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.

SOUND PROPAGATION AND SCATTERING IN BUBBLY LIQUIDS

In the ocean, natural and artificial processes generate clouds of bubbles which scatter and attenuate sound. Measurements have shown that at the individual bubble resonance frequency, sound propagation in this medium is highly attenuated and dispersive. Theory to explain this behavior exists in the literature, and is adequate away from resonance. However, due to excessive attenuation near resonance, little experimental data exists for comparison. An impedance tube was developed specifically for exploring this regime. Using the instrument, unique phase speed and attenuation measurements were made for void fractions ranging from 6.2 × 10^−5 to 2.7 × 10^−3 and bubble sizes centered around 0.62 mm in radius. Improved measurement speed, accuracy and precision is possible with the new instrument, and both instantaneous and time-averaged measurements were obtained. Behavior at resonance was observed to be sensitive to the bubble population statistics and agreed with existing theory, within the uncertainty of the bubble population parameters. Scattering from acoustically compact bubble clouds can be predicted from classical scattering theory by using an effective medium description of the bubbly fluid interior. Experimental verification was previously obtained up to the lowest resonance frequency. A novel bubble production technique has been employed to obtain unique scattering measurements with a bubbly-liquid-filled latex tube in a large indoor tank. The effective scattering model described these measurements up to three times the lowest resonance frequency of the structure.

THE ROLE OF ACOUSTIC CAVITATION IN ENHANCED ULTRASOUND-INDUCED HEATING IN A TISSUE-MIMICKING PHANTOM

A complete understanding of high-intensity focused ultrasound-induced temperature changes in tissue requires insight into all potential mechanisms for heat deposition. Applications of therapeutic ultrasound often utilize acoustic pressures capable of producing cavitation activity. Recognizing the ability of bubbles to transfer acoustic energy into heat generation, a study of the role bubbles play in tissue hyperthermia becomes necessary. These bubbles are typically less than 50μm. This dissertation examines the contribution of bubbles and their motion to an enhanced heating effect observed in a tissue-mimicking phantom. A series of experiments established a relationship between bubble activity and an enhanced temperature rise in the phantom by simultaneously measuring both the temperature change and acoustic emissions from bubbles. It was found that a strong correlation exists between the onset of the enhanced heating effect and observable cavitation activity. In addition, the likelihood of observing the enhanced heating effect was largely unaffected by the insonation duration for all but the shortest of insonation times, 0.1 seconds. Numerical simulations were used investigate the relative importance of two candidate mechanisms for heat deposition from bubbles as a means to quantify the number of bubbles required to produce the enhanced temperature rise. The energy deposition from viscous dissipation and the absorption of radiated sound from bubbles were considered as a function of the bubble size and the viscosity of the surrounding medium. Although both mechanisms were capable of producing the level of energy required for the enhanced heating effect, it was found that inertial cavitation, associated with high acoustic radiation and low viscous dissipation, coincided with the the nature of the cavitation best detected by the experimental system. The number of bubbles required to account for the enhanced heating effect was determined through the numerical study to be on the order of 150 or less.

PARAMETERS AFFECTING THE IMAGING AND DETECTION OF MICROBUBBLES IN BLOOD

Stabilized micron-sized bubbles, known as contrast agents, are often injected into the body to enhance ultrasound imaging of blood flow. The ability to detect such bubbles in blood depends on the relative magnitude of the acoustic power backscattered from the microbubbles (‘signal’) to the power backscattered from the red blood cells (‘noise’). Erythrocytes are acoustically small (Rayleigh regime), weak scatterers, and therefore the backscatter coefficient (BSC) of blood increases as the fourth power of frequency throughout the diagnostic frequency range. Microbubbles, on the other hand, are either resonant or super-resonant in the range 5-30 MHz. Above resonance, their total scattering cross-section remains constant with increasing frequency. In the present thesis, a theoretical model of the BSC of a suspension of red blood cells is presented and compared to the BSC of Optison® contrast agent microbubbles. It is predicted that, as the frequency increases, the BSC of red blood cell suspensions eventually exceeds the BSC of the strong scattering microbubbles, leading to a dramatic reduction in signal-to-noise ratio (SNR). This decrease in SNR with increasing frequency was also confirmed experimentally by use of an active cavitation detector for different concentrations of Optison® microbubbles in erythrocyte suspensions of different hematocrits. The magnitude of the observed decrease in SNR correlated well with theoretical predictions in most cases, except for very dense suspensions of red blood cells, where it is hypothesized that the close proximity of erythrocytes inhibits the acoustic response of the microbubbles.

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.

A FLOW-THROUGH ACOUSTIC WAVEGUIDE FOR TWO-PHASE BUBBLY FLOW VOID FRACTION MEASUREMENT

In the Spallation Neutron Source (SNS) facility at Oak Ridge National Laboratory (ORNL), the deposition of a high-energy proton beam into the liquid mercury target forms bubbles whose asymmetric collapse cause Cavitation Damage Erosion (CDE) to the container walls, thereby reducing its usable lifetime. One proposed solution for mitigation of this damage is to inject a population of microbubbles into the mercury, yielding a compliant and attenuative medium that will reduce the resulting cavitation damage. This potential solution presents the task of creating a diagnostic tool to monitor bubble population in the mercury flow in order to correlate void fraction and damage. Details of an acoustic waveguide for the eventual measurement of two-phase mercury-helium flow void fraction are discussed. The assembly’s waveguide is a vertically oriented stainless steel cylinder with 5.08cm ID, 1.27cm wall thickness and 40cm length. For water experiments, a 2.54cm thick stainless steel plate at the bottom supports the fluid, provides an acoustically rigid boundary condition, and is the mounting point for a hydrophone. A port near the bottom is the inlet for the fluid of interest. A spillover reservoir welded to the upper portion of the main tube allows for a flow-through design, yielding a pressure release top boundary condition for the waveguide. A cover on the reservoir supports an electrodynamic shaker that is driven by linear frequency sweeps to excite the tube. The hydrophone captures the frequency response of the waveguide. The sound speed of the flowing medium is calculated, assuming a linear dependence of axial mode number on modal frequency (plane wave). Assuming that the medium has an effective-mixture sound speed, and that it contains bubbles which are much smaller than the resonance radii at the highest frequency of interest (Wood’s limit), the void fraction of the flow is calculated. Results for water and bubbly water of varying void fraction are presented, and serve to demonstrate the accuracy and precision of the apparatus.

AN IMPEDANCE TUBE FOR THE IN-SITU CLASSIFICATION OF BUBBLY LIQUIDS

It is well documented that the presence of even a few air bubbles in water can signifi- cantly alter the propagation and scattering of sound. Air bubbles are both naturally and artificially generated in all marine environments, especially near the sea surface. The abil- ity to measure the acoustic propagation parameters of bubbly liquids in situ has long been a goal of the underwater acoustics community. One promising solution is a submersible, thick-walled, liquid-filled impedance tube. Recent water-filled impedance tube work was successful at characterizing low void fraction bubbly liquids in the laboratory [1]. This work details the modifications made to the existing impedance tube design to allow for submersed deployment in a controlled environment, such as a large tank or a test pond. As well as being submersible, the useable frequency range of the device is increased from 5 - 9 kHz to 1 - 16 kHz and it does not require any form of calibration. The opening of the new impedance tube is fitted with a large stainless steel flange to better define the boundary condition on the plane of the tube opening. The new device was validated against the classic theoretical result for the complex reflection coefficient of a tube opening fitted with an infinite flange. The complex reflection coefficient was then measured with a bubbly liquid (order 250 micron radius and 0.1 - 0.5 % void fraction) outside the tube opening. Results from the bubbly liquid experiments were inconsistent with flanged tube theory using current bubbly liquid models. The results were more closely matched to unflanged tube theory, suggesting that the high attenuation and phase speeds in the bubbly liquid made the tube opening appear as if it were radiating into free space.