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.

PHOTOREFRACTIVE CRYSTAL-BASED ACOUSTO-OPTIC IMAGING IN THE NEAR-INFRARED AND ITS APPLICATIONS

Acousto-optic (AO) sensing and imaging (AOI) is a dual-wave modality that combines ultrasound with diffusive light to measure and/or image the optical properties of optically diffusive media, including biological tissues such as breast and brain. The light passing through a focused ultrasound beam undergoes a phase modulation at the ultrasound frequency that is detected using an adaptive interferometer scheme employing a GaAs photorefractive crystal (PRC). The PRC-based AO system operating at 1064 nm is described, along with the underlying theory, validating experiments, characterization, and optimization of this sensing and imaging apparatus. The spatial resolution of AO sensing, which is determined by spatial dimensions of the ultrasound beam or pulse, can be sub-millimeter for megahertz-frequency sound waves.A modified approach for quantifying the optical properties of diffuse media with AO sensing employs the ratio of AO signals generated at two different ultrasound focal pressures. The resulting “pressure contrast signal” (PCS), once calibrated for a particular set of pressure pulses, yields a direct measure of the spatially averaged optical transport attenuation coefficient within the interaction volume between light and sound. This is a significant improvement over current AO sensing methods since it produces a quantitative measure of the optical properties of optically diffuse media without a priori knowledge of the background illumination. It can also be used to generate images based on spatial variations in both optical scattering and absorption. Finally, the AO sensing system is modified to monitor the irreversible optical changes associated with the tissue heating from high intensity focused ultrasound (HIFU) therapy, providing a powerful method for noninvasively sensing the onset and growth of thermal lesions in soft tissues. A single HIFU transducer is used to simultaneously generate tissue damage and pump the AO interaction. Experimental results performed in excised chicken breast demonstrate that AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposure parameters, results in more predictable lesion formation.

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.