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.

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.

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%).

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.