Non invasive and real time evaluation of mice aortic stiffness by ultrafast ultrasound imaging: a new tool for evaluation of preclinical vascular disease models

Abstract

Background: Mice models of arterial disease are critical for a better understanding of vascular diseases. Pulse wave velocity (PWV) is widely used as an index of arterial stiffness. Indeed, its evaluation has been reported through invasive measurement by the ratio of distance between 2 arterial cannula tips divided by transit time or non-invasively by MRI which requires a long acquisition time. Our goal was to evaluate the capacity of a new ultrasound ultrafast imaging technique, at high frame rate (up to 5 kHz) to determine non-invasively in real-time, the abdominal aortic PWV at different levels of blood pressure. Methods: Littermates BalbC wild type mice (n=6) were used with comparable ages (303±95days) and weights (27±3g). Invasive arterial blood pressure (BP) catheter allowed to measure acute pressor responses to increasing doses of phenylephrine (PE) (0.01-700 μg/kg) infused via a venous catheter in anesthetized mice with pentobarbital sodique (60mg/kg/ip). The abdominal aorta was imaged using a conventional linear ultrasonic probe (15MHz, 256 elements) connected to a unique ultrafast scanner (SuperSonic Imagine, France) acquiring at 5400 frames/s which allows to visualize aortic PWV. Tissue velocities of the arterial walls were computed off line and analyzed by speckle tracking technique to provide the pulse wave velocity. Results are mean±SD. Results: We identified 2 PWVs one at the ECG-peak-R-wave, at the time of aortic diastolic blood pressure (PWV-DBP) and one at the ECG-end-T-wave at the time of aortic systolic blood pressure (PWV-SBP). Heart Rate was 415±50bpm These 2 PWVs were forward waves running along the arterial wall. The mean difference between PWV-DBP and PWV-SBP was 2.3±1.4 m/s. A linear relationship between PWV and BP was observed for the 2 PWVs ranging from 2.5 and 10.0 m/s for a pressure range of 55 to 265 mmHg. Interestingly this linear relation of aortic BP was similar in diastole and in systole with respective slope of 0.037±0.008m/s/mmHg and 0.035±0.010m/s/mmHg, with a good fit: r2= 0.90 and 0.83 respectively. Conclusion: We demonstrated the capability of new ultrafast ultrasound scanner to visualize and calculate non invasively in real time mice aortic PWV at different times of cardiac cycle despite very high heart rate in mice. Moreover, this new technology allows to better characterize the aortic wall biomechanical properties by evaluation of the PWV-BP slope. We hope that this breakthrough will allow in the near future to better evaluate aorta biomechanical properties in preclinical models of vascular disease.