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Genetic and surgical mouse models are commonly used to study cerebrovascular disease, but their size makes invasive hemodynamic testing technically challenging. The purpose of this study was to demonstrate a noninvasive measurement of cerebrovascular impedance and wave reflection in mice using high-frequency ultrasound in the left common carotid artery (LCCA), and to examine whether microvascular changes associated with hypercapnia could be detected with such an approach. Ten mice (C57BL/6J) were studied using a high-frequency ultrasound system (40 MHz). Lumen area and blood flow waveforms were obtained from the LCCA and used to calculate pulse-wave velocity, input impedance, and reflection amplitude and transit time under both normocapnic and hypercapnic (5% CO2) ventilation. With hypercapnia, vascular resistance was observed to decrease by 87%±12%. Although the modulus of input impedance was unchanged with hypercapnia, a phase decrease indicative of increased total arterial compliance was observed at low harmonics together with an increased reflection coefficient in both the time (0.57±0.08 versus 0.68±0.08, P=0.04) and frequency domains (0.62±0.08 versus 0.73±0.06, P=0.02). Interestingly, the majority of LCCA blood flow was found to pass into the internal carotid artery (range=76% to 90%, N=3), suggesting that hemodynamic measurements in this vessel are a good metric for intracerebral reactivity in mouse.

Evaluation of Cerebrovascular Impedance and Wave Reflection in Mouse by Ultrasound