Estimating concentration of ultrasound contrast agents with backscatter coefficients: Experimental and theoretical aspects

Abstract

Ultrasound contrast agents (UCAs) have been explored as a means to enhance therapeutic techniques. Because the effectiveness of these techniques relies on the UCA concentration at a target site, it would be beneficial to estimate UCA concentration noninvasively. In this study, a noninvasive method for estimating UCA concentration was developed in vitro. Backscatter coefficients (BSCs) estimated from measurements of Definity V R UCAs were fitted to a theoretical scattering model in the 15-25 MHz range using a Levenberg-Marquardt regression technique. The model was defined by the UCA size distribution and concentration, and therefore concentration estimates were extracted directly from the fit. Calculation of the BSC was accomplished using planar reference measurements from the back wall of a Plexiglas V R chamber and an average of 500 snapshots of ultrasonic backscatter from UCAs flowing through the chamber. In order to verify the ultrasonically derived UCA concentration estimates, a sample of the UCAs was extracted from the flow path and the concentration was estimated with a hemacytometer. UCA concentrations of 1, 2, and 5 times the dose recommended by the manufacturer were used in experiments. All BSC-based estimates were within one standard deviation of hemacytometer based estimates for peak rarefactional pressures of 100-400 kPa.

Estimating Cell Concentration in Three-Dimensional Engineered Tissues Using High Frequency Quantitative Ultrasound

“…19 Many ultrasound tissue characterization techniques currently under investigation are applied to a broad range of native tissues. 9 Among numerous applications, 9 quantitative ultrasound techniques have been used to characterize various tumors, 10,20 monitor cell death, 18,21 assess cardiac abnormalities, 22 characterize ultrasound contrast agents, 23 and evaluate therapeutic responses of diseased and normal tissues. 24,25 In addition, quantitative ultrasound techniques that extract spectral parameters from the backscatter RF signals can be used to characterize tissue microstructure, such as the number, size, and organization of tissue scatterers.…”

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

“…31,41-43 In native tissues, quantitative ultrasound techniques have been used to characterize tumors, 43 monitor cell death, 37,44 assess cardiac abnormalities, 45 characterize ultrasound contrast agents, 46 and evaluate therapeutic responses of diseased tissues after treatments with high intensity focused ultrasound or chemotherapeutic agents. 38,47,48 Furthermore, employing high-frequency ultrasound increases the backscatter coefficient of sub-resolution scatterers in tissues, such as cells and collagen fibers.…”