Characterization of cerebrovascular responses to hyperoxia and hypercapnia using MRI in rat

Understanding cerebrovascular responses to hyperoxia and hypercapnia is important for investigating exogenous regulation of cerebral hemodynamics. We characterized gas-induced vascular changes in the brains of anesthetized healthy rats using magnetic resonance imaging (MRI) while the rats inhaled 100% O2 (hyperoxia) and 5% CO2 (hypercapnia). We used echo planar imaging (EPI), arterial spin labeling (ASL), and intravascular superparamagnetic iron oxide nanoparticles (SPION) to quantify vascular responses as measured by blood oxygenation level dependence (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), microvascular volume (MVV), and vessel size index (VSI) in multiple brain regions. Hyperoxia resulted in a statistically significant increase in BOLD-weighted MRI signal and significant decrease in CBF and CBV (P < 0.05). During hypercapnia, we observed significant increases in BOLD signal, CBF, MVV, and CBV (P < 0.05). Despite the regional variability, general trends of vasoconstriction and vasodilation were reflected in VSI changes during O2 and CO2 challenges. Interestingly, there was an evident spatial disparity between the O2 and CO2 stimuli-induced functional activation maps; that is, cortical and subcortical regions of the brain exhibited notable differences in response to the two gases. Hemodynamic parameters measured in the cortical regions showed greater reactivity to CO2, whereas these same parameters measured in subcortical regions showed greater responsivity to O2. Our results demonstrate significant changes of hemodynamic MRI parameters during systemic hypercapnia and hyperoxia in normal cerebral tissue. These gas-dependent changes are spatiotemporally distinctive, suggesting important feasibility for exogenously controlling local cerebral perfusion.