An analysis of propagation of thermal interface in tumour tissue subject to hyperthermal necrosis

Abstract

The abnormal nature of tumour mass (i.e. malignant progression, oncogenesis, and metastatic spread) in terms of its heterogeneous structure and uncontrolled growth lies behind any treatment failure. This may lead to a variety of therapeutic approaches including hyperthermia either invasive or minimally invasive. However, the recent trends in the care of cancer patients emphasize minimizing invasiveness while improving the effectiveness of treatment while also utilizing medical resources in a cost-effective manner. Concomitant with the above emphasis, this study analyzes thermal interface propagation in tumour tissue subject to irreversible coagulative necrosis for patients undergoing minimally invasive hyperthermia procedure with nano-particle mediated heat source. Hyperthermic procedure is a therapeutic technique, used for tumours therapy, in which body tissue is exposed to high temperatures ranged between 62-100oC to cause irreversible necrosis in the undesirable section of the affected tissue, such as liver tissue. However, due to inadequate delivery of temperature, hyperthermia is still considered as experimental modality according to the National Cancer Institute. Recently, research studies deduce that a combination of hyperthermia and radiotherapy may show significant improvements in clinical outcomes. However researchers claim that heating tumour has not significantly evolved because of the lack of support technology. Consequently, relying on the surgeon's experience and judgment alone without a computerized algorithm, mathematical model and programmable equipment which could be implemented in a treatment plan, could bring serious injury and side effects to the patient likely caused by human error. Therefore, this study investigates bio-heat transfer modeling using finite element analysis (FEA) for thermal ablation of a liver tumour model. A gold nano-particle, acting a s a heat source, has been mediated in this study to deliver heat into the tumour region, Due to a biological procedure nanoparticles of 110nm diameter can attach themselves to an affected tissue then destroy malignant cells with local heating in response to incoming radiation. Concomitant with this investigation, the study also envisages using images of affected liver tissue obtained from research studies on magnetic resonance imaging (MRI), as the basis for guidance techniques in the process of hyperthermic destruction of affected tissue or size reduction of benign tumours. Unlike conventional procedures of thermal ablation including radiofrequency ablation (RFA), this study proposed to conduct further examination of energy propagation in the tumour region with help of molecular dynamics (MDs) analysis. Hence, a simple atomic model has been developed from the integration of Lennard- Jones (LJ) and finite extensible non-elastic potential interaction models. As part of this examination, an atomic algorithm has been generated to simulate behavior of atoms due to the temperature gradient within a bulk of 500 atoms located between two slabs of 256 atoms each at two different temperatures, acting as a thermal source and thermal sink. The algorithm is called the bio-heat molecular dynamics simulation algorithm and denoted in the rest of this study by Bio-MDsA. The methodology developed in this study consists of: i) thermal conductivity recalculation at micro-level, ii) examining the traditional Pennes' model, and iii) enhancing the outcome of Pennes' model by using results obtained in molecular dynamics (MDs) simulation. In Chapter Three, molecular dynamics simulation takes place in order to examine energy propagation at micro-level. As a part of this simulation, a comprehensive understanding of atomic motion due to high temperatures is obtained from the number of the bonds and the cluster size. The results show that at high temperature the atoms at a short distance cross an energy barrier giving rise to permanent bond formations, representing tissue coagulation at macro-level. MDs simulation also allowed the calculation of the thermal conductivity term. Finite element analysis (FEA) is used in Chapter Four to quantify temperature distribution in a liver tumour tissue model using Pennes' model as bio-heat mathematical heat transfer model. Tumours of 3cm diameter show efficient results with 84% cell injury at 423K. In Chapter Five, FEA has been also used to measure the effectiveness of using the new thermal conductivity value in order to enhance the Pennes' model. The results show a significant progress, as 89% of the affected tissue was subject to cell injury. This rate dropped to 60% for tumours greater than 3cm and up to 6cm diameter. Finally, this study contributes to hyperthermic treatment by investigating related issues at two levels: micro- and macro-levels to enhance the Pennes' model, leading to an effective monitoring of temperature distribution within tumours up to 3cm diameter. Future work may require investigation into an optimization problem concerning nanoparticles distribution and location for treating large tumours.

Date of Award	2010
Original language	English