The ultimate objective of the research which led to this thesis is to increase the efficacy and safety of radiofrequency catheter ablation (RFCA) of cardiac tissue. The purpose of RFCA is to carefully heat selected locations in the heart. The resulting thermal injury creates lesions which prevent the generation or propagation of arrhythmias. The ability to predict the appropriate amount of energy required at any ablation site is essential to increasing the efficacy and safety of RFCA. The research documented in this thesis focuses on the development of an approximate thermal model of the time-dependent temperature profile within the myocardium during an RFCA procedure. It is anticipated that this model will ultimately give electrophysiologists the ability to accurately titrate energy delivery in clinical situations. The approximate thermal model uses a convective boundary condition to account for convective cooling of the myocardial surface. This model also uses a point source rather than the complicated heat generation function that accounts for the spatial variation of the voltage in the cardiac tissue. A C program was written to evaluate the engineering model. The effect of the convection coefficient (h), the depth at which the point source is located (zo), and the power dissipation rate (P) on the 50 ˚C isotherm in the cardiac tissue is shown. The accuracy of the approximate model depends greatly on the values of these three parameters. Rigorous three-dimensional numerical modeling was done in order to validate the engineering model. The numerical model was done using a commercial computational fluid dynamics (CFD) package. This software solved the steady, incompressible Reynolds-Averaged Navier-Stokes (RANS) equations—along with the Reynolds-Averaged energy transport equation—using an unstructured, segregated, pressure-based finite-volume procedure. This model is different from other numerical RF ablation models in that it took into account the turbulent flow of the blood. It also accounted for the effect of the flow past the electrode and the spatially varying heat generation function. The heat generation function was found from the solution of the Laplace equation to find the voltage distribution in the tissue. The three unknown parameters governing the approximate thermal model were changed manually and good fits of the approximate model with the numerical model resulted, proving that the engineering model can accurately predict the size of the 50 ˚C isotherm in the cardiac tissue.

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Intra-cellular sodium (23Na) concentration is directly related to cellular health. Thus, sodium magnetic resonance imaging (MRI) can provide metabolic information on tissue health that a routine clinical (proton) MRI cannot. 23Na-MRI could be a valuable tool to assist physicians in the diagnosis, prognosis, and monitoring of a variety of pathologies. However, due to factors that include quantum mechanical limitations and biological restrictions, the signal-to-noise ratio (SNR) of a sodium scan is much lower than that of a standard proton scan, which limits the practicality of 23Na-MRI in a clinical setting. This project looks to improve the viability of 23Na-MRI and focuses on an often overlooked facet of MRI development, the radio frequency (RF) coil. Fractal antennas have been used in telecommunication systems for years, and are generally exploited for their compact nature, allowing for the same performance of a larger antenna, in a smaller space. They have also been shown to be capable of a wider transmission bandwidth (BW) than a standard antenna and with MRI applications they have been shown to provide a small SNR increase in proton imaging. It is hypothesized that a surface coil with a Koch snowflake fractal geometry can provide increased SNR for a sodium MRI scan, compared to that of a standard circular geometry coil, by producing a more homogeneous magnetic field in both space and frequency. To test the hypothesis two coils, one circular and the other a Koch snowflake fractal, were simulated. The simulated magnetic fields were compared on their homogeneity and magnitude before the two coils were constructed and implemented with a variety of sodium MRI scans. B1+ maps were acquired to measure RF field homogeneity, and SNR was determined for both coil geometries. The coils were also tested for their homogeneity over varied transmit BWs by comparing images with various field of view (FOV) sizes. Finally the coils were compared for clinical viability in a test of healthy human knee imaging. The circular coil had a more homogeneous B1+ field than the fractal at depths between 10-40mm, and had a higher SNR in its produced images. The circular coil acquired more signal in vivo which provided a higher detail image, but the fractal coil's SNR was higher due to reduced noise. The fractal coil performed better over a wider BW which indicates that further research should be conducted into the applications of fractal coils in multi-nuclear MRI scans. / Thesis / Master of Applied Science (MASc)

Intracellular hyperthermic therapy may prove to be a unique and novel approach to the management of pancreatic cancer. Utilizing the principle of photothermal destruction, selective killing of cancer cells with minimal injury to normal tissues may be possible. This dissertation investigated the role of antibody targeted metal nanoparticles and the cytotoxic effects of nonionizing radiofrequency fields in pancreatic cancer. Cancer cell death was induced by heat release from intracellular metal nanoparticles after radiofrequency field exposure. Fluorescent and gold nanoparticles were delivered with two antibodies, cetuximab and PAM-4, to pancreatic cancer cells in vitro and mouse xenografts in vivo. Selective delivery of these nanoparticles induced cell death in vitro and decreased tumor burden in vivo after whole animal RF field exposure. This occurred through both apoptosis and necrosis. In addition, activated caspase-3 was increased after antibody treatment and RF field exposure. Furthermore, although there was non-specific uptake by the liver and spleen in vivo, there was no evidence of acute or chronic toxicity in the animals. These results are in agreement with the principle that malignant cells are more thermally sensitive than normal cells or tissues. Selective intracellular delivery of metal nanoparticles coupled with whole body RF field exposure may be a beneficial therapy against micrometastases and unresectable pancreatic cancer in the future. Further studies are planned with more specific antibodies, other nanoparticles, and other cancer targets.

UA Open Access Publishing Fund / Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal- as well as systemic- level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements. Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

Liver cancer is a major cause of death worldwide and the impact that it has is set to increase in the coming decades. More than half a million cases are diagnosed each year and it is likely many more sufferers are dying unidentified in parts of the world with poor healthcare. Survival rates for untreated cases after diagnosis are low with few patients living beyond one year. A key cause for low survival rates being that the standard treatment is surgical resection; fewer than one quarter of patients are suitable for invasive surgery and five year survival rates rarely exceeds 66 %. RadioFrequency Ablation (RFA) is a minimally invasive technique which utilises the electrically resistive property of tissue to deposit heat energy locally in the vicinity of the tips of an RFA needle. Heat is transferred away through the tissue by conduction, convection of large blood vessels, and bulk flow of blood in smaller vessels. Liver cells, both cancerous and benign, when exposed to the resultant abnormally high temperatures die considerably more rapidly than in cases of natural hyperthermia. It is thus the radiotherapist’s objective to place the RFA needle in a position that maximises destruction of tumour cells, but minimises the collateral damage of surrounding healthy cells. The learning curve of this nontrivial task is reflected unfavourably in the statistics that relate patient survival rate to clinician experience. In this thesis two mathematical models are presented that could be combined into a ‘global’ model of the effects of RFA. To predict cell death in these conditions under RFA, the O’NeillModel is presented in which cells are accounted for by one of three states: alive, vulnerable, and dead. A mechanistic interpretation of the O’Neill Model is attained through comparison to a model from the literature. A known, but little investigated occurrence of tissue swelling in the annular region peripheral to the ablation volume is modelled in a novel way through equations from the literature that track ion transport across the cell membrane; the O’Neill Model for cell death is also incorporated into this model of oedema.

This thesis aims to determine whether RF pulsed exposures from mobile phones can influence nervous function within the human brain and heart. In order to address this objective, a robust double-blind study to investigate mobile phone exposures on nervous response has been undertaken by means of analysis of electrophysiological test measures of brain wave activity and heart responses. Generally, test measurements of the electroencephalogram (EEG), the electrocardiogram (ECG), and the pulse plethysmogram (PPG) (for indications of blood pressure response) have been undertaken whilst participants are exposed and sham exposed to various GSM mobile phone radiofrequency and low-frequency protocols. In initial work, both standby and full-power mode GSM exposures have been investigated (Chapter 3 - EEG investigated only), while pulsed 900 MHz and 1800 MHz continuous wave exposures have been investigated in the final experimental work involving 100 test participants (Ch apter 8 - EEG, ECG, and PPG measures are investigated). Four predominant outcomes are determined from the final experimental work conducted. These main outcomes specifically include: 1. A new 'characteristic' finding in the EEG alpha band (8-13 Hz) as due to 900 MHz exposures is observed from almost all recording sites, over both brain hemispheres. Notably, this response only appears at 900 MHz, though is not observable for the 1800 MHz exposure; 2. An EEG effect due to both pulsed 900 MHz and 1800 MHz exposures notably appearing at 16 Hz is a new critical finding and is observed across both hemispheres. Most importantly, at this beta rhythm only a decreasing tendency in EEG power can be noted for the 900 MHz exposure tested but only an increasing tendency in EEG power may be noted at 1800 MHz, suggesting that the direction of the effect in EEG power may be dependent on the RF component; 3. Effects at 900 MHz on the contralateral side to exposure at central, temporal, and parietal sites appear to indicate a common median difference response between sham and exposure EEG spectral power density, which does not appear on the ipsilateral side to exposure; 4. As consistent with most previously published research, 900 MHz or 1800 MHz exposures pulsed at 217 Hz do not appear to alter heart rate, heart rate variability (HRV), or blood pressure variability (BPV). To reduce confounding factors and errors in experimental results, several novel approaches were developed as described (Chapters 4 - 8). These approaches include the development and testing of an experimental handset to support multiple mobile phone signals, a comparative analysis of 900 MHz and 1800 MHz exposures (near the health protection limits) on the same group of participants in simultaneous experiments, development of a statistical analysis approach to EEG that addresses both type 1 and type 11 errors at high resolution, and quantification of potential effects of EEG recording leads on SAR and electric field distribution (at both 900 MHz and 1800 MHz) inside a SAM phantom and realistic computational head model. Outcomes of this research address forefront international health concerns regarding almost 2-billion mobile phone users worldwide.

Surgical resection is the best option for both liver and kidney cancers, which providing the long term survival. However intraoperative blood loss can be a significant challenge, and is clearly associated with morbidity and mortality. Radiofrequency ablation (RFA) precoagulation has been introduced into liver and kidney surgery. Promising results have already achieved in reduction of intraoperative blood loss. In this thesis, a detailed explanation on precoagulation by RFA has been given. Our group developed a novel bipolar multi-array RFA device ??? InLine (ILRFA). In this thesis, we have investigated the performance in a variety of fields. In the study of ILRFA-assisted laparoscopic liver resection, ILRFA was easily employed through a hand port and achieved significant decrease of blood loss compared to control group (p < 0.05). In the liver trauma study, ILRFA produced a 63.88% reduction of blood loss in peripheral injury and 53.57% in central injury respectively. In postoperative evaluation of ILRFA-assisted liver resection, animals underwent an uneventful recovery, no complications occurred. Histological examination revealed a typical post RFA evolution. In ILRFA-assisted partial nephrectomy, the mean intraoperative blood loss 35 ?? 7 ml in the ILRFA and 152 ?? 94 ml in the control, a 77.0% reduction (P = 0.024). The mean blood loss per centimetre resection area was 2.09 ?? 1.41 ml/cm2 in the ILRFA compared with 12.79 ?? 1.68 ml/cm2 in controls, the reduction was 79.0% (P = 0.019). In ILRFAassisted laparoscopic partial nephrectomy, the mean intraoperative blood loss was 32 ?? 15 ml in the ILRFA and 187 ?? 69 ml in the control group, a 77.0% reduction (P = 0.043). The mean blood loss per centimetre resection area was 2.27 ?? 0.95 ml/cm2 in the ILRFA compared with 26.46 ?? 8.81 ml/cm2 in controls, the reduction was 79.0% (P = 0.047). In the renal trauma experiment, ILRFA also achieved promising results in haemostasis. We believe that ILRFA is a useful device which may help in the treatment of patients with liver and kidney illness.

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Introduction: Most literatures researched radiofrequency ablation (RFA) for early hepatocellular carcinoma (HCC) defined the early tumor size as 3cm or less. However, detection rate of HCC smaller than 2 cm became increasing since high risk patients had received regular screening and the imaging techniques has been much improved. Whether RFA or percutaneous ethanol injection (PEI) is better for a patient with such a small HCC is still controversial. Methods: We retrospectively obtained patients with single HCC 2 cm in diameter or smaller from the computerized medical records database in a local teaching hospital located at southern Taiwan, diagnosed during January 1, 2002 to April 30, 2008. Those patients received RFA (RFA group) or PEI (PEI group) as the first-line nonsurgical treatments were enrolled for further analysis. We compared baseline characteristics of RFA and PEI groups, including gender, age, possible risk factors of recurrence, and prognostic factors. Then, we analyzed recurrent rate, time to recurrence, survival rate, complication rate, mean cost of each treatment, and hospital stay of RFA and PEI groups. Results: There were 32 patients qualified for the study design, including 22 in PEI group¡G13 males and 9 females with mean age was 63.73 years; and 10 in RFA group¡G7 males and 3 females with mea age was 58.30 years¡CNo statistically significant differences between RFA and PEI groups were observed with respect to baseline characteristics. Nevertheless, there was significant difference between these two groups with respect to mean hospital stay (p=0.007) and mean cost (p¡Õ0.001): mean cost of PEI was NTD $16934.7; mean cost of RFA was NTD $51677.6, the difference was NTD $34732.9. There was no difference respect to complication rate, recurrent rate, time to recurrence and overall survival rate between RFA and PEI groups. Conclusion: For patients with single HCC 2 cm in diameter or smaller (i.e. very early HCC), we concluded that: if under similar basic background, the cost of RFA was much higher than that of PEI, but no difference in the complication rate, recurrent rate, time to recurrence and overall survival rate between these two treatment.