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.

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.

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.

Numerical Analysis of Transcranial Magnetic Stimulation Application in Patients With Orofacial Pain.

In this paper, we monitored the accuracy of non-navigated application of repetitive Transcranial Magnetic Stimulation (rTMS) in 10 patients suffering from orofacial pain by using functional magnetic resonance (fMRI), computer modeling and numerical simulation. Through a unique process, each fMRI scan was used to define a Region of Interest (ROI) where the source of the orofacial pain was located, which was to be stimulated using rTMS. For each patient, MRI scans with a spatial resolution of 0.7 mm were converted into an anatomically accurate head model. The head model including the ROI was then co-registered with a model of the stimulation coil in an electromagnetic field numerical simulator. The accuracy of rTMS application was evaluated based on the calculations of electric field intensity distribution in the ROI. The research has yielded unique insight into ROIs (with average volume 904 mm3) in patients with orofacial pain and has also extended further possibilities of human head MRI image semi-automatic segmentation. According to the calculations performed, the average ROI volume that was stimulated by an electric field with an intensity of over 80 V/m was only 4.4%, with the maximum ROI volume being 20.5%. Furthermore, a numerical study of the impact of coil rotation and translation was performed. It demonstrated a) the optimal placement of the stimulation coil can significantly increase the volume of the stimulated ROI up to 60% and b) patients with orofacial pain would need precise coil positioning with a navigation error lower than 10 mm. Due to an acceptable proccessing time of up to 6 hours, described numerical simulation opens up new options for precise rTMS treatment planning. This planning platform together with patient-specific navigated rTMS, could lead to significant increase of treatment outcomes in patients suffering from orofacial pain.

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.

A Machine Learning Approach for Gearbox System Fault Diagnosis.

This study proposes a fully automated gearbox fault diagnosis approach that does not require knowledge about the specific gearbox construction and its load. The proposed approach is based on evaluating an adaptive filter's prediction error. The obtained prediction error's standard deviation is further processed with a support-vector machine to classify the gearbox's condition. The proposed method was cross-validated on a public dataset, segmented into 1760 test samples, against two other reference methods. The accuracy achieved by the proposed method was better than the accuracies of the reference methods. The accuracy of the proposed method was on average 9% higher compared to both reference methods for different support vector settings.

Generation of Electromagnetic Field by Microtubules.

The general mechanism of controlling, information and organization in biological systems is based on the internal coherent electromagnetic field. The electromagnetic field is supposed to be generated by microtubules composed of identical tubulin heterodimers with periodic organization and containing electric dipoles. We used a classical dipole theory of generation of the electromagnetic field to analyze the space-time coherence. The structure of microtubules with the helical and axial periodicity enables the interaction of the field in time shifted by one or more periods of oscillation and generation of coherent signals. Inner cavity excitation should provide equal energy distribution in a microtubule. The supplied energy coherently excites oscillators with a high electrical quality, microtubule inner cavity, and electrons at molecular orbitals and in 'semiconduction' and 'conduction' bands. The suggested mechanism is supposed to be a general phenomenon for a large group of helical systems.

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.

Novel Paradigm of Subdural Cortical Stimulation Does Not Cause Thermal Damage in Brain Tissue: A Simulation-Based Study.

The thermal effect of a novel effective electrical stimulation mapping (ESM) technique using an Ojemann's stimulation electrode in open craniotomy areas causes a nondestructive local increase in temperature. Another type of stimulating electrode is a subdural strip, routinely used in intraoperative electrocorticography (ECoG), which applies ESM in a covered subdural area over the motor cortex. ECoG electrode geometry produces a different electrical field, causing a different Joule heat distribution in tissue, one that is impossible to measure in subdural space. Therefore, the previous safety control study of the novel ESM technique needed to be extended to include an assessment of the thermal effect of ECoG strip electrodes. We adapted a previously well-validated numerical model and performed coupled complex electro-thermal transient simulations for short-time (28.4 ms) high-frequency (500 Hz) and hyperintense (peak 100 mA) ESM paradigm. The risk of heat-induced cellular damage was assessed by applying the Arrhenius equation integral on the computed time-dependent spatial distribution of temperature in the brain tissue during ESM stimulation and during the cooldown period. The results showed increases in temperature in the proximity around ECoG electrode discs in a safe range without destructive effects. As opposed to open craniotomy, subdural space is not cooled by the air; hence a higher - but still safe - induced temperature was observed. The presented simulation agrees with the previously published histopathological examination of the stimulated brain tissue, and confirms the safety of the novel ESM technique when applied using ECoG strip electrodes.

Introduction to Extreme Seeking Entropy.

Recently, the concept of evaluating an unusually large learning effort of an adaptive system to detect novelties in the observed data was introduced. The present paper introduces a new measure of the learning effort of an adaptive system. The proposed method also uses adaptable parameters. Instead of a multi-scale enhanced approach, the generalized Pareto distribution is employed to estimate the probability of unusual updates, as well as for detecting novelties. This measure was successfully tested in various scenarios with (i) synthetic data, (ii) real time series datasets, and multiple adaptive filters and learning algorithms. The results of these experiments are presented.

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.

Energy parasites trigger oncogene mutation.

PURPOSE: Cancer initialization can be explained as a result of parasitic virus energy consumption leading to randomized genome chemical bonding. MATERIALS AND METHODS: Analysis of experimental data on cell-mediated immunity (CMI) containing about 12,000 cases of healthy humans, cancer patients and patients with precancerous cervical lesions disclosed that the specific cancer and the non-specific lactate dehydrogenase-elevating (LDH) virus antigen elicit similar responses. The specific antigen is effective only in cancer type of its origin but the non-specific antigen in all examined cancers. CMI results of CIN patients display both healthy and cancer state. The ribonucleic acid (RNA) of the LDH virus parasitizing on energy reduces the ratio of coherent/random oscillations. Decreased effect of coherent cellular electromagnetic field on bonding electrons in biological macromolecules leads to elevating probability of random genome reactions. RESULTS: Overlapping of wave functions in biological macromolecules depends on energy of the cellular electromagnetic field which supplies energy to bonding electrons for selective chemical bonds. CMI responses of cancer and LDH virus antigens in all examined healthy, precancerous and cancer cases point to energy mechanism in cancer initiation. CONCLUSIONS: Dependence of the rate of biochemical reactions on biological electromagnetic field explains yet unknown mechanism of genome mutation.

Mitochondrial Dysfunction and Disturbed Coherence: Gate to Cancer.

Continuous energy supply, a necessary condition for life, excites a state far from thermodynamic equilibrium, in particular coherent electric polar vibrations depending on water ordering in the cell. Disturbances in oxidative metabolism and coherence are a central issue in cancer development. Oxidative metabolism may be impaired by decreased pyruvate transfer to the mitochondrial matrix, either by parasitic consumption and/or mitochondrial dysfunction. This can in turn lead to disturbance in water molecules' ordering, diminished power, and coherence of the electromagnetic field. In tumors with the Warburg (reverse Warburg) effect, mitochondrial dysfunction affects cancer cells (fibroblasts associated with cancer cells), and the electromagnetic field generated by microtubules in cancer cells has low power (high power due to transport of energy-rich metabolites from fibroblasts), disturbed coherence, and a shifted frequency spectrum according to changed power. Therapeutic strategies restoring mitochondrial function may trigger apoptosis in treated cells; yet, before this step is performed, induction (inhibition) of pyruvate dehydrogenase kinases (phosphatases) may restore the cancer state. In tumor tissues with the reverse Warburg effect, Caveolin-1 levels should be restored and the transport of energy-rich metabolites interrupted to cancer cells. In both cancer phenotypes, achieving permanently reversed mitochondrial dysfunction with metabolic-modulating drugs may be an effective, specific anti-cancer strategy.

Diseases caused by defects of energy level and loss of coherence in living cells.

Human and animal diseases are brought about by pathological alterations of production, composition, and conformation of macromolecules and structures in cells. Additional contributing factors include changes in physiological states caused by disturbances of energy supply, energy transduction, energy dissipation in moving or oscillating parts, and parasitic energy consumption. Disturbances of energy states may endanger existence of the system. The cell-mediated immunity (CMI) response of T lymphocytes correlating with their adherence properties was examined using antigen prepared from the serum of inbred laboratory mice strain C3H H(2k) infected with lactate dehydrogenase elevating (LDH) virus. LDH virus is a parasite on the cellular energy system. Significant CMI response was elicited in T lymphocytes prepared from the blood of patients with cancer of different phenotypes, acute myocardial infarctions, schizophrenia, and recurrent spontaneous abortions in early pregnancy from unknown reasons. The CMI response is assumed to monitor transferred information about decreased levels of energy states and decoherence in the cells caused by mitochondrial malfunction, parasitic consumption, production of lactate, and possibly other disturbances. The LDH virus infection or similar pathological processes caused by different agents might be connected with the diseases and monitored by the examined CMI response. A large amount of mitoses with chromosome defects in aborted fetuses suggest increased mutability of genomes caused by defective energy states.

Targeting mitochondria for cancer treatment - two types of mitochondrial dysfunction.

Two basic types of cancers were identified – those with the mitochondrial dysfunction in cancer cells (the Warburg effect) or in fibroblasts supplying energy rich metabolites to a cancer cell with functional mitochondria (the reverse Warburg effect). Inner membrane potential of the functional and dysfunctional mitochondria measured by fluorescent dyes (e.g. by Rhodamine 123) displays low and high values (apparent potential), respectively, which is in contrast to the level of oxidative metabolism. Mitochondrial dysfunction (full function) results in reduced (high) oxidative metabolism, low (high) real membrane potential, a simple layer (two layers) of transported protons around mitochondria, and high (low) damping of microtubule electric polar vibrations. Crucial modifications are caused by ordered water layer (exclusion zone). For the high oxidative metabolism one proton layer is at the mitochondrial membrane and the other at the outer rim of the ordered water layer. High and low damping of electric polar vibrations results in decreased and increased electromagnetic activity in cancer cells with the normal and the reverse Warburg effect, respectively. Due to nonlinear properties the electromagnetic frequency spectra of cancer cells and transformed fibroblasts are shifted in directions corresponding to their power deviations resulting in disturbances of interactions and escape from tissue control. The cancer cells and fibroblasts of the reverse Warburg effect tumors display frequency shifts in mutually opposite directions resulting in early generalization. High oxidative metabolism conditions high aggressiveness. Mitochondrial dysfunction, a gate to malignancy along the cancer transformation pathway, forms a narrow neck which could be convenient for cancer treatment.

Biophysical insights into cancer transformation and treatment.

Biological systems are hierarchically self-organized complex structures characterized by nonlinear interactions. Biochemical energy is transformed into work of physical forces required for various biological functions. We postulate that energy transduction depends on endogenous electrodynamic fields generated by microtubules. Microtubules and mitochondria colocalize in cells with microtubules providing tracks for mitochondrial movement. Besides energy transformation, mitochondria form a spatially distributed proton charge layer and a resultant strong static electric field, which causes water ordering in the surrounding cytosol. These effects create conditions for generation of coherent electrodynamic field. The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively, and shifted and rebuilt frequency spectra. Disturbed electrodynamic interaction forces between cancer and healthy cells may favor local invasion and metastasis. A therapeutic strategy of targeting dysfunctional mitochondria for restoration of their physiological functions makes it possible to switch on the natural apoptotic pathway blocked in cancer transformed cells. Experience with dichloroacetate in cancer treatment and reestablishment of the healthy state may help in the development of novel effective drugs aimed at the mitochondrial function.

Operator independent focused high frequency ISM band for fat reduction: porcine model.

BACKGROUND: Selective fat reduction has been clearly shown for various methods and energy modalities including cryolipolysis and high intensity focused thermal ultrasound. Mathematical modeling of focused high frequency of the EM spectrum has indicated that selective heating of fat is possible using wavelengths not previous explored. The purpose of this study was to demonstrate in the porcine model that selective heating of fat is possible with a non-contact, operator independent device. METHODS: High frequencies of the Industrial, Scientific and Medical (ISM) RF band were utilized to reduce abdominal fat in a porcine model. Practical application of mathematical modeling allowed an auto-feedback loop to be developed to allow operator independent adjustment of energy to maintain subcutaneous fat at 45-46°C while overlying skin remained at 40-41°C. RESULTS: Treatments of three Vietnamese pigs were performed under anesthesia in a certified veterinary facility. Gross and microscopic histologic results demonstrated a marked reduction in adipocytes of the treated area after 4 treatments of a total of 30 minutes each, with incremental fat diminution after each treatment. A final 70% reduction of the abdominal fat layer was seen in the treated areas. Duplex ultrasound revealed a reduction of fat layer from 7.6 to 2.9 mm. Histologic evaluation revealed that epidermis, dermis, and adnexal structures such as hair follicles were unaffected by the treatment, while adipocytes were significantly affected. CONCLUSION: A new model of fat reduction using high frequency RF has been successfully achieved in a porcine model. This has very positive implications in the development of an operator independent, contact free device for reduction of fat in clinical practice.