Spikes with and without concurrent high-frequency oscillations: Topographic relationship and neural correlates using EEG-fMRI.

OBJECTIVE: Epilepsy surgery is the best therapeutic option for patients with drug-resistant focal epilepsy. During presurgical investigation, interictal spikes can provide important information on eligibility, lateralisation and localisation of the surgical target. However, their relationship to epileptogenic tissue is variable. Interictal spikes with concurrent high-frequency oscillations (HFOs) have been postulated to reflect epileptogenic tissue more reliably. Here, we studied the voltage distribution of scalp-recorded spikes with and without concurrent HFO and identified their respective haemodynamic correlates using simultaneous electroencephalography and functional Magnetic Resonance Imaging (EEG-fMRI). METHODS: The scalp topography of spikes with and without concurrent HFOs were assessed in 31 consecutive patients with focal drug-resistant epilepsy who showed interictal spikes during presurgical evaluation. Simultaneous EEG-fMRI was then used in 17 patients with spikes and concurrent HFOs. Haemodynamic changes were obtained from the spatial correlation between the patient-specific voltage map of each spike population and the intra-scanner EEG. The haemodynamic response of spikes with and without HFOs were compared in terms of their spatial similarity, strength, the distance between activation peaks and concordance with interictal localisation. RESULTS: Twenty-five patients showed spikes with and without concurrent HFOs. Among patients with both types of spikes, most spikes were not associated with HFOs (p < 0.0001, Mann-Whitney test). Twenty of the 25 patients showed an average of 8 ± 6 (standard deviation) electrodes with significant voltage differences (p = 0.025, permutation test corrected for multiple comparisons) on scalp electrodes within and distant to the spike field. Comparing the haemodynamic response between both spike populations, we found no significant differences in the peak strength (p = 0.71, Mann-Whitney test), spatial distribution (p = 0.113, One-sample Wilcoxon test) and distance between activation peaks (p = 0.5, One-sample Wilcoxon test), with all peaks being co-localised in the same lobe. SIGNIFICANCE: Our data showed that spikes with and without HFOs have different scalp voltage distributions. However, when assessing the haemodynamic changes of each spike type, we found that both elicit similar haemodynamic changes and share high spatial similarity suggesting that the epileptic networks of spikes with and without HFOs have the same underlying neural substrate.

Blood-brain barrier dysfunction significantly correlates with serum matrix metalloproteinase-7 (MMP-7) following traumatic brain injury.

OBJECTIVES: To determine if radiological evidence of blood brain barrier (BBB) dysfunction, measured using Dynamic Contrast Enhanced MRI (DCE-MRI), correlates with serum matrix metalloproteinase (MMP) levels in traumatic brain injury (TBI) patients, and thereby, identify a potential biomarker for BBB dysfunction. PATIENTS AND METHODS: 20 patients with a mild, moderate, or severe TBI underwent a DCE-MRI scan and BBB dysfunction was interpreted from KTrans. KTrans is a measure of capillary permeability that reflects the efflux of gadolinium contrast into the extra-cellar space. The serum samples were concurrently collected and later analysed for MMP-1, -2, -7, -9, and -10 levels using an ELISA assay. Statistical correlations between MMP levels and the KTrans value were calculated. Multiple testing was corrected using the Benjamin-Hochberg method to control the false-discovery rate (FDR). RESULTS: Serum MMP-1 values ranged from 1.5 to 49.6 ng/ml (12 ± 12.7), MMP-2 values from 58.3 to 174.1 ng/ml (109.5 ± 26.7), MMP-7 from 1.5 to 31.5 ng/mL (10 ± 7.4), MMP-9 from 128.6 to 1917.5 ng/ml (647.7 ± 749.6) and MMP-10 from 0.1 to 0.6 ng/mL (0.3 ± 0.2). Non-parametric Spearman correlation analysis on the data showed significant positive relationship between KTrans and MMP-7 (r = 0.55, p < 0.01). Correlations were also found between KTrans and MMP-1 (r = 0.74, p < 0.0002) and MMP-2 (r = 0.5, p < 0.025) but the actual MMP values were not above reference ranges, limiting the interpretation of results. Statistically significant correlations between KTrans and either MMP-9 or -10 were not found. CONCLUSION: This is the first study to show a correlation between DCE measures and MMP values in patients with a TBI. Our results support the suggestion that serum MMP-7 may be considered as a peripheral biomarker quantifying BBB dysfunction in TBI patients.

Functional connectivity of the irritative zone identified by electrical source imaging, and EEG-correlated fMRI analyses.

OBJECTIVE: The irritative zone - the area generating epileptic spikes - can be studied non-invasively during the interictal period using Electrical Source Imaging (ESI) and simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI). Although the techniques yield results which may overlap spatially, differences in spatial localization of the irritative zone within the same patient are consistently observed. To investigate this discrepancy, we used Blood Oxygenation Level Dependent (BOLD) functional connectivity measures to examine the underlying relationship between ESI and EEG-fMRI findings. METHODS: Fifteen patients (age 20-54), who underwent presurgical epilepsy investigation, were scanned using a single-session resting-state EEG-fMRI protocol. Structural MRI was used to obtain the electrode localisation of a high-density 64-channel EEG cap. Electrical generators of interictal epileptiform discharges were obtained using a distributed local autoregressive average (LAURA) algorithm as implemented in Cartool EEG software. BOLD activations were obtained using both spike-related and voltage-map EEG-fMRI analysis. The global maxima of each method were used to investigate the temporal relationship of BOLD time courses and to assess the spatial similarity using the Dice similarity index between functional connectivity maps. RESULTS: ESI, voltage-map and spike-related EEG-fMRI methods identified peaks in 15 (100%), 13 (67%) and 8 (53%) of the 15 patients, respectively. For all methods, maxima were localised within the same lobe, but differed in sub-lobar localisation, with a median distance of 22.8 mm between the highest peak for each method. The functional connectivity analysis showed that the temporal correlation between maxima only explained 38% of the variance between the time course of the BOLD response at the maxima. The mean Dice similarity index between seed-voxel functional connectivity maps showed poor spatial agreement. SIGNIFICANCE: Non-invasive methods for the localisation of the irritative zone have distinct spatial and temporal sensitivity to different aspects of the local cortical network involved in the generation of interictal epileptiform discharges.

7T GRE-MRI signal compartments are sensitive to dysplastic tissue in focal epilepsy.

Ultra-high field magnetic resonance imaging data obtained using a multi-echo gradient echo sequence has been shown to contain information on tissue microstructure. Quantitative assessment of water fraction, relaxation time and frequency shift using multi-compartment signal modelling may help improve our understanding of diseases and disorders affecting the human brain. In this study, we explored tissue microstructure information by analysing voxel compartment water fraction and frequency shifts derived from 7 T multi-echo gradient recalled echo MRI data. We aimed to test whether the parameters of a three compartment model could distinguish the normal cortex from the cortex affected by focal cortical dysplasia. We compartmentalised normal and dysplastic cortical regions in patients diagnosed with focal cortical dysplasia. We found the frequency shift parameter of the shortest T2⁎ signal compartment to be sensitive to regions of dysplastic tissue. We conclude that mathematical modelling of echo time dependent gradient recalled echo MRI signals in patients with focal cortical dysplasia can potentially delineate cortical areas that have undergone microstructural changes in comparison to normal tissue.

Echo time-dependent quantitative susceptibility mapping contains information on tissue properties.

PURPOSE: Magnetic susceptibility is a physical property of matter that varies depending on chemical composition and abundance of different molecular species. Interest is growing in mapping of magnetic susceptibility in the human brain using magnetic resonance imaging techniques, but the influences affecting the mapped values are not fully understood. METHODS: We performed quantitative susceptibility mapping on 7 Tesla (T) multiple echo time gradient recalled echo data and evaluated the trend in 10 regions of the human brain. Temporal plots of susceptibility were performed in the caudate, pallidum, putamen, thalamus, insula, red nucleus, substantia nigra, internal capsule, corpus callosum, and fornix. We implemented an existing three compartment signal model and used optimization to fit the experimental result to assess the influences that could be responsible for our findings. RESULTS: The temporal trend in susceptibility is different for different brain regions, and subsegmentation of specific regions suggests that differences are likely to be attributable to variations in tissue structure and composition. Using a signal model, we verified that a nonlinear temporal behavior in experimentally computed susceptibility within imaging voxels may be the result of the heterogeneous composition of tissue properties. CONCLUSIONS: Decomposition of voxel constituents into meaningful parameters may lead to informative measures that reflect changes in tissue microstructure. Magn Reson Med 77:1946-1958, 2017. © 2016 International Society for Magnetic Resonance in Medicine.