Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

Ultra-high field magnetic resonance imaging in human epilepsy: A systematic review.

RATIONALE: Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥ 7 Tesla (T), may increase the sensitivity to detect such a lesion. METHODS: A keyword search strategy was submitted to Pubmed, EMBASE, Cochrane Database and clinicaltrials.gov to select studies on UHF MRI in patients with epilepsy. Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on I) diagnostic gain of UHF- over conventional MRI, II) concordance of MRI-detected lesion, seizure onset zone and surgical decision-making, and III) postoperative histopathological diagnosis and seizure outcome. RESULTS: Sixteen observational cohort studies, all using 7T MRI were included. Diagnostic gain of 7T over conventional MRI ranged from 8% to 67%, with a pooled gain of 31%. Novel techniques to visualize pathological processes in epilepsy and lesion detection are discussed. Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients. 7T could influence surgical decision-making, with high concordance of lesion and seizure onset zone. Focal cortical dysplasia (54%), hippocampal sclerosis (12%) and gliosis (8.1%) were the most frequently diagnosed histopathological entities. SIGNIFICANCE: UHF MRI increases, yet variably, the sensitivity to detect an epileptogenic lesion, showing potential for use in clinical practice. It remains to be established whether this results in improved seizure outcome after surgical treatment. Prospective studies with larger cohorts of epilepsy patients, uniform scan and sequence protocols, and innovative post-processing technology are equally important as further increasing field strengths. Besides technical ameliorations, improved correlation of imaging features with clinical semiology, histopathology and clinical outcome has to be established.

Parallel-transmission-enabled magnetization-prepared rapid gradient-echo T1-weighted imaging of the human brain at 7 T.

One of the promises of Ultra High Field (UHF) MRI scanners is to bring finer spatial resolution in the human brain images due to an increased signal to noise ratio. However, at such field strengths, the spatial non-uniformity of the Radio Frequency (RF) transmit profiles challenges the applicability of most MRI sequences, where the signal and contrast levels strongly depend on the flip angle (FA) homogeneity. In particular, the MP-RAGE sequence, one of the most commonly employed 3D sequences to obtain T1-weighted anatomical images of the brain, is highly sensitive to these spatial variations. These cause deterioration in image quality and complicate subsequent image post-processing such as automated tissue segmentation at UHF. In this work, we evaluate the potential of parallel-transmission (pTx) to obtain high-quality MP-RAGE images of the human brain at 7 T. To this end, non-selective transmit-SENSE pulses were individually tailored for each of 8 subjects under study, and applied to an 8-channel transmit-array. Such RF pulses were designed both for the low-FA excitation train and the 180° inversion preparation involved in the sequence, both utilizing the recently introduced k(T)-point trajectory. The resulting images were compared with those obtained from the conventional method and from subject-specific RF-shimmed excitations. In addition, four of the volunteers were scanned at 3 T for benchmarking purposes (clinical setup without pTx). Subsequently, automated tissue classification was performed to provide a more quantitative measure of the final image quality. Results indicated that pTx could already significantly improve image quality at 7 T by adopting a suitable RF-Shim. Exploiting the full potential of the pTx-setup, the proposed k(T)-point method provided excellent inversion fidelity, comparable to what is commonly only achievable at 3 T with energy intensive adiabatic pulses. Furthermore, the cumulative energy deposition was simultaneously reduced by over 40% compared to the conventional adiabatic inversions. Regarding the low-FA k(T)-point based excitations, the FA uniformity achieved at 7 T surpassed what is typically obtained at 3 T. Subsequently, automated white and gray matter segmentation not only confirmed the expected improvements in image quality, but also suggests that care should be taken to properly account for the strong local susceptibility effects near cranial cavities. Overall, these findings indicate that the k(T)-point-based pTx solution is an excellent candidate for UHF 3D imaging, where patient safety is a major concern due to the increase of specific absorption rates.

Eight-channel phased array coil and detunable TEM volume coil for 7 T brain imaging.

An eight-channel receive-only brain coil and table-top detunable volume transmit coil were developed and tested at 7 T for human imaging. Optimization of this device required attention to sources of interaction between the array elements, between the transmit and receive coils and minimization of common mode currents on the coaxial cables. Circular receive coils (85 mm dia.) were designed on a flexible former to fit tightly around the head and within a 270-mm diameter TEM transmit volume coil. In the near cortex, the array provided a fivefold increase in SNR compared to a TEM transmit-receive coil, a gain larger than that seen in comparable coils at 3 T. The higher SNR gain is likely due to strong dielectric effects, which cause the volume coil to perform poorly in the cortex compared to centrally. The sensitivity and coverage of the array is demonstrated with high-resolution images of the brain cortex.

Comparison of physiological noise at 1.5 T, 3 T and 7 T and optimization of fMRI acquisition parameters.

Previous studies have shown that under some conditions, noise fluctuations in an fMRI time-course are dominated by physiological modulations of the image intensity with secondary contributions from thermal image noise and that these two sources scale differently with signal intensity, susceptibility weighting (TE) and field strength. The SNR of the fMRI time-course was found to be near its asymptotic limit for moderate spatial resolution measurements at 3 T with only marginal gains expected from acquisition at higher field strengths. In this study, we investigate the amplitude of image intensity fluctuations in the fMRI time-course at magnetic field strengths of 1.5 T, 3 T, and 7 T as a function of image resolution, flip angle and TE. The time-course SNR was a similar function of the image SNR regardless of whether the image SNR was modulated by flip angle, image resolution, or field strength. For spatial resolutions typical of those currently used in fMRI (e.g., 3 x 3 x 3 mm(3)), increases in image SNR obtained from 7 T acquisition produced only modest increases in time-course SNR. At this spatial resolution, the ratio of physiological noise to thermal image noise was 0.61, 0.89, and 2.23 for 1.5 T, 3 T, and 7 T. At a resolution of 1 x 1 x 3 mm(3), however, the physiological to thermal noise ratio was 0.34, 0.57, and 0.91 for 1.5 T, 3 T and 7 T for TE near T2*. Thus, by reducing the signal strength using higher image resolution, the ratio of physiologic to image noise could be reduced to a regime where increased sensitivity afforded by higher field strength still translated to improved SNR in the fMRI time-series.

Analyzing the neocortical fine-structure.

Cytoarchitectonic fields of the human neocortex are defined by characteristic variations in the composition of a general six-layer structure. It is commonly accepted that these fields correspond to functionally homogeneous entities. Diligent techniques were developed to characterize cytoarchitectonic fields by staining sections of post-mortem brains and subsequent statistical evaluation. Fields were found to show a considerable interindividual variability in extent and relation to macroscopic anatomical landmarks. With upcoming new high-resolution magnetic resonance imaging (MRI) protocols, it appears worthwhile to examine the feasibility of characterizing the neocortical fine-structure from anatomical MRI scans, thus, defining neocortical fields by in vivo techniques. A fixated brain hemisphere was scanned at a resolution of approximately 0.3 mm. After correcting for intensity inhomogeneities in the dataset, the cortex boundaries (the white/grey matter and grey matter/background interfaces) were determined as a triangular mesh. Radial intensity profiles following the shortest path through the cortex were computed and characterized by a sparse set of features. A statistical similarity measure between features of different regions was defined, and served to define the extent of Brodmann's Areas 4, 17, 44 and 45 in this dataset.

Separating distractor rejection and target detection in posterior parietal cortex--an event-related fMRI study of visual marking.

Successful survival in a competitive world requires the employment of efficient procedures for selecting new in preference to old information. Recent behavioral studies have shown that efficient selection is dependent not only on properties of new stimuli but also on an intentional bias that we can introduce against old stimuli. Event-related analysis of functional magnetic resonance imaging data from a task involving visual search across time as well as space indicates that the superior parietal lobule is specifically involved in processes leading to the efficient segmentation of old from new items, whereas the temporoparietal junction area and the ascending limb of the right intraparietal sulcus are involved in the detection of salient new items and in response preparation. The study provides evidence for the functional segregration of brain regions within the posterior parietal lobe.

Hemodynamic and electroencephalographic responses to illusory figures: recording of the evoked potentials during functional MRI.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning using higher level cognitive stimuli was studied. Using responses to illusory figures in a visual oddball task, evoked potentials were obtained with their expected configurations and latencies. A rapid stimulation scheme using randomly varied trial lengths was employed, and class-wise characteristics of the hemodynamic response were obtained by a nonlinear analysis of the fMRI time series. Implications and limitations of conducting combined ERP-fMRI experiments using higher level cognitive stimuli are discussed. EEG/fMRI results revealed a sequential activation of striate and extrastriate occipital cortex along the ventral path of object processing for Kanizsa figures. Interestingly, Kanizsa figures activated the human motion area MT. Targets resulted in activations of frontal and parietal cortex which were not activated for standard stimuli.

A qualitative test of the balloon model for BOLD-based MR signal changes at 3T.

The aim of this study was to adapt the balloon model for BOLD-based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion-weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise-time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented.

Thrombotic thrombocytopenic purpura: MRI demonstration of persistent small cerebral infarcts after clinical recovery.

Abnormalities in the brain of patients with thrombotic thrombocytopenic purpura (TTP) are infrequent on MRI, often reversible and mainly limited to symptomatic stages of the disease. We report a case in which high-resolution MRI demonstrated multiple persistent small cortical infarcts after clinical remission. High-resolution MRI investigations may detect clinically latent but permanent brain damage, and complement clinical judgement in guiding therapeutic decisions.

Dissociation of memory retrieval and search processes: an event-related fMRI study.

A cognitive task can often be subdivided into several subprocesses, which follow a specific temporal order. Here, we report an event-related functional magnetic resonance imaging (fMRI) experiment on memory search, in which the temporal onset of search in primary memory was varied relative to retrieval from secondary memory. Furthermore, previous behavioral studies demonstrated that search times in primary memory depend on the number of items in a memory set, whereas retrieval from secondary memory is a set-size independent process. We analyzed the dependency of the blood oxygenation level dependent (BOLD)-response on the temporal onset of memory search on the one hand and on memory set size on the other hand to differentiate the contribution of retrieval from secondary memory, maintenance in primary memory, item search in primary memory, and response-related processes. The timing of activation followed cue presentation bilaterally in the middle frontal gyri (Brodmann area (BA) 9,46) and the inferior parts of the precentral gyri (BA6). In all other regions of interest (ROI), supplementary motor area (SMA), posterior parietal cortex, antero-superior insula, and primary motor cortex, the onset of activation was delayed with delayed probe presentation, ruling out participation in retrieval from secondary memory. The amplitude of the BOLD-response increased with increasing memory set size in all ROI except primary motor cortex and left posterior parietal cortex. All areas with cue-associated BOLD onset, suggesting involvement in retrieval, showed prolonged BOLD activation, suggesting that they also support maintenance of the retrieved information.

Recording of the event-related potentials during functional MRI at 3.0 Tesla field strength.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning was studied. Using an alternating checkerboard stimulus in a blocked presentation, visually evoked potentials were obtained with their expected configuration and latencies. A clustered echoplanar imaging protocol was applied to observe the hemodynamic response due to the visual stimulus interleaved with measuring ERPs. Influences of the electrode/amplifier set up on MRI scanning and the scanning process on the recording of electrophysiological signals are reported and discussed. Artifacts overlaid on the electrophysiological recordings were corrected by post hoc filtering methods presented here. Implications and limitations of conducting combined ERP/fMRI experiments using higher-level cognitive stimuli are discussed. Magn Reson Med 44:277-282, 2000.

Estimating achievable signal-to-noise ratios of MRI transmit-receive coils from radiofrequency power measurements: applications in quality control.

The inverse relationship between the radiofrequency (RF) power needed to transmit a 90 degree RF pulse, and the signal-to-noise ratio (SNR) available from a transmit-receive RF coil is well known. The theory is restated and a formula given for the signal-to-noise ratio from water, achievable from a single-shot MRI experiment, in terms of the net forward RF power needed for a rectangular 90 degree RF pulse of known shape and duration. The result is normalized to a signal bandwidth of 1 Hz and a sample mass of 1 g. The RF power information needed is available on most commercial scanners, as it is used to calculate specific absorption rates for RF tissue heating. The achievable SNR figure will normally be larger that that actually observed, mainly because of receiver noise, but also because of inaccuracies in setting RF pulse angles, and relaxation effects. Phantom experiments were performed on the transmit-receive RF head coil of a commercial MRI system at 0.95 T using a projection method. The measured SNR agreed with that expected from the formula for achievable SNR once a correction was made for the noise figure of the receiving chain. Comparisons of measured SNR figures with those calculated from RF power measurements are expected to be of value in acceptance testing and quality control.

Prefrontal cortex activation in task switching: an event-related fMRI study.

When a switch between two tasks has to be carried out, performance is slower than in trials where the same task is performed repeatedly. This finding has been attributed to time-consuming control processes required for task switching. Previous results of other paradigms investigating cognitive control processes suggested that prefrontal cortex is involved in executive control. We used event-related fMRI to investigate prefrontal cortex involvement in task switching. Regions in the lateral prefrontal and premotor cortex bilaterally, the anterior insula bilaterally, the left intraparietal sulcus, the SMA/pre-SMA region and the cuneus/precuneus were activated by the task repetition condition and showed additional activation in the task switch condition. This confirmed the hypothesis that lateral prefrontal cortex is involved in task switching. However, the results also showed that this region is neither the only region involved in task switching nor a region specifically involved in task switching.

Event-related fMRI: comparison of conditions with varying BOLD overlap.

Recently, event-related fMRI-experiments have been reported in which subsequent trials were separated by only 2 sec or less. Because the BOLD response needs 10 sec and longer to return to baseline, the event-related signal in these experiments has to be extracted from the overlapping responses elicited by successive trials. Usually it is assumed that this convolved signal is a summation of the overlapping BOLD responses. We tested this assumption by comparing event-related signals in conditions with little and with substantial BOLD overlap in two fMRI experiments of a task-switching paradigm. We analyzed the difference in the activational time course elicited by a critical task and a baseline task when trials of both tasks were separated by intertrial intervals of 15 sec or when the critical trials were embedded in a stream of baseline trials with ISI = 1 sec. The change of the BOLD signal elicited by the critical trials showed a high correspondence between both experiments in five out of six cortical ROI. Our data support the view that BOLD overlap leads to largely linear signal changes. In the present study, task-related increases in the BOLD response were detected equally well with substantial BOLD overlap as with mostly nonoverlapping BOLD responses.

Use of short intertrial intervals in single-trial experiments: a 3T fMRI-study.

We investigated the detectability of task-related changes in the fMRI-signal in an averaged single trial design under systematic variation of intertrial intervals (ITI) in the range between 4 and 12 s. Investigation of the signal timecourses showed a shortening of the baseline period and subsequently a reduction in signal amplitude with decreasing ITI. The main finding is that effect size, i.e., the ratio of task-related signal changes and error variance remained approximately constant from ITI of 12 s down to 6 s. At ITI = 4 s, the effect size was reduced by about 50%. The effects of ITI reduction were comparable in all six cortical ROI which were analyzed. In two subcortical ROI, effect size was already reduced at longer ITI. At ITI = 4 s, the rising flank of the BOLD response was delayed compared to longer ITI. When the data were corrected for the temporal overlap of successive BOLD-responses, the signal amplitudes at ITI = 4 s were comparable to the amplitudes measured at an interval of 12 s. This indicated that the amplitude reduction was mainly due to a linear superposition of the contiguous BOLD-responses.

"Willed action": a functional MRI study of the human prefrontal cortex during a sensorimotor task.

Functional MRI (fMRI) was used to examine human brain activity within the dorsolateral prefrontal cortex during a sensorimotor task that had been proposed to require selection between several responses, a cognitive concept termed "willed action" in a positron emission tomography (PET) study by Frith et al. [Frith, C. D., Friston, K., Liddle, P. F. & Frackowiak, R. S. J. (1991) Proc. R. Soc. London Ser. B 244, 241-246]. We repeated their sensorimotor task, in which the subject chooses to move either of two fingers after a stimulus, by fMRI experiments in a 2.1-T imaging spectrometer. Echo-planar images were acquired from four coronal slices in the prefrontal cortex from nine healthy subjects. Slices were 5 mm thick, centers separated by 7 mm, with nominal in-plane spatial resolution of 9.6 x 5.0 mm2 for mean data. Our mean results are in agreement with the PET results in that we saw similar bilateral activations. The present results are compared with our previously published fMRI study of a verbal fluency task, which had also been proposed by Frith et al. to elicit a "willed action" response. We find a clear separation of activation foci in the left dorsolateral prefrontal cortex for the sensorimotor (Brodmann area 46) and verbal fluency (Brodmann area 45) tasks. Hence, assigning a particular activated region to "willed action" is not supported by the fMRI data when examined closely because identical regions are not activated with different modalities. Similar modality linked activations can be observed in the original PET study but the greater resolution of the fMRI data makes the modality linkages more definite.