ACR White Paper on Magnetoencephalography and Magnetic Source Imaging: A Report from the ACR Commission on Neuroradiology.

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease. Recent years have seen an increased utilization of this technique for both clinical practice and research, in the United States and worldwide. This report summarizes current thinking, presents recommendations for clinical implementation, and offers an outlook for emerging new clinical indications.

Repeatability of Standardized and Normalized Relative CBV in Patients with Newly Diagnosed Glioblastoma.

BACKGROUND AND PURPOSE: For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques. MATERIALS AND METHODS: The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naïve and pathologically proved glioblastoma multiforme (men = 20; mean age = 55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method. RESULTS: When ordered by the repeatability coefficient, methods using postprocessing leakage correction and ΔR2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor (P = .31), yet inferior in tumor for normalized relative CBV (P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%-20%) than normalized relative CBV estimates (24%-67%). The minimum number of participants needed to detect a change of 10% or 20% is 118-643 or 30-161 for normalized relative CBV and 109-215 or 28-54 for standardized relative CBV. CONCLUSIONS: The ΔR2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and requiring fewer participants to detect a change compared with normalized relative CBV.

EEG functional connectivity is partially predicted by underlying white matter connectivity.

Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlying white matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales.

Language lateralization represented by spatiotemporal mapping of magnetoencephalography.

BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤-0.10 was considered left- or right-hemisphere dominance, respectively; a LI between -0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

Multimodal imaging of spike propagation: a technical case report.

We report an 11-year-old boy with intractable epilepsy, who had cortical dysplasia in the right superior frontal gyrus. Spatiotemporal source analysis of MEG and EEG spikes demonstrated a similar time course of spike propagation from the superior to inferior frontal gyri, as observed on intracranial EEG. The tractography reconstructed from DTI showed a fiber connection between these areas. Our multimodal approach demonstrates spike propagation and a white matter tract guiding the propagation.

Quantification of the benefit from integrating MEG and EEG data in minimum l2-norm estimation.

Source current estimation from electromagnetic (MEG and EEG) signals is an ill-posed problem that often produces blurry or inaccurately positioned estimates. The two modalities have distinct factors limiting the resolution, e.g., MEG cannot detect radially oriented sources, while EEG is sensitive to accuracy of the head model. This makes combined EEG+MEG estimation techniques desirable, but different acquisition noise statistics, complexity of the head models, and lack of pertinent metrics all complicate the assessment of the resulting improvements. We investigated analytically the effect of including EEG recordings in MEG studies versus the addition of new MEG channels when computing noise-normalized minimum l(2)-norm estimates. Three-compartment boundary-element forward models were constructed using structural MRI scans for four subjects. Singular value analysis of the resulting forward models predicted better performance of the EEG+MEG case in the form of higher matrix rank. MNE inverse operators for EEG, MEG and EEG+MEG were constructed using the sensor noise covariance estimated from data. Metrics derived from the resolution matrices predicted higher spatial resolution in EEG+MEG as compared to MEG due to decreased spread (lower spatial dispersion, higher resolution index) with no reduction in dipole localization error. The effect was apparent in all source locations, with increased magnitude for deep areas such as the cingulate cortex. We were also able to corroborate the results for the somatosensory cortex using median nerve responses.

Magnetoencephalographic mapping of interictal spike propagation: a technical and clinical report.

Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 11-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe.

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.

3T phased array MRI improves the presurgical evaluation in focal epilepsies: a prospective study.

BACKGROUND: Although detection of concordant lesions on MRI significantly improves postsurgical outcomes in focal epilepsy (FE), many conventional MR studies remain negative. The authors evaluated the role of phased array surface coil studies performed at 3 Tesla (3T PA MRI). METHODS: Forty patients with medically intractable focal epilepsies were prospectively imaged with 3T PA-MRI including high matrix TSE T2, fluid attenuated inversion recovery, and magnetization prepared rapid gradient echo. All patients were considered candidates for epilepsy surgery. 3T PA-MRIs were reviewed by a neuroradiologist experienced in epilepsy imaging with access to clinical information. Findings were compared to reports of prior standard 1.5T MRI epilepsy studies performed at tertiary care centers. RESULTS: Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% (15/40), this additional information motivated a change in clinical management. In the subgroup of patients with prior 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). CONCLUSION: Phased array surface coil studies performed at 3 Tesla read by an experienced unblinded neuroradiologist can improve the presurgical evaluation of patients with focal epilepsy when compared to routine clinical 1.5T studies read at tertiary care centers.

Cortical thickness in a case of congenital unilateral perisylvian syndrome.

In congenital perisylvian syndrome, there is polymicrogyric cortex distributed in variable extensions around the sylvian fissure. Unilateral cases usually present with congenital hemiparesis, while bilateral cases have pseudobulbar paralysis of the oropharingoglossal region. Both unilateral and bilateral cases have a high rate of epilepsy. Polymicrogyric cortex is characterized by too many small convolutions. Often there are no intervening sulci, and almost no white matter can be seen under them. On MRI they appear to have increased thickness. Bilateral and symmetric polimycrogiria can be hard to recognize on standard MRIs. Accurate and automated methods for measuring the thickness of cerebral cortex are available. They have mainly been used to study a variety of disorders with diminished cortical thickness. We studied a case of right perisylvian polymicrogyria, who presented in adult life with epilepsy and had a normal neurological exam. Fischl and Dale's automated cortical thickness analysis rendered a very clear picture of increased cortical thickness with values up to 9 mm in the affected areas (normal cortical thickness varies between 1 and 4.5 mm). The thickest areas were seen over grossly abnormal gyri on the reconstructed cerebral cortex. On MEG he presented a prominent and monotonous 9 Hz activity that was located within the limits of a thick gyrus. There was a significant difference of thickness between homologous hemispheric areas. To our surprise some areas of the left hemisphere also appeared to have increased thickness, raising the question of a bilateral asymmetric case.

Objective detection and localization of multiple sclerosis lesions on magnetic resonance brainstem images: validation with auditory evoked potentials.

To develop an objective method for detecting multiple sclerosis (MS) brainstem lesions, magnetic resonance (MR) images (multiple planar, spin-echo, acquired in three planes of section) of sixteen MS patients and fourteen normal subjects were analyzed with an algorithm that detected regions with a relatively increased intensity on both a spin-echo image and a T2 image. To be considered a lesion, such regions had to overlap in at least two orthogonal planes. Using a digitized atlas of the human brainstem, the lesion locations were mapped with respect to the brainstem anatomy. This method was evaluated by comparing the location of MS lesions with the brainstem auditory evoked potentials obtained from these subjects. Brainstem lesions were detected in five MS patients; four had lesions impinging upon the auditory system and one did not. All four had abnormal evoked potentials. The fourteen normal subjects, the one MS patient with brainstem lesions outside the auditory pathway, and the eleven other MS patients with no brainstem lesions all had normal evoked potentials. The requirement that lesions be detected in at least two planes of section greatly improved the specificity of the algorithm. The consistency between the MR and brainstem auditory evoked potentials results supports the validity of this imaging analysis algorithm for objectively localizing brainstem lesions.

Latency of the auditory evoked neuromagnetic field components: stimulus dependence and insights toward perception.

This review will focus on investigations of the auditory evoked neuromagnetic field component, the M100, detectable in the magnetoencephalogram recorded during presentation of auditory stimuli, approximately 100 milliseconds after stimulus onset. In particular, the dependence of M100 latency on attributes of the stimulus, such as intensity, pitch and timbre will be discussed, along with evidence relating M100 latency observations to perceptual features of the stimuli. Comparison with investigation of the analogous electrical potential component, the N1, will be made. Parametric development of stimuli from pure tones through complex tones to speech elements will be made, allowing the influence of spectral pitch, virtual pitch and perceptual categorization to be delineated and suggesting implications for the role of such latency observations in the study of speech processing. The final section will deal with potential clinical applications offered by M100 latency measurements, as objective indices of normal and abnormal cortical processing.

Temporal encoding in auditory evoked neuromagnetic fields: stochastic resonance.

Recent investigations have demonstrated that temporal patterns of sensory neural activity detected by magnetoencephalography (MEG) reflect features of the stimulus. In this study, neuromagnetic activity was investigated using an event detection algorithm based on the correlation coefficient. The results of the technique are compared with widely used methods of analysis in two experimental conditions and are shown to identify features in the single-trial MEG response that are not apparent in the response obtained by averaging across repeated trials. As an example of the technique, the physiologic jitter in latency associated with the M100 of auditory evoked fields was reproducibly measured. Specifically, higher intensity sounds were associated with an increased reliability. The technique was also applied to the noise-enhanced evoked auditory response, producing an objective demonstration of a cortical manifestation of the phenomenon of stochastic resonance-the paradoxical enhancement in the measurement of the signal-to-noise ratio (SNR) induced by optimal addition of noise to system input.

Peri-threshold encoding of stimulus frequency and intensity in the M100 latency.

Recent work has suggested that, in addition to spatial tonotopy, pitch and timbre information may be encoded in the temporal activity of the auditory cortex. Specifically, the post-stimulus latency of the maximal cortical evoked neuromagnetic field (M100 or N1m) is a function of stimulus frequency. We investigated the additional effect of varying the stimulus intensity on the M100 response. A 37-channel biomagnetometer recorded neuromagnetic fields over the temporal lobe of healthy volunteers in response to monaurally presented tones. The frequency dependence of the M100 latency remained remarkably invariant even at low stimulus intensity. Thus, for peri-threshold stimuli, frequency information appears encoded in the temporal form of the evoked response.

Information theoretic analysis of dynamical encoding by four identified primary sensory interneurons in the cricket cercal system.

1. The stimulus/response properties of four identified primary sensory interneurons in the cricket cercal sensory system were studied using electrophysiological techniques. These four cells are thought to represent a functionally discrete subunit of the cercal system: they are the only cells that encode information about stimulus direction to higher centers for low intensity stimuli. Previous studies characterized the quantity of information encoded by these cells about the direction of air currents in the horizontal plane. In the experiments reported here, we characterized the quantity and quality of information encoded in the cells' elicited responses about the dynamics of air current waveforms presented at their optimal stimulus directions. The total sample set included 22 cells. 2. This characterization was achieved by determining the cells' frequency sensitivities and encoding accuracy using the methods of stochastic systems analysis and information theory. The specific approach used for the analysis was the "stimulus reconstruction" technique in which a functional expansion was derived to transform the observed spike train responses into the optimal estimate (i.e., "reconstruction") of the actual stimulus. A novel derivation of the crucial equations is presented. The reverse approach is compared with the more traditional forward analysis, in which an expansion is derived that transforms the stimulus to a prediction of the spike train response. Important aspects of the application of these analytical approaches are considered. 3. All four interneurons were found to have identical frequency tuning, as assessed by the accuracy with which different frequency components of stimulus waveforms could be reconstructed with a linear expansion. The interneurons encoded significant information about stimulus frequencies between 5 and 80 Hz, which peak sensitivities at approximately 15 Hz. 4. All four interneurons were found to have identical stimulus/response latencies. The mean latency between a stimulus component and the corresponding elicited spike was 17 ms. All four interneurons also had identical integration times. The integration time, measured by the duration of stimulus, which could affect the probability of spiking, was approximately 50 ms. 5. The accuracy of the encoding can be expressed as a signal-to-noise ratio, where the noise is a scaled difference between the original signal and the best estimate of the signal. Peak signal-to-noise ratios of approximately 1 were obtained for the cells across all stimulus power levels, using only the linear expansion term. Analysis of the data indicated that the consideration of second-order nonlinear transformations of the stimulus would not have increased the calculated encoding accuracy. 6. The encoding accuracy also can be expressed in the information theoretic units of bits/second, which characterizes the information transmission rate of the cell. Bits/second values varied between 10 and 80 for the 22 different cells in our experimental set. The information rate values were highly correlated with the mean spike rates of the interneurons, but were not correlated with the stimulus power levels. However, normalizing the absolute information rates by the mean spike rate in each case yielded a measure of bits/spike that was remarkably invariant across all experiments. The measured bits/spike rate was approximately 1 for all experiments. This result is discussed in the context of recent theoretical studies on optimal encoding. 7. Although the dynamic sensitivities of the four interneurons were identical, their directional sensitivities are known to be orthogonal. Thus the cells are complementary to one another from a functional standpoint: whereas a particular cell will be insensitive to air currents from some directions, one or more of the other three cells will be sensitive to stimuli from those directions...

Multiple sclerosis lesions of the auditory pons are not silent.

To understand the relationship between brainstem lesions and auditory neurology in patients with multiple sclerosis, we compared behavioural, electrophysiological and imaging data in 38 patients with probable or definite multiple sclerosis and normal or near normal hearing. Behavioural measures included (i) general hearing tests (audiogram, speech discrimination) and (ii) hearing tests likely to be critically dependent upon brainstem processing (masking level difference, interaural time and level discrimination). Brainstem auditory evoked potentials provided the electrophysiological data. Multiplanar high-resolution MRI of the brainstem provided the anatomical data. Interaural time discrimination for high-frequency sounds was by far the most sensitive of all tests with abnormalities in 71% of all subjects. Whenever any other test was abnormal this test was always abnormal. Interaural time discrimination for low-frequency sounds and evoked potentials were closely related and next most sensitive with abnormalities in approximately 40% of all subjects. Interaural level discrimination and masking level difference were least sensitive with abnormalities in < 10% of subjects. Speech discrimination scores correlated significantly with the masking level differences, as well as with interaural time discrimination for high-frequency sounds. Pontine lesions were found in five of the 16 patients, in whom an objective method for detecting magnetic resonance lesions could be applied. All four with lesions involving the pontine auditory pathway had marked abnormalities in interaural time discrimination and evoked potentials. None of the other 12 had evoked potentials abnormalities. We conclude that neurological tests requiring precise neural timing can reveal behavioural deficits for multiple sclerosis lesions of the auditory pons that are otherwise 'silent'. Of all neurological systems the auditory system at the level of the pons is probably the most sensitive to multiple sclerosis lesions, because of its exceptional dependence upon neural timing in the microsecond range and the lack of redundancy in the encoding of high-frequency sounds. Precise neural timing may be critical for some aspects of speech processing.

Binaural auditory processing in multiple sclerosis subjects.

In order to relate human auditory processing to physiological and anatomical experimental animal data, we have examined the interrelationships between behavioral, electrophysiological and anatomical data obtained from human subjects with focal brainstem lesions. Thirty-eight subjects with multiple sclerosis were studied with tests of interaural time and level discrimination (just noticeable differences or jnds), brainstem auditory evoked potentials and magnetic resonance (MR) imaging. Interaural testing used two types of stimuli, high-pass (> 4000 Hz) and low-pass (< 1000 Hz) noise bursts. Abnormal time jnds (Tjnd) were far more common than abnormal level jnds (70% vs 11%); especially for the high-pass (Hp) noise (70% abnormal vs 40% abnormal for low-pass (Lp) noise). The HpTjnd could be abnormal with no other abnormalities; however, whenever the BAEPs, LpTjnd and/or level jnds were abnormal HpTjnd was always abnormal. Abnormal wave III amplitude was associated with abnormalities in both time jnds, but abnormal wave III latency with only abnormal HpTjnds. Abnormal wave V amplitude, when unilateral, was associated with a major HpTjnd abnormality, and, when bilateral, with both HpTjnd and LpTjnd major abnormalities. Sixteen of the subjects had their MR scans obtained with a uniform protocol and could be analyzed with objective criteria. In all four subjects with lesions involving the pontine auditory pathway, the BAEPs and both time jnds were abnormal. Of the twelve subjects with no lesions involving the pontine auditory pathway, all had normal BAEPs and level jnds, ten had normal LpTjnds, but only five had normal HpTjnds. We conclude that interaural time discrimination is closely related to the BAEPs and is dependent upon the stimulus spectrum. Redundant encoding of low-frequency sounds in the discharge patterns of auditory neurons, may explain why the HpTjnd is a better indicator of neural desynchrony than the LpTjnd. Encroachment of MS lesions upon the pontine auditory pathway always is associated with abnormal BAEPs and abnormal interaural time discrimination but may have normal interaural level discrimination. Our data provide one of the most direct demonstrations in humans of relationships among auditory performance, evoked potentials and anatomy. We present a model showing that many of these interrelationships can be readily interpreted using ideas developed from work on animals, even though these relationships could not have been predicted with confidence beforehand. This work provides a clear advance in our understanding of human auditory processing and should serve as a basis for future studies.

Effects of multiple sclerosis brainstem lesions on sound lateralization and brainstem auditory evoked potentials.

Magnetic resonance (MR) imaging, brainstem auditory evoked potentials (BAEPs), and tests of interaural time and level discrimination were performed on sixteen subjects with multiple sclerosis (MS). Objective criteria were used to define MR lesions. Of the eleven subjects in whom no pontine lesions were detected and the one subject who had pontine lesions that did not encroach upon the auditory pathways, all had normal BAEPs and interaural level discrimination, although a few had abnormal interaural time discrimination. Of four subjects with lesions involving the pontine auditory pathway, all had both abnormal BAEPs and abnormal interaural time discrimination; one also had abnormal interaural level discrimination. Analysis of the data suggest the following: waves I and II are generated peripheral to the middle of the ventral acoustic stria (VAS); wave III is generated ipsilaterally in the region of the rostral VAS, caudal superior olivary complex (SOC) and trapezoid body (TB); and waves V and L are generated contralaterally, rostral to the SOC-TB. The region of the ipsilateral rostral SOC-TB is implicated as part of the pathway involved in the generation of waves V and L. Interaural time discrimination of both high and low frequency stimuli were affected by all brainstem lesions that encroached on auditory pathways. A unilateral lesion in the region of the LL affected interaural time discrimination for low-frequency stimuli less severely than bilateral lesions of the LL or a unilateral lesion of the VAS. The only interaural level discrimination abnormality occurred for a subject with a unilateral lesion involving the entire rostral VAS. It appears that detailed analysis of lesion locations coupled with electrophysiological and psychophysical data holds promise for testing hypotheses concerning the function of various human auditory brainstem structures.