published_or_final_version / abstract / Surgery / Master / Master of Surgery

No description available.

Surgically implanted thermoregulating ferromagnetic seeds as a mean of inducing hyperthermia in malignant tumors has been successfully introduced in a clinical environment at the University of Arizona. This work covers topics in quality assurance for the method on two levels. The first level deals with the magnetic induction system where magnetic and electric fields are measured. A discussion on safety levels for patients and treatment personnel is given, and an optically coupled probe for magnetic field measurements is described. The second level treats the electrical characteristics of the ferromagnetic seeds. Systems to measure the permeability and conductivity of the seeds are presented with some typical results. Finally, hysteresis power loss in a seed is measured and compared to losses due to eddy currents.

During hyperthermia therapy it is desirable to know the entire temperature field in the treatment region. Tikhonov regularization of order zero has been implemented. The accuracy of the estimates depends upon the value of regularization parameter, which has an optimal value that is dependent on the perfusion pattern and magnitude. The transient power-off time sampling length (i.e. the amount of transient data used) influences the accuracy of the estimates, and an optimal sampling length exists. The effects of additive noise are investigated, as are the effects of the initial guess of the perfusion values, and the effect of both symmetric and asymmetric blood perfusion patterns. The asymmetric patterns with noisy data are the most difficult cases to evaluate. The cases studied are not a comprehensive set, but a representative set whose results continue to show the feasibility of using state and parameter estimation methods to reconstruct the entire temperature field. (Abstract shortened with permission of author.)

The purpose of this research was to investigate the feasibility of using high temperature ultrasonic pulses to administer therapeutic hyperthermia treatments independent of changes in blood perfusion and tissue properties. The use of a computer simulation program was used to study the effects of blood perfusion, tissue properties, transducer characteristics, and treatment geometry on the temperature elevation and thermal dose delivered by short high temperature ultrasonic pulses. Experiments were conducted in vitro and in vivo to investigate the effects of blood perfusion changes. Other experiments were carried out in dog thigh muscle to determine the effects of changes in tissue properties. A final study was done where murine melanoma in mice were treated with high temperature ultrasound. Results show that shorter pulse lengths (≤ 2 s) and smaller focal diameters (≤ 3 mm) give practically perfusion independent temperature elevation and thermal dose. Normal fluctuations in tissue properties should not have a significant effect on the treatment provided that proper choice of transducer is made for each individual application. High temperature ultrasonic pulses have also been shown to induce tumor responses. Based on this research, this technique is a feasible means of administering hyperthermia for cancer therapy.

Power deposition in ferromagnetic implants of cylindrical and spherical shape from an externally applied uniform time harmonic radio-frequency magnetic field has been investigated by means of quasi-static analysis. Inductive heating efficiency is related to the relative permeability and temperature dependence of permeability can be exploited to limit the maximum temperature rise to the desired value by proper choice of Curie point of ferromagnetic material. It is found that theoretically calculated power absorption versus orientation of the cylindrical implant with the direction of magnetic field is in good agreement with the experimental results. The parametric studies are based on a two-dimensional finite difference model for calculating temperature distribution in perfused tissues due to induction heating of an array of implants. An approximate analytical model was developed for a large regular array of implants in perfused tissues. The results of the analytical model are compared with those of the numerical model. (Abstract shortened with permission of author.)

Hyperthermia based cancer treatments delivered under various modalities have the potential to become an effective option to eradicate the disease, maintain functionality of infected organs, and minimize complications and relapse. Moreover, hyperthermia therapies are a form of minimally invasive cancer treatment which are key to improving the quality of life post-treatment. Many modalities are available for delivering the heat source. However, the ability to control the energy deposition to prevent damage to adjacent healthy tissue is a limiting factor in all forms of thermal therapies, including cryotherapy, microwave, radio-frequency, ultrasound, and laser. The application of a laser heat source under the guidance of real-time treatment data has the potential to provide unprecedented control over the temperature field induced within the biological domain. The computational infrastructure developed in this work combines a computational model of bioheat transfer based on a nonlinear version of the Pennes equation for heterogeneous media with the precise timing and orchestration of the real-time solutions to the problems of calibration, optimal control, data transfer, registration, finite element mesh refinement, cellular damage prediction, and laser control; it is an example of Dynamic-Data-Driven Applications System (DDDAS) in which simulation models interact with measurement devices and assimilates data over a computational grid for the purpose of producing high-fidelity predictions of physical events. The tool controls the thermal source, provides a prediction of the entire outcome of the treatment and, using intra-operative data, updates itself to increase the accuracy of the prediction. A precise mathematical framework for the real-time finite element solution of the problems of calibration, optimal heat source control, and goal-oriented error estimation applied to the equations of bioheat transfer is presented. It is demonstrated that current finite element technology, parallel computer architecture, data transfer infrastructure, and thermal imaging modalities are capable of inducing a precise computer controlled temperature field within a biological domain. The project thus addresses a set of problems falling in the intersection of applied mathematics, imaging physics, computational science, computer science and visualizations, biomedical engineering, and medical science. The work involves contributions in the three component areas of the CAM program; A, Applicable Mathematics; B, Numerical Analysis and Scientific Computing; and C, Mathematical modeling and Applications. The ultimate goal of this research is to provide the medical community a minimally invasive clinical tool that uses predictive computational techniques to provide the optimal hyperthermia laser treatment procedure given real-time, patient specific data. / text

A simulation program to study the three dimensional temperature distributions produced by hyperthermia in anatomically realistic inhomogeneous tissue models has been developed. The anatomical data for the inhomogeneous tissues of the human body are entered on a digitizing tablet from serial CT scans. The program not only predicts temperature distributions in regions dominated by blood perfusion (with large number of small capillaries), but it can also predict the temperatures inside of and at the vicinity of large blood vessels. The program can be used for different power deposition patterns from various heating modalities, but they must be calculated independently. In this study, the author's attention has been focused on ferromagnetic implants. The program has been used to comparatively evaluate two and three dimensional simulations in a series of parametric calculations based on simple tissue models for both uniform power deposition and ferromagnetic implants. The conclusions drawn from these studies are that two dimensional simulations can lead to significant errors in many situations, and therefore three dimensional simulations will be necessary for accurate patient treatment planning. The conclusion from the geometrically simple model is substantiated by the results obtained using the full 3D model for actual patient anatomical simulations. The program has also been used for several parametric studies. The effect of the thermal conductivity used in the models on the temperature field has been studied, and the results show that its value in the range of 0.4 to 0.6 W/m/°C (valid for most soft tissues) has only a slight effect on the resultant temperature fields. The heating ability of the ferromagnetic implants has also been investigated for different blood perfusions. The effects of the Curie point of the ferromagnetic seeds, and seed spacing are also studied. Finally, the impact of large blood vessels on the resultant temperatures are studied, and the results show that the effect is dramatic and therefore it must be included in the simulations in order to predict accurate temperature fields. Finally, the program has been used to analyze a previously performed dog experiment, and a previously performed clinical treatment. A comparison between the predicted temperatures and the measured ones show that good agreement has been achieved for the clinical treatment, but not for the dog experiment. These results are studied in detail, and the conditions under which this program can be used as a hyperthermia patient treatment planning tool is discussed.

published_or_final_version / abstract / toc / Surgery / Doctoral / Doctor of Philosophy

A thesis submitted to the Faculty of Engineering and the Built Environment, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2016 / The theoretical and experimental investigation of electron spin-resonance relaxation to deposit thermal energy into liquid gadolinium-based contrast agents for cancer hyperthermia treatment is presented. Previous works suggest that using protons in water are inadequate, with a thermal deposition rate of approximately 1 ◦C per two years. A novel component of this research relies on the use of gadolinium-chelated molecules, which are currently used as contrast agents in clinical MRI scans. The chelating agents, or ligands, investigated are Gadobenate (MultiHance R ), Gadopentetate (Magnevist R ), Gadoterate (DotaremR ) and Gadoteridol (ProHance R ). The gadolinium atom has seven unpaired electrons in its inner f shell orbital and as a result has a 660 times stronger paramagnetic response when placed in an external magnetic field. The research tests the hypothesis that by using an appropriate external homogeneous DC magnetic field, together with a radiofrequency excited resonator, that a measurable amount of thermal energy is deposited into a liquid gadolinium-based contrast agent. The aim of this research is to ultimately discover a new cancer hyperthermia treatment. The research theory suggests that a temperature rate of 13.4 ◦C · s−1 can be achieved using the gadolinium-based contrast agents under certain experimental conditions, and a maximum of 29.4 ◦C · s−1 under more optimal conditions. The temperature rates are calculated using parameter values commonly found in literature and practice. The simulation and design of the DC magnetic field coil system is discussed, together with the simulation results and design parameters of the radiofrequency loop-gap resonator. The experimental results and analysis indicate that the selected contrast agents have varied responses based on their chemical nature and that only two out of the four contrast agents, Dotarem and ProHance, show a measurable effect albeit sufficiently small that statistical techniques were necessary to distinguish the effect from background. A model fit to the data is performed in order to determine the spin-lattice relaxation time of the contrast agents under the specified experimental conditions. The model estimate is significantly smaller than the values found in literature under similar conditions, with a spin-lattice relaxation time τ1e of approximately 0.2 ps compared to the literature value of 0.1 ns. Although the observed electron spin resonance heating rate is in the milli-Watt range it is still notably larger (167 000 times) compared to the heating rate obtained using protons. The low temperature rates suggest that a more suitable agent or molecule with a larger spin-relaxation time be used, in order to achieve clinical useful temperature rates in the range of 14 ◦C · s−1. / MT2017