An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the ΔCBF/ΔBOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between ΔCBF/ΔBOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR

BOLD and perfusion changes during epileptic generalised spike wave activity

It is unclear whether neurovascular coupling is maintained during epileptic discharges. Knowing this is important to allow appropriate inferences from functional imaging studies of epileptic activity. Recent blood oxygen level-dependent (BOLD) functional MRI (fMRI) studies have demonstrated negative BOLD responses (NBR) in frontal, parietal and posterior cingulate cortices during generalised spike wave activity (GSW). We hypothesized that GSW-related NBR commonly reflect decreased cerebral blood flow (CBF). We measured BOLD and cerebral blood flow responses using simultaneous EEG with BOLD and arterial spin label (ASL) fMRI at 3 T. Four patients with epilepsy were studied; two with idiopathic generalized epilepsy (IGE) and two with secondary generalized epilepsy (SGE). We found GSW-related NBR in frontal, parietal and posterior cingulate cortices. We measured the coupling between BOLD and CBF changes during GSW and normal background EEG and found a positive correlation between the simultaneously measured BOLD and CBF throughout the imaged volume. Frontal and thalamic activation were seen in two patients with SGE, concordant with the electro-clinical features of their epilepsy. There was striking reproducibility of the GSW-associated BOLD response in subjects previously studied at 1.5 T. Our results show a preserved relationship between BOLD and CBF changes during rest and GSW activity consistent with normal neurovascular coupling in patients with generalized epilepsy and in particular during GSW activity. Cortical activations appear to reflect areas of discharge generation whilst deactivations reflect changes in conscious resting state activity

Implementation and evaluation of simultaneous video-electroencephalography and functional magnetic resonance imaging

The objective of this study was to demonstrate that the addition of simultaneous and synchronised video to electroencephalography (EEG)-correlated functional magnetic resonance imaging (fMRI) could increase recorded information without data quality reduction. We investigated the effect of placing EEG, video equipment and their required power supplies inside the scanner room, on EEG, video and MRI data quality, and evaluated video-EEG-fMRI by modelling a hand motor task. Gradient-echo, echo-planner images (EPI) were acquired on a 3-T MRI scanner at variable camera positions in a test object [with and without radiofrequency (RF) excitation], and human subjects. EEG was recorded using a commercial MR-compatible 64-channel cap and amplifiers. Video recording was performed using a two-camera custom-made system with EEG synchronization. An in-house script was used to calculate signal to fluctuation noise ratio (SFNR) from EPI in test object with variable camera positions and in human subjects with and without concurrent video recording. Five subjects were investigated with video-EEG-fMRI while performing hand motor task. The fMRI time series data was analysed using statistical parametric mapping, by building block design general linear models which were paradigm prescribed and video based. Introduction of the cameras did not alter the SFNR significantly, nor did it show any signs of spike noise during RF off conditions. Video and EEG quality also did not show any significant artefact. The Statistical Parametric Mapping{T} maps from video based design revealed additional blood oxygen level-dependent responses in the expected locations for non-compliant subjects compared to the paradigm prescribed design. We conclude that video-EEG-fMRI set up can be implemented without affecting the data quality significantly and may provide valuable information on behaviour to enhance the analysis of fMRI data

Safety of localizing epilepsy monitoring intracranial electroencephalograph electrodes using MRI: radiofrequency-induced heating

Purpose: To investigate heating during postimplantation localization of intracranial electroencephalograph (EEG) electrodes by MRI. Materials and Methods: A phantom patient with a realistic arrangement of electrodes was used to simulate tissue heating during MRI. Measurements were performed using 1.5 Tesla (T) and 3T MRI scanners, using head- and body-transmit RF-coils. Two electrode-lead configurations were assessed: a standard condition with external electrode-leads physically separated and a fault condition with all lead terminations electrically shorted. Results: Using a head-transmit-receive coil and a 2.4 W/kg head-average specific absorption rate (SAR) sequence, at 1.5T the maximum temperature change remained within safe limits (<1°C). Under standard conditions, we observed greater heating (2.0°C) at 3T on one system and similar heating (<1°C) on a second, compared with the 1.5T system. In all cases these temperature maxima occurred at the grid electrode. In the fault condition, larger temperature increases were observed at both field strengths, particularly for the depth electrodes. Conversely, with a body-transmit coil at 3T significant heating (+6.4°C) was observed (same sequence, 1.2/0.5 W/kg head/body-average) at the grid electrode under standard conditions, substantially exceeding safe limits. These temperature increases neglect perfusion, a major source of heat dissipation in vivo. Conclusion: MRI for intracranial electrode localization can be performed safely at both 1.5T and 3T provided a head-transmit coil is used, electrode leads are separated, and scanner-reported SARs are limited as determined in advance for specific scanner models, RF coils and implant arrangements. Neglecting these restrictions may result in tissue injury

Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study

In epilepsy patients who have electrodes implanted in their brains as part of their pre-surgical assessment, simultaneous intracranial EEG and fMRI (icEEG-fMRI) may provide important localising information and improve understanding of the underlying neuropathology. However, patient safety during icEEG-fMRI has not been addressed. Here the potential health hazards associated with icEEG-fMRI were evaluated theoretically and the main risks identified as: mechanical forces on electrodes from transient magnetic effects, tissue heating due to interaction with the pulsed RF fields and tissue stimulation due to interactions with the switched magnetic gradient fields. These potential hazards were examined experimentally in vitro on a Siemens 3 T Trio, 1.5 T Avanto and a GE 3 T Signa Excite scanner using a Brain Products MR compatible EEG system. No electrode flexion was observed. Temperature measurements demonstrated that heating well above guideline limits can occur. However heating could be kept within safe limits (< 1.0 °C) by using a head transmit RF coil, ensuring EEG cable placement to exit the RF coil along its central z-axis, using specific EEG cable lengths and limiting MRI sequence specific absorption rates (SARs). We found that the risk of tissue damage due to RF-induced heating is low provided implant and scanner specific SAR limits are observed with a safety margin used to account for uncertainties (e.g. in scanner-reported SAR). The observed scanner gradient switching induced current (0.08 mA) and charge density (0.2 μC/cm2) were well within safety limits (0.5 mA and 30 μC/cm2, respectively). Site-specific testing and a conservative approach to safety are required to avoid the risk of adverse events

Simultaneous intracranial EEG and fMRI of interictal epileptic discharges in humans

Simultaneous scalp EEG–fMRI measurements allow the study of epileptic networks and more generally, of the coupling between neuronal activity and haemodynamic changes in the brain. Intracranial EEG (icEEG) has greater sensitivity and spatial specificity than scalp EEG but limited spatial sampling. We performed simultaneous icEEG and functional MRI recordings in epileptic patients to study the haemodynamic correlates of intracranial interictal epileptic discharges (IED). Two patients undergoing icEEG with subdural and depth electrodes as part of the presurgical assessment of their pharmaco-resistant epilepsy participated in the study. They were scanned on a 1.5 T MR scanner following a strict safety protocol. Simultaneous recordings of fMRI and icEEG were obtained at rest. IED were subsequently visually identified on icEEG and their fMRI correlates were mapped using a general linear model (GLM). On scalp EEG–fMRI recordings performed prior to the implantation, no IED were detected. icEEG–fMRI was well tolerated and no adverse health effect was observed. intra-MR icEEG was comparable to that obtained outside the scanner. In both cases, significant haemodynamic changes were revealed in relation to IED, both close to the most active electrode contacts and at distant sites. In one case, results showed an epileptic network including regions that could not be sampled by icEEG, in agreement with findings from magneto-encephalography, offering some explanation for the persistence of seizures after surgery. Hence, icEEG–fMRI allows the study of whole-brain human epileptic networks with unprecedented sensitivity and specificity. This could help improve our understanding of epileptic networks with possible implications for epilepsy surgery

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

Functional MRI with active, fully implanted, deep brain stimulation systems: Safety and experimental confounds

We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0 T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1 °C) was detected at 1.5 T, and at 3 T temperature elevations were less than 0.5 °C, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/kg and 2.34 W/kg (at 1.5 T and 3 T, respectively) were prescribed and elicited temperature increases (> 1 °C) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI, the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully implanted rather than externalised DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit coil configurations and DBS arrangements

A Quantitative Model of Energy Release and Heating by Time-dependent, Localized Reconnection in a Flare with a Thermal Loop-top X-ray Source

We present a quantitative model of the magnetic energy stored and then released through magnetic reconnection for a flare on 26 Feb 2004. This flare, well observed by RHESSI and TRACE, shows evidence of non-thermal electrons only for a brief, early phase. Throughout the main period of energy release there is a super-hot (T>30 MK) plasma emitting thermal bremsstrahlung atop the flare loops. Our model describes the heating and compression of such a source by localized, transient magnetic reconnection. It is a three-dimensional generalization of the Petschek model whereby Alfven-speed retraction following reconnection drives supersonic inflows parallel to the field lines, which form shocks heating, compressing, and confining a loop-top plasma plug. The confining inflows provide longer life than a freely-expanding or conductively-cooling plasma of similar size and temperature. Superposition of successive transient episodes of localized reconnection across a current sheet produces an apparently persistent, localized source of high-temperature emission. The temperature of the source decreases smoothly on a time scale consistent with observations, far longer than the cooling time of a single plug. Built from a disordered collection of small plugs, the source need not have the coherent jet-like structure predicted by steady-state reconnection models. This new model predicts temperatures and emission measure consistent with the observations of 26 Feb 2004. Furthermore, the total energy released by the flare is found to be roughly consistent with that predicted by the model. Only a small fraction of the energy released appears in the super-hot source at any one time, but roughly a quarter of the flare energy is thermalized by the reconnection shocks over the course of the flare. All energy is presumed to ultimately appear in the lower-temperature T<20 MK, post-flare loops

Trapping of Single Atoms with Single Photons in Cavity QED

Two recent experiments have reported the trapping of individual atoms inside optical resonators by the mechanical forces associated with single photons [Hood et al., Science 287, 1447 (2000) and Pinkse et al., Nature 404, 365 (2000)]. Here we analyze the trapping dynamics in these settings, focusing on two points of interest. Firstly, we investigate the extent to which light-induced forces in these experiments are distinct from their free-space counterparts. Secondly, we explore the quantitative features of the resulting atomic motion and how these dynamics are mapped onto variations of the intracavity field. Not surprisingly, qualitatively distinct atomic dynamics arise as the coupling and dissipative rates are varied. For the experiment of Hood et al., we show that atomic motion is largely conservative and is predominantly in radial orbits transverse to the cavity axis. A comparison with the free-space theory demonstrates that the fluctuations of the dipole force are suppressed by an order of magnitude. This effect is based upon the Jaynes-Cummings eigenstates of the atom-cavity system and represents qualitatively new physics for optical forces at the single-photon level. By contrast, even in a regime of strong coupling in the experiment of Pinkse et al., there are only small quantitative distinctions between the free-space theory and the quantum theory, so it is not clear that description of this experiment as a novel single-quantum trapping effect is necessary. The atomic motion is strongly diffusive, leading to an average localization time comparable to the time for an atom to transit freely through the cavity and to a reduction in the ability to infer aspects of the atomic motion from the intracavity photon number.Comment: 19 pages, 22 figure files, REVTEX, corrected spelling, LaTeX now produces postscript which includes figures, minor changes to figures. Final version to be published in Physical Review A, expanded summary of results in introduction, minor changes to figures and tex