Independent component analysis: a reliable alternative to general linear model for task-based fMRI.

Background: Functional magnetic resonance imaging (fMRI) is a valuable tool for the presurgical evaluation of patients undergoing neurosurgeries. Although many pre-processing steps have been modified according to advances in recent years, statistical analysis has remained largely the same since the first days of fMRI. In this study, we examined the ability of Independent Component Analysis (ICA) to separate the activation of a language task in fMRI, and we compared it with the results of the General Lineal Model (GLM). Methods: Sixty patients undergoing evaluation for brain surgery due to various brain lesions and/or epilepsy and 20 control subjects completed an fMRI language mapping protocol that included three tasks, resulting in 259 fMRI scans. Depending on brain lesion characteristics, patients were allocated to (1) static/chronic not-expanding lesions (Group 1) and (2) progressive/expanding lesions (Group 2). GLM and ICA statistical maps were evaluated by fMRI experts to assess the performance of each technique. Results: In the control group, ICA and GLM maps were similar without any superiority of either technique. In Group 1 and Group 2, ICA performed statistically better than GLM, with a p-value of < 0.01801 and < 0.0237, respectively. This indicated that ICA performs as well as GLM when the subjects are able to cooperate well (less movement, good task performance), but ICA could outperform GLM in the patient groups. When both techniques were combined, 240 out of 259 scans produced reliable results, showing that the sensitivity of task-based fMRI can be increased when both techniques are integrated with the clinical setup. Conclusion: ICA may be slightly more advantageous, compared to GLM, in patients with brain lesions, across the range of pathologies included in our population and independent of symptoms chronicity. Our findings suggest that GLM analysis may be more susceptible to brain activity perturbations induced by a variety of lesions or scanner-induced artifacts due to motion or other factors. In our research, we demonstrated that ICA is able to provide fMRI results that can be used in surgery, taking into account patient and task-wise aspects that differ from those when fMRI is used in research.

Standardization of presurgical language fMRI in Greek population: Mapping of six critical regions.

BACKGROUND: Mapping the language system has been crucial in presurgical evaluation especially when the area to be resected is near relevant eloquent cortex. Functional magnetic resonance imaging (fMRI) proved to be a noninvasive alternative of Wada test that can account not only for language lateralization but also for localization when appropriate tasks and MRI sequences are being used. The tasks utilized during the fMRI acquisition are playing a crucial role as to which areas will be activated. Recent studies demonstrated that key language regions exist outside the classical model of "Wernicke-Lichtheim-Geschwind," but sensitive tasks must take place in order to be revealed. On top of that, the tasks should be in mother tongue for appropriate language mapping to be possible. METHODS: For that reason, in this study, we adopted an English protocol that can reveal six language critical regions even in clinical setups and we translated it into Greek to prove its efficacy in Greek population. Twenty healthy right-handed volunteers were recruited and performed the fMRI acquisition in a standardized manner. RESULTS: Results demonstrated that all six language critical regions were activated in all subjects as well as the group mean map. Furthermore, activations were found in the thalamus, the caudate, and the contralateral cerebellum. CONCLUSION: In this study, we standardized an fMRI protocol in Greek and proved that it can reliably activate six language critical regions. We have validated its efficacy for presurgical language mapping in Greek patients capable to be adopted in clinical setup.

A Comparative Analysis of White Matter Structural Networks on SCLC Patients After Chemotherapy.

Previous sMRI, DTI and rs-fMRI studies in small cell lung cancer (SCLC) patients have reported that patients after chemotherapy had gray and white matter structural alterations along with functional deficits. Nonetheless, few are known regarding the potential alterations in the topological organization of the WM structural network in SCLC patients after chemotherapy. In this context, the scope of the present study is to evaluate the WM structural network of 20 SCLC patients after chemotherapy and to 14 healthy controls, by applying a combination of DTI with graph theory. The results revealed that both SCLC and healthy controls groups demonstrated small world properties. The SCLC patients had decreased values in the clustering coefficient, local efficiency and degree metrics as well as increased shortest path length when compared to the healthy controls. Moreover, the two groups reported different topological reorganization of hub distribution. Lastly, the SCLC patients exhibited significantly decreased structural connectivity in comparison to the healthy group. These results underline that the topological organization of the WM structural network in SCLC patients was disrupted and hence constitute new vital information regarding the effects that chemotherapy and cancer may have in the patients' brain at network level.

Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

The golden standard of treating Small Cell Lung Cancer (SCLC) entails application of platinum-based chemotherapy, is often accompanied by Prophylactic Cranial Irradiation (PCI), which have been linked to neurotoxic side-effects in cognitive functions. The related existing neuroimaging research mainly focuses on the effect of PCI treatment in life quality and expectancy, while little is known regarding the distinct adverse effects of chemotherapy. In this context, a multimodal MRI analysis based on structural and functional brain data is proposed in order to evaluate chemotherapy-specific effects on SCLC patients. Data from 20 patients (after chemotherapy and before PCI) and 14 healthy controls who underwent structural MRI, DTI and resting state fMRI were selected in this study. From a structural aspect, the proposed analysis included volumetry and thickness measurements on structural MRI data for assessing gray matter dissimilarities, as well as deterministic tractography and Tract-Based Spatial Statistics (TBSS) on DTI data, aiming to investigate potential white matter abnormalities. Functional data were also processed on the basis of connectivity analysis, evaluating brain network parameters to identify potential manifestation of functional inconsistencies. By comparing patients to healthy controls, the obtained results revealed statistically significant differences, with the patients' brains presenting reduced volumetry/thickness and fractional anisotropy values, accompanied by prominent differences in functional connectivity measurements. All above mentioned findings were observed in patients that underwent chemotherapy.

A condition-independent framework for the classification of error-related brain activity.

The cognitive processing and detection of errors is important in the adaptation of the behavioral and learning processes. This brain activity is often reflected as distinct patterns of event-related potentials (ERPs) that can be employed in the detection and interpretation of the cerebral responses to erroneous stimuli. However, high-accuracy cross-condition classification is challenging due to the significant variations of the error-related ERP components (ErrPs) between complexity conditions, thus hindering the development of error recognition systems. In this study, we employed support vector machines (SVM) classification methods, based on waveform characteristics of ErrPs from different time windows, to detect correct and incorrect responses in an audio identification task with two conditions of different complexity. Since the performance of the classifiers usually depends on the salience of the features employed, a combination of the sequential forward floating feature selection (SFFS) and sequential forward feature selection (SFS) methods was implemented to detect condition-independent and condition-specific feature subsets. Our framework achieved high accuracy using a small subset of the available features both for cross- and within-condition classification, hence supporting the notion that machine learning techniques can detect hidden patterns of ErrP-based features, irrespective of task complexity while additionally elucidating complexity-related error processing variations. Graphical abstract A schematic of the proposed approach. (a) EEG recordings in an auditory experiment in two conditions of different complexity. (b) Characteristic event related activity feature extraction. (c) Selection of feature vector subsets for easy and hard conditions corresponding to correct (Class1) and incorrect (Class2) responses. (d) Performance for individual and cross-condition classification.

Real-Time Passive Brain Monitoring System Using Near-Field Microwave Radiometry.

OBJECTIVE: Near-field microwave radiometry has emerged as a tool for real-time passive monitoring of local brain activation, possibly attributed to local changes in blood flow that correspond to temperature and/or conductivity changes. The aim of this study is to design and evaluate a prototype system based on microwave radiometry intended to detect local changes of temperature and conductivity in depth in brain tissues. A novel radiometric system that comprises a four port total power Dicke-switch sensitive receiver that operates at 1.5 GHz has been developed. METHODS AND RESULTS: The efficacy of the system was assessed through simulation and experiment on brain tissue mimicking phantoms under different setup conditions, where temperature and conductivity changes were accurately detected. In order to validate the radiometer's capability to sense low power signals occurring spontaneously from regions in the human brain, the somatosensory cortices of one volunteer were measured under pain-inducing psychophysiological conditions. The promising results from the initial in vivo measurements prove the system's potential for more extensive investigative trials. CONCLUSION AND SIGNIFICANCE: The significance of this study lies on the development of a compact and sensitive radiometer for totally passive monitoring of local brain activation as a potential complementary tool for contributing to the research effort for investigating brain functionality.

Documentation of a New Intracavitary Applicator for Transrectal Hyperthermia Designed for Prostate Cancer Cases: A Phantom Study.

Concerning clinical trials, intracavitary hyperthermia has already shown antitumor activity and has a potential role in the treatment of prostate cancer. The aim of this study was to document a new intracavitary applicator operating at 433 MHz, designed for transrectal hyperthermia, as well as to assess the specific absorption rate (SAR) distributions in terms of temperature measurements in a soft-tissue phantom. The microwave applicator consists of a dipole-type λ/2, a reflector, and the cooling system. The applicator was placed into a soft-tissue gel-phantom box that was mimicking the dielectric properties of the normal tissue. A calibrated thermometer was implanted inside the phantom at specific locations, to calculate temperature distributions. The maximum value of the SAR was 108 W/kg on the surface's central area at the footprint of the antenna, while the penetration depth was at around 3 cm. Our experimental measurements confirmed the role of the reflector concerning the directivity in a certain area and non icotropic, by means of protecting normal tissues around the prostate. The SAR experimental measurements showed that our applicator might be used effectively as a treatment device for prostate cancer, demonstrating a clear advantage over other similar transrectal devices.

The effect of using a dielectric matching medium in focused microwave radiometry: an anatomically detailed head model study.

Microwave radiometry is a passive technique used to measure in-depth temperature distributions inside the human body, potentially useful in clinical applications. Experimental data imply that it may provide the capability of detecting in-depth local variations of temperature and/or conductivity of excitable tissues at microwave frequencies. Specifically, microwave radiometry may allow the real-time monitoring of brain temperature and/or conductivity changes, associated with local brain activation. In this paper, recent results of our ongoing research regarding the capabilities of focused microwave radiometry for brain intracranial applications are presented. Electromagnetic and thermal simulation analysis was performed using an anatomically detailed head model and a dielectric cap as matching medium placed around it, in order to improve the sensitivity and the focusing attributes of the system. The theoretical results were compared to experimental data elicited while exploring that the sensing depth and spatial resolution of the proposed imaging method at 2.1 GHz areas located 3 cm deep inside the brain can be measured, while at 2.5 GHz, the sensing area is confined specifically to the area of interest. The results exhibit the system's potential as a complementary brain imaging tool for multifrequency in-depth passive monitoring which could be clinically useful for therapeutic, diagnostic, and research applications.

Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study.

Previous studies in small-cell lung cancer (SCLC) patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI). Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI) to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN), the Sensorimotor Network, and the Task-Positive Network (TPN). Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.

Two 27 MHz Simple Inductive Loops, as Hyperthermia Treatment Applicators: Theoretical Analysis and Development.

BACKGROUND: Deep heating is still the main subject for research in hyperthermia treatment. AIM: The purpose of this study was to develop and analyze a simple loop as a heating applicator. METHODS: The performance of two 27 MHz inductive loop antennas as potential applicators in hyperthermia treatment was studied theoretically as well as experimentally in phantoms. Two inductive loop antennas with radii 7 cm and 9 cm were designed, simulated, and constructed. The theoretical analysis was performed by using Green's function and Bessel's function technique. Experiments were performed with phantoms radiated by the aforementioned loop antennas. RESULTS: The specific absorption rate (SAR) distributions were estimated from the respective local phantom temperature measurements. Comparisons of the theoretical, simulation, and experimental studies showed satisfying agreement. The penetration depth was measured theoretically and experimentally in the range of 2-3.5 cm. CONCLUSION: The theoretical and experimental analysis showed that current loops are efficient in the case where the peripheral heating of spherical tumor formation located at 2-3.5 cm depth is required.

Imaging of Conductivity Changes of Excitable Tissues Based on Focused Passive Microwave.

AIMS: Modeling of ionic distribution fluctuations of excitable tissues based on data elicited using focused microwave radiometry. METHODOLOGY: Focused Microwave Radiometry implemented to carry out measurements of in depth body temperature distributions, may provide the capability of sensing local electrical conductivity fluctuations during the cycle of actions potentials in the case of brain excitable cell clusters. An analog beamformer consisting of a conductive inner-surface ellipsoidal cavity is used to focus the chaotic-black body radiation emerging from human tissues by providing convergence of the electromagnetic energy from one focus area where the phantom or subject is placed, to the other where the antennas of sensitive radiometric receivers are positioned. During the past 10 years numerous phantom, animal and human volunteer experiments have been performed with the focused radiometry imaging system. The results show that the detected changes of the output radiometric voltage are attributed to temperature and/or conductivity changes that occur locally concentrated at the areas of interest under measurement. Theoretical and experimental studies are continuously carried out at various frequency bands in conjunction with the use of matching materials placed around the human head or phantom to improve focusing and detection depth. It seems that the manipulation of the focusing area in the tissue in terms of detection depth and spatial resolution is feasible depending on the suitable combination of operation frequencies and matching material. In this paper, theoretical analysis of ion charge diffusion during the cycle of action potentials, propagating along the axons in case of measurements of specific cortical regions is presented. The ion charge diffusion modeling is based on electromagnetic diffusion analogies in the effort to explain the observed experimental results obtained under various psychophysiological conditions in the case of human volunteer measurements. RESULTS: By implementing an analysis based on the continuity equations of ionic charges it is concluded that the microwave radiometry output voltage is not affected by the temporal and spatial average fluctuations of Na(+), K(+), and Cl(-) ions of neural cell axons. CONCLUSION: The analysis of conductivity fluctuations in the central neural system in conjunction with the electromagnetic analysis of the system, leads to the interpretation of the previously acquired experimental data. The application of this technique with other brain functional mapping methods, may provide complementary knowledge to the understanding of the functional organization of psychophysiological processes.

Theoretical analysis, design and development of a 27-MHz folded loop antenna as a potential applicator in hyperthermia treatment.

PURPOSE: A hyperthermia system using a folded loop antenna applicator at 27 MHz for soft tissue treatment was investigated both theoretically and experimentally to evaluate its clinical value. MATERIALS AND METHODS: The electromagnetic analysis of a 27-MHz folded loop antenna for use in human tissue was based on a customised software tool and led to the design and development of the proposed hyperthermia system. The system was experimentally validated using specific absorption rate (SAR) distribution estimations through temperature distribution measurements of a muscle tissue phantom after electromagnetic exposure. Various scenarios for optimal antenna positioning were also performed. RESULTS: Comparison of the theoretical and experimental analysis results shows satisfactory agreement. The SAR level of 50% reaches 8 cm depth in the tissue phantom. Thus, based on the maximum observed SAR values that were of the order of 100 W/kg, the antenna specified is suitable for deep tumour heating. CONCLUSIONS: Theoretical and experimental SAR distribution results as derived from this study are in agreement. The proposed folded loop antenna seems appropriate for use in hyperthermia treatment, achieving proper planning and local treatment of deeply seated affected areas and lesions.

Transformation of physical DVHs to radiobiologically equivalent ones in hypofractionated radiotherapy analyzing dosimetric and clinical parameters: a practical approach for routine clinical practice in radiation oncology.

PURPOSE: The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. METHODS AND MATERIALS: To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. RESULTS: Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D50 (P < 0.001) and V60 (P = 0.001) dosimetric parameters, calculated for α/ß = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V(≥60) dosimetric parameter, calculated for both α/ß = 2.3 Gy (P < 0.001) and α/ß = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. CONCLUSIONS: Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions.

Motive related positivity: decision-making during a prisoners' dilemma task.

The neural mechanisms underlying decision-making to cooperate or defect were investigated using event-related potentials during an iterated computer Prisoner's Dilemma task, adapted to induce working memory operation. Event-related potentials from 64 leads of 22 participants were recorded during 90 trials and averaged depending on the condition of cooperation and defect. The P200 component of the event-related potentials provided evidence for activation differences between cooperation and defect. Cooperation elicited significantly increased P200 activation at parieto-occipital leads, while defect activated primarily the prefrontal electrodes. Functional mapping using Low Resolution Electromagnetic Tomography indicated that in the 150-180 ms time window Brodmann areas 19 (precuneus) and 17 (lingual gyrus), exhibited increased activation during cooperation, while Brodmann area 6 (precentral gyrus) exhibited increased activation when participants defected. In conclusion, the current study provides evidence that cooperation and defect elicit different brain activation at specific loci and within specific time windows.

Temporal processing dysfunction in schizophrenia as measured by time interval discrimination and tempo reproduction tasks.

OBJECTIVE: Time perception deficiency has been implicated in schizophrenia; however the exact nature of this remains unclear. The present study was designed with the aim to delineate timing deficits in schizophrenia by examining performance of patients with schizophrenia and healthy volunteers in an interval discrimination test and their accuracy and precision in a pacing reproduction­replication test. METHODS: The first task involved temporal discrimination of intervals, in which participants (60 patients with schizophrenia and 35 healthy controls) had to judge whether intervals were longer, shorter or equal than a standard interval. The second task required repetitive self-paced tapping to test accuracy and precision in the reproduction and replication of tempos. RESULTS: Patients were found to differ significantly from the controls in the psychoticism scale of EPQ, the proportion of correct responses in the interval discrimination test and the overall accuracy and precision in the reproduction and replication of sound sequences (p < 0.01). Within the patient group bad responders concerning the ability to discriminate time intervals were associated with increased scores in the Positive and Negative Syndrome Scale (PANSS) and in the Brief Psychiatric Rating Scale (BPRS) in comparison to good responders (p < 0.01). There were no gender effects and there were no differences between subgroups of patients taking different kinds or combinations of drugs. CONCLUSIONS: Analysis has shown that performance on timing tasks decreased with increasing psychopathology and therefore that timing dysfunctions are directly linked to the severity of the illness. Different temporal dysfunctions can be traced to different psychophysiological origins that can be explained using the Scalar Expectancy Theory (SET).

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.

Classification of Error-Related Negativity (ERN) and Positivity (Pe) potentials using kNN and Support Vector Machines.

Error processing in subjects performing actions has been associated with the Event-Related Potential (ERP) components called Error-Related Negativity (ERN) and Error Positivity (Pe). In this paper, features based on statistical measures of the sample of averaged ERP recordings are used for classifying correct from incorrect actions. Three feature selection techniques were used and compared. Classification was done by means of a kNN and a Support Vector Machines (SVM) classifier. The use of a leave-one-out approach in the feature selection provided sensitivity and specificity values concurrently higher than or equal to 87.5%, for both classifiers. The classification results were significantly better for the time window that included only the ERN, as compared to time windows including also Pe.

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.

Passive monitoring using a combination of focused and phased array radiometry: a simulation study.

Aim of this simulation study is to use the focusing properties of a conductive ellipsoidal reflector in conjunction with directive phased microwave antenna configurations in order to achieve brain passive monitoring with microwave radiometry. One of the main modules of the proposed setup which ensures the necessary beamforming and focusing on the body and brain areas of interest is a symmetrical axis ellipsoidal conductive wall cavity. The proposed system operates in an entirely non-invasive contactless manner providing temperature and/or conductivity variations monitoring and is designed to also provide hyperthermia treatment. In the present paper, the effect of the use of patch antennas as receiving antennas on the system's focusing properties and specifically the use of phased array setups to achieve scanning of the areas under measurement is investigated. Extensive simulations to compute the electric field distributions inside the whole ellipsoidal reflector and inside two types of human head models were carried out using single and two element microstrip patch antennas. The results show that clear focusing (creation of "hot spots") inside the head models is achieved at 1.53GHz. In the case of the two element antennas, the "hot spot" performs a linear scan around the brain area of interest while the phase difference of the two microstrip patch antennas significantly affects the way the scanning inside the head model is achieved. In the near future, phased array antennas with multiband and more elements will be used in order to enhance the system scanning properties toward the acquisition of tomography images without the need of subject movement.

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.