[Show abstract][Hide abstract] ABSTRACT: The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001–0.023 Hz) and low frequency (LF 0.023–0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases.
Full-text · Article · Dec 2015 · Journal of Cerebral Blood Flow & Metabolism
[Show abstract][Hide abstract] ABSTRACT: Objective:
The present study aims to investigate whether a newly developed fast fMRI called MREG (magnetic resonance encephalography) measures metabolic changes related to interictal epileptic discharges (IED). For this purpose BOLD changes are correlated with the IED distribution and variability.
Patients with focal epilepsy underwent EEG-MREG using a 64 channel cap. IED voltage maps were generated using 32 and 64 channels and compared regarding their correspondence to the BOLD response. The extents of IEDs (defined as number of channels with >50% of maximum IED negativity) were correlated with the extents of positive and negative BOLD responses. Differences in inter-spike variability were investigated between interictal epileptic discharges (IED) sets with and without concordant positive or negative BOLD responses.
17 patients showed 32 separate IED types. In 50% of IED types the BOLD changes could be confirmed by another independent imaging method. The IED extent significantly correlated with the positive BOLD extent (p = 0.04). In 6 patients the 64-channel EEG voltage maps better reflected the positive or negative BOLD response than the 32-channel EEG; in all others no difference was seen. Inter-spike variability was significantly lower in IED sets with than without concordant positive or negative BOLD responses (with p = 0.04).
Higher density EEG and fast fMRI seem to improve the value of EEG-fMRI in epilepsy. The correlation of positive BOLD and IED extent could suggest that widespread BOLD responses reflect the IED network. Inter-spike variability influences the likelihood to find IED concordant positive or negative BOLD responses, which is why single IED analysis may be promising.
[Show abstract][Hide abstract] ABSTRACT: Introduction: EEG-fMRI detects BOLD changes associated with epileptic interictal discharges (IED) and can identify epileptogenic networks in epilepsy patients. Besides positive BOLD changes, negative BOLD changes have sometimes been observed in the default-mode network, particularly using group analysis. A new fast fMRI sequence called MREG (Magnetic Resonance Encephalography) shows increased sensitivity to detect IED-related BOLD changes compared to the conventional EPI sequence, including frequent occurrence of negative BOLD responses in the DMN. The present study quantifies the concordance between the DMN and negative BOLD related to IEDs of temporal and extra-temporal origin.
Methods: Focal epilepsy patients underwent simultaneous EEG-MREG. Areas of overlap were calculated between DMN regions, defined as precuneus, posterior cingulate, bilateral inferior parietal and mesial prefrontal cortices according to a standardized atlas, and significant negative BOLD changes revealed by an event-related analysis based on the timings of IED seen on EEG. Correlation between IED number/lobe of origin and the overlap were calculated.
Results: 15 patients were analyzed, some showing IED over more than one location resulting in 30 different IED types. The average overlap between negative BOLD and DMN was significantly larger in temporal (23.7 ± 19.6 cm3) than extra-temporal IEDs (7.4 ± 5.1 cm3, p = 0.008). There was no significant correlation between the number of IEDs and the overlap between DMN structures and negative BOLD areas.
Discussion: MREG results in an increased sensitivity to detect negative BOLD responses related to focal IED in single patients, with responses often occurring in DMN regions. In patients with high overlap with the DMN, this suggests that epileptic IEDs may be associated with a brief decrease in attention and cognitive ability. Interestingly this observation was not dependent on the frequency of IED but more common in IED of temporal origin.
Full-text · Article · Nov 2014 · Frontiers in Neuroscience
[Show abstract][Hide abstract] ABSTRACT: Functional connectivity of the resting state networks (RSNs) of the brain is thought to be mediated by very low frequency fluctuations (VLFFs < 0.1 Hz) in neuronal activity. However, vasomotor waves and cardiorespiratory pulsations influence indirect measures of brain function, such as the functional MRI (fMRI) blood oxygen level-dependent (BOLD) signal. How strongly physiological oscillations correlate with spontaneous BOLD signals is not known, partially due to differences in the data sampling rates of different methods. Recent ultrafast inverse imaging sequences, including magnetic resonance encephalography (MREG), enable critical sampling of these signals. In this study, we describe a multimodal concept, referred to as Hepta-scan, which incorporates synchronous MREG with scalp electroencephalography (EEG), near-infrared spectroscopy (NIRS), non-invasive blood pressure (NIBP) and anesthesia monitoring. Our preliminary results support the idea that, in the absence of aliased cardiorespiratory signals, very low frequency fluctuations in the BOLD signal are affected by vasomotor and electrophysiological sources. Furthermore, MREG signals showed a high correlation coefficient between the ventromedial default mode network (DMNvmpf) and electrophysiological signals, especially in the VLF range. Also oxy- and deoxyhemoglobin and vasomotor waves were found to correlate with DMNvmpf. Intriguingly, using shorter time windows in these correlation measurements produced significantly (p<0.05) higher positive and negative correlation coefficients, suggesting temporal non-stationary behavior between the measurements. Focusing on the VLF range strongly increased correlation strength.
Full-text · Article · Aug 2014 · Brain Connectivity
[Show abstract][Hide abstract] ABSTRACT: Respiration induced dynamic field map changes in the brain are quantified and the influence on the magnitude signal (physiological noise) is investigated. Dynamic off-resonance correction allows to reduce the signal fluctuations overlaying the blood oxygenation level dependent signal in -weighted functional imaging.
A single-shot whole brain imaging technique with 100 ms temporal resolution was used to measure dynamic off-resonance maps that were calculated from the incremental changes of the image phase. These off-resonance maps are then used to dynamically update the off-resonance corrected reconstruction.
A global resonance offset and a pronounced gradient in head–foot direction were identified as the main components of the change during a respiration cycle. On average, correction for these fluctuations decreases the magnitude fluctuations by around 30%.
Single shot 3D imaging allows for a robust quantification of dynamic off-resonance changes in the brain. Correction for these fluctuations removes the physiological noise component associated with dynamic point spread function changes. Magn Reson Med 71:1093–1102, 2014.
No preview · Article · Mar 2014 · Magnetic Resonance in Medicine
[Show abstract][Hide abstract] ABSTRACT: EEG-fMRI is a unique method to combine the high temporal resolution of EEG with the high spatial resolution of MRI to study generators of intrinsic brain signals such as sleep grapho-elements or epileptic spikes. While the standard EPI sequence in fMRI experiments has a temporal resolution of around 2.5-3 s a newly established fast fMRI sequence called MREG (Magnetic-Resonance-Encephalography) provides a temporal resolution of around 100 ms. This technical novelty promises to improve statistics, facilitate correction of physiological artifacts and improve the understanding of epileptic networks in fMRI. The present study compares simultaneous EEG-EPI and EEG-MREG analyzing epileptic spikes to determine the yield of fast MRI in the analysis of intrinsic brain signals.
[Show abstract][Hide abstract] ABSTRACT: The study analyzes the occurrence of high frequency oscillations in different types of focal cortical dysplasia in 22 patients with refractory epilepsy. High frequency oscillations are biomarkers for epileptic tissue, but it is unknown whether they can reflect increasingly dysplastic tissue changes as well as epileptic disease activity.
High frequency oscillations (80-450 Hz) were visually marked by two independent reviewers in all channels of intracranial implanted grid, strips, and depth electrodes in patients with focal cortical dysplasia and refractory epilepsy. Rates of high frequency oscillations in patients with pathologically confirmed focal cortical dysplasia of Palmini type 1a and b were compared with those in type 2a and b.
Patients with focal cortical dysplasia type 2 had significantly more seizures than those with type 1 (p < 0.001). Rates of high frequency oscillations were significantly higher in patients with focal cortical dysplasia type 2 versus type 1 (p < 0.001). In addition, it could be confirmed that rates of high frequency oscillations were significantly higher in presumed epileptogenic areas than outside (p < 0.001).
Activity of high frequency oscillations mirrors the higher epileptogenicity of focal cortical dysplasia type 2 lesions compared to type 1 lesions. Therefore, rates of high frequency oscillations can reflect disease activity of a lesion. This has implications for the use of high frequency oscillations as biomarkers for epileptogenic areas, because a detailed analysis of their rates may be necessary to use high frequency oscillations as a predictive tool in epilepsy surgery.
[Show abstract][Hide abstract] ABSTRACT: The combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allows the investigation of neuronal activity with high temporal and spatial resolution. While much progress has been made to overcome the multiple technical challenges associated with the recording of EEG inside the MR scanner, the ballistocardiographic (BCG) artifact, which is caused by cardiac-related motion inside the magnetic field, remains a major issue affecting EEG quality. The BCG is difficult to remove by standard average artifact subtraction (AAS) methods due to its variability across cardiac cycles. We thus investigate the possibility of directly recording the BCG motion using an optical motion-tracking system. In 5 subjects, the system is shown to accurately measure BCG motion. Regressing out linear and quadratic functions of the measured motion parameters resulted in a significant reduction (p<0.05) in root-mean-square (RMS) amplitudes across cardiac cycles compared to AAS. A further significant RMS reduction was obtained when applying the regression and AAS methods sequentially, resulting in RMS amplitudes that were not significantly different from those of EEG recorded outside the scanner, although with higher residual variability. The large contributions of pure translational parameters and of non-linear terms to the BCG waveforms indicate that non-rigid motion of the EEG wires (originating from rigid head motion) is likely an important cause of the artifact.
[Show abstract][Hide abstract] ABSTRACT: MR-Encephalography allows the observation of functional signal in the brain at a frequency of 10Hz, permitting filtering of physiological "noise" and the detection of single event activations. High temporal resolution is achieved by the use of undersampled non-Cartesian trajectories, parallel imaging and regularized image reconstruction. MR-Encephalography is based on 3D-encoding, allowing undersampling in two dimensions and providing advantages in terms of signal to noise ratio. Long readout times, which are necessary for single shot whole brain imaging (up to 75ms), cause off-resonance artifacts. To meet this issue, a spherical stack of spirals trajectory is proposed in this work. By examining the trajectories in local k-space, it is shown that in areas of strong susceptibility gradients spatial information is fundamentally lost, making a meaningful image reconstruction impossible in the affected areas. It is shown that the loss of spatial information is reduced when using a stack of spirals trajectory compared to concentric shells.
[Show abstract][Hide abstract] ABSTRACT: Current resting-state network analysis often looks for coherent spontaneous BOLD signal fluctuations at frequencies below 0.1Hz in a multiple-minutes scan. However hemodynamic signal variation can occur at a faster rate, causing changes in functional connectivity at a smaller time scale. In this study we proposed to use MREG technique to increase the temporal resolution of resting-state fMRI. A three-dimensional single-shot concentric shells trajectory was used instead of conventional EPI, with a TR of 100ms and a nominal spatial resolution of 4×4×4mm(3). With this high sampling rate we were able to resolve frequency components up to 5Hz, which prevents major physiological noises from aliasing with the BOLD signal of interest. We used a sliding-window method on signal components at different frequency bands, to look at the non-stationary connectivity maps over the course of each scan session. The aim of the study paradigm was to specifically observe visual and motor resting-state networks. Preliminary results have found corresponding networks at frequencies above 0.1Hz. These networks at higher frequencies showed better stability in both spatial and temporal dimensions from the sliding-window analysis of the time series, which suggests the potential of using high temporal resolution MREG sequences to track dynamic resting-state networks at sub-minute time scale.
[Show abstract][Hide abstract] ABSTRACT: MR-encephalography is a technique that allows real-time observation of functional changes in the brain with a time-resolution of 100 ms. The high sampling rate is enabled by the use of undersampled image acquisition with regularized reconstruction. The article describes a novel imaging method for fast three-dimensional-MR-encephalography whole brain coverage based on undersampled, single-shot concentric shells trajectories and the use of multiple small receiver coils. The technique allows the observation of changes in blood oxygenation level dependent signal as a measure of brain physiology at very high temporal resolution.
No preview · Article · Aug 2012 · Magnetic Resonance in Medicine
[Show abstract][Hide abstract] ABSTRACT: In this article we aim at improving the performance of whole brain functional imaging at very high temporal resolution (100 ms or less). This is achieved by utilizing a nonlinear regularized parallel image reconstruction scheme, where the penalty term of the cost function is set to the L(1)-norm measured in some transform domain. This type of image reconstruction has gained much attention recently due to its application in compressed sensing and has proven to yield superior spatial resolution and image quality over e.g. Tikhonov regularized image reconstruction. We demonstrate that by using nonlinear regularization it is possible to more accurately localize brain activation from highly undersampled k-space data at the expense of an increase in computation time.
[Show abstract][Hide abstract] ABSTRACT: In simultaneous scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), blood oxygen level dependent (BOLD) changes occurring before the spike have been sometimes described but could not be explained. To characterize the origin of this prespike BOLD signal change, we looked for electrographic changes in stereo-EEG (SEEG) possibly preceding the scalp spike in patients that showed early BOLD response in EEG/fMRI.
We studied four patients with drug-resistant focal epilepsy who underwent EEG/fMRI, showed a prespike BOLD response, and were then studied with depth electrodes for presurgical localization of the epileptic generator. Early BOLD responses in the region of the spike field were analyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike. SEEG recordings in the period and location corresponding to the early HRF responses were analyzed to detect if electrographic changes were present in the SEEG before the scalp abnormality.
One of the four patients presented a SEEG interictal discharge in the period corresponding to the early BOLD response. In the other three, no electrographic changes were detected in the SEEG in the period corresponding to early BOLD changes.
Although the early BOLD activity may sometimes be explained by a synchronized neural discharge detectable with SEEG but not visible on the scalp EEG, in most cases the early BOLD response reflects a metabolic phenomenon that does not appear to result from a synchronized neuronal discharge. Prespike metabolic responses can result from synchronized or nonsynchronized neuronal activity, or from nonneuronal mechanisms including glia.
[Show abstract][Hide abstract] ABSTRACT: Most EEG-fMRI studies in epileptic patients are analyzed using the general linear model (GLM), which assumes a known hemodynamic response function (HRF) to epileptic spikes. In contrast, independent component analysis (ICA) can extract blood-oxygenation level dependent (BOLD) responses without imposing constraints on the HRF. ICA might therefore detect responses that vary in time and shape, and that are not detected in the GLM analysis. In this study, we compared the findings of ICA and GLM analyses in 12 patients with idiopathic generalized epilepsy. Spatial ICA was used to extract independent components from the functional magnetic resonance imaging (fMRI) data. A deconvolution method identified component time courses significantly related to the generalized EEG discharges, without constraining the shape of the HRF. The results from the ICA analysis were compared to those from the GLM analysis. GLM maps and ICA maps showed significant correlation and revealed BOLD responses in the thalamus, caudate nucleus, and default mode areas. In patients with a low rate of discharges per minute, the GLM analysis detected BOLD signal changes within the thalamus and the caudate nucleus that were not revealed by the ICA. In conclusion, ICA is a viable alternative technique to GLM analyses in EEG-fMRI studies related to generalized discharges. This study demonstrated that the BOLD response largely resembles the standard HRF and that GLM analysis is adequate. However, ICA is more dependent on a sufficient number of events than GLM analysis.
No preview · Article · Feb 2011 · Human Brain Mapping
[Show abstract][Hide abstract] ABSTRACT: Absences are characterized by an abrupt onset and end of generalized 3-4 Hz spike and wave discharges (GSWs), accompanied by unresponsiveness. Although previous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) studies showed that thalamus, default mode areas, and caudate nuclei are involved in absence seizures, the contribution of these regions throughout the ictal evolution of absences remains unclear. Furthermore, animal models provide evidence that absences are initiated by a cortical focus with a secondary involvement of the thalamus. The aim of this study was to investigate dynamic changes during absences.
Seventeen absences from nine patients with absence epilepsy and classical pattern of 3-4 Hz GSWs during EEG-fMRI recording were included in the study. The absences were studied in a sliding window analysis, providing a temporal sequence of blood oxygen-level dependent (BOLD) response maps.
Thalamic activation was found in 16 absences (94%), deactivation in default mode areas in 15 (88%), deactivation of the caudate nuclei in 10 (59%), and cortical activation in patient-specific areas in 10 (59%) of the absences. Cortical activations and deactivations in default mode areas and caudate nucleus occurred significantly earlier than thalamic responses.
Like a fingerprint, patient-specific BOLD signal changes were remarkably consistent in space and time across different absences of one patient but were quite different from patient to patient, despite having similar EEG pattern and clinical semiology. Early frontal activations could support the cortical focus theory, but with an addition: This early activation is patient specific.
[Show abstract][Hide abstract] ABSTRACT: In simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), increased neuronal activity from epileptiform spikes commonly elicits positive blood oxygenation level-dependent (BOLD) responses. Negative responses are also occasionally seen and have not been explained. Recent studies describe BOLD signal changes before focal EEG spikes. We aimed to systematically study if the undershoot of a preceding positive response might explain the negative BOLD seen in the focus.
Eighty-two patients with focal epilepsy who underwent EEG-fMRI at 3T were retrospectively studied. Studies with a focal negative BOLD response in the region of the spike field were reanalyzed using models with hemodynamic response functions (HRFs) peaking from -9 to +9 s around the spike.
Eight patients met the inclusion criteria, showing negative BOLD responses in the spike field on standard analysis. None had positive BOLD responses immediately adjacent to the areas of deactivation. Regions of deactivation were found to have congruent preceding positive responses in two cases. These early activations were seen at the combined maps of -5 to -9 s.
This study indicates that in a small proportion of patients with focal epilepsy in whom the standard analysis reveals focal negative responses, an earlier positive BOLD response is probably the cause. The origin of negative BOLD signal changes in the focus as a result of an epileptic event remains, however, unexplained in most of the patients in whom it occurs.