Heating technology for malignant tumors: a review.

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 °C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 °C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.

Numerical simulation of microwave ablation incorporating tissue contraction based on thermal dose.

Tissue contraction plays an important role during high temperature tumor ablation, particularly during device characterization, treatment planning and imaging follow up. We measured such contraction in 18 ex vivo bovine liver samples during microwave ablation by tracking fiducial motion on CT imaging. Contraction was then described using a thermal dose dependent model and a negative thermal expansion coefficient based on the empirical data. FEM simulations with integrated electromagnetic wave propagation, heat transfer, and structural mechanics were evaluated using temperature-dependent dielectric properties and the negative thermal expansion models. Simulated temperature and displacement curves were then compared with the ex vivo experimental results on different continuous output powers. The optimized thermal dose model indicated over 50% volumetric contraction occurred at the temperature over 102.1 °C. The numerical simulation results on temperature and contraction-induced displacement showed a good agreement with experimental results. At microwave powers of 55 W, the mean errors on temperature between simulation and experimental results were 8.25%, 2.19% and 5.67% at 5 mm, 10 mm and 20 mm radially from the antenna, respectively. The simulated displacements had mean errors of 16.60%, 14.08% and 23.45% at the same radial locations. Compared to the experimental results, the simulations at the other microwave powers had larger errors with 10-40% mean errors at 40 W, and 10-30% mean errors at 25 W. The proposed model is able to predict temperature elevation and simulate tissue deformation during microwave ablation, and therefore may be incorporated into treatment planning and clinical translation from numerical simulations.

Microwave ablation in primary and secondary liver tumours: technical and clinical approaches.

Thermal ablation is increasingly being utilised in the treatment of primary and metastatic liver tumours, both as curative therapy and as a bridge to transplantation. Recent advances in high-powered microwave ablation systems have allowed physicians to realise the theoretical heating advantages of microwave energy compared to other ablation modalities. As a result there is a growing body of literature detailing the effects of microwave energy on tissue heating, as well as its effect on clinical outcomes. This article will discuss the relevant physics, review current clinical outcomes and then describe the current techniques used to optimise patient care when using microwave ablation systems.

Interstitial microwave treatment for cancer: historical basis and current techniques in antenna design and performance.

The use of microwaves (MW) for thermal cancer treatment began in the late 1970s. At first, hyperthermia was induced by using single antennas applied interstitially. This was followed by arrays of multiple interstitial antennas driven synchronously at 915 or 2450 MHz. This early work focused on hyperthermia as an adjuvant therapy, but more recently has evolved into a thermally ablative monotherapy. Increased power required to thermally ablate tissues required additional developments such as internally cooled antennas. Larger tumours have also been ablated with MW antenna arrays activated synchronously or non-synchronously. Numerical modelling has provided clinical treatment planning guidance and device design insight throughout this history. MW thermal therapy systems, treatment planning, navigation and image guidance continue to evolve to provide better tools and options for clinicians and patients in order to provide targeting optimisation with the goal of improved treatment for the patient and durable cancer eradication. This paper reviews the history and related technological developments, including antenna design, of MW heating for both hyperthermia and ablation.

Hepatic Thermal Ablation: Effect of Device and Heating Parameters on Local Tissue Reactions and Distant Tumor Growth.

Purpose To determine whether variable hepatic microwave ablation (MWA) can induce local inflammation and distant pro-oncogenic effects compared with hepatic radiofrequency ablation (RFA) in an animal model. Materials and Methods In this institutional Animal Care and Use Committee-approved study, F344 rats (150 gm, n = 96) with subcutaneous R3230 breast adenocarcinoma tumors had normal non-tumor-bearing liver treated with RFA (70°C × 5 minutes), rapid higher-power MWA (20 W × 15 seconds), slower lower-power MWA (5 W × 2 minutes), or a sham procedure (needle placement without energy) and were sacrificed at 6 hours to 7 days (four time points; six animals per arm per time point). Ablation settings produced 11.4 mm ± 0.8 of coagulation for all groups. Distant tumor growth rates were determined to 7 days after treatment. Liver heat shock protein (HSP) 70 levels (at 72 hours) and macrophages (CD68 at 7 days), tumor proliferative indexes (Ki-67 and CD34 at 7 days), and serum and tissue levels of interleukin 6 (IL-6) at 6 hours, hepatocyte growth factor (HGF) at 72 hours, and vascular endothelial growth factor (VEGF) at 72 hours after ablation were assessed. All data were expressed as means ± standard deviations and were compared by using two-tailed t tests and analysis of variance for selected group comparisons. Linear regression analysis of tumor growth curves was used to determine pre- and posttreatment growth curves on a per-tumor basis. Results At 7 days, hepatic ablations with 5-W MWA and RFA increased distant tumor size compared with 20-W MWA and the sham procedure (5-W MWA: 16.3 mm ± 1.1 and RFA: 16.3 mm ± 0.9 vs sham: 13.6 mm ± 1.3, P < .01, and 20-W MWA: 14.6 mm ± 0.9, P < .05). RFA and 5-W MWA increased postablation tumor growth rates compared with the 20-W MWA and sham arms (preablation growth rates range for all arms: 0.60-0.64 mm/d; postablation: RFA: 0.91 mm/d ± 0.11, 5-W MWA: 0.91 mm/d ± 0.14, P < .01 vs pretreatment; 20-W MWA: 0.69 mm/d ± 0.07, sham: 0.56 mm/d ± 1.15; P = .48 and .65, respectively). Tumor proliferation (Ki-67 percentage) was increased for 5-W MWA (82% ± 5) and RFA (79% ± 5), followed by 20-W MWA (65% ± 2), compared with sham (49% ± 5, P < .01). Likewise, distant tumor microvascular density was greater for 5-W MWA and RFA (P < .01 vs 20-W MWA and sham). Lower-energy MWA and RFA also resulted in increased HSP 70 expression and macrophages in the periablational rim (P < .05). Last, IL-6, HGF, and VEGF elevations were seen in 5-W MWA and RFA compared with 20-W MWA and sham (P < .05). Conclusion Although hepatic MWA can incite periablational inflammation and increased distant tumor growth similar to RFA in an animal tumor model, higher-power, faster heating protocols may potentially mitigate such undesired effects. © RSNA, 2016.

Modeling and validation of microwave ablations with internal vaporization.

Numerical simulation is increasingly being utilized for computer-aided design of treatment devices, analysis of ablation growth, and clinical treatment planning. Simulation models to date have incorporated electromagnetic wave propagation and heat conduction, but not other relevant physics such as water vaporization and mass transfer. Such physical changes are particularly noteworthy during the intense heat generation associated with microwave heating. In this paper, a numerical model was created that integrates microwave heating with water vapor generation and transport by using porous media assumptions in the tissue domain. The heating physics of the water vapor model was validated through temperature measurements taken at locations 5, 10, and 20 mm away from the heating zone of the microwave antenna in homogenized ex vivo bovine liver setup. Cross-sectional area of water vapor transport was validated through intraprocedural computed tomography (CT) during microwave ablations in homogenized ex vivo bovine liver. Iso-density contours from CT images were compared to vapor concentration contours from the numerical model at intermittent time points using the Jaccard index. In general, there was an improving correlation in ablation size dimensions as the ablation procedure proceeded, with a Jaccard index of 0.27, 0.49, 0.61, 0.67, and 0.69 at 1, 2, 3, 4, and 5 min, respectively. This study demonstrates the feasibility and validity of incorporating water vapor concentration into thermal ablation simulations and validating such models experimentally.

Microwave ablation energy delivery: influence of power pulsing on ablation results in an ex vivo and in vivo liver model.

PURPOSE: The purpose of this study was to compare the impact of continuous and pulsed energy deliveries on microwave ablation growth and shape in unperfused and perfused liver models. METHODS: A total of 15 kJ at 2.45 GHz was applied to ex vivo bovine liver using one of five delivery methods (n = 50 total, 10 per group): 25 W continuous for 10 min (25 W average), 50 W continuous for 5 min (50 W average), 100 W continuous for 2.5 min (100 W average), 100 W pulsed for 10 min (25 W average), and 100 W pulsed for 5 min (50 W average). A total of 30 kJ was applied to in vivo porcine livers (n = 35, 7 per group) using delivery methods similar to the ex vivo study, but with twice the total ablation time to offset heat loss to blood perfusion. Temperatures were monitored 5-20 mm from the ablation antenna, with values over 60 °C indicating acute cellular necrosis. Comparisons of ablation size and shape were made between experimental groups based on total energy delivery, average power applied, and peak power using ANOVA with post-hoc pairwise tests. RESULTS: No significant differences were noted in ablation sizes or circularities between pulsed and continuous groups in ex vivo tissue. Temperature data demonstrated more rapid heating in pulsed ablations, suggesting that pulsing may overcome blood perfusion and coagulate tissues more rapidly in vivo. Differences in ablation size and shape were noted in vivo despite equivalent energy delivery among all groups. Overall, the largest ablation volume in vivo was produced with 100 W continuous for 5 min (265.7 ± 208.1 cm(3)). At 25 W average, pulsed-power ablation volumes were larger than continuous-power ablations (67.4 ± 34.5 cm(3) versus 23.6 ± 26.5 cm(3), P = 0.43). Similarly, pulsed ablations produced significantly greater length (P ≤ 0.01), with increase in diameter (P = 0.09) and a slight decrease in circularity (P = 0.97). When comparing 50 W average power groups, moderate differences in size were noted (P ≥ 0.06) and pulsed ablations were again slightly more circular. CONCLUSIONS: Pulsed energy delivery created larger ablation zones at low average power compared to continuous energy delivery in the presence of blood perfusion. Shorter duty cycles appear to provide greater benefit when pulsing.

Computational modelling of microwave tumour ablations.

Microwave tissue heating is being increasingly utilised in several medical applications, including focal tumour ablation, cardiac ablation, haemostasis and resection assistance. Computational modelling of microwave ablations is a precise and repeatable technique that can assist with microwave system design, treatment planning and procedural analysis. Advances in coupling temperature and water content to electrical and thermal properties, along with tissue contraction, have led to increasingly accurate computational models. Developments in experimental validation have led to broader acceptability and applicability of these newer models. This review will discuss the basic theory, current trends and future direction of computational modelling of microwave ablations.

Dual-slot antennas for microwave tissue heating: parametric design analysis and experimental validation.

PURPOSE: Design and validate an efficient dual-slot coaxial microwave ablation antenna that produces an approximately spherical heating pattern to match the shape of most abdominal and pulmonary tumor targets. METHODS: A dual-slot antenna geometry was utilized for this study. Permutations of the antenna geometry using proximal and distal slot widths from 1 to 10 mm separated by 1-20 mm were analyzed using finite-element electromagnetic simulations. From this series, the most optimal antenna geometry was selected using a two-term sigmoidal objective function to minimize antenna reflection coefficient and maximize the diameter-to-length aspect ratio of heat generation. Sensitivities to variations in tissue properties and insertion depth were also evaluated in numerical models. The most optimal dual-slot geometry of the parametric analysis was then fabricated from semirigid coaxial cable. Antenna reflection coefficients at various insertion depths were recorded in ex vivo bovine livers and compared to numerical results. Ablation zones were then created by applying 50 W for 2-10 min in simulations and ex vivo livers. Mean zone diameter, length, aspect ratio, and reflection coefficients before and after heating were then compared to a conventional monopole antenna using ANOVA with post-hoc t-tests. Statistical significance was indicated for P <0.05. RESULTS: Antenna performance was highly sensitive to dual-slot geometry. The best-performing designs utilized a proximal slot width of 1 mm, distal slot width of 4 mm +/- 1 mm and separation of 8 mm +/- 1 mm. These designs were characterized by an active choking mechanism that focused heating to the distal tip of the antenna. A dual-band resonance was observed in the most optimal design, with a minimum reflection coefficient of -20.9 dB at 2.45 and 1.25 GHz. Total operating bandwidth was greater than 1 GHz, but the desired heating pattern was achieved only near 2.45 GHz. As a result, antenna performance was robust to changes in insertion depth and variations in relative permittivity of the surrounding tissue medium. In both simulations and ex vivo liver, the dual-slot antenna created ablations greater in diameter than a coaxial monopole (35 mm +/- 2 mm versus 31 mm +/- 2 mm; P<0.05), while also shorter in length (49 mm +/- 2 mm versus 60 mm +/- 6 mm; P < 0.001) after 10 min. Similar results were obtained after 2 and 5 min as well. CONCLUSIONS: Dual-slot antennas can produce more spherical ablation zones while retaining low reflection coefficients. These benefits are obtained without adding to the antenna diameter. Further evaluation for clinical microwave ablation appears warranted.

Periodic contrast-enhanced computed tomography for thermal ablation monitoring: a feasibility study.

Image-guided tumor ablation is rapidly gaining acceptance for treating many tumors. While imaging diagnosis, treatment targeting and follow-up continue to improve, little progress has been made in developing practical imaging techniques for monitoring ablation treatments. In this study we demonstrate the feasibility of using contrast-enhanced computed tomography (CECT) to monitor ablation zone growth with 2 min temporal resolution. Highly constrained back-projection (HYPR) post-processing is applied to the time-series of CECT images, improving image quality by a factor of four after acquiring ten time frames. Such improvements limit the amount of radiation and iodinated contrast material required to visualize the ablation zone, especially at early time points. Additional study of periodic CECT with HYPR processing appears warranted.

Temperature-dependent dielectric properties of liver tissue measured during thermal ablation: toward an improved numerical model.

The development of microwave tumor ablation devices depends largely on numerical simulations of antenna characteristics and transient electromagnetic heating. However, without an adequate tissue model simulation predictions can vary widely from experimental results. In this study, tissue dielectric properties are measured to capture changes induced by temperature, cellular makeup and water content during thermal ablation. Measurements made using this technique agree closely with previous measurements for temperatures up to 50 degrees C, but both relative permittivity and conductivity decrease by as much as 50 percent when temperatures approach 100 degrees C.