Characterization of Cavitation Effects in Therapeutic Ultrasound: Sonophoresis Experiments and Quantitative Emission Measurement

Fundamental to the use of ultrasound for therapeutic benefit is a comprehensive understanding and identification of the underlying mechanisms. Specifically, consequential bioeffects during therapeutic ultrasound commonly coincide with the onset of microbubble cavitation, especially for drug-delivery applications. Hence, there is a need for monitoring and characterization techniques that provide quantitative metrics for assessing cavitation activity during ultrasound exposure in order to monitor treatment progress, identify interactions of cavitation with tissue, and provide dosimetry metrics for avoiding potentially harmful exposures both for therapeutic and diagnostic purposes.;The primary goal of the work presented in this dissertation was to characterize the role of cavitation during sonophoresis using quantitative and system-independent approaches. First, this goal was accomplished using traditional passive cavitation detection techniques to monitor cavitation emissions during in vitro intermediate- (IFS, insonation frequency f 0 = 0.1--1 MHz) and high-frequency sonophoresis (HFS, f0 >1 MHz) treatments of in vitro porcine skin samples in Chapter 2. The relative intensity of subharmonic acoustic emissions from stable cavitation occurring near the skin surface was measured using a single-element PCD and was shown to correspond with reductions in skin resistivity, a surrogate measure of permeability, for all sonophoresis treatments. However, the acoustic emissions measured during sonophoresis provided incommensurable quantities between the different treatment regimes due to unaccounted frequency-dependent variations in the sensitivity of the PCD and diffraction effects in the cavitation-radiated pressure field received by the PCD.;Second, methods were developed and employed to characterize the wideband absolute receive sensitivity of single-element focused and unfocused receivers in Chapter 3. By employing these characterization techniques and by accounting for the frequency-dependent response of the receiving system, the cavitation-radiated pressure incident on a PCD can be elicited from the system-measured voltage. Guidelines for accurate calibration measurements were established via simulation and the receive sensitivity of various PCDs were measured, including that of the PCD employed for sonophoresis in Chapter 2.;Third, in Chapter 4, a method for relating PCD-measured pressures, and by extension the system-measured voltage, to the acoustic power radiated by cavitation within a defined region of interest (ROI) was developed. This approach is accomplished by compensating PCD-measured pressures with a derived factor that accounts for the diffraction-dependent spatial variations in PCD sensitivity. The accuracy of this method was investigated via simulation. Further, this approach was employed to characterize the acoustic power radiated by stable cavitation over the skin surface during IFS and HFS using the system-dependent emission measurements made in Chapter 2, the PCD characterization conducted in Chapter 3, and the compensation factor calculated in Chapter 4.;The PCD calibration and measurement compensation methods developed here are broadly applicable for different single-element receivers, cavitation-monitoring applications, and frequencies. Hence, this approach enables a system-independent technique for characterization of cavitation-radiated acoustic powers, which may serve as a standard characterization technique.