Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Physics

Department

Physics

First Advisor

Oleg A. Andreev

Abstract

Microwave ablation (MWA) is a minimally-invasive modality that is playing an increasingly vital role in the treatment of cancer and benign disease. These procedures involve the use of a microwave antenna (or an array of antennas) to deliver energy to raise tissue temperature above a thermal threshold to induce irreversible cell damage. Commonly used clinical MWA systems operate at frequencies of 2450 MHz and 915 MHz. Image-guided percutaneous MWA treatments can be guided by intraoperative ultrasound or computed tomography (CT) fluoroscopy, which allows the physician to deliver treatments precisely. As such, image-guided MWA has received substantial attention for the treatment of cancer in the past decade that is performed in combination with other therapies (radiation therapy) or used as an alternative to other more invasive procedures (surgical resection). There has been increasing interest in improving the efficacy and specificity of MWA through improving energy delivery and application techniques in this domain. This review outlines clinical percutaneous MWA technology detailing concepts related to thermal dosimetry, the physics of microwave heating, modeling of MWA in tissue, and future goals of treatment planning in the context of image-guided MWA procedures.

Microwave ablation (MWA) treatment is an important alternative to surgical resection of tumor in cancer treatment; however, the naive planning tools currently available are of limited practical use in real clinical decision making. These geometric planning guidelines are insufficient treatment planning tools for accounting for the level of unpredicted treatment variability seen during MWA procedures. Unanticipated treatment variability may potentially be a cause of cancer recurrence, and it is difficult to measure treatment variability during MWA procedures on patients. Biothermal models have been employed to simulate these types of procedures and aid in quantifying the level of treatment variability seen in the clinically. In general, there are too many variables to measure and include for a patient-specific physically-based simulation. A physically based simulation that accounts for tissue heterogeneities, perfusion, and temperature dependent effects will provide improved predictive accuracy over existing geometric models. Nevertheless, it is still unclear as to which parameters are important, and it we cannot measure their effect on real patients. A potential solution to this problem would be to create a validated physically based model to simulate and explore the effect of a range of different patient specific variables so that we can focus on the most important ones. This will be a critical component in developing MWA planning and guidance tools for accurate and precise treatment delivery.

Image-guided MWA has emerged as a promising modality for tissue ablation. Currently, available systems in clinical use operate at 915 MHz or 2.45 GHz. Model-based predictive planning tools are under investigation for guiding clinical delivery of ablation treatments. Currently, most MWA modeling approaches have been focused on ablation systems operating at 2.45 GHz. Improving our understanding of the dynamics of 915 MHz MWA ablation will lead to better MWA prediction models of treatments at this frequency. As progress towards this, the finite element method was used to simulate MWA procedures in liver with a clinical 915 MHz ablation applicator. A coupled electromagnetic-thermal solver incorporating temperature dependent tissue biophysical properties of liver was implemented. Model-based predictions of transient temperature profiles and ablation zone dimensions were compared against experiments in ex vivo bovine liver tissue. Broadband dielectric properties of tissue within different regions of the ablation zone were measured and reported at 915 MHz and 2.45 GHz. The resultant simulated transverse diameter and axial lengths of the ablation zone were in good agreement with ex vivo measurements at 30 W (1.0 mm and 1.0 mm) and 60 W (within 0.5 mm and 2.5 mm). Experimentally measured radial temperature profiles were within 2-8 °C of the simulated profiles. These results will aid in the development of a computational modeling framework for predictive planning of ablation procedures.

While computational models can afford the flexibility for including detailed tissue anatomy and heterogeneity, a balance between model complexity, accuracy, and required computational resources must be struck for practical clinical application. Investigating the contributing factors to ablation variance is therefore important because they provide guidelines for the level of detail needed for patient-specific modeling of microwave ablation procedures. To that end through simulation the impact of 1) heterogeneity of biophysical parameters in tumor vs. healthy tissue, 2) applicator placement relative to the tumor, and 3) proximity to large blood vessels on microwave ablation (MWA) treatment effect area. This will help identify the biophysical properties that have the greatest impact on improving clinical modeling of MWA procedures. Our approach was to develop two-compartment models with variable tissue properties and simulate MWA procedures performed in liver with Perseon Medical’s 915 MHz ST applicator. Input parameters for the dielectric and thermal properties considered in this study were based on measurements for healthy and malignant (primary or metastatic) liver tissue previously reported in the literature. Compartment 1 (C1) represented normal, fatty, or cirrhotic liver, and compartment 2 (C2) represented a primary hepatocellular carcinoma (HCC) tumor sample embedded within C1. To evaluate the sensitivity to tissue parameters, a range of clinically-relevant tissue properties were simulated. To evaluate the impact of MWA antenna position, we simulated various tumor perfusion models with the antenna shifted 5 mm anteriorly and posteriorly. To evaluate the effect of local vasculature, we simulated an additional heat-sink of various diameters and distances from the tumor. Dice coefficient statistics were used to evaluate ablation zone effects from these local heat sinks. The models showed less than 11% of volume variability (1 cm3 increase) in ablation treatment effect region when accounting for the difference in relative permittivity and electrical conductivity between malignant and healthy liver tissue. There was a 27% increase in volume when simulating thermal conductivity of fatty liver disease versus the baseline simulation. The ablation zone volume increased more than 36% when simulating cirrhotic surrounding liver tissue. Antenna placement relative to the tumor had minimal sensitivity to the absolute size of the treatment effect area, with less than 1.5 mm variation. However, when considering the overlap between the ablation zone and the ideal clinical margin when the antenna was displaced 5 mm anteriorly and posteriorly, there was approximately a 6 mm difference in the margins. Dice coefficient statistics showed as much as an 11% decrease in the ablation margin due to the presence of vessel heat sinks within the model. The results from simulating the variance in malignant tissue thermal and electrical properties will help guide better approximations for MWA treatments. The results suggest that assuming malignant and healthy liver tissues have similar dielectric properties is a reasonable first approximation. Antenna placement relative to the tumor has minimal impact on the absolute size of the ablation zone; yet it, does cause relevant variation between desired treatment margin and ablation zone. Blood vessel cooling, especially hepatic vessels close to the region of interest may be a significant factor to consider in treatment planning. Further data needs to be collected for assessing treatment planning utility of modeling MWA in this context.

Computational modeling techniques are under investigation for application to patient-specific planning of microwave ablation (MWA) treatments. Knowledge of the antenna design is necessary for accurate simulations; however, the proprietary design of applicators in clinical use is often unknown. Characterizing the specific absorption rate (SAR) during MWA experimentally and comparing to a multi-physics simulation will provide a potential method for more accurately simulating MWA when the antenna geometry is unknown, as in most clinical situations. To accomplish this, an infrared (IR) camera (Mikron M7500) was used to determine the spatial SAR during MWA within a split ex vivo liver model. Perseon Medical’s short-tip (ST) and long-tip (LT) MWA antenna were placed on top of a tissue sample. Microwave power (15W) was applied for 6 min, while intermittently interrupting power. Tissue surface temperature was recorded via IR camera (3.3 fps, 320x240 resolution). SAR was calculated from initial rate of temperature rise, and intermittently based on slope before and after power shut-down; these data were compared to SAR profiles calculated from simulations. Experimentally measured SAR changed considerably once tissue temperatures exceeded 100 ºC, contrary to simulation results. The simulation and average experimentally measured transverse and axial ablation diameters were 1.28cm and 1.30cm (+/- 0.0327cm) and 2.10 cm and 2.66cm (+/-0.223cm); Dice coefficient was on average 0.832 (+/- 0.0248), suggesting good agreement with the simulated ablation zone. The viability of characterization for MWA antennas via measurements of the specific absorption rate (SAR) within tissue was demonstrated. This method has potential for more accurately simulating MWA when the antenna geometry is unknown, as in most clinical situations.

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