Fast human brain magnetic resonance responses associated with epileptiform spikes

Abstract

Neuronal currents produce local electromagnetic fields that can potentially modulate the phase of the magnetic resonance signal and thus provide a contrast mechanism tightly linked to neuronal activity. Previous work has demonstrated the feasibility of direct MRI of neuronal activity in phantoms and cell culture, but in vivo efforts have yielded inconclusive, conflicting results. The likelihood of detecting and validating such signals can be increased with (i) fast gradient-echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal activity, (ii) subjects with epilepsy, who frequently experience stereotypical electromagnetic discharges between seizures, expressed as brief, localized, high-amplitude spikes (interictal discharges), and (iii) concurrent electroencephalography. This work demonstrates that both MR magnitude and phase show large-amplitude changes concurrent with electroencephalography spikes. We found a temporal derivative relationship between MR phase and scalp electroencephalography, suggesting that the MR phase changes may be tightly linked to local cerebral activity. We refer to this manner of MR acquisition, designed explicitly to track the electroencephalography, as encephalographic MRI (eMRI). Potential extension of this technique into a general purpose functional neuroimaging tool requires further study of the MR signal changes accompanying lower amplitude neuronal activity than those discussed here.

FIG. 1

a: Interictal epileptiform spike as seen on referential EEG. Signal shown was measured at the left temporal electrode (T7). Spikes are seen at 2.3 and 3.3 sec, and are clearly distinguishable from background activity. b: Electrode placement on MR-compatible EEG cap, according to the International 10–20 system. As per neurology convention, odd-numbered electrodes are on the left, even on the right, and “z” electrodes along the midline. Letters designate the anatomic area: F, frontal; P, parietal; C, central; T, temporal; O, occipital; GND, ground; REF, reference. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIG. 2

a: Raw EEG (all channels shown) recorded inside the MR scanner during imaging contains high amplitude gradient and cardioballistic artifacts. Gradient artifacts may be as large as 50 times the amplitude of the underlying EEG, rendering the EEG signal invisible. Both artifacts can be removed using software algorithms. b: EEG recorded inside the MR scanner with artifacts removed (eight channels shown). Same 5-sec segment as in Fig. 1a, shown on a bipolar montage. The two left temporo-parietal epileptiform spikes seen in Fig. 1 are intact, as seen at 2.3 and 3.3 sec. Principal negativity occurs at T7-P7, as evidenced by the cancellation of potentials in that derivation, the downward deflection at F7-T7, and the upward deflection at P7-O1. Also shown on the x-axis are the TTL markers sent from the scanner to the EEG amplifier (red markers, one for each TR).

FIG. 3

a, b Tight temporal correspondence between the interictal spike seen on EEG (black plot, top panel), percent change in MR magnitude (middle panel) and phase change in radians (bottom panel). The red curve shows the time course of the voxel showing the largest phase change. Temporal derivative of the largest MR phase time course (green curve, top panel) closely tracks EEG. M(h–g) and P(a–h) show percent change in MR magnitude and MR phase change in radians, at times (a–h), respectively. Results from correlation analyses between MR magnitude signal and the filtered EEG, and between the temporal derivative of the MR phase signal and the EEG, are also shown in the panels on the right. The significant voxels (as determined by the correlation coefficient, r, and the corrected P-values) are overlaid (in yellow) on the corresponding EPI slice. All spikes are from patient E12. In (c), we show MR magnitude and phase change time courses for a 3-sec “quiet” segment (i.e., no epileptiform events) from the same epilepsy subject (E12).

FIG. 4

a–d: Consistent focal MR magnitude signal increase concurrent with EEG spikes in a patient with localized left temporal lobe epilepsy (patient E10). Figures a–d show 3-sec segments corresponding to four distinct spikes observed in repeated scans of the same volume. We show the EEG spike (top), percent changes in MR magnitude [M(a–d), corresponding to times (a–d)], and the corresponding EPI magnitude image and the T₁ anatomical image. The MR response patterns are consistent with the localization of the patient’s seizure focus in the temporal lobe. The largest MR magnitude signal increase (71.5%) corresponds to the largest amplitude spike (Fig. 4a). e: shows interleaved multislice magnitude data for the spike in Fig. 4(c), with M_ai representing the magnitude change at slice level i at time a. While these data were acquired at the cost of slower temporal resolution (TR = 141 msec), spatial contiguity in the magnitude responses across multiple slices can be seen. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIG. 5

eMRI acquisition (single-slice) without EEG equipment (patient E6). Magnitude and phase changes are similar to the acquisitions with EEG present. The derivative (green) of the maximal voxel phase response (red) is shown on the top plot and shows morphology similar to EEG epileptiform spikes. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

FIG. 6

Concurrent EEG and head motion tracking outside the MR scanner (patients E9, E11). In (a), an interictal spike (*) is seen in the 3-sec EEG segment (referential montage). Head motion (red) was found to be uncorrelated with the EEG spike activity (correlation coefficient = 0.0043). In (b), multiple interictal spikes (*) are seen in the 11-sec EEG segment shown. Head motion (in red) was again measured (with positional root-means-squared (RMS) = 0.7 mm), and found to be uncorrelated with EEG spike activity (correlation coefficient = 0.0068). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]