poorly understood. We assessed cocaine’s effects on cerebrovascular anatomy and function in the somatosensory cortex of the rat’s brain. Optical coherence tomography was used for in vivo imaging of three-dimensional cerebral blood flow (CBF) networks and to quantify CBF velocities (CBFv), and multiwavelength laser-speckle-imaging was used to simultaneously measure changes in CBFv, oxygenated (Δ[HbO2]) and deoxygenated hemoglobin (Δ[HbR]) concentrations prior to and after an acute cocaine challenge in chronically cocaine exposed rats. Immunofluorescence techniques on brain slices were used to quantify microvasculature density and levels of vascular endothelial growth factor (VEGF). After chronic cocaine (2 and 4 weeks), CBFv in small vessels decreased, whereas vasculature density and VEGF levels increased. Acute cocaine further reduced CBFv and decreased Δ[HbO2] and this decline was larger and longer lasting in 4 weeks than 2 weeks cocaine-exposed rats, which indicates that risk for ischemia is heightened during intoxication and that it increases with chronic exposures. These results provide evidence of cocaine-induced angiogenesis in cortex. The CBF reduction after chronic cocaine exposure, despite the increases in vessel density, indicate that angiogenesis was insufficient to compensate for cocaine-induced disruption of cerebrovascular function.
Ultra-high resolution optical Doppler coherence tomography (μODT) is a promising tool for brain functional imaging. However, its sensitivity for detecting slow flows in capillary beds may limit its utility in visualizing and quantifying subtle changes in brain microcirculation. To address this limitation, we developed a novel method called contrast-enhanced μODT (c-μODT) in which intralipid is injected into mouse tail vein to enhance μODT detection sensitivity. We demonstrate that after intralipid injection, the flow detection sensitivity of μODT is dramatically enhanced by 230% as quantified by the fill factor (FF) of microvasculature. More importantly, we show that c-μODT preserves the quantitative properties for flow imaging, i.e., showing a comparable change ratio of hypercapnia-induced flow increase in the capillary network before and after injecting intralipid.