Thermal analysis of temperature-controlled radiofrequency Ablation of cancerous tissue

Abstract

With the advancement in modern imaging techniques, the detection rate of early-stage small tumor has increased dramatically. Owing to which, there has been a positive shift in recent years towards the treatment of tumor with minimally invasive thermal ablative techniques, viz., radiofrequency ablation (RFA), laser ablation, microwave ablation, cryoablation and high-intensity focused ultrasound ablation. Importantly, thermal ablation of tumors is the local application of extreme temperatures to induce irreversible cell injury and ultimately tumor apoptosis and coagulative necrosis. Among the different minimally invasive thermal ablative techniques, RFA is the most extensively studied and widely applied technique in clinical practices due to its low cost and ability to spare the surrounding healthy tissue. Earlier studies have demonstrated that, RFA is not only an effective treatment modality for primary hepatocellular carcinoma and colorectal metastases to the liver, but has also gained interest in the treatment of tumors in lung, brain, kidney, prostate and bone. However, the application of RFA in treating breast cancer is still a developing area of research with most of the initial studies limited only to assess its safety and feasibility. Breast as an organ seems to be particularly suitable for RFA application because of its superficial location on the thorax and due to the absence of intervening organs. Also, as there are no large blood vessels located in the parenchyma of the breast, convectional heat loss is improbable to occur. Further, treating breast cancer using RFA technique would lead to better cosmesis and in turn could warrant psychological well-being and quality of life post therapy to the patient. In view of this, the major portion of the thesis is motivated to evaluate the efficacy of RFA in treating early-stage breast tumor.

Theoretical modeling and computational simulations have become powerful tools for predicting the ablation zone and temperature rise within the target tissue during RFA, rapidly and at a low cost. Also, the pre-clinical computational models help in providing a priori information to the clinical practitioners about the possible complicacies and risks involved before the onset of RFA application. Therefore, utilizing the rigorous simulation tools combined with more efficient and robust numerical techniques can go a long way to improve the patient care and mitigation of inadequacies. Thus, the thesis is aimed at developing more realistic numerical models to simulate temperature-controlled RFA in different tumorous tissues for estimating temperature distribution, ablation volume and treatment time.

The first part of the thesis investigates the efficacy of temperature-controlled RFA in four tissue sites and nine different clinical scenarios, viz., tumor in normal liver, tumor in cirrhotic liver, metastatic colorectal tumor in liver, adenocarcinoma in lung, squamous carcinoma in lung, tumor in kidney, tumor in breast gland, tumor in breast muscle and tumor in breast fat. The nonlinear piecewise model of blood perfusion has been incorporated along with the temperature dependent changes in electrical and thermal conductivities to achieve better correlation with the clinical RFA. The variations in required input voltage, temperature distribution, ablation volume and treatment time in different tissues during RFA have been reported, by incorporating clinically realistic properties for both tissue and tumor. A side-by-side comparison of ablation volume produced during RFA along with the damage to the surrounding healthy tissue for different clinical scenarios in liver, lung, kidney and breast have been provided. This comparison could play a vital role in enabling a risk-free and safe clinical application of RFA technique on different tissues. It has been observed that the surrounding tissue environment significantly affects the size of ablation volume attained during temperaturecontrolled RFA. The relationship between the ablation zone and the target tip temperature during temperature-controlled RFA in different tissues has been quantified. The simplified novel correlations between the ablation volume and treatment time have been proposed for different values of target tip temperature in different tissues during RFA. The developed correlation will mitigate the need of conducting time-consuming simulations for predicting the coagulation volume at different values of ablation time.

In the second part of the thesis, the efficacy of temperature-controlled RFA in treating breast tumor with different breast density levels {viz., extremely dense (ED), heterogeneously dense (HD), scattered fibroglandular (SF) and predominantly fatty (PF)} has been investigated. A three-dimensional multi-layer heterogeneous breast model comprising of fat, glandular and muscular tissue layers has been used in the finite element based simulations. It has been observed that, the individual variation in the glandular and fatty tissues of breast leads to a significant variation in RFA outcomes. Parametric sensitivity analysis has been conducted using Taguchi’s L16 orthogonal array to quantify the relative influence of breast density composition, target tip temperature, tumor blood perfusion rate and location of tumor from body core on the size of ablation volume generated during RFA. Analysis of variance (ANOVA) has also been performed to quantify the ranking and contribution of each critical parameter on the size of ablation volume produced during temperature-controlled RFA of breast tumor.

The third part of the thesis investigates the influence of inaccuracies in electrode placement relative to the geometric center of the breast tumor on the input energy, treatment time and damage to the surrounding healthy tissue during temperaturecontrolled RFA. The maximum offset upto 5 mm from the actual perfect position of electrode has been considered that is frequently encountered in clinical practices. It has been observed that even a slight error in positioning of electrode results in significant mismatch in the shape of ablation volume produced during RFA application. Next, the differences between the Fourier and non-Fourier bioheat transfer models during RFA of breast tumor has been investigated. It has been observed that for the case of RFA of breast tumor where treatment time varies between 12 to 20 min, Fourier bioheat model will provide reasonable results as long as there is no large blood vessel in close proximity of tumor.

Further, the numerical models fidelity and integrity have been evaluated by comparing the obtained numerical results with experimental in-vitro results on polyacrylamide based tissue-mimicking phantom gel using commercially available RFA device. The validation of mathematical models of temperature-controlled RFA have been done considering both temperature measurement and size of ablation volume approaches. A good agreement between the temperature distribution and coagulation volume obtained from computational and experimental results have been observed.