Experimental study of a hybrid microwave radiometry-hyperthermia apparatus with the use of an anatomical head phantom.

This paper presents the latest progress made concerning a hybrid diagnostic and therapeutic system able to provide focused microwave radiometric temperature and/or conductivity variation measurements and hyperthermia treatment. Previous experimental studies of our group have demonstrated the system performance and focusing properties in phantom as well as human experiments. The system is able to detect temperature and conductivity variations with frequency-dependent detection depth and spatial sensitivity. Numerous studies have also demonstrated the improvement of the system focusing properties attributed to the use of dielectric and left handed matching layers. In this study, similar experimental procedures are performed but this time using an anatomical head model as phantom aiming to achieve a more accurate modeling of the system's future real function. This way, another step is made toward the deeper understanding of the system's capabilities, with the view to further use it in experimental procedures with laboratory animals and human volunteers.

Effect of frequency deviance direction on performance and mismatch negativity.

The mismatch negativity (MMN) component of the auditory event-related potential is associated with automatic perceptual inference concerning changes in auditory stimulation. Recent studies have addressed the question whether performance and MMN is affected by the direction of frequency deviance. In the present study, the frequency MMN and performance is investigated during an auditory identification task. Specifically, we examined the effect of positive and negative differences between the present stimulus and the previous response frequencies on performance as well as on the characteristics of stimulus-locked ERPs and brain activation maps. The results show that frequency deviants creating mismatch conditions increase the likelihood of error commission. The decrease in performance achieves statistical significance in the case of positive frequency deviants. In the latter case, ERP amplitude values of the Fz electrode at 164 ms after stimulus onset are statistically larger for mismatch as opposed to no-mismatch condition. This corresponds to significance differences in the activation maps at Brodmann area 11, superior frontal gyrus, and the frontal lobe. The present findings revealed dissociations in behavioral and ERP responses in the processing of positive and negative frequency deviance, lending support to the notion that MMN is more sensitive to increments than to decrements in frequency.

Noninvasive focused monitoring and irradiation of head tissue phantoms at microwave frequencies.

In this study, new aspects of our research regarding a novel hybrid system able to provide focused microwave radiometric temperature and/or conductivity measurements and hyperthermia treatment via microwave irradiation are presented. On one hand, it is examined whether the system is capable of sensing real-time progressive local variations of temperature and/or conductivity in customized phantom setups; on the other hand, the focusing attributes of the system are explored for different positions and types of phantoms used for hyperthermia in conjunction with dielectric matching layers surrounding the areas of interest. The main module of the system is an ellipsoidal cavity, which provides the appropriate focusing of the electromagnetic energy on the area of interest. The system has been used for the past few years in experiments with different configuration setups including phantom, animal, and human volunteer measurements yielding promising outcome. The present results show that the system is able to detect local concentrated gradual temperature and conductivity variations expressed as an increase of the output radiometric voltage. Moreover, when contactless focused hyperthermia is performed, the results show significant temperature increase at specific phantom areas. In this case, the effect of the dielectric matching layers placed around the phantoms is critical, thus resulting in the enhancement of the energy penetration depth.

Mismatch task conditions and error related ERPs.

BACKGROUND: The N200 component of event related potentials (ERPs) is considered an index of monitoring error related responses. The aim of the present work was to study the effect of mismatch conditions on the subjects' responses in an auditory identification task and their relation to the N200 of stimulus-locked ERPs. METHODS: An auditory identification task required to correctly map a horizontal slider onto an active frequency range by selecting a slider position that matched the stimulus tone in each trial. Fourteen healthy volunteers participated in the study and ERPs were recorded by 32 leads. RESULTS: Results showed that the subjects' erroneous responses were equally distributed within trials, but were dependent on mismatch conditions, generated by large differences between the frequencies of the tones of consecutive trials. Erroneous trials showed a significantly greater negativity within the time window of 164-191 ms after stimulus, located mainly at the Cz and Fz electrodes. The LORETA solution showed that maximum activations, as well as maximum differences, were localized mainly at the frontal lobe. CONCLUSIONS: These findings suggest that the fronto-central N200 component, conceived an index of "reorientation of attention", represents a correlate of an error signal, being produced when representation of the actual response and the required response are compared. Furthermore the magnitude of the amplitude of the N200 rests on the relation between the present and the previous stimulus.

Enhancing the focusing properties of a prototype non-invasive brain hyperthermia system: a simulation study.

Aim of this study is the improvement of the focusing properties of a prototype system for deep brain hyperthermia able to provide also passive measurements of temperature distributions inside the human body and especially the brain. One of the main modules of the system which ensures the necessary beamforming and focusing on the body and brain cortex areas of interest is the symmetrical axis ellipsoidal conductive wall cavity. The proposed system operates in a total non-invasive contactless passive manner and is designed to provide hyperthermia treatment and temperature monitoring. Extensive simulations to compute electric field distributions and SAR values at several frequencies inside the human head model and inside the whole ellipsoidal reflector were carried out. One of the main problems that have to be tackled in order to achieve the desired depth and focusing resolution is to reduce back scattering while improving penetration. With this view, the FEM simulations using a commercial tool aimed at improving the system's focusing properties following various approaches. In order to enhance the matching conditions on the air-head interface, layers made of metamaterials (left handed materials) and dielectric materials were placed around the human head model. The results show that the use of a metamaterial layer in conjunction with a layer of lossless dielectric material generates the largest improvement. Measurements using phantoms with the proposed focusing improvement techniques in future studies will complement the present research and reveal the potential practical value of the system.

FDTD study of the focusing properties of a hybrid hyperthermia and radiometry imaging system using a realistic human head model.

Aim of this study is twofold; on one hand, the investigation of the focusing attributes of a microwave radiometry tomography system with the use of a realistic human head model and on the other hand, the system's ability to perform a hyperthermia treatment. The operation principle of the device is based on an ellipsoidal conductive wall cavity, which provides the required beamforming and focusing. The biological tissue under treatment and/or measurement is placed on one of the two focal points whereas on the other one, a radiating or receiving antenna, which measures the black body type radiation emitted from the head's tissue, is placed. In previous studies simple spherical head models were used, comprising one or two layers for simulating the head tissues, along with a commercial FEM tool. In this work, a realistic adult head model developed from MRI scans of a human head is used. The realistic model with detailed structural and electromagnetic tissue characteristics enables more in depth theoretical investigation of the system capabilities. Extensive simulations using a commercial FDTD tool are performed in a wide range of operating frequencies. In order to explore the feasibility of heating and monitoring specific brain areas, the capability of focusing the electric field in specific areas inside the human head is investigated and further discussed. The results show that simple spherical head models, used in previous studies, provide similar results with the realistic one used herein for the given geometry; that is, the electric field focuses on the head's center, assuming the head as a homogeneous sphere. However, the deposition of the electromagnetic energy on the head tissues depends on the operating frequency and position of the head in the given geometry, so in therefore calculated, revealing the ability of the system to operate as a hyperthermia clinical tool, not as a stand alone device but in conjunction with other already validated devices/methods.

The "Oncosimulator": a multilevel, clinically oriented simulation system of tumor growth and organism response to therapeutic schemes. Towards the clinical evaluation of in silico oncology.

The "Oncosimulator" is at the same time a concept of multilevel integrative cancer and (treatment affected) normal tissue biology, an algorithmic construct and a software tool which aims at supporting the clinician in the process of optimizing cancer treatment on the patient individualized basis. Additionally it is a platform for better understanding and exploring the natural phenomenon of cancer as well as training doctors and interested patients alike. In order to achieve all of these goals it has to undergo a thorough clinical optimization and validation process. This is one of the goals of the European Commission funded integrated project "ACGT: Advancing Clinicogenomic Trials on Cancer". Nephroblastoma (Wilms' tumor) and breast cancer have been selected to serve as two paradigms to clinically specify and evaluate the "Oncosimulator" as well as the emerging domain of in silico oncology.

Study of a brain hyperthermia system providing also passive brain temperature monitoring.

A newly developed system for deep brain hyperthermia able to provide also passive measurements of temperature distributions inside the human body and especially the brain, is presented in this paper. The proposed system able to comprise both therapeutic and diagnostic modules operates in a totally non-invasive contactless way based on the use of an ellipsoidal conductive wall cavity to achieve beamforming and focusing on the areas under treatment and temperature monitoring. The performance of the system's diagnostic module designed and developed for brain imaging, has been previously studied in phantom, animal and human tests illustrating promising results. In the present paper theoretical analysis of the therapeutic module designed for hyperthermia treatment, elicited during simulation performance, exhibit the system's focusing attributes. Moreover, initial phantom experimental results verify the proof of concept. Taking into consideration the present initial theoretical and experimental study and the great advantage of the proposed brain hyperthermia system of being non invasive and with a very acceptable cost, it is concluded that further research is required in order to explore its potentials at becoming a part of the standard treatment protocol of brain malignancy in the future.

Long-term abstinence syndrome in heroin addicts: indices of P300 alterations associated with a short memory task.

Attentional deficits have been implicated in the pathophysiology of opioid addicts. The P300 component of event-related potentials (ERPs) is considered as a manifestation of attentional operations. The authors' goal was the comparison of P300 elicited during a short memory test between subjects with prolonged heroin abstinence and current heroin users as well as healthy controls. The P300 component was evaluated during the anticipatory period of a short memory task in 20 patients characterized by a past history of opioid dependence (6 months abstinence), in 18 current heroin users and in 20 healthy comparison subjects, matched for age, sex and educational level. Abstinent heroin addicts exhibited significant reduction of P300 amplitude at central frontal region, relative to the other two groups. The findings are discussed in connection to the aim of identifying psychophysiological indices, addressing issues in opioid use disorders, and suggest that knowledge about cognitive operations, such as those reflected by P300 component, could provide further insight into psychophysiological mechanisms underlying the long-term abstinence state of heroin addicts.