Zoomed MRI Guided by Combined EEG/MEG Source Analysis: A Multimodal Approach for Optimizing Presurgical Epilepsy Work-up and its Application in a Multi-focal Epilepsy Patient Case Study

Abstract

In recent years, the use of source analysis based on electroencephalography (EEG) and magnetoencephalography (MEG) has gained considerable attention in presurgical epilepsy diagnosis. However, in many cases the source analysis alone is not used to tailor surgery unless the findings are confirmed by lesions, such as, e.g., cortical malformations in MRI. For many patients, the histology of tissue resected from MRI negative epilepsy shows small lesions, which indicates the need for more sensitive MR sequences. In this paper, we describe a technique to maximize the synergy between combined EEG/MEG (EMEG) source analysis and high resolution MRI. The procedure has three main steps: (1) construction of a detailed and calibrated finite element head model that considers the variation of individual skull conductivities and white matter anisotropy, (2) EMEG source analysis performed on averaged interictal epileptic discharges (IED), (3) high resolution (0.5 mm) zoomed MR imaging, limited to small areas centered at the EMEG source locations. The proposed new diagnosis procedure was then applied in a particularly challenging case of an epilepsy patient: EMEG analysis at the peak of the IED coincided with a right frontal focal cortical dysplasia (FCD), which had been detected at standard 1 mm resolution MRI. Of higher interest, zoomed MR imaging (applying parallel transmission, 'ZOOMit') guided by EMEG at the spike onset revealed a second, fairly subtle, FCD in the left fronto-central region. The evaluation revealed that this second FCD, which had not been detectable with standard 1 mm resolution, was the trigger of the seizures.

Keywords: Combined EEG/MEG; Epileptic activity; Focal cortical dysplasia type IIb; Realistic finite element head model; Skull conductivity calibration; Source reconstruction; Zoomed MRI.

Fig. 1

Clinical work-up of the patient. A Diagnostic MRI at 3 T (including 3D-FLAIR with 1 mm voxel edge length) showed the right frontal FCD IIB (full arrow) but was negative for the second FCD (dotted arrow). Morphometric MRI-analysis (B) led to a suspicion of the existence of two FCDs in the junction analysis. After transforming the junction analysis abnormalities into ROIs (C) a minimal invasive, confirmative implantation strategy was chosen to document interictal activity and seizure onset in either suspected FCD. Panel D shows the ROI-based implantation of each one depth electrode into the right and left frontal FCD (D1 MRI documentation of the right frontal depth electrode; D2 according to overlay with CT the depth electrodes penetrate the ROI perfectly; D3 and 4: same for the left frontal FCD). Note radiological convention on MR images: patient’s right is viewer’s left. Interictal EEG showed the typical discharge pattern often seen in FCD IIB in both lesions. Seizure onset, however, was documented only in the left FCD IIB. Panel E: blue traces represent the right frontal FCD, red traces the left frontal FCD, traces 1–3 represent the intralesional contacts; note that the short seizure is running in the left frontal FCD while the interictal discharge pattern in the right frontal FCD continues unaffected. (Color figure online)

Fig. 2

Scheme of the analysis strategy

Fig. 3

Segmented MRI (upper row), T1w MRI (middle row) and the source space points (blue points) shown on T1w (lower row) MRI. Sagittal (left column), coronal (middle column) and axial (right column) slices are shown. Please note that the slices selected in the lower row are different from the top two rows in order to better visualize the source space points. The color codes for the tissues in the segmented MRI are scalp (green), skull compacta (brown), skull spongiosa (beige), dura mater (dark turquoise), CSF (light turquoise), gray matter (burgundy) and white matter (red). White letters on the MRIs show the directions (L left, R right, A anterior, P posterior). (Color figure online)

Fig. 4

Butterfly plots for the averaged signals of spikes marked on EEG or MEG (upper), only from EEG (middle row), and only from MEG (bottom row). The numbers of spikes averaged for each group are given in parentheses. In butterfly plots (left column) MEG is shown by green and EEG by blue lines. MGFP stands for mean global field power and is given for EEG and MEG. The topographies are shown at 0 ms (close to the peak of the spike) and −23 ms (the preceding peak on MEG) as indicated by dashed lines on the butterfly plots. (Color figure online)

Fig. 5

Butterfly plots (top left) for MEG (green) and EEG (blue), and topographies of MEG (upper topography) and EEG (bottom topography) for the averaged spike at 11 different time instances. The time points at 0 ms (peak of the spike) and −23 ms (the preceding peak on MEG) are indicated by dashed vertical lines in butterfly plots (top left). The MEG and EEG topographies are shown for every ∼3.3 ms starting from 0 ms and going backwards in time until −33 ms. In MEG and EEG topographies, the blue (red) isopotential lines indicate negativity (positivity). The increments between contour lines for each map are shown on upper left corners and the units for EEG and MEG are μV and fT respectively. Letters in topographies indicate the orientation (L left, R right, A anterior, P posterior). (Color figure online)

Fig. 6

EMEG source localizations at −7 ms. In the left column the sLORETA results projected onto the FLAIR MRI are shown (only results obtained with a threshold of 85% for the maximum F-value are shown). In the middle column, the FLAIR image without the localizations is shown, in order to enable the identification of the FCDs (pointed to by green arrows). The right column shows the result of ZOOMit MRI with the green arrow indicating the FCD. White letters on the MRIs show the directions (L left, R right, A anterior, P posterior). (Color figure online)

Fig. 7

EMEG source localizations at −23 ms, slices selected according to the left hemispheric activity. In the left column, the sLORETA results registered to the FLAIR MRI are shown (only results obtained with a threshold of 85% for the maximum F-value are shown). In the middle column, the FLAIR image without localizations is shown, in order to enable the identification of the FCDs (pointed to by green arrows). The right column shows the ZOOMit MRI for the localization cluster (detected with sLORETA) at the left fronto-central region with the green arrow indicating the FCD. White letters on the MRIs show the directions (L left, R right, A anterior, P posterior). (Color figure online)

Fig. 8

EMEG source localizations at −23 ms, slices selected according to the right hemispheric activity. The sLORETA results registered to the FLAIR MRI are shown in the left column (only results obtained with a threshold of 85% for the maximum F-value are shown). In the right column, the FLAIR image without the localizations is shown. The white letters on MRIs indicate the direction (L left, R right, A anterior, P posterior)

Fig. 9

The results of DTI tractography. The green paths show the tracts that were found between the two FCDs indicated by blue spheres. (Color figure online)

Fig. 10

EMEG (top two rows), EEG only (third row from the top) and MEG only (bottom row) based source reconstructions at −23 ms (left column) and −7 ms (right column). A threshold of 85% of the maximum F-value was used for the results. The FCDs detected with MRI are indicated by the blue spheres. (Color figure online)