Histology-validated electromagnetic characterization of ex-vivo ovine lung tissue for microwave-based medical applications.

Microwave thermal ablation is an established therapeutic technique for treating malignant tissue in various organs. Its success greatly depends on the knowledge of dielectric properties of the targeted tissue and on how they change during the treatment. Innovation in lung navigation has recently increased the clinical interest in the transbronchial microwave ablation treatment of lung cancer. However, lung tissue is not largely characterized, thus its dielectric properties investigation prior and post ablation is key. In this work, dielectric properties of ex-vivo ovine lung parenchyma untreated and ablated at 2.45 GHz were recorded in the 0.5-8 GHz frequency range. The measured dielectric properties were fitted to 2-pole Cole-Cole relaxation model and the obtained model parameters were compared. Based on observed changes in the model parameters, the physical changes of the tissue post-ablation were discussed and validated through histology analysis. Additionally, to investigate the link of achieved results with the rate of heating, another two sets of samples, originating from both ovine and porcine tissues, were heated with a microwave oven for different times and at different powers. Dielectric properties were measured in the same frequency range. It was found that lung tissue experiences a different behavior according to heating rates: its dielectric properties increase post-ablation while a decrease is found for low rates of heating. It is hypothesized, and validated by histology, that during ablation, although the tissue is losing water, the air cavities deform, lowering air content and increasing the resulting tissue properties.

Fetal monitoring technologies for the detection of intrapartum hypoxia - challenges and opportunities.

Intrapartum fetal hypoxia is related to long-term morbidity and mortality of the fetus and the mother. Fetal surveillance is extremely important to minimize the adverse outcomes arising from fetal hypoxia during labour. Several methods have been used in current clinical practice to monitor fetal well-being. For instance, biophysical technologies including cardiotocography, ST-analysis adjunct to cardiotocography, and Doppler ultrasound are used for intrapartum fetal monitoring. However, these technologies result in a high false-positive rate and increased obstetric interventions during labour. Alternatively, biochemical-based technologies including fetal scalp blood sampling and fetal pulse oximetry are used to identify metabolic acidosis and oxygen deprivation resulting from fetal hypoxia. These technologies neither improve clinical outcomes nor reduce unnecessary interventions during labour. Also, there is a need to link the physiological changes during fetal hypoxia to fetal monitoring technologies. The objective of this article is to assess the clinical background of fetal hypoxia and to review existing monitoring technologies for the detection and monitoring of fetal hypoxia. A comprehensive review has been made to predict fetal hypoxia using computational and machine-learning algorithms. The detection of more specific biomarkers or new sensing technologies is also reviewed which may help in the enhancement of the reliability of continuous fetal monitoring and may result in the accurate detection of intrapartum fetal hypoxia.

A Predictive and an Optimization Mathematical Model for Device Design in Cardiac Pulsed Field Ablation Using Design of Experiments.

Cardiac catheter ablation (CCA) is a common method used to correct cardiac arrhythmia. Pulsed Field Ablation (PFA) is a recently-adapted CCA technology whose ablation is dependent on electrode and waveform parameters (factors). In this work, the use of the Design of Experiments (DoE) methodology is investigated for the design and optimization of a PFA device. The effects of the four factors (input voltage, electrode spacing, electrode width, and on-time) and their interactions are analyzed. An empirical model is formed to predict and optimize the ablation size responses. Based on the ranges tested, the significant factors were the input voltage, the electrode spacing, and the on time, which is in line with the literature. Two-factor interactions were found to be significant and need to be considered in the model. The resulting empirical model was found to predict ablation sizes with less than 2.1% error in the measured area and was used for optimization. The findings and the strong predictive model developed highlight that the DoE approach can be used to help determine PFA device design, to optimize for certain ablation zone sizes, and to help inform device design to tackle specific cardiac arrhythmias.

Development and Characterization of Interstitial-Fluid-Mimicking Solutions for Pre-Clinical Assessment of Hypoxia.

Asphyxia, a leading cause of illness and death in newborns, can be improved by early detection and management. Arterial blood gas (ABG) analysis is commonly used to diagnose and manage asphyxia, but it is invasive and carries risks. Dermal interstitial fluid (ISF) is an alternative physiological fluid that can provide valuable information about a person's health. ISF is more sensitive to severe hypoxia and metabolic disorders compared to blood, making it an attractive option for minimally invasive asphyxia detection using biosensors. However, obtaining ISF samples from humans is challenging due to ethical concerns and sampling difficulties. To address this, researchers are developing ISF-mimicking solutions as substitutes for early testing and evaluation of biosensors. This paper focuses on the development of these solutions for bench-based testing and validation of continuous asphyxia-monitoring biosensors. With an understanding of the factors influencing system quality and performance, these solutions can aid in the design of biosensors for in vivo monitoring of dermal ISF. Monitoring interstitial fluid pH levels can provide valuable insights into the severity and progression of asphyxia, aiding in accurate diagnosis and informed treatment decisions. In this study, buffer solutions were prepared to mimic the pH of ISF, and their electrical properties were analyzed. The results suggest that certain buffers can effectively mimic metabolic acidosis associated with asphyxia (pH < 7.30), while others can mimic metabolic alkalosis (pH > 7.45). Overall, this research contributes to the development of ISF-mimicking solutions and lays the groundwork for biosensor systems that monitor dermal ISF in real time.

In Vitro Models for Improved Therapeutic Interventions in Atrial Fibrillation.

Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly caused by hyper excitation of specific areas in the atrium resulting in dyssynchronous atrial contractions, leading to severe consequences such as heart failure and stroke. Current therapeutics aim to target this condition through both pharmacological and non-pharmacological approaches. To test and validate any of these treatments, an appropriate preclinical model must be carefully chosen to refine and optimise the therapy features to correctly reverse this condition. A broad range of preclinical models have been developed over the years, with specific features and advantages to closely mimic the pathophysiology of atrial fibrillation. In this review, currently available models are described, from traditional animal models and in vitro cell cultures to state-of-the-art organoids and organs-on-a-chip. The advantages, applications and limitations of each model are discussed, providing the information to select the appropriate model for each research application.

Histology-Validated Dielectric Characterisation of Lung Carcinoma Tissue for Microwave Thermal Ablation Applications.

Microwave thermal ablation is a promising emerging treatment for early-stage lung cancer. Applicator design optimisation and treatment planning rely on accurate knowledge of dielectric tissue properties. Limited dielectric data are available in the literature for human lung tissue and pulmonary tumours. In this work, neoplastic and non-neoplastic lung dielectric properties are characterised and correlated with gross and histological morphology. Fifty-six surgical specimens were obtained from twelve patients undergoing lung resection for lung cancer in University Hospital of Galway, Ireland. Dielectric spectroscopy in the microwave frequency range (500 MHz-8.5 GHz) was performed on the ex vivo lung specimens with the open-ended coaxial probe technique (in the Department of Pathology). Dielectric data were analysed and correlated with the tissue histology. The dielectric properties of twelve lung tumours (67% non-small cell carcinoma (NSCC)) and uninvolved lung parenchyma were obtained. The values obtained from the neoplastic lung specimens (relative permittivity: 52.0 ± 5.4, effective conductivity: 1.9 ± 0.2 S/m, at 2.45 GHz) were on average twice the value of the non-neoplastic lung specimens (relative permittivity: 28.3 ± 6.7, effective conductivity: 1.0 ± 0.3 S/m, at 2.45 GHz). Dense fibrosis was comparable with tumour tissue (relative permittivity 49.3 ± 4.6, effective conductivity: 1.8 ± 0.1 S/m, at 2.45 GHz).

Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes.

OBJECTIVES: To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes. DESIGN: Evaluation and in vitro validation study SETTING: Ventilator shortage during the SARS-CoV-2 pandemic. PARTICIPANTS: The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals. METHODS: Using clinically available components, a system of ventilation consisting of two ventilatory limbs was assembled and connected to a ventilator. Monitors for each limb were developed using open-source software. Firstly, the effect of altering ventilator settings on tidal volumes delivered to each limb was determined. Secondly, the impact of altering the compliance and resistance of one limb on the tidal volumes delivered to both limbs was analysed. Experiments were repeated three times to determine system variability. RESULTS: The system permitted accurate and reproducible titration of tidal volumes to each limb over a range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures, of respiratory rates, and I:E ratio resulted in very similar tidal volumes delivered to each limb. Alteration of compliance and resistance in one limb resulted in reproducible alterations in tidal volume to that test lung, with little change to tidal volumes in the other lung. All tidal volumes delivered were reproducible. CONCLUSIONS: We demonstrate the reliability of a shared ventilation system assembled using commonly available clinical components that allows titration of individual tidal volumes. This system may be useful as a strategy of last resort for Covid-19, or other mass casualty situations, where the need for ventilators exceeds supply.

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.

Computational design and experimental analysis of a novel visor for COVID-19 patients receiving high-flow nasal oxygen therapy.

The Covid-19 global pandemic has reshaped the requirements of healthcare sectors worldwide. Following the exposure risks associated with Covid-19, this paper aims to design, optimise, and validate a wearable medical device that reduces the risk of transmission of contagious droplets from infected patients in a hospital setting. This study specifically focuses on those receiving high-flow nasal oxygen therapy. The design process consisted of optimising the geometry of the visor to ensure that the maximum possible percentage of harmful droplets exhaled by the patient can be successfully captured by a vacuum tube attached to the visor. This has been completed by deriving a number of concept designs and assessing their effectiveness, based on numerical analysis, computational fluid dynamics (CFD) simulations and experimental testing. The CFD results are validated using various experimental methods such as Schlieren imaging, particle measurement testing and laser sheet visualisation. Droplet capturing efficiency of the visor was measured through CFD and validated through experimental particle measurement testing. The results presented a 5% deviation between CFD and experimental results. Also, the modifications based on the validated CFD results improved the visor effectiveness by 47% and 38% for breathing and coughing events, respectively.

MWA Performed at 5.8 GHz through 'Side Firing' Approach: An Exploratory Study.

Recent studies have shown that ablation techniques have the potential to eradicate adrenal adenomas while preserving the functionalities of the adrenal gland and the surrounding anatomical structures. This study explores a new microwave ablation (MWA) approach operating at 5.8 GHz and using anatomical and dielectric characteristics of the target tissue to create directional heating patterns. Numerical simulations are executed in planar and 3D adrenal models, considering two energy doses. The numerical study is refined accounting for the vaporization of the tissue water content. Ex vivo experimental evaluations on porcine adrenal models complete the study. The numerical and experimental results show that spherical ablation zones are able to cover the target for both energy doses considered. Nonetheless, most of the non-targeted tissues can be preserved from excessive heating when low energy level is used. Numerical models accounting for water vaporization are capable to foresee the experimental temperature values. This study shows that the proposed MWA directional approach operating at 5.8 GHz can be considered for creating effective and selective ablation zones.

Pulsed Electric Field Ablation of Epicardial Autonomic Ganglia: Computer Analysis of Monopolar Electric Field across the Tissues Involved.

BACKGROUND AND OBJECTIVES: Pulsed Electric Field (PEF) ablation has been proposed as a non-thermal energy to treat atrial fibrillation (AF) by epicardial ablation of ganglionated plexi (GP), which are embedded within epicardial fat. Our objective was to study the distribution of the electric field through the involved tissues (fat, GPs, myocardium and blood) during epicardial PEF ablation. METHODS: A two-dimensional model was built considering different tissue layers below the ablation device which consists of an irrigated electrode. The 1000 V/cm threshold was used to estimate the 'PEF-zone'. RESULTS: The PEF-zone was almost 100% circumscribed in the epicardial fat layer, with very little incidence in the myocardium. The presence of the saline on the epicardial fat causes the PEF-zone to spread laterally around the electrode from ~5 mm to ~15 mm, relatively independently of how embedded the electrode is in the saline layer. For a saline layer well spread over the tissue surface and an electrode fully embedded in the saline layer, the PEF-zone width decreases as the fat layer thickens: from ~15 mm for fat thickness of 1 and 2 mm, down to ~10 mm for fat thickness of 5 mm. The presence of a GP in the center of the fat layer hardly affects the size of the PEF-zone, but significantly alters the distribution of the electric field around the GP, resulting in progressively lower values than in the surrounding adipose tissue as the fat layer thickness increased. CONCLUSIONS: Our results suggest how some procedural (irrigation) and anatomical parameters (fat thicknesses and presence of GPs) could be relevant in terms of the size of the tissue area affected by pulsed field ablation.

Probe Contact Force Monitoring during Conductivity Measurements of the Left Atrial Appendage to Support the Design of Novel Diagnostic and Therapeutic Procedures.

The electrical properties of many biological tissues are freely available from the INRC and the IT'IS databases. However, particularly in lower frequency ranges, few studies have investigated the optimal measurement protocol or the key confounders that need to be controlled, monitored, and reported. However, preliminary work suggests that the contact force of the measurement probe on the tissue sample can affect the measurements. The aim of this paper is to investigate the conductivity change due to the probe contact force in detail. Twenty ex vivo bovine heart samples are used, and conductivity measurements are taken in the Left Atrial Appendage, a common target for medical device developments. The conductivity measurements reported in this work (between 0.14 S/m and 0.24 S/m) align with the literature. The average conductivity is observed to change by -21% as the contact force increases from 2 N to 10 N. In contrast, in conditions where the fluid concentration in the measurement area is expected to be lower, very small changes are observed (less than 2.5%). These results suggest that the LAA conductivity is affected by the contact force due to the fluid concentration in the tissue. This work suggests that contact force should be controlled for in all future experiments.

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.

Management of adreno-cortical adenomas using microwave ablation: study of the effects of the fat tissue.

BACKGROUND AND OBJECTIVES: Adrenocortical neoplasms are the main causes of secondary hypertension and related comorbidities including hypokalemia and cardiovascular diseases. Conventional techniques for the management of this condition are often invasive and not resolutive. Recent studies proposed microwave thermal ablation (MWA) to eradicate adrenocortical adenomas arising in proximity to sensitive structures. This study explores a new MWA approach to selectively direct the electromagnetic energy into the target and shield the surrounding tissues. The new solution relies on the anatomical and dielectric characteristics of the adrenal gland and the surrounding fat capsule. METHODS: A 3 D model of the adrenal gland is developed, and a cooled microwave applicator is placed parallel to the interface between the fat and adrenal tissue. Numerical simulations are conducted at 2.45 GHz accounting for two energy delivery settings, two orientations of the applicator and blood perfusion of the tissues. Ex vivo and in vivo ablation procedures are conducted on ovine adrenal glands. Histology analysis completes the experimental studies. RESULTS: Numerical results show asymmetric ablation profiles in ex vivo and in vivo conditions. The asymmetry ratio is influenced by the procedure settings and orientation of the applicator. Ablation zones obtained experimentally agree with those predicted by the numerical simulations. Histology analysis confirms irreversible cellular changes only in the adrenal tissue close to the applicator. CONCLUSIONS: The outcomes show that the dielectric contrast between the fat layer and tissue target can be a tool in MWA to shape ablation zones to protect the surrounding structures from excessive temperature increases.

Electroporation Parameters for Human Cardiomyocyte Ablation In Vitro.

Cardiac ablation with irreversible electroporation (IRE) is quickly being established as a modality of choice for atrial fibrillation treatment. While it has not yet been optimised, IRE has the potential to significantly limit collateral damage and improve cell-specific targeting associated with other energy sources. However, more tissue and cell-specific evidence is required to demonstrate the selective threshold parameters for human cells. The aim here is to determine the optimal ablation threshold parameters related to lesion size for human cardiomyocytes in 2D culture. Conventional biphasic pulses of different field strengths and on-times were delivered in a monolayer culture system of human AC16 cardiomyocytes. The dynamics of cell death and lesion dimensions were examined at different time points. Human cardiomyocytes are susceptible to significant electroporation and cell death at a field strength of 750 V/cm or higher with 100 µs pulses. Increasing the IRE on-time from 3 ms to 60 ms reduces the effective field threshold to 250 V/cm. Using very short pulses of 2 µs and 5 µs also causes significant cell death, but only at fields higher than 1000 V/cm. A longer on-time results in more cell death and induced greater lesion area in 2D models. In addition, different forms of cell death are predicted based on the evolution of cell death over time. This study presents important findings on the ability of different IRE parameters to induce human cardiomyocyte cell death. Lesion size can be tuned by appropriate choice of IRE parameters and cardiomyocytes display an upregulation of delayed cell death 24 h after electroporation, which is an important consideration for clinical practice.

Establishing electroporation thresholds for targeted cell specific cardiac ablation in a 2D culture model.

BACKGROUND: Irreversible electroporation has emerged as a new modality to overcome issues associated with other energy sources for cardiac ablation. Strong evidence on the optimal, effective, and selective voltage threshold is lacking for both in vitro and preclinical in vivo studies. The aim of this study is to examine the optimal threshold for selective cell ablation on cardiac associated cell types. METHODS: Conventional monophasic and biphasic pulses of different field strength were delivered in a monolayer culture system of cardiomyocytes, neurons, and adipocytes. The dynamics of cell death mechanisms were examined at different time points. RESULTS: Neurons exhibit higher susceptibility to electroporation and cell death at higher field strength of 1250 V/cm in comparison to cardiomyocytes. Cardiac adipocytes showed lower susceptibility to electroporation in comparison to other cell types. A significant proportion of cardiomyocytes recovered after 24 h postelectroporation, while neuronal cell death remained consistent but with a significant delayed cell death at a higher voltage threshold. Caspase 3/7 activity was observed in both cardiomyocytes and neurons, with a higher level of activity in cardiomyocytes in response to electroporation. Biphasic and monophasic pulses showed no significant difference in both cell types, and significantly lower cell death in neurons when inter pulse interval was reduced. CONCLUSIONS: This study presents important findings on the differences in the susceptibility of neurons and cardiomyocytes to irreversible electroporation. Cell type alone yielded selective and different dynamics in terms of the evolution and signaling mechanism of cell death in response to electroporation.

Barrier materials for prevention of surgical adhesions: systematic review.

BACKGROUND: Postoperative surgical adhesions constitute a major health burden internationally. A wide range of materials have been evaluated, but despite constructive efforts and the obvious necessity, there remains no specific barrier widely utilized to prevent postoperative adhesion formation. The aim of this study was to highlight and characterize materials used for prevention of postoperative surgical adhesions in both animal and human studies. METHODS: A systematic review was performed of all original research articles presenting data related to the prevention of postoperative adhesions using a barrier agent. All available observational studies and randomized trials using animal models or human participants were included, with no restrictions related to type of surgery. PubMed and Embase databases were searched using key terms from inception to August 2019. Standardized data collection forms were used to extract details for each study and assess desirable characteristics of each barrier and success in animal and/or human studies. RESULTS: A total of 185 articles were identified for inclusion in the review, with a total of 67 unique adhesion barrier agents (37 natural and 30 synthetic materials). Desirable barrier characteristics of an ideal barrier were identified on review of the literature. Ten barriers achieved the primary outcome of reducing the incidence of postoperative adhesions in animal studies followed with positive outputs in human participants. A further 48 materials had successful results from animal studies, but with no human study performed to date. DISCUSSION: Multiple barriers showed promise in animal studies, with several progressing to success, and fulfilment of desirable qualities, in human trials. No barrier is currently utilized commonly worldwide, but potential barriers have been identified to reduce the burden of postoperative adhesions and associated sequelae.

Full torso and limited-domain computer models for epicardial pulsed electric field ablation.

BACKGROUND AND OBJECTIVES: Pulsed Electric Field (PEF) ablation has been proposed as a non-thermal energy to treat atrial fibrillation (AF) by ablation of ganglionated plexi using the epicardial approach. The electric field distribution at the target site (heart) and its surroundings has not yet been assessed previously, using epicardial ablation technique. Our objective was to develop computational models, incorporating the real anatomy of the heart and the patient's torso, to assess the electric field distribution when applying epicardial monopolar PEF. METHODS: A novel 3D realistic full torso model was built with the multi-electrode ablation device placed on the epicardium and a dispersive pad on the patient's back to evaluate the electric field distribution. The 400 V/cm isoline was used to estimate the 'PEF-zone'. A 3D limited-domain model was also built including only the region of interest around the ablation device to assess its validity in comparison with the full torso model. RESULTS: The electrical field is mainly limited to the target site (PEF-zone with lengths of 25.79 to 29.00 mm, depths of 5.98-7.02 mm and maximum widths of 8.75-10.57 mm) and is practically negligible in adjacent organs (<30 V/cm and <36 V/cm in oesophagus and lungs, respectively). The electrical currents ranged from 3.67 A to 7.44 A. The 3D limited-domain model provided a similar electric field distribution to those obtained from the 3D full torso models (differences < 0.5 mm in PEF-zone depth). CONCLUSIONS: Computational results suggest that PEF-zone is very focused around the ablation catheter. Limited-domain models offer similar results in terms of PEF-zone size, reducing the complexity of the modelling.

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.

Trends in Adaptive Design Methods in Dialysis Clinical Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Adaptive design methods are intended to improve the efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to determine the use of adaptive designs in dialysis clinical trials and quantify trends in their use over time. STUDY DESIGN: We completed a novel full-text systematic review that used a machine learning classifier (RobotSearch) for filtering randomized controlled trials and adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. SETTING & STUDY POPULATIONS: We searched MEDLINE (PubMed) and ClinicalTrials.gov using sensitive dialysis search terms. SELECTION CRITERIA FOR STUDIES: We included all randomized clinical trials with patients receiving dialysis or clinical trials with dialysis as a primary or secondary outcome. There was no restriction of disease type or intervention type. DATA EXTRACTION & ANALYTICAL APPROACH: We performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data. RESULTS: 57 studies, available as 68 articles and 7 ClinicalTrials.gov summaries, were included after full-text review (initial search, 209,033 PubMed abstracts and 6,002 ClinicalTrials.gov summaries). 31 studies were conducted in a dialysis population and 26 studies included dialysis as a primary or secondary outcome. Although the absolute number of adaptive design methods is increasing over time, the relative use of adaptive design methods in dialysis trials is decreasing over time (6.12% in 2009 to 0.43% in 2019, with a mean of 1.82%). Group sequential designs were the most common type of adaptive design method used. Adaptive design methods affected the conduct of 50.9% of trials, most commonly resulting in stopping early for futility (41.2%) and early stopping for safety (23.5%). Acute kidney injury was studied in 32 trials (56.1%), kidney failure requiring dialysis was studied in 24 trials (42.1%), and chronic kidney disease was studied in 1 trial (1.75%). 27 studies (47.4%) were supported by public funding. 44 studies (77.2%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic review. LIMITATIONS: We limited our search to 2 databases (PubMed and ClinicalTrials.gov) due to the scale of studies sourced (209,033 and 6,002 results, respectively). CONCLUSIONS: Adaptive design methods are used in dialysis trials but there has been a decline in their relative use over time.