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.

Directional microwave ablation in spine: experimental assessment of computational modeling.

BACKGROUND: Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by ex vivo and pilot in vivo experiments in porcine vertebral bodies. MATERIALS AND METHODS: A 3D computational model of microwave ablation within porcine vertebral bodies was developed. Ex vivo porcine vertebra experiments using a dMWA applicator measured temperatures approximately 10.1 mm radially from the applicator in the direction of MW radiation (T1) and approximately 2.4 mm in the contra-lateral direction (T2). Histologic assessment of ablated ex vivo tissue was conducted and experimental results compared to simulations. Pilot in vivo experiments in porcine vertebral bodies assessed ablation zones histologically and with CT and MRI. RESULTS: Experimental T1 and T2 temperatures were within 3-7% and 11-33% of simulated temperature values. Visible ablation zones, as indicated by grayed tissue, were smaller than those typical in other soft tissues. Posthumous MRI images of in vivo ablations showed hyperintensity. In vivo experiments illustrated the technical feasibility of creating directional microwave ablation zones in porcine vertebral body. CONCLUSION: Computational models and experimental studies illustrate the feasibility of controlled dMWA in bone tissue.

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.

Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.

A Computational Modeling Approach to Investigate the Influence of Hyperthermia on the Tumor Microenvironment.

The biophysical properties of the tumor microenvironment differ substantially from normal tissues. A constellation of features, including decreased vascularity, lack of lymphatic drainage, and elevated interstitial pressure, diminishes the penetration of therapeutics into tumors. Local hyperthermia within the tumor can alter microenvironmental properties, such as interstitial fluid pressure, potentially leading to improvements in drug penetration. In this context, multi-physics computational models can provide insight into the interplay between the biophysical parameters within the tumor microenvironment and can guide the design and interpretation of experiments that test the bioeffects of local hyperthermia. This paper describes a step-by-step workflow for a computational model coupling partial differential equations describing electrical current distribution, bioheat transfer, and fluid dynamics. The main objective is to study the effects of hyperthermia delivered by a bipolar radiofrequency device on the interstitial fluid pressure within the tumor. The system of mathematical expressions linking electrical current distribution, bioheat transfer, and interstitial fluid pressure is presented, emphasizing the changes in the distribution of the interstitial fluid pressure that could be induced by the thermal intervention.

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.

Effects of Ballistocardiogram Peak Detection Jitters on the Quality of Heart Rate Variability Features: A Simulation-Based Case Study in the Context of Sleep Staging.

Heart rate variability (HRV) features support several clinical applications, including sleep staging, and ballistocardiograms (BCGs) can be used to unobtrusively estimate these features. Electrocardiography is the traditional clinical standard for HRV estimation, but BCGs and electrocardiograms (ECGs) yield different estimates for heartbeat intervals (HBIs), leading to differences in calculated HRV parameters. This study examines the viability of using BCG-based HRV features for sleep staging by quantifying the impact of these timing differences on the resulting parameters of interest. We introduced a range of synthetic time offsets to simulate the differences between BCG- and ECG-based heartbeat intervals, and the resulting HRV features are used to perform sleep staging. Subsequently, we draw a relationship between the mean absolute error in HBIs and the resulting sleep-staging performances. We also extend our previous work in heartbeat interval identification algorithms to demonstrate that our simulated timing jitters are close representatives of errors between heartbeat interval measurements. This work indicates that BCG-based sleep staging can produce accuracies comparable to ECG-based techniques such that at an HBI error range of up to 60 ms, the sleep-scoring error could increase from 17% to 25% based on one of the scenarios we examined.

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.

Experimental Validation of Diffraction Lithography for Fabrication of Solid Microneedles.

Microneedles are highly sought after for medicinal and cosmetic applications. However, the current manufacturing process for microneedles remains complicated, hindering its applicability to a broader variety of applications. As diffraction lithography has been recently reported as a simple method for fabricating solid microneedles, this paper presents the experimental validation of the use of ultraviolet light diffraction to control the liquid-to-solid transition of photosensitive resin to define the microneedle shape. The shapes of the resultant microneedles were investigated utilizing the primary experimental parameters including the photopattern size, ultraviolet light intensity, and the exposure time. Our fabrication results indicated that the fabricated microneedles became taller and larger in general when the experimental parameters were increased. Additionally, our investigation revealed four unique crosslinked resin morphologies during the first growth of the microneedle: microlens, first harmonic, first bell-tip, and second harmonic shapes. Additionally, by tilting the light exposure direction, a novel inclined microneedle array was fabricated for the first time. The fabricated microneedles were characterized with skin insertion and force-displacement tests. This experimental study enables the shapes and mechanical properties of the microneedles to be predicted in advance for mass production and wide practical use for biomedical or cosmetic applications.

A Review of In Vitro Instrumentation Platforms for Evaluating Thermal Therapies in Experimental Cell Culture Models.

Thermal therapies, the modulation of tissue temperature for therapeutic benefit, are in clinical use as adjuvant or stand-alone therapeutic modalities for a range of indications, and are under investigation for others. During delivery of thermal therapy in the clinic and in experimental settings, monitoring and control of spatio-temporal thermal profiles contributes to an increased likelihood of inducing desired bioeffects. In vitro thermal dosimetry studies have provided a strong basis for characterizing biological responses of cells to heat. To perform an accurate in vitro thermal analysis, a sample needs to be subjected to uniform heating, ideally raised from, and returned to, baseline immediately, for a known heating duration under ideal isothermal condition. This review presents an applications-based overview of in vitro heating instrumentation platforms. A variety of different approaches are surveyed, including external heating sources (i.e., CO2 incubators, circulating water baths, microheaters and microfluidic devices), microwave dielectric heating, lasers or the use of sound waves. We discuss critical heating parameters including temperature ramp rate (heat-up phase period), heating accuracy, complexity, peak temperature, and technical limitations of each heating modality.

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.

Shaping the future of microwave tumor ablation: a new direction in precision and control of device performance.

Microwave ablation (MWA) is becoming an increasingly important minimally invasive treatment option for localized tumors in many organ systems due to recent advancements in microwave technology that have conferred many advantages over other tumor ablation modalities. Despite these improvements in technology and development of applicators for site-specific tumor applications, the vast majority of commercially available MWA applicators are generally designed to create large-volume, symmetric, ellipsoid or spherically-shaped treatment zones and often lack the consistency, predictability, and spatial control needed to treat tumor targets near critical structures that are vulnerable to inadvertent thermal injury. The relatively new development and ongoing translation of directional microwave ablation (DMWA) technology, however, has the potential to confer an added level of control over the treatment zone shape relative to applicator position, and shows great promise to expand MWA's clinical applicability in treating tumors in challenging locations. This paper presents a review of the industry-standard commercially available MWA technology, its clinical applications, and its limitations when used for minimally-invasive tumor treatment in medical practice followed by discussion of new advancements in experimental directional microwave ablation (DMWA) technology, various techniques and approaches to its use, and examples of how this technology may be used to treat tumors in challenging locations that may otherwise preclude safe treatment by conventional omni-directional MWA devices.

A Non-Invasive Hydration Monitoring Technique Using Microwave Transmission and Data-Driven Approaches.

Dehydration in the human body arises due to inadequate replenishment of fluids. An appropriate level of hydration is essential for optimal functioning of the human body, and complications ranging from mild discomfort to, in severe cases, death, could result from a neglected imbalance in fluid levels. Regular and accurate monitoring of hydration status can provide meaningful information for people operating in stressful environmental conditions, such as athletes, military professionals and the elderly. In this study, we propose a non-invasive hydration monitoring technique employing non-ionizing electromagnetic power in the microwave band to estimate the changes in the water content of the whole body. Specifically, we investigate changes in the attenuation coefficient in the frequency range 2-3.5 GHz between a pair of planar antennas positioned across a participant's arm during various states of hydration. Twenty healthy young adults (10M, 10F) underwent controlled hypohydration and euhydration control bouts. The attenuation coefficient was compared among trials and used to predict changes in body mass. Volunteers lost 1.50±0.44% and 0.49±0.54% body mass during hypohydration and euhydration, respectively. The microwave transmission-based attenuation coefficient (2-3.5 GHz) was accurate in predicting changes in hydration status. The corresponding regression analysis demonstrates that building separate estimation models for dehydration and rehydration phases offer better predictive performance (88%) relative to a common model for both the phases (76%).

Extracorporeal Removal of Thermosensitive Liposomal Doxorubicin from Systemic Circulation after Tumor Delivery to Reduce Toxicities.

Thermosensitive liposomal doxorubicin (TSL-Dox) combined with localized hyperthermia enables targeted drug delivery. Tumor drug uptake occurs only during hyperthermia. We developed a novel method for removal of systemic TSL-Dox remaining after hyperthermia-triggered delivery to reduce toxicities. The carotid artery and jugular vein of Norway brown rats carrying two subcutaneous BN-175 tumors were catheterized. After allowing the animals to recover, TSL-Dox was infused at 7 mg/kg dose. Drug delivery to one of the tumors was performed by inducing 15 min microwave hyperthermia (43 °C). At the end of hyperthermia, an extracorporeal circuit (ECC) comprising a heating module to release drug from TSL-Dox followed by an activated carbon filter to remove free drug was established for 1 h (n = 3). A computational model simulated TSL-Dox pharmacokinetics, including ECC filtration, and predicted cardiac Dox uptake. In animals receiving ECC, we were able to remove 576 ± 65 mg of Dox (29.7 ± 3.7% of the infused dose) within 1 h, with a 2.9-fold reduction of plasma AUC. Fluorescent monitoring enabled real-time quantification of blood concentration and removed drug. Computational modeling predicted that up to 59% of drug could be removed with an ideal filter, and that cardiac uptake can be reduced up to 7×. We demonstrated removal of drug remaining after tumor delivery, reduced plasma AUC, and reduced cardiac uptake, suggesting reduced toxicity.

A computational model of radiofrequency ablation in the stomach, an emerging therapy for gastric dysrhythmias.

Gastric ablation has recently emerged as a promising potential therapy for bioelectrical dysrhythmias that underpin many gastrointestinal disorders. Despite similarities to well-developed cardiac ablation, gastric ablation is in early development and has thus far been limited to temperature-controlled, non-irrigated settings. A computational model of gastric ablation is needed to enable in silico testing and optimization of ablation parameters and techniques. In this study, we developed a computational model of radio-frequency (RF) gastric ablation. Model parameters and boundary conditions were established based on the current in vivo experimental application of serosal gastric ablation with a non-irrigated RF catheter. The Pennes bioheat transfer equation was used to model the thermal component of RF ablation, and Laplace's equation was used to model the Joule heating component. Tissue, blood, and catheter parameters were obtained from literature. The performance of the model was compared to previously established experimental values of temperature measured from various distances from the catheter tip. The model produced temperature estimations that were within 6% of the maximum experimental temperature at 2.5 mm from the catheter, and within 13% of the maximum temperature change at 4.7 mm. This model now provides a computational basis through which to conduct in silico testing of gastric ablation, and can be usefully applied to optimize gastric ablation parameters. In future, the model can be expanded to include irrigation of the catheter tip and power-controlled RF settings.Clinical Relevance- This work presents a computational model of gastric ablation that can now guide the in silico development of effective ablation parameters and therapeutic strategies, expanding the breadth of this promising therapy.

Preclinical Studies in Small Animals for Advanced Drug Delivery Using Hyperthermia and Intravital Microscopy.

This paper presents three devices suitable for the preclinical application of hyperthermia via the simultaneous high-resolution imaging of intratumoral events. (Pre)clinical studies have confirmed that the tumor micro-environment is sensitive to the application of local mild hyperthermia. Therefore, heating is a promising adjuvant to aid the efficacy of radiotherapy or chemotherapy. More so, the application of mild hyperthermia is a useful stimulus for triggered drug release from heat-sensitive nanocarriers. The response of thermosensitive nanoparticles to hyperthermia and ensuing intratumoral kinetics are considerably complex in both space and time. To obtain better insight into intratumoral processes, longitudinal imaging (preferable in high spatial and temporal resolution) is highly informative. Our devices are based on (i) an external electric heating adaptor for the dorsal skinfold model, (ii) targeted radiofrequency application, and (iii) a microwave antenna for heating of internal tumors. These models, while of some technical complexity, significantly add to the understanding of effects of mild hyperthermia warranting implementation in research on hyperthermia.