INVESTIGATION OF BUBBLE DYNAMICS AND HEATING DURING FOCUSED ULTRASOUND INSONATION IN TISSUE-MIMICKING MATERIALS

The deposition of ultrasonic energy in tissue can cause tissue damage due to local heating. For pressures above a critical threshold, cavitation will occur in tissue and bubbles will be created. These oscillating bubbles can induce a much larger thermal energy deposition in the local region. Traditionally, clinicians and researchers have not exploited this bubble-enhanced heating since cavitation behavior is erratic and very difficult to control. The present work is an attempt to control and utilize this bubble-enhanced heating. First, by applying appropriate bubble dynamic models, limits on the asymptotic bubble size distribution are obtained for different driving pressures at 1 MHz. The size distributions are bounded by two thresholds: the bubble shape instability threshold and the rectified diffusion threshold. The growth rate of bubbles in this region is also given, and the resulting time evolution of the heating in a given insonation scenario is modeled. In addition, some experimental results have been obtained to investigate the bubble-enhanced heating in an agar and graphite based tissue- mimicking material. Heating as a function of dissolved gas concentrations in the tissue phantom is investigated. Bubble-based contrast agents are introduced to investigate the effect on the bubble-enhanced heating, and to control the initial bubble size distribution. The mechanisms of cavitation-related bubble heating are investigated, and a heating model is established using our understanding of the bubble dynamics. By fitting appropriate bubble densities in the ultrasound field, the peak temperature changes are simulated. The results for required bubble density are given. Finally, a simple bubbly liquid model is presented to estimate the shielding effects which may be important even for low void fraction during high intensity focused ultrasound (HIFU) treatment.

HEATING IN VASCULAR TISSUE AND FLOW-THROUGH TISSUE PHANTOMS INDUCED BY FOCUSED ULTRASOUND

High intensity focused ultrasound (HIFU) can be used to control bleeding, both from individual blood vessels as well as from gross damage to the capillary bed. This process, called acoustic hemostasis, is being studied in the hope that such a method would ultimately provide a lifesaving treatment during the so-called "golden hour", a brief grace period after a severe trauma in which prompt therapy can save the life of an injured person. Thermal effects play a major role in occlusion of small vessels and also appear to contribute to the sealing of punctures in major blood vessels. However, aggressive ultrasound-induced tissue heating can also impact healthy tissue and can lead to deleterious mechanical bioeffects. Moreover, the presence of vascularity can limit one’s ability to elevate the temperature of blood vessel walls owing to convective heat transport. In an effort to better understand the heating process in tissues with vascular structure we have developed a numerical simulation that couples models for ultrasound propagation, acoustic streaming, ultrasound heating and blood cooling in Newtonian viscous media. The 3-D simulation allows for the study of complicated biological structures and insonation geometries. We have also undertaken a series of in vitro experiments, in non-uniform flow-through tissue phantoms, designed to provide a ground truth verification of the model predictions. The calculated and measured results were compared over a range of values for insonation pressure, insonation time, and flow rate; we show good agreement between predictions and measurements. We then conducted a series of simulations that address two limiting problems of interest: hemostasis in small and large vessels. We employed realistic human tissue properties and considered more complex geometries. Results show that the heating pattern in and around a blood vessel is different for different vessel sizes, flow rates and for varying beam orientations relative to the flow axis. Complete occlusion and wall- puncture sealing are both possible depending on the exposure conditions. These results concur with prior clinical observations and may prove useful for planning of a more effective procedure in HIFU treatments.

IDENTIFYING AND MONITORING THE ROLES OF CAVITATION IN HEATING FROM HIGH-INTENSITY FOCUSED ULTRASOUND

For high-intensity focused ultrasound (HIFU) to continue to gain acceptance for cancer treatment it is necessary to understand how the applied ultrasound interacts with gas trapped in the tissue. The presence of bubbles in the target location have been thought to be responsible for shielding the incoming pressure and increasing local heat deposition due to the bubble dynamics. We lack adequate tools for monitoring the cavitation process, due to both limited visualization methods and understanding of the underlying physics. The goal of this project was to elucidate the role of inertial cavitation in HIFU exposures in the hope of applying noise diagnostics to monitor cavitation activity and control HIFU-induced cavitation in a beneficial manner. A number of approaches were taken to understand the relationship between inertial cavitation signals, bubble heating, and bubble shielding in agar-graphite tissue phantoms. Passive cavitation detection (PCD) techniques were employed to detect inertial bubble collapses while the temperature was monitored with an embedded thermocouple. Results indicate that the broadband noise amplitude is correlated to bubble-enhanced heating. Monitoring inertial cavitation at multiple positions throughout the focal region demonstrated that bubble activity increased prefocally as it diminished near the focus. Lowering the HIFU duty cycle had the effect of maintaining a more or less constant cavitation signal, suggesting the shielding effect diminished when the bubbles had a chance to dissolve during the HIFU off-time. Modeling the effect of increasing the ambient temperature showed that bubbles do not collapse as violently at higher temperatures due to increased vapor pressure inside the bubble. Our conclusion is that inertial cavitation heating is less effective at higher temperatures and bubble shielding is involved in shifting energy deposition at the focus. The use of a diagnostic ultrasound imaging system as a PCD array was explored. Filtering out the scattered harmonics from the received RF signals resulted in a spatially- resolved inertial cavitation signal, while the amplitude of the harmonics showed a correlation with temperatures approaching the onset of boiling. The result is a new tool for detecting a broader spectrum of bubble activity and thus enhancing HIFU treatment visualization and feedback.

Nonlinear Acoustics in Underwater and Biomedical Applications: Array Performance Degradation and Time Reversal Invariance

This dissertation describes a model for acoustic propagation in inhomogeneous flu- ids, and explores the focusing by arrays onto targets under various conditions. The work explores the use of arrays, in particular the time reversal array, for underwater and biomedical applications. Aspects of propagation and phasing which can lead to reduced focusing effectiveness are described. An acoustic wave equation was derived for the propagation of finite-amplitude waves in lossy time-varying inhomogeneous fluid media. The equation was solved numerically in both Cartesian and cylindrical geometries using the finite-difference time-domain (FDTD) method. It was found that time reversal arrays are sensitive to several debilitating factors. Focusing ability was determined to be adequate in the presence of temporal jitter in the time reversed signal only up to about one-sixth of a period. Thermoviscous absorption also had a debilitating effect on focal pressure for both linear and nonlinear propagation. It was also found that nonlinearity leads to degradation of focal pressure through amplification of the received signal at the array, and enhanced absorption in the shocked waveforms. This dissertation also examined the heating effects of focused ultrasound in a tissue-like medium. The application considered is therapeutic heating for hyperther- mia. The acoustic model and a thermal model for tissue were coupled to solve for transient and steady temperature profiles in tissue-like media. The Pennes bioheat equation was solved using the FDTD method to calculate the temperature fields in tissue-like media from focused acoustic sources. It was found that the temperature-dependence of the medium's background prop- erties can play an important role in the temperature predictions. Finite-amplitude effects contributed excess heat when source conditions were provided for nonlinear ef- fects to manifest themselves. The effect of medium heterogeneity was also found to be important in redistributing the acoustic and temperature fields, creating regions with hotter and colder temperatures than the mean by local scattering and lensing action. These temperature excursions from the mean were found to increase monotonically with increasing contrast in the medium's properties.