Transcriptional Levels of Intercellular Junction Proteins in an Alveolar Epithelial Cell Line Exposed to Irradiation or Bleomycin.

We performed a comparative study of the effects of X-ray irradiation and bleomycin on the mRNA levels of E-cadherin and tight junction proteins (claudin-3, claudin-4, claudin-18, ZO-2, and occludin) in an alveolar epithelial cell line L2. Irradiation decreased claudin-4 levels and increased occludin levels, while the levels of other mRNAs remained unchanged. Bleomycin increased the expression levels of all proteins examined except claudin-3. Irradiation and bleomycin have different effects on the expression level of intercellular junction proteins, indicating different reactions triggered in alveolar epithelial cells and a great prospects of further comparative studies.

Classification of EEG abnormalities in partial epilepsy with simultaneous EEG-fMRI recordings.

Scalp EEG recordings and the classification of interictal epileptiform discharges (IED) in patients with epilepsy provide valuable information about the epileptogenic network, particularly by defining the boundaries of the "irritative zone" (IZ), and hence are helpful during pre-surgical evaluation of patients with severe refractory epilepsies. The current detection and classification of epileptiform signals essentially rely on expert observers. This is a very time-consuming procedure, which also leads to inter-observer variability. Here, we propose a novel approach to automatically classify epileptic activity and show how this method provides critical and reliable information related to the IZ localization beyond the one provided by previous approaches. We applied Wave_clus, an automatic spike sorting algorithm, for the classification of IED visually identified from pre-surgical simultaneous Electroencephalogram-functional Magnetic Resonance Imagining (EEG-fMRI) recordings in 8 patients affected by refractory partial epilepsy candidate for surgery. For each patient, two fMRI analyses were performed: one based on the visual classification and one based on the algorithmic sorting. This novel approach successfully identified a total of 29 IED classes (compared to 26 for visual identification). The general concordance between methods was good, providing a full match of EEG patterns in 2 cases, additional EEG information in 2 other cases and, in general, covering EEG patterns of the same areas as expert classification in 7 of the 8 cases. Most notably, evaluation of the method with EEG-fMRI data analysis showed hemodynamic maps related to the majority of IED classes representing improved performance than the visual IED classification-based analysis (72% versus 50%). Furthermore, the IED-related BOLD changes revealed by using the algorithm were localized within the presumed IZ for a larger number of IED classes (9) in a greater number of patients than the expert classification (7 and 5, respectively). In contrast, in only one case presented the new algorithm resulted in fewer classes and activation areas. We propose that the use of automated spike sorting algorithms to classify IED provides an efficient tool for mapping IED-related fMRI changes and increases the EEG-fMRI clinical value for the pre-surgical assessment of patients with severe epilepsy.

Improving the sensitivity of EEG-fMRI studies of epileptic activity by modelling eye blinks, swallowing and other video-EEG detected physiological confounds.

RATIONALE: To improve the sensitivity and specificity of simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) it is prudent to devise modelling strategies explaining the residual variance. The purpose of this study is to investigate the potential value of including additional regressors for physiological activities, derived from video-EEG, in the modelling of haemodynamic patterns linked to interictal epileptiform discharges (IEDs) using simultaneously recorded video-EEG-fMRI. METHODS: Ten patients with IED (focal epilepsy: 6, idiopathic generalized epilepsy (IGE):4) were studied. BOLD-sensitive fMRI images were acquired on a 3T MRI scanner. 64-channel EEG was recorded using MR-compatible system. A custom made, dual-video-camera system synchronised with EEG was used to record video simultaneously. IEDs and physiological activities were identified and labelled on video-EEG using Brain Analyzer2. fMRI time-series data were pre-processed and analysed using SPM5 software. Two general linear models (GLM) were created; GLM1: IEDs were convolved with the canonical haemodynamic response function and its derivatives. Realignment parameters and pulse regressors were included in the design matrix as confounds, GLM2: GLM1 and additional regressors identified on video-EEG including: eye blinks, hand or foot movement, chewing and swallowing were also included in the design matrix. SPM [F] maps (p<0.05, corrected for family wise error and p<0.001, uncorrected) were generated for both models. We compared the resulting blood oxygen level dependent (BOLD) maps for cluster size, statistical significance and degree of concordance with the irritative zone. RESULTS: BOLD changes relating to physiological activities were generally seen in expected brain areas. In patients with focal epilepsy, the extent and Z-score of the IED-related global maximum BOLD clusters increased in 4/6 patients and additional IED-related BOLD clusters were observed in 3/6 patients for GLM2. Also, the degree of concordance of IED-related maps with irritative zone improved for one patient for GLM2 and was unchanged for the other cases. In patients with IGE, the size and statistical significance for global maximum and other BOLD clusters increased in 2/4 patients. We conclude that the inclusion of additional regressors, derived from video based information, in the design matrix explains a greater amount of variance and can reveal additional IED-related BOLD clusters which may be part of the epileptic networks.

Simultaneous intracranial EEG-fMRI in humans: protocol considerations and data quality.

We have recently performed simultaneous intracranial EEG and fMRI recordings (icEEG-fMRI) in patients with epilepsy. In this technical note, we examine limited thermometric data for potential electrode heating during our protocol and found that heating was ≤0.1 °C in-vitro at least 10 fold less than in-vivo limits. We quantify EEG quality, which can be degraded by MRI scanner-induced artefacts, and fMRI image (gradient echo echo-planar imaging: GE-EPI) signal quality around the electrodes, which can be degraded by electrode interactions with B1 (radiofrequency) and B0 (static) magnetic fields. We recorded EEG outside and within the MRI scanner with and without scanning. EEG quality was largely preserved during scanning and in particular heartbeat-related artefacts were small compared to epileptic events. To assess the GE-EPI signal reduction around the electrodes, we compared image signal intensity along paths into the brain normal to its surface originating from the individual platinum-iridium electrode contacts. GE-EPI images were obtained at 1.5 T with an echo time (TE) of 40 ms and repetition time (TR) of 3000 ms and a slice thickness of 2.5 mm. We found that GE-EPI signal intensity reduction was confined to a 10 mm radius and that it was reduced on average by less than 50% at 5mm from the electrode contacts. The GE-EPI image signal reduction also varied with electrode orientation relative to the MRI scanner axes; in particular, cortical grid contacts with a normal along the scanner's main magnetic field (B(0)) axis have higher artefact levels relative to those with a normal perpendicular to the z-axis. This suggests that the artefacts were predominantly susceptibility-related rather than due to B1 interactions. This information can be used to guide interpretation of results of icEEG-fMRI experiments proximal to the electrodes, and to optimise artefact reduction strategies.

Rupture prone aneurysm of the inferior mesenteric artery complicated by mid aortic syndrome with occluded celiac and superior mesenteric arteries.

We present the case of a 45-year-old male patient with a large aneurysm of the inferior mesenteric artery complicated by mid aortic syndrome with occlusion of the celiac trunk and superior mesenteric artery. The vascular pathology was detected by CT imaging after presentation and hospitalization with symptoms of acute cholecystitis. After resolve of the acute symptoms, the aneurysm was resected and the proximal inferior mesenteric artery interponated with a reversed saphenous vein bypass graft. Besides presenting this case we review the literature concerning the rare descriptions of inferior mesenteric artery aneurysms.

Novel LaCl3(Ce)-based spectrometer for deuterium plasma neutron diagnostics.

This work studies in detail the application possibility of a chlorine-based cerium-doped scintillator crystal [LaCl3(Ce)] to the task of D-D neutron spectrometry. We conducted an experimental campaign aimed at deriving the optimal setup parameters and energy calibration using a variety of available neutrons and γ-sources. The GEANT4 code was used for modeling the detector response to γ-ray irradiation. By observing the intrinsic background α-activity of the crystal, we were able to fine-tune the pulse-shape discrimination parameters, achieving a satisfactory α/n/γ pulse selection. We also investigated the LaCl3(Ce)-based spectrometer response under D-D-neutron irradiation by means of the ING-07D neutron generator with the yield of 1 × 107 n/s. The GEANT4 simulation provided us with the comprehensive overview of detector performance. The acquired results demonstrate the possibility of using the LaCl3(Ce) scintillation spectrometer for the purposes of deuterium plasma neutron diagnostics.

Continuous EEG source imaging enhances analysis of EEG-fMRI in focal epilepsy.

INTRODUCTION: EEG-correlated fMRI (EEG-fMRI) studies can reveal haemodynamic changes associated with Interictal Epileptic Discharges (IED). Methodological improvements are needed to increase sensitivity and specificity for localising the epileptogenic zone. We investigated whether the estimated EEG source activity improved models of the BOLD changes in EEG-fMRI data, compared to conventional << event-related >> designs based solely on the visual identification of IED. METHODS: Ten patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI. EEG Source Imaging (ESI) was performed on intra-fMRI averaged IED to identify the irritative zone. The continuous activity of this estimated IED source (cESI) over the entire recording was used for fMRI analysis (cESI model). The maps of BOLD signal changes explained by cESI were compared to results of the conventional IED-related model. RESULTS: ESI was concordant with non-invasive data in 13/15 different types of IED. The cESI model explained significant additional BOLD variance in regions concordant with video-EEG, structural MRI or, when available, intracranial EEG in 10/15 IED. The cESI model allowed better detection of the BOLD cluster, concordant with intracranial EEG in 4/7 IED, compared to the IED model. In 4 IED types, cESI-related BOLD signal changes were diffuse with a pattern suggestive of contamination of the source signal by artefacts, notably incompletely corrected motion and pulse artefact. In one IED type, there was no significant BOLD change with either model. CONCLUSION: Continuous EEG source imaging can improve the modelling of BOLD changes related to interictal epileptic activity and this may enhance the localisation of the irritative zone.

Imaging haemodynamic changes related to seizures: comparison of EEG-based general linear model, independent component analysis of fMRI and intracranial EEG.

BACKGROUND: Simultaneous EEG-fMRI can reveal haemodynamic changes associated with epileptic activity which may contribute to understanding seizure onset and propagation. METHODS: Nine of 83 patients with focal epilepsy undergoing pre-surgical evaluation had seizures during EEG-fMRI and analysed using three approaches, two based on the general linear model (GLM) and one using independent component analysis (ICA): The results were compared with intracranial EEG. RESULTS: The canonical GLM analysis revealed significant BOLD signal changes associated with seizures on EEG in 7/9 patients, concordant with the seizure onset zone in 4/7. The Fourier GLM analysis revealed changes in BOLD signal corresponding with the results of the canonical analysis in two patients. ICA revealed components spatially concordant with the seizure onset zone in all patients (8/9 confirmed by intracranial EEG). CONCLUSION: Ictal EEG-fMRI visualises plausible seizure related haemodynamic changes. The GLM approach to analysing EEG-fMRI data reveals localised BOLD changes concordant with the ictal onset zone when scalp EEG reflects seizure onset. ICA provides additional information when scalp EEG does not accurately reflect seizures and may give insight into ictal haemodynamics.

The spatio-temporal mapping of epileptic networks: combination of EEG-fMRI and EEG source imaging.

Simultaneous EEG-fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG-fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG-fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG-fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks.

Study of the triton-burnup process in different JET scenarios using neutron monitor based on CVD diamond.

We present the results of analysis of triton burn-up process using the data from diamond detector. Neutron monitor based on CVD diamond was installed in JET torus hall close to the plasma center. We measure the part of 14 MeV neutrons in scenarios where plasma current varies in a range of 1-3 MA. In this experiment diamond neutron monitor was also able to detect strong gamma bursts produced by runaway electrons arising during the disruptions. We can conclude that CVD diamond detector will contribute to the study of fast particles confinement and help predict the disruption events in future tokamaks.

T2 mapping outperforms normalised FLAIR in identifying hippocampal sclerosis.

RATIONALE: Qualitatively, FLAIR MR imaging is sensitive to the detection of hippocampal sclerosis (HS). Quantitative analysis of T2 maps provides a useful objective measure and increased sensitivity over visual inspection of T2-weighted scans. We aimed to determine whether quantification of normalised FLAIR is as sensitive as T2 mapping in detection of HS. METHOD: Dual echo T2 and FLAIR MR images were retrospectively analysed in 27 patients with histologically confirmed HS and increased T2 signal in ipsilateral hippocampus and 14 healthy controls. Regions of interest were manually segmented in all hippocampi aiming to avoid inclusion of CSF. Hippocampal T2 values and measures of normalised FLAIR Signal Intensity (nFSI) were compared in healthy and sclerotic hippocampi. RESULTS: HS was identified on T2 values with 100% sensitivity and 100% specificity. HS was identified on nFSI measures with 60% sensitivity and 93% specificity. CONCLUSION: T2 mapping is superior to nFSI for identification of HS.

Homocysteine in lipoprotein apheresis patients--retrospective data analysis in apheresis center of a university hospital.

INTRODUCTION: There is an obvious contrast between the data from the epidemiological studies on hyperhomocysteinemia and the negative results of the homocysteine-lowering clinical trials. Moderate hyperhomocysteinemia might only be relevant in certain subgroups of subjects. The current study was focused on lipoprotein apheresis patients; the study goals were to determine the prevalence of hyperhomocysteinemia, to identify the association between homocysteine levels and cardiovascular events and to test the effects of lipoprotein apheresis and of the conventional homocysteine-lowering therapy. MATERIALS AND METHODS: Sixty patients from our Lipoprotein Apheresis Center (37 males, 23 females, age 63.1 ± 10.8 years) were included in the study. All patients' records were reviewed with respect to age, sex, BMI, dyslipidemias, arterial hypertension, diabetes mellitus and incidence of vascular events in coronaries, carotids and lower extremities. Homocysteine was measured before and immediately after the apheresis procedure. We also observed the effects of conventional homocysteine-lowering therapy. RESULTS: The prevalence of hyperhomocysteinemia was 50%. Homocysteine levels correlated positively with number of cardiovascular events (p < 0.03) and serum creatinine (p < 0.0001) and negatively with serum HDL-cholesterol (p < 0.03). Neither oral nor intravenous medication with vitamin B and folic acid showed a significant homocysteine lowering effect. The median relative change value of homocysteine after apheresis session was -12% but was not statistically significant. CONCLUSIONS: The prevalence of hyperhomocysteinemia in lipoprotein apheresis patients is high. Neither apheresis nor more conventional methods appear to markedly influence homocysteine serum levels.

Independent component analysis of interictal fMRI in focal epilepsy: comparison with general linear model-based EEG-correlated fMRI.

The general linear model (GLM) has been used to analyze simultaneous EEG-fMRI to reveal BOLD changes linked to interictal epileptic discharges (IED) identified on scalp EEG. This approach is ineffective when IED are not evident in the EEG. Data-driven fMRI analysis techniques that do not require an EEG derived model may offer a solution in these circumstances. We compared the findings of independent components analysis (ICA) and EEG-based GLM analyses of fMRI data from eight patients with focal epilepsy. Spatial ICA was used to extract independent components (IC) which were automatically classified as either BOLD-related, motion artefacts, EPI-susceptibility artefacts, large blood vessels, noise at high spatial or temporal frequency. The classifier reduced the number of candidate IC by 78%, with an average of 16 BOLD-related IC. Concordance between the ICA and GLM-derived results was assessed based on spatio-temporal criteria. In each patient, one of the IC satisfied the criteria to correspond to IED-based GLM result. The remaining IC were consistent with BOLD patterns of spontaneous brain activity and may include epileptic activity that was not evident on the scalp EEG. In conclusion, ICA of fMRI is capable of revealing areas of epileptic activity in patients with focal epilepsy and may be useful for the analysis of EEG-fMRI data in which abnormalities are not apparent on scalp EEG.