Quantification of flow using ultrasound and microbubbles: a disruption replenishment model based on physical principles.

Contrast-enhanced ultrasound (CEUS) is a promising clinical tool capable of noninvasively quantifying flow and relative vascular volume within the microcirculation. Quantification can be performed by recording the replenishment intensity time course of the imaging plane after the local disruption of agent during a constant infusion. Traditional analyses of the time-intensity curves have relied on mathematical functions (e.g., mono-exponential) that fail to consider the underlying physical principles of the flow system and the influence of the measurement device. In reality, the time-intensity curve reflects the hemodynamics and morphology of the vascular system being measured, the ultrasound field distribution and microbubble properties. We introduce a general analytic disruption replenishment model that attempts to account for these parameters and compare its performance to the established model in a flow phantom. Specifically, the proposed model incorporates the hemodynamic properties of the flow system (velocity distribution and vascular cross section); includes the elevation and axial plane pressure distributions; and accounts for the distinct high and low mechanical index (MI) disruption and detection boundaries. In addition, we demonstrated the importance of the ultrasound beam profile for accurate velocity quantification. It was shown that velocity estimates vary by up to 56% if the depth-dependent elevation thickness is not properly accounted for. Compared with the currently accepted mono-exponential model, the presented formalism was shown to be more robust in the presence of simulated motion artifacts and demonstrated better agreement in both the quality of the fit and estimation of velocity (approximately 3 to 10% vs. 90% error) for the same flow and acoustic conditions.