Transseptal puncture in left atrial appendage closure guided by 3D printing and multiplanar CT reconstruction.

BACKGROUND: The presented study investigates the application of bi-arterial 3D printed models to guide transseptal puncture (TSP) in left atrial appendage closure (LAAC). AIMS: The objectives are to (1) test the feasibility of 3D printing (3DP) for TSP guidance, (2) analyse the distribution of the optimal TSP locations, and (3) define a CT-derived 2D parameter suitable for predicting the optimal TSP locations. METHODS: Preprocedural planning included multiplanar CT reconstruction, 3D segmentation, and 3DP. TSP was preprocedurally simulated in vitro at six defined sites. Based on the position of the sheath, TSP sites were classified as optimal, suboptimal, or nonoptimal. The aim was to target the TSP in the recommended position during the procedure. Procedure progress was assessed post hoc by the operator. RESULTS: Of 68 screened patients, 60 patients in five centers (mean age of 74.68 ± 7.64 years, 71.66% males) were prospectively analyzed (3DP failed in one case, and seven patients did not finally undergo the procedure). In 55 patients (91.66%), TSP was performed in the optimal location as recommended by the 3DP. The optimal locations for TSP were postero-inferior in 45.3%, mid-inferior in 45.3%, and antero-inferior in 37.7%, with a mean number of optimal segments of 1.34 ± 0.51 per patient. When the optimal TSP location was achieved, the procedure was considered difficult in only two (3.6%) patients (but in both due to complicated LAA anatomy). Comparing anterior versus posterior TSP in 2D CCT, two parameters differed significantly: (1) the angle supplementary to the LAA ostium and the interatrial septum angle (160.83° ± 9.42° vs. 146.49° ± 8.67°; p = 0.001), and (2) the angle between the LAA ostium and the mitral annulus (95.02° ± 3.73° vs. 107.38° ± 6.76°; p < 0.001), both in the sagittal plane. CONCLUSIONS: In vitro TSP simulation accurately determined the optimal TSP locations for LAAC and facilitated the procedure. More than one-third of the optimal TSP sites were anterior.

Assessment of the thermal tissue models for the head and neck hyperthermia treatment planning.

PURPOSE: To compare different thermal tissue models for head and neck hyperthermia treatment planning, and to assess the results using predicted and measured applied power data from clinical treatments. METHODS: Three commonly used temperature models from literature were analysed: "constant baseline", "constant thermal stress" and "temperature dependent". Power and phase data of 93 treatments of 20 head and neck patients treated with the HYPERcollar3D applicator were used. The impact on predicted median temperature T50 inside the target region was analysed with maximum allowed temperature of 44 °C in healthy tissue. The robustness of predicted T50 for the three models against the influence of blood perfusion, thermal conductivity and the assumed hotspot temperature level was analysed. RESULTS: We found an average predicted T50 of 41.0 ± 1.3 °C (constant baseline model), 39.9 ± 1.1 °C (constant thermal stress model) and 41.7 ± 1.1 °C (temperature dependent model). The constant thermal stress model resulted in the best agreement between the predicted power (P = 132.7 ± 45.9 W) and the average power measured during the hyperthermia treatments (P = 129.1 ± 83.0 W). CONCLUSION: The temperature dependent model predicts an unrealistically high T50. The power values for the constant thermal stress model, after scaling simulated maximum temperatures to 44 °C, matched best to the average measured powers. We consider this model to be the most appropriate for temperature predictions using the HYPERcollar3D applicator, however further studies are necessary for developing of robust temperature model for tissues during heat stress.

On the Role of Training Data for SVM-Based Microwave Brain Stroke Detection and Classification.

The aim of this work was to test microwave brain stroke detection and classification using support vector machines (SVMs). We tested how the nature and variability of training data and system parameters impact the achieved classification accuracy. Using experimentally verified numerical models, a large database of synthetic training and test data was created. The models consist of an antenna array surrounding reconfigurable geometrically and dielectrically realistic human head phantoms with virtually inserted strokes of arbitrary size, and different dielectric parameters in different positions. The generated synthetic data sets were used to test four different hypotheses, regarding the appropriate parameters of the training dataset, the appropriate frequency range and the number of frequency points, as well as the level of subject variability to reach the highest SVM classification accuracy. The results indicate that the SVM algorithm is able to detect the presence of the stroke and classify it (i.e., ischemic or hemorrhagic) even when trained with single-frequency data. Moreover, it is shown that data of subjects with smaller strokes appear to be the most suitable for training accurate SVM predictors with high generalization capabilities. Finally, the datasets created for this study are made available to the community for testing and developing their own algorithms.

Red-backed shrike (Lanius collurio) versus common cuckoo (Cuculus canorus): An example of ineffective cuckoo-hawk mimicry.

The red-backed shrike (Lanius collurio) used to be one of the most common hosts of the common cuckoo (Cuculus canorus). Nevertheless, during the last 30 years, there is increasing evidence from Central Europe that the occurrence of cuckoo chicks in shrike nests has become scarcer, and that in some locations they have disappeared completely. Multiple hypotheses have been suggested to explain this abandonment. Here, we test the hypothesis that shrikes vigorously attack adult cuckoos, potentially resulting in ineffective parasitism. Adult common cuckoos resemble in appearance the Eurasian sparrowhawk (Accipiter nisus), a common predator of small passerines. One hypothesis presumes that the cuckoo has evolved this mimicry to avoid attack by small passerines when searching for their nests. Our results show that shrikes defending their nests attacked cuckoos very vigorously, more often, and more intensively than they did sparrowhawks. In the presence of a sparrowhawk dummy, parent shrikes only produced alarm calls and flew over the dummy. This suggests that cuckoo-hawk mimicry is ineffective in the case of shrikes and that they attack them much more often than they do any other presented intruder. Therefore, this activity could possibly result in the abandonment of shrikes as potential hosts for cuckoos.

Microwave Catheter Navigation System for the Radiofrequency Liver Ablation.

Thermal ablation is a well-known method used in interventional radiology to treat cancer. The treatment success is closely related to the exact catheter location in the treated area. Current navigation methods are based mostly on ultrasound or computed tomography. This work explores the possibility of tracking the catheter position during ablation treatment of hepatocellular carcinomas (HCC) using an ultra-wideband (UWB) antenna array and microwave radar imaging based on the "Delay and Sum" (DAS) algorithm. The feasibility was first numerically studied on a simple homogeneous liver model. A heterogeneous anthropomorphic 3D model of the treated region consisting of the main organs within the treated area was then used. Various standard radiofrequency ablation (RFA) catheters were placed virtually in the heterogeneous model. The location and orientation of the antenna elements of the developed imaging system and the applied frequency band were studied. Subsequently, an experimental setup consisting of a 3D printed homogeneous anthropomorphic model, eight UWB dipole antennas, and catheters was created and used in a series of measurements. The average accuracy determining the catheter position from simulated and experimental data was 3.88 ± 0.19 and 6.13 ± 0.66 mm, which are close to the accuracy of clinical navigation systems.

Isoprenaline modified the lipidomic profile and reduced ß-oxidation in HL-1 cardiomyocytes: In vitro model of takotsubo syndrome.

Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid ß-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective ß-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5'-triphosphate (ATP) production and ß-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time - polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased ß-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.

Microwave Hyperthermia of Brain Tumors: A 2D Assessment Parametric Numerical Study.

Due to the clinically proven benefit of hyperthermia treatments if added to standard cancer therapies for various tumor sites and the recent development of non-invasive temperature measurements using magnetic resonance systems, the hyperthermia community is convinced that it is a time when even patients with brain tumors could benefit from regional microwave hyperthermia, even if they are the subject of a treatment to a vital organ. The purpose of this study was to numerically analyze the ability to achieve a therapeutically relevant constructive superposition of electromagnetic (EM) waves in the treatment of hyperthermia targets within the brain. We evaluated the effect of the target size and position, operating frequency, and the number of antenna elements forming the phased array applicator on the treatment quality. In total, 10 anatomically realistic 2D human head models were considered, in which 10 circular hyperthermia targets with diameters of 20, 25, and 30 mm were examined. Additionally, applicators with 8, 12, 16, and 24 antenna elements and operating frequencies of 434, 650, 915, and 1150 MHz, respectively, were analyzed. For all scenarios considered (4800 combinations), the EM field distributions of individual antenna elements were calculated and treatment planning was performed. Their quality was evaluated using parameters applied in clinical practice, i.e., target coverage (TC) and the target to hot-spot quotient (THQ). The 12-antenna phased array system operating at 434 MHz was the best candidate among all tested systems for HT treatments of glioblastoma tumors. The 12 antenna elements met all the requirements to cover the entire target area; an additional increase in the number of antenna elements did not have a significant effect on the treatment quality.

Application of photogrammetry reconstruction for hyperthermia quality control measurements.

PURPOSE: Hyperthermia is a cancer treatment in which the target region is heated to temperatures of 40-44 °C usually applying external electromagnetic field sources. The behavior of the hyperthermia applicators (antennas) in clinical practice should be periodically checked with phantom experiments to verify the applicator's performance over time. The purpose of this study was to investigate the application of photogrammetry reconstructions of 3D applicator position in these quality control procedure measurements. METHODS: Photogrammetry reconstruction was applied at superficial hyperthermia scenario using the Lucite cone applicator (LCA) and phased-array heating in the head and neck region using the HYPERcollar3D. Wire-frame models of the entire measurement setups were created from multiple-view images and used for recreation of the setup inside 3D electromagnetic field simulation software. We evaluated applicator relation (Ra) between measured and simulated absolute specific absorption rate (SAR) for manually created and photogrammetry reconstructed simulation setups. RESULTS: We found a displacement of 7.9 mm for the LCA and 8.2 mm for the HYPERcollar3D setups when comparing manually created and photogrammetry reconstructed applicator models placements. Ra improved from 1.24 to 1.18 for the LCA and from 1.17 to 1.07 for the HYPERcollar3D when using photogrammetry reconstructed simulation setups. CONCLUSION: Photogrammetry reconstruction technique holds promise to improve measurement setup reconstruction and agreement between measured and simulated absolute SAR.

A Guide for Water Bolus Temperature Selection for Semi-Deep Head and Neck Hyperthermia Treatments Using the HYPERcollar3D Applicator.

During hyperthermia cancer treatments, especially in semi-deep hyperthermia in the head and neck (H&N) region, the induced temperature pattern is the result of a complex interplay between energy delivery and tissue cooling. The purpose of this study was to establish a water bolus temperature guide for the HYPERcollar3D H&N applicator. First, we measured the HYPERcollar3D water bolus heat-transfer coefficient. Then, for 20 H&N patients and phase/amplitude settings of 93 treatments we predict the T50 for nine heat-transfer coefficients and ten water bolus temperatures ranging from 20-42.5 °C. Total power was always tuned to obtain a maximum of 44 °C in healthy tissue in all simulations. As a sensitivity study we used constant and temperature-dependent tissue cooling properties. We measured a mean heat-transfer coefficient of h = 292 W m-2K-1 for the HYPERcollar3D water bolus. The predicted T50 shows that temperature coverage is more sensitive to the water bolus temperature than to the heat-transfer coefficient. We propose changing the water bolus temperature from 30 °C to 35 °C which leads to a predicted T50 increase of +0.17/+0.55 °C (constant/temperature-dependent) for targets with a median depth < 20 mm from the skin surface. For deeper targets, maintaining a water bolus temperature at 30 °C is proposed.

Feasibility Evaluation of Metamaterial Microwave Sensors for Non-Invasive Blood Glucose Monitoring.

The use of microwave technology is currently under investigation for non-invasive estimation of glycemia in patients with diabetes. Due to their construction, metamaterial (MTM)-based sensors have the potential to provide higher sensitivity of the phase shift of the S21 parameter (∠S21) to changes in glucose concentration compared to standard microstrip transmission line (MSTL)-based sensors. In this study, a MSTL sensor and three MTM sensors with 5, 7, and 9 MTM unit cells are exposed to liquid phantoms with different dielectric properties mimicking a change in blood glucose concentration from 0 to 14 mmol/L. Numerical models were created for the individual experiments, and the calculated S-parameters show good agreement with experimental results, expressed by the maximum relative error of 8.89% and 0.96% at a frequency of 1.99 GHz for MSTL and MTM sensor with nine unit cells, respectively. MTM sensors with an increasing number of cells show higher sensitivity of 0.62° per mmol/L and unit cell to blood glucose concentration as measured by changes in ∠S21. In accordance with the numerical simulations, the MTM sensor with nine unit cells showed the highest sensitivity of the sensors proposed by us, with an average of 3.66° per mmol/L at a frequency of 1.99 GHz, compared to only 0.48° per mmol/L for the MSTL sensor. The multi-cell MTM sensor has the potential to proceed with evaluation of human blood samples.

Simulation guided design of the MRcollar: a MR compatible applicator for deep heating in the head and neck region.

PURPOSE: To develop a head and neck hyperthermia phased array system compatible with a 1.5 T magnetic resonance (MR) scanner for noninvasive thermometry. METHODS: We designed a dielectric-parabolic-reflector antenna (DiPRA) based on a printed reflector backed dipole antenna and studied its predicted and measured performance in a flat configuration (30 mm thick water bolus and muscle equivalent layer). Thereafter, we designed a phased array applicator model ('MRcollar') consisting of 12 DiPRA modules placed on a radius of 180 mm. Theoretical heating performance of the MRcollar model was benchmarked against the current clinical applicator (HYPERcollar3D) using specific (3D) head and neck models of 28 treated patients. Lastly, we assessed the influence of the DiPRA modules on MR scanning quality. RESULTS: The predicted and measured reflection coefficients (S11) of the DiPRA module are below -20 dB. The maximum specific absorption rate (SAR) in the area under the antenna was 47% higher than for the antenna without encasing. Compared to the HYPERcollar3D, the MRcollar design incorporates 31% less demineralized water (-2.5 L), improves the predicted TC25 (target volume enclosed by 25% iso-SAR contour) by 4.1% and TC50 by 8.5%, while the target-to-hotspot quotient (THQ) is minimally affected (-1.6%). MR experiments showed that the DiPRA modules do not affect MR transmit/receive performance. CONCLUSION: Our results suggest that head and neck hyperthermia delivery quality with the MRcollar can be maintained, while facilitating simultaneous noninvasive MR thermometry for treatment monitoring and control.

Ultra-Wideband Temperature Dependent Dielectric Spectroscopy of Porcine Tissue and Blood in the Microwave Frequency Range.

The knowledge of frequency and temperature dependent dielectric properties of tissue is essential to develop ultra-wideband diagnostic technologies, such as a non-invasive temperature monitoring system during hyperthermia treatment. To this end, we characterized the dielectric properties of animal liver, muscle, fat and blood in the microwave frequency range from 0.5 GHz to 7 GHz and in the temperature range between 30 °C and 50 °C. The measured data were modeled to a two-pole Cole-Cole model and a second-order polynomial was introduced to fit the Cole-Cole parameters as a function of temperature. The parametric model provides access to the dielectric properties of tissue at any frequency and temperature in the specified range.

Preliminary Investigations for Non-invasive Temperature Change Detection in Thermotherapy by Means of UWB Microwave Radar.

Non-invasive differential temperature monitoring by means of ultra-wideband sensing is a promising approach concerning temperature controlling during thermotherapy. In this paper the principal of temperature difference detection by UWB radar is explained and appropriate phantom measurements are discussed. In a first step, temperature dependent dielectric properties of the phantom materials (sunflower oil and distilled water) are analyzed. Subsequently, temperature dependent phantom measurements are conducted where the temperature dependent signal changes of the received UWB signals are investigated. Results show a linear behavior between the received differential radar signals and the temperature differences of the target in the considered temperature range. Furthermore, investigations show that temperature changes of the target, which are common in thermal therapy (e.g., hyperthermia), are detectable by means of UWB radar.