Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy

Our main goal of research is to develop novel biomarkers of epilepsy that augment the presurgical evaluation process and improve the surgical outcome of children suffering from drug-resistant epilepsy. We're trying to investigate whether non-invasive methods can precisely localize brain areas that correspond to the epigenetic tissue. The most recent developments in our field are the ability to record MEG and high density EEG data simultaneously with a high number of sensors, new EEG technologies offering minimal preparation time, which is critical in children, and advanced algorithms that combine electric magnetic source imaging into a unique solution.

We present evidence that combined electric and magnetic source imaging on simultaneous MEG and high density EEG recordings outperform either modality alone in terms of localized accuracy. This is most likely due to the complementary and confirmatory sensitivity profiles of MEG and EEG signals and the increased number of sensors. We demonstrate a state-of-the-art setup that allows the simultaneous recording of magnetic and electric brain activity with more than 500 sensors covering the entire head.

With this setup, we demonstrate the non-invasive localization of interictal and ictal epileptic form activity and the mapping of the local areas so as not to resect during surgery. Our findings will help us understand the complementary and confirmatory information that magnetoencephalography and high density electroencephalography recordings provide in different clinical scenarios where the localization of the epileptogenic focus is challenging due to the deep location of the source or its radial orientation with respect to the patient's cortical surface. To begin, have the subject in a hospital gown sitting comfortably on a wooden chair.

Measure the subject's head circumference to select the appropriate EEG net size. Soak the correct size EEG net for five minutes in a solution of warm tap water, electrolytes and baby shampoo. Using micropore paper tape, place five magnet coils serving as head position indicators, or HPI, at known locations directly on the scalp.

To record the subject's heartbeat, place two ECG electrodes on the right and left side of the chest below the collarbone respectively. For vertical eye movements or blinks recording, place two EOG electrodes on the upper and lower side of the right eye respectively. Tape two pairs of non-disposable cup electrodes on the first dorsal interosseous and abductor pollicis brevis of each hand to measure muscle activity during the visual motor task.

Place the reference receiver through the plastic goggles on the subject's head. Through the primary stylus receiver, locate the fiducial anatomical landmarks, the five HPI coils position and uniformly sample additional scalp points. Before applying the EEG net, put both hands inside the net and spread it.

Place the stretched net on the subject's head and adjust its position. Using an EEG impedance meter, ensure that all scalp electrode impedances are in the zero to 50 kiloohm range. To determine the three dimensional positions of the EEG electrodes, ask the subject to sit comfortably and look straight ahead.

On the optical scanner software, select the sensor template that matches the EEG sensor layout used during the recordings and initiate the scanning process. Slowly move the scanner around the subject's head following arced swaths from the top to the bottom to record the physical locations of all sensors. Next, probe the fiducial points in four alignment sensors using the wireless optical probe to align the three dimensional sensors cloud to the selected sensor template.

For the resting or sleeping data, set the gantry of the MEG system to the supine position. Transfer the subject inside the magnetically shielded room, or MSR, and assist to sit on the edge of the bed and lie down on it. Gently move the subject's head until it touches the inside of the helmet.

Plug the HPI coils, ECG, and EOG electrodes on the corresponding panels of the MEG system. Connect the EEG net to the amplifier unit until it is inside the MSR. Check the measurements of the head's coordinates from the acquisition workstation outside the MSR.

For the visual motor task, set the gantry of the MEG system to the upright position and arrange the MEG chair so that the subject's head is under the gantry. Assist the subject to sit on the non-magnetic and compatible chair. Plug the HPI coils, ECG, EOG, first dorsal, interosseous and abductor pollicis brevis electrodes on the right panel of the MEG machine.

Connect the EEG net to the amplifier unit inside the MSR. Raise the chair using the elevation pedal until the subject's head lightly touches the inside of the helmet. Place the projection screen in front of the subject and instruct the subject to tap their index finger on the table only when the visual stimulus appears on the screen.

Use the same setup for auditory stimulation and help the subject wear headphones. While listening to the sound trigger, instruct the subject to fixate on the stimuli projected on the screen. For the somatosensory stimulation, attach thin elastic membranes directly to the distal volar parts of three digits of both hands for tactile stimulation.

Ask the subject about their video preference to watch on the projector screen. Before starting the recording, close the door of the MSR. Through the voice intercom system, confirm the comfort of the subject inside the MSR and instruct the subject to maintain a still position for approximately 30 seconds before starting the task.

For each recording session, press the recording button on the EEG data acquisition software to begin the EEG recording. Then, press the recording button on the MEG data acquisition software to begin the MEG recording. Finally, press the start button on the stimulation computer software to display the visual stimuli.

Record approximately one hour of simultaneous MEG and EEG signals for resting or sleeping data. Similarly, record MEG and EEG signals during the visual motor task for approximately one hour. For auditory stimulations record about 20 minutes, and for somatosensory stimulation, record about 14 minutes of simultaneous MEG and EEG data.

After recording, ask the subject to sit on a chair outside the MSR. Pull out the EEG net from the subject's head with both hands until it is completely peeled away. On Brainstorm, import the simultaneous MEG and HD EEG signal.

Using the standard display setting of 10 seconds per page, mark the negative peak of each IED that occurs on both MEG and EEG recordings, as well as on each modality alone. Localize the underlying generators of the selected interictal spikes using the unconstrained ECD method on the MEG, EEG and combined MEG and EEG sensors array separately. Mark the negative peak of each burst of epileptiform discharges occurring during the ictal event on MEG and EEG, as well as on each modality alone.

Similarly, localize the underlying generators of the selected ictal discharges using the unconstrained ECD method on the MEG, EEG, and combined MEG and EEG sensors array separately. For motor cortex mapping, mark the tapping event of the left hand by selecting the first peak of muscle activation different from the baseline on the FDI pair electrode. Next, apply the average reference montage and estimate the average across stimuli to obtain the event evoked fields and potentials.

For each event evoked field and potential, compute the cortical sources on the averaged events using DSPM for the MEG, EEG and combined MEG and EEG sensors array separately. For a 10-year-old female, EMSI indicated focal clusters of dipoles at the bilateral frontotemporal regions in line with ESI performed on benchmark iEEG. For a 13-year-old male, EMSI revealed localization of the ictal onset within the temporal lobe concordant with ESI on benchmark iEEG.

In a 15-year-old female, EMSI performed on the averaged visual, motor, auditory and somatosensory evoked responses showed maximal cortical activation at the eloquent regions involved.