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.

Quantitative Particle Characterization by Scattered Ultrasound

The topic of this thesis is an acoustic scattering technique for detennining the compressibility and density of individual particles. The particles, which have diameters on the order of 10 µm, are modeled as fluid spheres. Ultrasonic tone bursts of 2 µsec duration and 30 MHz center frequency scatter from individual particles as they traverse the focal region of two confocally positioned transducers. One transducer acts as a receiver while the other both transmits and receives acoustic signals. The resulting scattered bursts are detected at 90° and at 180° (backscattered). Using either the long wavelength (Rayleigh) or the weak scatterer (Born) approximations, it is possible to detennine the compressibility and density of the particle provided we possess a priori knowledge of the particle size and the host properties. The detected scattered signals are digitized and stored in computer memory. With this information we can compute the mean compressibility and density averaged over a population of particles ( typically 1000 particles) or display histograms of scattered amplitude statistics. An experiment was run first run to assess the feasibility of using polystyrene polymer microspheres to calibrate the instrument. A second study was performed on the buffy coat harvested from whole human blood. Finally, chinese hamster ovary cells which were subject to hyperthermia treatment were studied in order to see if the instrument could detect heat induced membrane blebbing.

APPLICATION OF THE KHOKHLOV-ZABOLOTSKAYA-KUZNETSOV EQUATION TO MODELING HIGH-INTENSITY FOCUSED ULTRASOUND BEAMS

High-intensity focused ultrasound is a form of therapeutic ultrasound which uses high amplitude acoustic waves to heat and ablate tissue. HIFU employs acoustic amplitudes that are high enough that nonlinear propagation effects are important in the evolution of the sound field. A common model for HIFU beams is the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation which accounts for nonlinearity, diffraction, and absorption. The KZK equation models diffraction using the parabolic or paraxial approximation. Many HIFU sources have an aperture diameter similar to the focal length and the paraxial approximation may not be appropriate. Here, results obtained using the “Texas code,” a time-domain numerical solution to the KZK equation, were used to assess when the KZK equation can be employed. In a linear water case comparison with the O’Neil solution, the KZK equation accurately predicts the pressure field in the focal region. The KZK equation was also compared to simulations of the exact fluid dynamics equations (no paraxial approximation). The exact equations were solved using the Fourier-Continuation (FC) method to approximate derivatives in the equations. Results have been obtained for a focused HIFU source in tissue. For a low focusing gain transducer (focal length 50λ and radius 10λ), the KZK and FC models showed excellent agreement, however, as the source radius was increased to 30λ, discrepancies started to appear. Modeling was extended to the case of tissue with the appropriate power law using a relaxation model. The relaxation model resulted in a higher peak pressure and a shift in the location of the peak pressure, highlighting the importance of employing the correct attenuation model. Simulations from the code that were compared to experimental data in water showed good agreement through the focal plane.

ACOUSTO-OPTIC IMAGING IN DIFFUSE MEDIA USING PULSED ULTRASOUND AND THE PHOTOREFRACTIVE EFFECT

Acousto-optic imaging (AOI) in optically diffuse media is a hybrid imaging modality in which a focused ultrasound beam is used to locally phase modulate light inside of turbid media. The modulated optical field carries with it information about the optical properties in the region where the light and sound interact. The motivation for the development of AOI systems is to measure optical properties at large depths within biological tissue with high spatial resolution. A photorefractive crystal (PRC) based interferometry system is developed for the detection of phase modulated light in AOI applications. Two-wave mixing in the PRC creates a reference beam that is wavefront matched to the modulated optical field collected from the specimen. The phase modulation is converted to an intensity modulation at the optical detector when these two fields interfere. The interferometer has a high optical etendue, making it well suited for AOI where the scattered light levels are typically low. A theoretical model for the detection of acoustically induced phase modulation in turbid media using PRC based interferometry is detailed. An AOI system, using a single element focused ultrasound transducer to pump the AO interaction and the PRC based detection system, is fabricated and tested on tissue mimicking phantoms. It is found that the system has sufficient sensitivity to detect broadband AO signals generated using pulsed ultrasound, allowing for AOI at low time averaged ultrasound output levels. The spatial resolution of the AO imaging system is studied as a function of the ultrasound pulse parameters. A theoretical model of light propagation in turbid media is used to explore the dependence of the AO response on the experimental geometry, light collection aperture, and target optical properties. Finally, a multimodal imaging system combining pulsed AOI and conventional B- mode ultrasound imaging is developed. B-mode ultrasound and AO images of targets embedded in both highly diffuse phantoms and biological tissue ex vivo are obtained, and millimeter resolution is demonstrated in three dimensions. The AO images are intrinsically co-registered with the B-mode ultrasound images. The results suggest that AOI can be used to supplement conventional B-mode ultrasound imaging with optical information.

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.

EVALUATION OF HARMONIC MOTION ELASTOGRAPHY AND ACOUSTO-­OPTIC IMAGING FOR MONITORING LESION FORMATION BY HIGH INTENSITY FOCUSED ULTRASOUND

Malignant or benign tumors may be ablated with high‐intensity focused ultrasound (HIFU). This technique, known as focused ultrasound surgery (FUS), has been actively investigated for decades, but slow to be implemented and difficult to control due to lack of real‐time feedback during ablation. Two methods of imaging and monitoring HIFU lesions during formation were implemented simultaneously, in order to investigate the efficacy of each and to increase confidence in the detection of the lesion. The first, Acousto‐Optic Imaging (AOI) detects the increasing optical absorption and scattering in the lesion. The intensity of a diffuse optical field in illuminated tissue is mapped at the spatial resolution of an ultrasound focal spot, using the acousto‐optic effect. The second, Harmonic Motion Imaging (HMI), detects the changing stiffness in the lesion. The HIFU beam is modulated to force oscillatory motion in the tissue, and the amplitude of this motion, measured by ultrasound pulse‐echo techniques, is influenced by the stiffness. Experiments were performed on store‐bought chicken breast and freshly slaughtered bovine liver. The AOI results correlated with the onset and relative size of forming lesions much better than prior knowledge of the HIFU power and duration. For HMI, a significant artifact was discovered due to acoustic nonlinearity. The artifact was mitigated by adjusting the phase of the HIFU and imaging pulses. A more detailed model of the HMI process than previously published was made using finite element analysis. The model showed that the amplitude of harmonic motion was primarily affected by increases in acoustic attenuation and stiffness as the lesion formed and the interaction of these effects was complex and often counteracted each other. Further biological variability in tissue properties meant that changes in motion were masked by sample‐to‐sample variation. The HMI experiments predicted lesion formation in only about a quarter of the lesions made. In simultaneous AOI/HMI experiments it appeared that AOI was a more robust method for lesion detection.

Amorphous Placement and Informed Diffusion for Timely Monitoring by Autonomous, Resource-Constrained, Mobile Sensors

Personal communication devices are increasingly equipped with sensors for passive monitoring of encounters and surroundings. We envision the emergence of services that enable a community of mobile users carrying such resource-limited devices to query such information at remote locations in the field in which they collectively roam. One approach to implement such a service is directed placement and retrieval (DPR), whereby readings/queries about a specific location are routed to a node responsible for that location. In a mobile, potentially sparse setting, where end-to-end paths are unavailable, DPR is not an attractive solution as it would require the use of delay-tolerant (flooding-based store-carry-forward) routing of both readings and queries, which is inappropriate for applications with data freshness constraints, and which is incompatible with stringent device power/memory constraints. Alternatively, we propose the use of amorphous placement and retrieval (APR), in which routing and field monitoring are integrated through the use of a cache management scheme coupled with an informed exchange of cached samples to diffuse sensory data throughout the network, in such a way that a query answer is likely to be found close to the query origin. We argue that knowledge of the distribution of query targets could be used effectively by an informed cache management policy to maximize the utility of collective storage of all devices. Using a simple analytical model, we show that the use of informed cache management is particularly important when the mobility model results in a non-uniform distribution of users over the field. We present results from extensive simulations which show that in sparsely-connected networks, APR is more cost-effective than DPR, that it provides extra resilience to node failure and packet losses, and that its use of informed cache management yields superior performance.

An Information Theoretic Framework for Field Monitoring Using Autonomously Mobile Sensors

We consider a mobile sensor network monitoring a spatio-temporal field. Given limited cache sizes at the sensor nodes, the goal is to develop a distributed cache management algorithm to efficiently answer queries with a known probability distribution over the spatial dimension. First, we propose a novel distributed information theoretic approach in which the nodes locally update their caches based on full knowledge of the space-time distribution of the monitored phenomenon. At each time instant, local decisions are made at the mobile nodes concerning which samples to keep and whether or not a new sample should be acquired at the current location. These decisions account for minimizing an entropic utility function that captures the average amount of uncertainty in queries given the probability distribution of query locations. Second, we propose a different correlation-based technique, which only requires knowledge of the second-order statistics, thus relaxing the stringent constraint of having a priori knowledge of the query distribution, while significantly reducing the computational overhead. It is shown that the proposed approaches considerably improve the average field estimation error by maintaining efficient cache content. It is further shown that the correlation-based technique is robust to model mismatch in case of imperfect knowledge of the underlying generative correlation structure.

Developing wireless measurement system for building deployed capacitive sensors with optimized RF front end circuit

In this paper, a prototype of miniaturized, low power, bi-directional wireless sensor node for wireless sensor networks (WSN) was designed for doors and windows building monitoring. The capacitive pressure sensors have been developed particularly for such application, where packaging size and minimization of the power requirements of the sensors are the major drivers. The capacitive pressure sensors have been fabricated using a 2.4 mum thick strain compensated heavily boron doped SiGeB diaphragm is presented. In order to integrate the sensors with the wireless module, the sensor dice was wire bonded onto TO package using chip on board (COB) technology. The telemetric link and its capabilities to send information for longer range have been significantly improved using a new design and optimization process. The simulation tool employed for this work was the Designerreg tool from Ansoft Corporation.

Continuous non-destructive monitoring of cell health using impedance based interdigitated electrode structured sensors

This article examines some preliminary tests which were performed in order to evaluate the best electrode configuration (width and spacing) for cell culture analyses. Biochips packaged with indium tin oxide (ITO) interdigitated electrodes (IDEs) were used to perform impedance measurements on A549 cells cultured on the surface of the biochip. Several tests were carried out using a 10 mM solution of Sodium Chloride (NaCl), cell medium and the cell culture itself to characterize some of the configurations already fabricated in the facilities at Tyndall National Institute.

Antenna tuning for wearable wireless sensors

When miniaturized wireless sensors are placed on or close to the human body, they can experience a significant loss inperformance due to antenna detuning, resulting in degradationof wireless performance as well as decreased battery lifetime.Several antenna tuning technologies have been proposed formobile wireless devices but devices suitable for widespread integration have yet to emerge. This paper highlights the possible advantages of antenna tuning for wearable wireless sensors and presents the design and characterization of a prototype 433MHz tuner module.

Trade-off between minimum number of wireless sensors and the accuracy of temperature profile in cold rooms: a model-based framework

Evaluation of temperature distribution in cold rooms is an important consideration in the design of food storage solutions. Two common approaches used in both industry and academia to address this question are the deployment of wireless sensors, and modelling with Computational Fluid Dynamics (CFD). However, for a realworld evaluation of temperature distribution in a cold room, both approaches have their limitations. For wireless sensors, it is economically unfeasible to carry out large-scale deployment (to obtain a high resolution of temperature distribution); while with CFD modelling, it is usually not accurate enough to get a reliable result. In this paper, we propose a model-based framework which combines the wireless sensors technique with CFD modelling technique together to achieve a satisfactory trade-off between minimum number of wireless sensors and the accuracy of temperature profile in cold rooms. A case study is presented to demonstrate the usability of the framework.

Use of oxygen sensors for the non destructive measurement of oxygen in packaged food and beverage products and its impact on product quality and shelf life

The principal objective of this thesis was to investigate the ability of reversible optical O2 sensors to be incorporated into food/beverage packaging systems to continuously monitor O2 levels in a non-destructive manner immediately postpackaging and over time. Residual levels of O2 present in packs can negatively affect product quality and subsequently, product shelf-life, especially for O2-sensitive foods/beverages. Therefore, the ability of O2 sensors to continuously monitor O2 levels present within food/beverage packages was considered commercially relevant in terms of identifying the consequences of residual O2 on product safety and quality over time. Research commenced with the development of a novel range of O2 sensors based on phosphorescent platinum and palladium octaethylporphyrin-ketones (OEPk) in nano-porous high density polyethylene (HDPE), polypropylene (PP) polytetrafluoroethylene (PTFE) polymer supports. Sensors were calibrated over a temperature range of -10°C to +40°C and deemed suitable for food and beverage packaging applications. This sensor technology was used and demonstrated itself effective in determining failures in packaging containment. This was clearly demonstrated in the packaging of cheese string products. The sensor technology was also assessed across a wide range of packaged products; beer, ready-to-eat salad products, bread and convenience-style, muscle-based processed food products. The O2 sensor technology performed extremely well within all packaging systems. The sensor technology adequately detected O2 levels in; beer bottles prior to and following pasteurisation, modified atmosphere (MA) packs of ready-to-eat salad packs as respiration progressed during product storage and MA packs of bread and convenience-style muscle-based products as mycological growth occurred in food packs over time in the presence and absence of ethanol emitters. The use of the technology, in conjunction with standard food quality assessment techniques, showed remarkable usefulness in determining the impact of actual levels of O2 on specific quality attributes. The O2 sensing probe was modified, miniaturised and automated to screen for the determination of total aerobic viable counts (TVC) in several fish species samples. The test showed good correlation with conventional TVC test (ISO:4833:2003), analytical performance and ruggedness with respect to variation of key assay parameters (probe concentration and pipetting volume). Overall, the respirometric fish TVC test was simple to use, possessed a dynamic microbial range (104-107 cfu/g sample), had an accuracy of +/- one log(cfu/g sample) and was rapid. Its ability to assess highly perishable products such as fish for total microbial growth in <12 hr demonstrates commercial potential.

A comprehensive description of the competencies required for the performance of an ultrasound-guided axillary brachial plexus blockade

We addressed four research questions, each relating to the training and assessment of the competencies associated with the performance of ultrasound-guided axillary brachial plexus blockade (USgABPB). These were: (i) What are the most important determinants of learning of USgABPB? (ii) What is USgABPB? What are the errors most likely to occur when trainees learn to perform this procedure? (iii) How should end-user input be applied to the development of a novel USgABPB simulator? (iv) Does structured simulation based training influence novice learning of the procedure positively? We demonstrated that the most important determinants of learning USgABPB are: (a) Access to a formal structured training programme. (b) Frequent exposure to clinical learning opportunity in an appropriate setting (c) A clinical learning opporunity requires an appropriate patient, trainee and teacher being present at the same time, in an appropriate environment. We carried out a comprehensive description of the procedure. We performed a formal task analysis of USgABPB, identifying (i) 256 specific tasks associated with the safe and effective performance of the procedure, and (ii) the 20 most critical errors likely to occur in this setting. We described a methodology for this and collected data based on detailed, sequential evaluation of prototypes by trainees in anaesthesia. We carried out a pilot randomised control trial assessing the effectiveness of a USgABPB simulator during its development. Our data did not enable us to draw a reliable conclusion to this question; the trail did provide important new learning (as a pilot) to inform future investigation of this question. We believe that the ultimate goal of designing effective simulation-based training and assessment of ultrasound-guided regional anaesthesia is closer to realisation as a result of this work. It remains to be proven if this approach will have a positive impact on procedural performance, and more importantly improve patient outcomes.