Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound

Relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and blood flow speed are key parameters that characterize cerebral hemodynamics. We used contrast-enhanced functional micro-ultrasound (fMUS) imaging employing a disruption-replenishment imaging sequence to quantify these hemodynamic parameters in the anesthetized rat brain. The method has a spatial resolution of about 100 μm in-plane and around 600 μm through-plane, which is comparable to fMRI, and it has a superior temporal resolution of 40 ms per frame. We found no significant difference in rCBV of cortical and subcortical gray matter (0.89 ± 0.08 and 0.61 ± 0.09 times the brain-average value, respectively). The rCBV was significantly higher in the vascular regions on the pial surface (3.89 ± 0.71) and in the area of major vessels in the subcortical gray matter (2.02 ± 0.31). Parametric images of rCBV, rCBF, and blood flow speed demonstrate spatial heterogeneity of these parameters on the 100 μm scale. Segmentation of the cortex in arteriolar and venular-dominated regions identified through color Doppler imaging showed that rCBV is higher and flow speed is lower in venules than in arterioles. Finally, we show that the dependence of rCBV on rCBF was significantly different in cortical versus subcortical gray matter: the exponent α in the power law relation rCBV=s·rCBF(α) was 0.37 ± 0.13 in cortical and 0.75 ± 0.16 in subcortical gray matter. This work demonstrates that functional micro-ultrasound imaging affords quantification of hemodynamic parameters in the anesthetized rodent brain. This modality is a promising tool for neuroscientists studying these parameters in rodent models of diseases with a cerebrovascular component, such as stroke, neurodegeneration, and venous collagenosis. It is of particular import for studying conditions that selectively affect arteriolar versus venular compartments.