Characterization of a Biochemical Mouse Model of Primary Aldosteronism for Thermal Therapies.

Introduction: Aldosterone-producing adenoma (APA) is the most common cause of endocrine-related hypertension but surgery is not always feasible. Current medical interventions are associated with significant side effects and poor patient compliance. New APA animal models that replicate basic characteristics of APA and give physical and biochemical feedback are needed to test new non-surgical treatment methods, such as image-guided thermal ablation. Methods: A model of APA was developed in nude mice using HAC15 cells, a human adrenal carcinoma cell line. Tumor growth, aldosterone production, and sensitivity to angiotensin II were characterized in the model. The utility of the model was validated via treatment with microwave ablation and characterization of the resulting physical and biochemical changes in the tumor. Results: The APA model showed rapid and relatively homogeneous growth. The tumors produced aldosterone and steroid precursors in response to angiotensin II challenge, and plasma aldosterone levels were significantly higher in tumor bearing mice two hours after challenge verses non-tumor bearing mice. The model was useful for testing microwave ablation therapy, reducing aldosterone production by 80% in treated mice. Conclusion: The HAC15 model is a useful tumor model to study and develop localized treatment methods for APA.

T1-Mapping Characterization of Two Tumor Types.

T1- mapping is a quantitative method to characterize tissues with MR imaging in a quick and efficient manner. It utilizes the relaxation rate of protons to depict the underlying structures within the imaging frame. While T1-mapping techniques are used with some frequency in areas such as cardiac imaging, their application to understanding malignancies and identify tumor structures has yet to be thoroughly investigated. Utilizing a saturation recovery method to acquire T1-maps for two different tumor models has revealed that longitudinal relaxation mapping is sensitive enough to distinguish between normal and malignant tissue. This is seen even with decreased signal to noise ratios using small voxel sizes to obtain high-resolution images. In both tumor models it was revealed that relaxation mapping recorded significantly different relaxation values between regions encapsulating the tumor, muscle, kidney, or spleen, as well as between the cell lines themselves. This indicates a potential future application of relaxation mapping as a method to fingerprint various stages of tumor development and may prove a useful measure to identify micro-metastases.

Assessment of thermochromic phantoms for characterizing microwave ablation devices.

Background and Purpose: Thermochromic gel phantoms provide a controlled medium for visual assessment of thermal ablation device performance. However, there are limited studies reporting on the comparative assessment of ablation profiles assessed in thermochromic gel phantoms against those in ex vivo tissue. The objective of this study was to compare microwave ablation zones in a thermochromic tissue mimicking gel phantom and ex vivo bovine liver, and to report on measurements of the temperature dependent dielectric and thermal properties of the phantom. Methods: Thermochromic polyacrylamide phantoms were fabricated following a previously reported protocol. Phantom samples were heated to temperatures in the range of 20 - 90 °C in a temperature-controlled water bath, and colorimetric analysis of images of the phantom taken after heating were used to develop a calibration between color changes and temperature to which the phantom was heated. Using a custom, 2.45 GHz water-cooled microwave ablation antenna, ablations were performed in fresh ex vivo liver and phantoms using 65 W applied for 5 min or 10 min ( n = 3 samples in each medium for each power/time combination). Broadband (500 MHz - 6 GHz) temperature-dependent dielectric and thermal properties of the phantom were measured over the temperature range 22 - 100 °C. Measured dielectric and thermal properties of the phantom were employed in a previously validated computational model of microwave ablation to comparatively assess model predicted extents of heating against experimental observations in the phantom. Results: Colorimetric analysis showed that the sharp change in gel phantom color commences at a temperature of 57 °C. Short and long axes of the ablation zone in the phantom (as assessed by the 57 °C isotherm) for 65 W, 5 min ablations were aligned with extents of the ablation zone observed in ex vivo bovine liver. However, for the 65 W, 10 min setting, ablations in the phantom were on average 23.7% smaller in short axis and 7.4 % smaller in long axis than those observed in ex vivo liver. Measurements of the temperature dependent relative permittivity, thermal conductivity, and volumetric heat capacity of the phantom largely followed similar trends to published values for ex vivo liver tissue. After incorporating measured dielectric and thermal properties of the phantom, model predictions of ablation zone linear dimensions ranged between 16 - 50% larger than those observed experimentally. Conclusion: Thermochromic tissue mimicking phantoms provide a suitable, controlled, and reproducible medium for comparative assessment of microwave ablation devices and energy delivery settings, though ablation zone size and shapes may not accurately represent ablation sizes and shapes observed in ex vivo liver tissue under similar conditions.

Transmission Coefficient-Based Monitoring of Microwave Ablation: Development and Experimental Evaluation in Ex Vivo Tissue.

OBJECTIVES: To assess the feasibility of monitoring transient evolution of thermal ablation zones with a microwave transmission coefficient-based technique. METHODS: Microwave ablation was performed in ex vivo bovine liver with two 2.45 GHz directional antennas. A custom apparatus was developed to enable periodic switching between "heating mode" when power from the generator was coupled to the antennas, and "monitoring mode", when antennas were coupled to a network analyzer for broadband transmission coefficient ( s21) measurements. Experiments were performed with applied powers ranging between 30-50 W per antenna for 53-1219 s. Transient s21 spectra over the course of ablations were analyzed to determine feasibility of predicting extent of ablation zones and compared against ground truth assessment from images of sectioned tissue. A linear regression-based mapping between the two datasets was derived to predict ablation extent. RESULTS: Normalized average transmission coefficient initially rapidly decreased and then increased before asymptotically approaching steady state, with the transition time ranging between 53 s (45 W) and 109 s (30 W). Analysis of ground truth ablation zone images indicated time to complete ablation of 230-350 s. The relative prediction error for time to complete ablation derived from the s21 data was in the range of 1.6%-2.3% compared to ground truth. CONCLUSION: We have demonstrated the feasibility of monitoring transient evolution of thermal ablation zones using microwave transmission coefficient measurements in ex vivo tissue. SIGNIFICANCE: The presented technique has potential to contribute towards addressing the clinical need for a method of monitoring evolution of thermal ablation zones.

Computational modeling of microwave ablation with thermal accelerants.

PURPOSE: To develop a computational model of microwave ablation (MWA) with a thermal accelerant gel and apply the model toward interpreting experimental observations in ex vivo bovine and in vivo porcine liver. METHODS: A 3D coupled electromagnetic-heat transfer model was implemented to characterize thermal profiles within ex vivo bovine and in vivo porcine liver tissue during MWA with the HeatSYNC thermal accelerant. Measured temperature dependent dielectric and thermal properties of the HeatSYNC gel were applied within the model. Simulated extents of MWA zones and transient temperature profiles were compared against experimental measurements in ex vivo bovine liver. Model predictions of thermal profiles under in vivo conditions in porcine liver were used to analyze thermal ablations observed in prior experiments in porcine liver in vivo. RESULTS: Measured electrical conductivity of the HeatSYNC gel was ∼83% higher compared to liver at room temperature, with positive linear temperature dependency, indicating increased microwave absorption within HeatSYNC gel compared to tissue. In ex vivo bovine liver, model predicted ablation zone extents of (31.5 × 36) mm with the HeatSYNC, compared to (32.9 ± 2.6 × 40.2 ± 2.3) mm in experiments (volume differences 4 ± 4.1 cm3). Computational models under in vivo conditions in porcine liver suggest approximating the HeatSYNC gel spreading within liver tissue during ablations as a plausible explanation for larger ablation zones observed in prior in vivo studies. CONCLUSION: Computational models of MWA with thermal accelerants provide insight into the impact of accelerant on MWA, and with further development, could predict ablations with a variety of gel injection sites.

Sublethal Hyperthermia Transiently Disrupts Cortisol Steroidogenesis in Adrenocortical Cells.

Primary aldosteronism is the most common cause of secondary hypertension. The first-line treatment adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone-producing adenomas, while preserving adjacent normal adrenal cortex. To determine the extent of damage to adrenal cells upon exposure to hyperthermia, the steroidogenic adrenocortical cell lines H295R and HAC15 were treated with hyperthermia at temperatures between 37 and 50°C with the effects of hyperthermia on steroidogenesis evaluated following stimulation with forskolin and ANGII. Cell death, protein/mRNA expression of steroidogenic enzymes and damage markers (HSP70/90), and steroid secretion were analyzed immediately and 7 days after treatment. Following treatment with hyperthermia, 42°C and 45°C did not induce cell death and were deemed sublethal doses while ≥50°C caused excess cell death in adrenal cells. Sublethal hyperthermia (45°C) caused a significant reduction in cortisol secretion immediately following treatment while differentially affecting the expression of various steroidogenic enzymes, although recovery of steroidogenesis was evident 7 days after treatment. As such, sublethal hyperthermia, which occurs in the transitional zone during thermal ablation induces a short-lived, unsustained inhibition of cortisol steroidogenesis in adrenocortical cells in vitro.

In Vitro Measurement and Mathematical Modeling of Thermally-Induced Injury in Pancreatic Cancer Cells.

Thermal therapies are under investigation as part of multi-modality strategies for the treatment of pancreatic cancer. In the present study, we determined the kinetics of thermal injury to pancreatic cancer cells in vitro and evaluated predictive models for thermal injury. Cell viability was measured in two murine pancreatic cancer cell lines (KPC, Pan02) and a normal fibroblast (STO) cell line following in vitro heating in the range 42.5-50 °C for 3-60 min. Based on measured viability data, the kinetic parameters of thermal injury were used to predict the extent of heat-induced damage. Of the three thermal injury models considered in this study, the Arrhenius model with time delay provided the most accurate prediction (root mean square error = 8.48%) for all cell lines. Pan02 and STO cells were the most resistant and susceptible to hyperthermia treatments, respectively. The presented data may contribute to studies investigating the use of thermal therapies as part of pancreatic cancer treatment strategies and inform the design of treatment planning strategies.

Image-based computer modeling assessment of microwave ablation for treatment of adrenal tumors.

PURPOSE: To assess the feasibility of delivering microwave ablation for targeted treatment of aldosterone producing adenomas using image-based computational models. METHODS: We curated an anonymized dataset of diagnostic 11C-metomidate PET/CT images of 14 patients with aldosterone producing adenomas (APA). A semi-automated approach was developed to segment the APA, adrenal gland, and adjacent organs within 2 cm of the APA boundary. The segmented volumes were used to implement patient-specific 3D electromagnetic-bioheat transfer models of microwave ablation with a 2.45 GHz directional microwave ablation applicator. Ablation profiles were quantitatively assessed based on the extent of the APA target encompassed by an ablative thermal dose, while limiting thermal damage to the adjacent normal adrenal tissue and sensitive critical structures. RESULTS: Across the 14 patients, adrenal tumor volumes ranged between 393 mm3 and 2,395 mm3. On average, 70% of the adrenal tumor volumes received an ablative thermal dose of 240CEM43, while limiting thermal damage to non-target structures, and thermally sparing 83.5-96.4% of normal adrenal gland. Average ablation duration was 293 s (range: 60-600 s). Simulations indicated coverage of the APA with an ablative dose was limited when the axis of the ablation applicator was not well aligned with the major axis of the targeted APA. CONCLUSIONS: Image-based computational models demonstrate the potential for delivering microwave ablation to APA targets within the adrenal gland, while limiting thermal damage to surrounding non-target structures.

System for delivering microwave ablation to subcutaneous tumors in small-animals under high-field MRI thermometry guidance.

PURPOSE: Bio-effects following thermal treatments are a function of the achieved temperature profile in tissue, which can be estimated across tumor volumes with real-time MRI thermometry (MRIT). Here, we report on expansion of a previously developed small-animal microwave hyperthermia system integrated with MRIT for delivering thermal ablation to subcutaneously implanted tumors in mice. METHODS: Computational models were employed to assess suitability of the 2.45 GHz microwave applicators for delivering ablation to subcutaneous tumor targets in mice. Phantoms and ex-vivo tissues were heated to temperatures in the range 47-67 °C with custom-made microwave applicators for validating MRIT with the proton resonance frequency shift method against fiberoptic thermometry. HAC15 tumors implanted in nude mice (n = 6) were ablated in vivo and monitored with MRIT in multiple planes. One day post ablation, animals were euthanized, and excised tumors were processed for viability assessment. RESULTS: Average absolute error between temperatures from fiberoptic sensors and MRIT was 0.6 °C across all ex-vivo ablations. During in-vivo experiments, tumors with volumes ranging between 5.4-35.9 mm3 (mean 14.2 mm3) were ablated (duration: 103-150 s) to achieve 55 °C at the tumor boundary. Thermal doses ≥240 CEM43 were achieved across 90.7-98.0% of tumor volumes for four cases. Ablations were incomplete for remaining cases, attributed to motion-affected thermometry. Thermal dose-based ablative tumor coverage agreed with viability assessment of excised tumors. CONCLUSIONS: We have developed a system for delivering microwave ablation to subcutaneous tumors in small animals under MRIT guidance and demonstrated its performance in-vivo.

Temperature-dependent dielectric properties of human uterine fibroids over microwave frequencies.

Microwave ablation is under investigation as a minimally-invasive treatment for uterine fibroids. Computational models play a vital role in the development, evaluation and characterization of candidate ablation devices. The temperature-dependent dielectric properties of fibroid tissue are essential for accurate computational modeling.Objective:To measure the broadband temperature-dependent dielectric properties of uterine fibroids excised during hysterectomy procedures.Methods: The open-ended coaxial probe method was employed for measuring the broadband dielectric properties of freshly excised human uterine fibroid samples (n = 6) obtained from an IRB-approved tissue bank. The dielectric properties (relative permittivity,εr, and effective electrical conductivity,σeff) were evaluated at temperatures ranging from 23 °C-150 °C, over the frequency range of 0.5-6 GHz. Linear piecewise parametrization with respect to temperature and quadratic parametrization with respect to frequency was applied to characterize broadband temperature-dependent dielectric properties of fibroid tissue.Results: The baseline room temperature values ofεrvary from 57.5 ± 5.29 to 44.5 ± 5.77 units andσeffchanges from 0.91 ± 0.19 to 6.02 ± 0.7 S m-1over the frequency range of 0.5-6 GHz. At temperatures close to the water vaporization point,εr, drops considerably i.e. to 12%-14% of its baseline value for all measured frequencies.σeffvalues initially rise till 98 °C and then fall to 11%-13% of their baseline values at 125 °C for frequencies ≤2.45 GHz. Theσefffollows a decreasing trend for frequencies >2.45 GHz and drops to âˆ¼6 % of their baseline room temperature values.Conclusion:The temperature dependent dielectric properties of uterine fibroid tissues over microwave frequency range are reported for the first time in this study. Parametric models of uterine fibroid dielectric properties are also presented for incorporation within computational models of microwave ablation of fibroids.

Microwave ablation of lung tumors: A probabilistic approach for simulation-based treatment planning.

PURPOSE: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters. METHODS: We employed a biophysical simulation-based probabilistic treatment planning methodology to evaluate the likelihood of achieving a specified minimum margin for candidate treatment parameters (i.e., applied power and ablation duration for a given applicator position within a tumor). A set of simulations with varying tissue properties was evaluated for each considered combination of power and ablation duration, and for four different scenarios of contrast in tissue biophysical properties between tumor and normal lung. A treatment planning graph was then assembled, where distributions of achieved minimum ablation zone margins and collateral damage volumes can be assessed for candidate applied power and treatment duration combinations. For each chosen power and time combination, the operator can also visualize the histogram of ablation zone boundaries overlaid on the tumor and target volumes. We assembled treatment planning graphs for generic 1, 2, and 2.5 cm diameter spherically shaped tumors and also illustrated the impact of tissue heterogeneity on delivered treatment plans and resulting ablation histograms. Finally, we illustrated the treatment planning methodology on two example patient-specific cases of tumors with irregular shapes. RESULTS: The assembled treatment planning graphs indicate that 30 W, 6 min ablations achieve a 5-mm minimum margin across all simulated cases for 1-cm diameter spherical tumors, and 70 W, 10 min ablations achieve a 3-mm minimum margin across 90% of simulations for a 2.5-cm diameter spherical tumor. Different scenarios of tissue heterogeneity between tumor and lung tissue revealed 2 min overall difference in ablation duration, in order to reliably achieve a 4-mm minimum margin or larger each time for 2-cm diameter spherical tumor. CONCLUSIONS: An approach for simulation-based treatment planning for microwave ablation of lung tumors is illustrated to account for the impact of specific geometry of the treatment site, tissue property uncertainty, and heterogeneity between the tumor and normal lung.

Transcervical microwave ablation in type 2 uterine fibroids via a hysteroscopic approach: analysis of ablation profiles.

Type 2 uterine fibroids are challenging to resect surgically as ≥ 50% volume of myoma lies within the myometrium. A hysteroscopic approach for ablating fibroids is minimally-invasive, but places a considerable burden on the operator to accurately place the ablation applicator within the target. We investigated the sensitivity of transcervical microwave ablation outcome with respect to position of the ablation applicator within 1 - 3 cm type 2 fibroids.Methods:A finite element computer model was developed to simulate 5.8 GHz microwave ablation of fibroids and validated with experiments inex vivotissue. The ablation outcome was evaluated with respect to applicator insertion angles (30°, 45°, 60°) , depth and offset from the fibroid center (±2 mm for 3 cm fibroid and ±1 mm for 1 cm fibroid) with 35 W and 15 W applied power for 3 cm and 1 cm fibroids, respectively. Power deposition was stopped when thermal dose of 40 cumulative equivalent minutes at 43 °C (CEM43) was accrued in adjacent myometrium.Results:Within the range of all evaluated insertion angles, depths and offsets, the ablation coverage was less sensitive to variation in angle as compared to depth and offset, and ranged from 34.9 - 83.6% for 3 cm fibroid in 140 - 400 s and 34.1 - 67.9% for 1 cm fibroid in 30 - 50 s of heating duration. Maximum achievable ablation coverage in both fibroid cases reach âˆ¼ 90% if thermal dose is allowed to exceed 40 CEM43 in myometrium.Conclusion:The study demonstrates the technical feasibility of transcervical microwave ablation for fibroid treatment and the relationship between applicator position within the fibroid and fraction of fibroid that can be ablated while limiting thermal dose in adjacent myometrium.

Broadband Dielectric Properties of Ex Vivo Bovine Liver Tissue Characterized at Ablative Temperatures.

OBJECTIVE: To investigate the thermal and frequency dependence of dielectric properties of ex vivo liver tissue - relative permittivity and effective conductivity - over the frequency range 500 MHz to 6 GHz and temperatures ranging from 20 to 130 °C. METHODS: We measured the dielectric properties of fresh ex vivo bovine liver tissue using the open-ended coaxial probe method (n = 15 samples). Numerical optimization techniques were utilized to obtain parametric models for characterizing changes in broadband dielectric properties as a function of temperature and thermal isoeffective dose. The effect of heating tissue at rates over the range 6.4-16.9 °C/min was studied. The measured dielectric properties were used in simulations of microwave ablation to assess changes in simulated antenna return loss compared to experimental measurements. RESULTS: Across all frequencies, both relative permittivity and effective conductivity dropped sharply over the temperature range 89 - 107 °C. Below 91 °C, the slope of the effective conductivity changes from positive values at lower frequencies (0.5-1.64 GHz) to negative values at higher frequencies (1.64-6 GHz). The maximum achieved correlation values between transient reflection coefficients from measurements and simulations ranged between 0.83 - 0.89 and 0.68 - 0.91, respectively, when using temperature-dependent and thermal-dose dependent dielectric property parameterizations. CONCLUSION: We have presented experimental measurements and parametric models for characterizing changes in dielectric properties of bovine liver tissue at ablative temperatures. SIGNIFICANCE: The presented dielectric property models will contribute to the development of ablation systems operating at frequencies other than 2.45 GHz, as well as broadband techniques for monitoring growth of microwave ablation zones.

NIRS-based monitoring of kidney graft perfusion.

INTRODUCTION: Acute early vascular complications are rare, but serious complications after kidney transplantation. They often result in graft loss. For this reason, shortening the diagnostic process is crucial. Currently, it is standard procedure to monitor renal graft perfusion using Doppler ultrasound (DU). With respect to acute vascular complications, the main disadvantage of this type of examination is its periodicity. It would be of great benefit if graft blood perfusion could be monitored continuously during the early postoperative period. It appears evident that a well-designed near infrared spectroscopy (NIRS) monitoring system could prove very useful during the early post-transplantation period. Its role in the immediate diagnosis of vascular complications could result in a significant increase in graft salvage, thus improving the patient's overall quality of life and lowering morbidity and mortality for renal graft recipients. The aim of this study was to design, construct and test such a monitoring system. MATERIALS AND METHODS: We designed a rough NIRS-based system prototype and prepared a two-stage laboratory experiment based on a laboratory pig model. In the first stage, a total of 10 animals were used to verify and optimize the technical aspects and functionality of the prototype sensor by testing it on the animal kidneys in-vivo. As a result of these tests, a more specific prototype was designed. During the second stage, we prepared a unique laboratory model of a pig kidney autotransplantation and tested the system for long-term functionality on a group of 20 animals. Overall sensitivity and specificity were calculated, and a final prototype was prepared and completed with its own analytic software and chassis. RESULTS: We designed and constructed a NIRS-based system for kidney graft perfusion monitoring. The measurement system provided reliable performance and 100% sensitivity when detecting acute diminished blood perfusion of the transplanted kidneys in laboratory conditions. CONCLUSION: The system appears to be a useful tool for diagnosing diminished blood perfusion of kidney transplants during the early postoperative period. However, further testing is still required. We believe that applying our method in current human transplantation medicine is feasible, and we are confident that our prototype is ready for human testing.

Bronchoscopically delivered microwave ablation in an in vivo porcine lung model.

BACKGROUND: Percutaneous microwave ablation is clinically used for inoperable lung tumour treatment. Delivery of microwave ablation applicators to tumour sites within lung parenchyma under virtual bronchoscopy guidance may enable ablation with reduced risk of pneumothorax, providing a minimally invasive treatment of early-stage tumours, which are increasingly detected with computed tomography (CT) screening. The objective of this study was to integrate a custom microwave ablation platform, incorporating a flexible applicator, with a clinically established virtual bronchoscopy guidance system, and to assess technical feasibility for safely creating localised thermal ablations in porcine lungs in vivo. METHODS: Pre-ablation CTs of normal pigs were acquired to create a virtual model of the lungs, including airways and significant blood vessels. Virtual bronchoscopy-guided microwave ablation procedures were performed with 24-32 W power (at the applicator distal tip) delivered for 5-10 mins. A total of eight ablations were performed in three pigs. Post-treatment CT images were acquired to assess the extent of damage and ablation zones were further evaluated with viability stains and histopathologic analysis. RESULTS: The flexible microwave applicators were delivered to ablation sites within lung parenchyma 5-24 mm from the airway wall via a tunnel created under virtual bronchoscopy guidance. No pneumothorax or significant airway bleeding was observed. The ablation short axis observed on gross pathology ranged 16.5-23.5 mm and 14-26 mm on CT imaging. CONCLUSION: We have demonstrated the technical feasibility for safely delivering microwave ablation in the lung parenchyma under virtual bronchoscopic guidance in an in vivo porcine lung model.

Assessment of thermal damage to myometrium during microwave ablation of uterine fibroids.

Thermal ablation techniques are increasingly used for the treatment of symptomatic uterine fibroids. Thermal protection of myometrial tissue adjacent to the fibroid from ablation is critical to maximally preserve the uterus. This study presents a bench top experimental setup, using ex vivo bovine muscle as a surrogate tissue, for evaluating collateral thermal damage in tissues during fibroid ablation. The study reports on the effect of applicator insertion angles (67.5° and 90°) into a mock fibroid on the efficacy of treatment. 6 experiments were performed (3 for each insertion angle) with 30 W applied power at 2.45 GHz. The heating duration was restricted to the time at which a thermal dose of 10 cumulative equivalent minutes at 43 °C (10 CEM 43) was accrued at the boundary of the mock fibroid. Results showed that the volume of ablation inside the mock fibroid dropped considerably from 66% to 17% when the applicator insertion angle was changed from 90º to 67.5º, suggesting that insertion angle plays an important role during microwave ablation of fibroid. The proposed setup provides a method for validating computational models for accurate and safe delivery of ablation to target tissues in fibroid treatment.

Directional Microwave Ablation: Experimental Evaluation of a 2.45-GHz Applicator in Ex Vivo and In Vivo Liver.

PURPOSE: To experimentally characterize a microwave (MW) ablation applicator designed to produce directional ablation zones. MATERIALS AND METHODS: Using a 14-gauge, 2.45-GHz side-firing MW ablation applicator, 36 ex vivo bovine liver ablations were performed. Ablations were performed at 60 W, 80 W, and 100 W for 3, 5, and 10 minutes (n = 4 per combination). Ablation zone forward and backward depth and width were measured and directivity was calculated as the ratio of forward to backward depth. Thirteen in vivo ablations were performed in 2 domestic swine with the applicator either inserted into the liver (80 W, 5 min, n = 3; 100 W, 5 min, n = 3; 100 W, 10 min, n = 2) or placed on the surface of the liver with a nontarget tissue placed on the back side of the applicator (80 W, 5 min, n = 5). The animals were immediately euthanized after the procedure; the livers were harvested and sectioned perpendicular to the axis of the applicator. In vivo ablation zones were measured following viability staining and assessed on histopathology. RESULTS: Mean ex vivo ablation forward depth was 8.3-15.5 mm. No backward heating was observed at 60 W, 3-5 minutes; directivity was 4.7-11.0 for the other power and time combinations. In vivo ablation forward depth was 10.3-11.5 mm, and directivity was 11.5-16.1. No visible or microscopic thermal damage to nontarget tissues in direct contact with the back side of the applicator was observed. CONCLUSIONS: The side-firing MW ablation applicator can create directional ablation zones in ex vivo and in vivo tissues.

Broadband lung dielectric properties over the ablative temperature range: Experimental measurements and parametric models.

PURPOSE: Computational models of microwave tissue ablation are widely used to guide the development of ablation devices, and are increasingly being used for the development of treatment planning and monitoring platforms. Knowledge of temperature-dependent dielectric properties of lung tissue is essential for accurate modeling of microwave ablation (MWA) of the lung. METHODS: We employed the open-ended coaxial probe method, coupled with a custom tissue heating apparatus, to measure dielectric properties of ex vivo porcine and bovine lung tissue at temperatures ranging between 31 and 150  ∘ C, over the frequency range 500 MHz to 6 GHz. Furthermore, we employed numerical optimization techniques to provide parametric models for characterizing the broadband temperature-dependent dielectric properties of tissue, and their variability across tissue samples, suitable for use in computational models of microwave tissue ablation. RESULTS: Rapid decreases in both relative permittivity and effective conductivity were observed in the temperature range from 94 to 108  ∘ C. Over the measured frequency range, both relative permittivity and effective conductivity were suitably modeled by piecewise linear functions [root mean square error (RMSE) = 1.0952 for permittivity and 0.0650 S/m for conductivity]. Detailed characterization of the variability in lung tissue properties was provided to enable uncertainty quantification of models of MWA. CONCLUSIONS: The reported dielectric properties of lung tissue, and parametric models which also capture their distribution, will aid the development of computational models of microwave lung ablation.

Suppression of overlearning in independent component analysis used for removal of muscular artifacts from electroencephalographic records.

This paper addresses the overlearning problem in the independent component analysis (ICA) used for the removal of muscular artifacts from electroencephalographic (EEG) records. We note that for short EEG records with high number of channels the ICA fails to separate artifact-free EEG and muscular artifacts, which has been previously attributed to the phenomenon called overlearning. We address this problem by projecting an EEG record into several subspaces with a lower dimension, and perform the ICA on each subspace separately. Due to a reduced dimension of the subspaces, the overlearning is suppressed, and muscular artifacts are better separated. Once the muscular artifacts are removed, the signals in the individual subspaces are combined to provide an artifact free EEG record. We show that for short signals and high number of EEG channels our approach outperforms the currently available ICA based algorithms for muscular artifact removal. The proposed technique can efficiently suppress ICA overlearning for short signal segments of high density EEG signals.

Computational modeling of 915 MHz microwave ablation: Comparative assessment of temperature-dependent tissue dielectric models.

PURPOSE: The objective of this study is to develop a computational model for simulating 915 MHz microwave ablation (MWA), and verify the simulation predictions of transient temperature profiles against experimental measurements. Due to the limited experimental data characterizing temperature-dependent changes of tissue dielectric properties at 915 MHz, we comparatively assess two temperature-dependent approaches of modeling of dielectric properties: model A- piecewise linear temperature dependencies based on existing, but limited, experimental data, and model B- similar to model A, but augmented with linear decrease in electrical conductivity above 95 °C, as guided by our experimental measurements. METHODS: 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. Predictions of the transient temperature profiles and ablation zone dimensions for both model A and model B were compared against experimental measurements 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. RESULTS: Model B yielded peak tissue temperatures in closer agreement with experimental measurements, attributed to the inclusion of decrease in electrical conductivity at elevated temperature. The simulated transverse diameters of the ablation zone predicted by both models were greater than experimental measurements, which may be in part due to the lack of a tissue shrinkage model. At both considered power levels, predictions of transverse ablation zone diameters were in closer agreement with measurements for model B (max. discrepancy of 5 mm at 60 W, and 3 mm at 30 W), compared to model A (max. discrepancy of 9 mm at 60 W, and 6 mm at 30 W). Ablation zone lengths with both models were within 2 mm at 30 W, but overestimated by up to 10 mm at 60 W. CONCLUSIONS: The inclusion of decreased electrical conductivity above 95 °C, implemented with model B as guided by our experimental measurements, may be a good approach for approximating the dynamic changes that occur during MWA at 915 MHz. Although a step toward more effectively modeling MWA at 915 MHz, further investigation of the transition in dielectric properties with temperature and tissue shrinkage, especially at high temperatures is needed for more accurate simulations.