Thomas Witzel

Blipped-controlled aliasing in parallel imaging for simultaneous multislice echo planar imaging with reduced g-factor penalty

Simultaneous multislice Echo Planar Imaging (EPI) acquisition using parallel imaging can decrease the acquisition time for diffusion imaging and allow full‐brain, high‐resolution functional MRI (fMRI) acquisitions at a reduced repetition time (TR). However, the unaliasing of simultaneously acquired, closely spaced slices can be difficult, leading to a high g‐factor penalty. We introduce a method to create interslice image shifts in the phase encoding direction to increase the distance between aliasing pixels. The shift between the slices is induced using sign‐ and amplitude‐modulated slice‐select gradient blips simultaneous with the EPI phase encoding blips. This achieves the desired shifts but avoids an undesired “tilted voxel” blurring artifact associated with previous methods. We validate the method in 3× slice‐accelerated spin‐echo and gradient‐echo EPI at 3 T and 7 T using 32‐channel radio frequency (RF) coil brain arrays. The Monte‐Carlo simulated average g‐factor penalty of the 3‐fold slice‐accelerated acquisition with interslice shifts is <1% at 3 T (compared with 32% without slice shift). Combining 3× slice acceleration with 2× inplane acceleration, the g‐factor penalty becomes 19% at 3 T and 10% at 7 T (compared with 41% and 23% without slice shift). We demonstrate the potential of the method for accelerating diffusion imaging by comparing the fiber orientation uncertainty, where the 3‐fold faster acquisition showed no noticeable degradation. Magn Reson Med, 2012.

Task-modulated “what” and “where” pathways in human auditory cortex

Human neuroimaging studies suggest that localization and identification of relevant auditory objects are accomplished via parallel parietal-to-lateral-prefrontal “where” and anterior-temporal-to-inferior-frontal “what” pathways, respectively. Using combined hemodynamic (functional MRI) and electromagnetic (magnetoencephalography) measurements, we investigated whether such dual pathways exist already in the human nonprimary auditory cortex, as suggested by animal models, and whether selective attention facilitates sound localization and identification by modulating these pathways in a feature-specific fashion. We found a double dissociation in response adaptation to sound pairs with phonetic vs. spatial sound changes, demonstrating that the human nonprimary auditory cortex indeed processes speech-sound identity and location in parallel anterior “what” (in anterolateral Heschl’s gyrus, anterior superior temporal gyrus, and posterior planum polare) and posterior “where” (in planum temporale and posterior superior temporal gyrus) pathways as early as ≈70–150 ms from stimulus onset. Our data further show that the “where” pathway is activated ≈30 ms earlier than the “what” pathway, possibly enabling the brain to use top-down spatial information in auditory object perception. Notably, selectively attending to phonetic content modulated response adaptation in the “what” pathway, whereas attending to sound location produced analogous effects in the “where” pathway. This finding suggests that selective-attention effects are feature-specific in the human nonprimary auditory cortex and that they arise from enhanced tuning of receptive fields of task-relevant neuronal populations.

Assessing and improving the spatial accuracy in MEG source localization by depth-weighted minimum-norm estimates.

Cerebral currents responsible for the extra-cranially recorded magnetoencephalography (MEG) data can be estimated by applying a suitable source model. A popular choice is the distributed minimum-norm estimate (MNE) which minimizes the l2-norm of the estimated current. Under the l2-norm constraint, the current estimate is related to the measurements by a linear inverse operator. However, the MNE has a bias towards superficial sources, which can be reduced by applying depth weighting. We studied the effect of depth weighting in MNE using a shift metric. We assessed the localization performance of the depth-weighted MNE as well as depth-weighted noise-normalized MNE solutions under different cortical orientation constraints, source space densities, and signal-to-noise ratios (SNRs) in multiple subjects. We found that MNE with depth weighting parameter between 0.6 and 0.8 showed improved localization accuracy, reducing the mean displacement error from 12 mm to 7 mm. The noise-normalized MNE was insensitive to depth weighting. A similar investigation of EEG data indicated that depth weighting parameter between 2.0 and 5.0 resulted in an improved localization accuracy. The application of depth weighting to auditory and somatosensory experimental data illustrated the beneficial effect of depth weighting on the accuracy of spatiotemporal mapping of neuronal sources.

Spectral spatiotemporal imaging of cortical oscillations and interactions in the human brain.

This paper presents a computationally efficient source estimation algorithm that localizes cortical oscillations and their phase relationships. The proposed method employs wavelet-transformed magnetoencephalography (MEG) data and uses anatomical MRI to constrain the current locations to the cortical mantle. In addition, the locations of the sources can be further confined with the help of functional MRI (fMRI) data. As a result, we obtain spatiotemporal maps of spectral power and phase relationships. As an example, we show how the phase locking value (PLV), that is, the trial-by-trial phase relationship between the stimulus and response, can be imaged on the cortex. We apply the method to spontaneous, evoked, and driven cortical oscillations measured with MEG. We test the method of combining MEG, structural MRI, and fMRI using simulated cortical oscillations along Heschls gyrus (HG). We also analyze sustained auditory gamma-band neuromagnetic fields from MEG and fMRI measurements. Our results show that combining the MEG recording with fMRI improves source localization for the non-noise-normalized wavelet power. In contrast, noise-normalized spectral power or PLV localization may not benefit from the fMRI constraint. We show that if the thresholds are not properly chosen, noise-normalized spectral power or PLV estimates may contain false (phantom) sources, independent of the inclusion of the fMRI prior information. The proposed algorithm can be used for evoked MEG/EEG and block-designed or event-related fMRI paradigms, or for spontaneous MEG data sets. Spectral spatiotemporal imaging of cortical oscillations and interactions in the human brain can provide further understanding of large-scale neural activity and communication between different brain regions.

The Human Connectome Project and beyond: initial applications of 300 mT/m gradients.

The engineering of a 3 T human MRI scanner equipped with 300 mT/m gradients - the strongest gradients ever built for an in vivo human MRI scanner - was a major component of the NIH Blueprint Human Connectome Project (HCP). This effort was motivated by the HCPs goal of mapping, as completely as possible, the macroscopic structural connections of the in vivo healthy, adult human brain using diffusion tractography. Yet, the 300 mT/m gradient system is well suited to many additional types of diffusion measurements. Here, we present three initial applications of the 300 mT/m gradients that fall outside the immediate scope of the HCP. These include: 1) diffusion tractography to study the anatomy of consciousness and the mechanisms of brain recovery following traumatic coma; 2) q-space measurements of axon diameter distributions in the in vivo human brain and 3) postmortem diffusion tractography as an adjunct to standard histopathological analysis. We show that the improved sensitivity and diffusion-resolution provided by the gradients are rapidly enabling human applications of techniques that were previously possible only for in vitro and animal models on small-bore scanners, thereby creating novel opportunities to map the microstructure of the human brain in health and disease.

Three dimensional echo-planar imaging at 7 Tesla.

Functional MRI (fMRI) most commonly employs 2D echo-planar imaging (EPI). The advantages for fMRI brought about by the increasingly popular ultra-high field strengths are best exploited in high-resolution acquisitions, but here 2D EPI becomes impractical for several reasons, including the very long volume acquisitions times. In this study at 7 T, a 3D EPI sequence with full parallel and partial Fourier imaging capability along both phase encoding axes was implemented and used to evaluate the sensitivity of 3D and corresponding 2D EPI acquisitions at four different spatial resolutions ranging from small to typical voxel sizes (1.5-3.0 mm isotropic). Whole-brain resting state measurements (N=4) revealed a better, or at least comparable sensitivity of the 3D method for gray and white matter. The larger vulnerability of 3D to physiological effects was outweighed by the much shorter volume TR, which moreover allows whole-brain coverage at high resolution within fully acceptable limits for event-related fMRI: TR was only 3.07 s for 1.5 mm, 1.88 s for 2.0 mm, 1.38 s for 2.5 mm and 1.07 s for 3.0 mm isotropic resolution. In order to investigate the ability to detect and spatially resolve BOLD activation in the visual cortex, functional 3D EPI experiments (N=8) were performed at 1 mm isotropic resolution with parallel imaging acceleration of 3x3, resulting in a TR of only 3.2 s for whole-brain coverage. From our results, and several other practical advantages of 3D over 2D EPI found in the present study, we conclude that 3D EPI provides a useful alternative for whole-brain fMRI at 7 T, not only when high-resolution data are required.

Slice-Selective RF pulses for In-vivo B1+ Inhomogeneity Mitigation at 7 Tesla using Parallel RF Excitation with a 16-Element Coil

Slice‐selective RF waveforms that mitigate severe B  1+ inhomogeneity at 7 Tesla using parallel excitation were designed and validated in a water phantom and human studies on six subjects using a 16‐element degenerate stripline array coil driven with a butler matrix to utilize the eight most favorable birdcage modes. The parallel RF waveform design applied magnitude least‐squares (MLS) criteria with an optimized k‐space excitation trajectory to significantly improve profile uniformity compared to conventional least‐squares (LS) designs. Parallel excitation RF pulses designed to excite a uniform in‐plane flip angle (FA) with slice selection in the z‐direction were demonstrated and compared with conventional sinc‐pulse excitation and RF shimming. In all cases, the parallel RF excitation significantly mitigated the effects of inhomogeneous B  1+ on the excitation FA. The optimized parallel RF pulses for human B  1+ mitigation were only 67% longer than a conventional sinc‐based excitation, but significantly outperformed RF shimming. For example the standard deviations (SDs) of the in‐plane FA (averaged over six human studies) were 16.7% for conventional sinc excitation, 13.3% for RF shimming, and 7.6% for parallel excitation. This work demonstrates that excitations with parallel RF systems can provide slice selection with spatially uniform FAs at high field strengths with only a small pulse‐duration penalty. Magn Reson Med 60:1422–1432, 2008.

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients

OBJECTIVE To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Cancellation of EEG and MEG Signals Generated by Extended and Distributed Sources

Extracranial patterns of scalp potentials and magnetic fields, as measured with electro‐ and magnetoencephalography (EEG, MEG), are spatially widespread even when the underlying source in the brain is focal. Therefore, loss in signal magnitude due to cancellation is expected when multiple brain regions are simultaneously active. We characterized these cancellation effects in EEG and MEG using a forward model with sources constrained on an anatomically accurate reconstruction of the cortical surface. Prominent cancellation was found for both EEG and MEG in the case of multiple randomly distributed source dipoles, even when the number of simultaneous dipoles was small. Substantial cancellation occurred also for locally extended patches of simulated activity, when the patches extended to opposite walls of sulci and gyri. For large patches, a difference between EEG and MEG cancellation was seen, presumably due to selective cancellation of tangentially vs. radially oriented sources. Cancellation effects can be of importance when electrophysiological data are related to hemodynamic measures. Furthermore, the selective cancellation may be used to explain some observed differences between EEG and MEG in terms of focal vs. widespread cortical activity. Hum Brain Mapp, 2010.

Onset timing of cross‐sensory activations and multisensory interactions in auditory and visual sensory cortices

Here we report early cross‐sensory activations and audiovisual interactions at the visual and auditory cortices using magnetoencephalography (MEG) to obtain accurate timing information. Data from an identical fMRI experiment were employed to support MEG source localization results. Simple auditory and visual stimuli (300‐ms noise bursts and checkerboards) were presented to seven healthy humans. MEG source analysis suggested generators in the auditory and visual sensory cortices for both within‐modality and cross‐sensory activations. fMRI cross‐sensory activations were strong in the visual but almost absent in the auditory cortex; this discrepancy with MEG possibly reflects the influence of acoustical scanner noise in fMRI. In the primary auditory cortices (Heschl’s gyrus) the onset of activity to auditory stimuli was observed at 23 ms in both hemispheres, and to visual stimuli at 82 ms in the left and at 75 ms in the right hemisphere. In the primary visual cortex (Calcarine fissure) the activations to visual stimuli started at 43 ms and to auditory stimuli at 53 ms. Cross‐sensory activations thus started later than sensory‐specific activations, by 55 ms in the auditory cortex and by 10 ms in the visual cortex, suggesting that the origins of the cross‐sensory activations may be in the primary sensory cortices of the opposite modality, with conduction delays (from one sensory cortex to another) of 30–35 ms. Audiovisual interactions started at 85 ms in the left auditory, 80 ms in the right auditory and 74 ms in the visual cortex, i.e., 3–21 ms after inputs from the two modalities converged.