Evoked responses to rhythmic visual stimulation vary across sources of intrinsic alpha activity in humans.

Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying 'source-level' activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from -0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms.

Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression.

PURPOSE: To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. MATERIAL AND METHODS: At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier's performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. RESULTS: In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77-0.93 (sensitivity 0.91, 95% CI 0.81-0.97; specificity 0.71, 95% CI 0.44-0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72-0.9), 0.81 for [18F]-FET-PET (95% CI 0.7-0.89), and 0.81 for expert consensus (95% CI 0.7-0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. CONCLUSION: Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas.

PURPOSE: Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS: Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS: In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS: We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

MR Imaging of Individual Perfusion Reorganization Using Superselective Pseudocontinuous Arterial Spin-Labeling in Patients with Complex Extracranial Steno-Occlusive Disease.

BACKGROUND AND PURPOSE: Patients with multiple stenoses or occlusions of the extracranial arteries require an individualized diagnostic approach. We evaluated the feasibility and clinical utility of a novel MR imaging technique for regional perfusion imaging in this patient group. MATERIALS AND METHODS: Superselective pseudocontinuous arterial spin-labeling with a circular labeling spot enabling selective vessel labeling was added to routine imaging in a prospective pilot study in 50 patients (10 women, 70.05 ± 10.55 years of age) with extracranial steno-occlusive disease. Thirty-three had infarct lesions. DSC-MR imaging was performed in 16/50 (32%), and cerebral DSA, in 12/50 patients (24%). Vascular anatomy and the distribution of vessel stenoses and occlusions were defined on sonography and TOF-MRA. Stenoses were classified according to the NASCET criteria. Infarct lesions and perfusion deficits were defined on FLAIR and DSC-MR imaging, respectively. Individual perfusion patterns were defined on the superselective pseudocontinuous arterial spin-labeling maps and were correlated with vascular anatomy and infarct lesion localization. RESULTS: The superselective pseudocontinuous arterial spin-labeling imaging sequence could be readily applied by trained technicians, and the additional scan time of 12.7 minutes was well-tolerated by patients. The detected vessel occlusions/stenoses and perfusion patterns corresponded between cerebral DSA and superselective pseudocontinuous arterial spin-labeling maps in all cases. Perfusion deficits on DSC-CBF maps significantly correlated with those on superselective pseudocontinuous arterial spin-labeling maps (Pearson r = 0.9593, P < .01). Individual collateral recruitment patterns were not predictable from the vascular anatomy in 71% of our patients. CONCLUSIONS: Superselective pseudocontinuous arterial spin-labeling is a robust technique for regional brain perfusion imaging, suitable for the noninvasive diagnostics of individual perfusion patterns in patients with complex cerebrovascular disease.

Novel Metal Artifact Reduction Techniques with Use of Slice-Encoding Metal Artifact Correction and View-Angle Tilting MR Imaging for Improved Visualization of Brain Tissue near Intracranial Aneurysm Clips.

PURPOSE: The MR image quality after intracranial aneurysm clipping is often impaired because of artifacts induced by metal implants. The purpose of the present study was to evaluate the benefit of a new WARP sequence with slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) MR imaging as novel artifact reduction techniques. MATERIALS AND METHODS: A new WARP TSE (a work-in-progress software package provided by Siemens Healthcare) sequence was implemented for cranial applications based on a turbo spin echo (TSE) sequence. T1- and T2-weighted images with standard and WARP TSE sequences were acquired from 6 patients with 11 clipping sites, and the images were compared based on artifact size and general image quality. RESULTS: T2- and T1-weighted WARP TSE sequences resulted in a highly significant reduction of metal artifacts compared with standard sequences (T2w- WARP TSE: 89.8 ± 1.4 %; T1w- WARP TSE: 84.9 ± 2.9 %; p < 0.001) without a substantial loss of image quality. CONCLUSION: The use of a new WARP TSE sequence after aneurysm clipping is highly beneficial for increasing the diagnostic MR image quality due to a striking reduction of metal artifacts.

Double inversion recovery sequence of the cervical spinal cord in multiple sclerosis and related inflammatory diseases.

BACKGROUND AND PURPOSE: MR imaging plays an important role in diagnosing MS and other related inflammatory diseases; however, imaging of the spinal cord is still challenging. We hypothesized that a 3D double inversion recovery sequence for cervical spinal cord imaging would be more sensitive in detecting inflammatory lesions than a conventional 2D T2-weighted TSE sequence at 3T. MATERIALS AND METHODS: On a 3T MR imaging scanner, we examined 30 patients with suspected or established MS (MS, n = 16; clinically isolated syndrome, n = 12; isolated myelitis, n = 2) and 10 healthy controls. Newly developed 3D double inversion recovery and conventional 2D axial and sagittal T2-weighted TSE images of the cervical spinal cord were acquired. Two blinded neuroradiologists independently assessed the scans in pseudorandomized order for lesion numbers and rated lesion visibility and overall image quality on 5-point scales. A subsequent consensus reading delivered definite lesion counts. Standardized contrast-to-noise ratios were calculated in representative lesions of each patient. RESULTS: Overall, 28% more lesions could be detected with 3D double inversion recovery than with conventional T2WI (119 versus 93, P < .002). On average, the standardized contrast-to-noise ratio was significantly higher (P < .001) in double inversion recovery than in T2WI. Lesion visibility was rated significantly higher (P < .001) in double inversion recovery compared with T2WI despite lower image quality. CONCLUSIONS: The novel 3D double inversion recovery sequence allowed better detection of lesions in MS and related inflammatory diseases of the cervical spinal cord, compared with conventional 2D T2WI.

T2* mapping with background gradient correction using different excitation pulse shapes.

SUMMARY: Background gradients induced by magnetic susceptibility variations near air-filled cavities in the brain cause signal-intensity loss in gradient-echo images and shorten T2* considerably. With a correction method in which the exponential decay is restored with section-profile-dependent correction factors, parts of the signal intensity can be recovered. While uncorrected T2* values drop by 20% at a gradient strength of 75 µT/m, with correction and exponential excitation pulses, this boundary is pushed to 220 µT/m.

T1 mapping using spoiled FLASH-EPI hybrid sequences and varying flip angles.

In this work a method for considerably improving the signal-to-noise ratio (SNR) in T(1) maps based on the variable flip angle approach is proposed, employing spoiled fast low angle shot (FLASH) echo-planar imaging (EPI) hybrid sequences with two echoes per excitation. In phantom measurements it could be verified that the SNR improvement in the underlying images translated into an SNR increase in the T(1) maps exceeding theoretical predictions. Even a hybrid sequence with an 18% shorter measurement time than a standard FLASH readout with identical spatial coverage and resolution yielded an SNR gain of 23% in the resulting T(1) maps. Hybrid sequences with either identical measurement time (9:05 min) or bandwidth (9:30 min) yielded gains of 60% and 67%, respectively. These results could be confirmed by measurements on four healthy volunteers. The image quality of T(1) maps based on hybrid sequences was excellent and the SNR improvement was clearly visible. The measured SNR gains in T(1) maps were between 20% (shortest sequence, white matter) and 66% (sequence with identical bandwidth, gray matter). The resulting T(1) values were comparable, with a slight tendency toward higher values in the hybrid sequences. In summary, without prolonging experiment durations the method proposed yields SNR gains that are commonly achieved by acquiring two averages.

Influence of RF spoiling on the stability and accuracy of T1 mapping based on spoiled FLASH with varying flip angles.

There is increasing interest in quantitative T(1) mapping techniques for a variety of applications. Several methods for T(1) quantification have been described. The acquisition of two spoiled gradient-echo data sets with different flip angles allows for the calculation of T(1) maps with a high spatial resolution and a relatively short experimental duration. However, the method requires complete spoiling of transverse magnetization. To achieve this goal, RF spoiling has to be applied. In this work it is investigated whether common RF spoiling techniques are sufficiently effective to allow for accurate T(1) quantification. It is shown that for most phase increments the apparent T(1) can deviate considerably from the true value. Correct results may be achieved with phase increments of 118.2 degrees or 121.8 degrees. However, for these values the method suffers from instabilities. In contrast, stable results are obtained with a phase increment of 50 degrees. An algorithm is presented that allows for the calculation of corrected T(1) maps from the apparent values. The method is tested both in phantom experiments and in vivo by acquiring whole-brain T(1) maps of the human brain.

Voxel-based morphometry and diffusion-tensor MR imaging of the brain in long-term survivors of childhood leukemia.

The aims of this study were to detect morphological changes in neuroanatomical components in adult survivors of acute lymphoblastic leukemia (ALL). Voxel-based morphometry (VBM) can be used to detect subtle structural changes in brain morphology and via analysis of fractional anisotropy (FA), diffusion-tensor imaging (DTI) can non-invasively probe white matter (WM) integrity. We used VBM and DTI to examine 20 long-term survivors of ALL and 21 healthy matched controls. Ten ALL survivors received chemotherapy and irradiation; ten survivors received chemotherapy alone during childhood. Imaging was performed on a 3.0-T MRI. For VBM, group comparisons of segmented T1-weighted grey matter (GM) and WM images from controls and ALL survivors were performed separately for patients who received chemotherapy alone and who received chemotherapy and irradiation. For DTI, FA in WM was compared for the same groups. Survivors of childhood ALL who underwent cranial irradiation during childhood had smaller WM volumes and reduced GM concentration within the caudate nucleus and thalamus. The FA in WM was reduced in adult survivors of ALL but the effect was more severe after combined treatment with irradiation and chemotherapy. Our results indicate that DTI and VBM can reveal persistent long-term WM and caudate changes in children after ALL treatment, even without T2 changes in conventional imaging.

Differential opioid action on sensory and affective cerebral pain processing.

Low doses of morphine, the most commonly used opioid analgesic, have been shown to significantly reduce the affective but not the sensory intensive dimension of pain. This suggests differential dose-response relationships of opioid analgesia on the sensory and affective components of pain. We investigated the effects of different alfentanil plasma concentration levels (0, 19.6+/-2.7, 47.2+/-7.6, and 76.6+/-11.3 ng/ml) on pain-related brain activation achieved by short pulses of gaseous CO(2) delivered to the nasal mucosa, using functional magnetic resonance imaging (fMRI) on a 3.0 T MRI scanner in 16 non-carriers and 9 homozygous carriers of the mu-opioid receptor gene variant OPRM1 118A>G. Increasing opioid concentrations had differential effects in brain regions processing the sensory and affective dimensions of pain. In brain regions associated with the processing of the sensory intensity of pain (primary and secondary somatosensory cortices, posterior insular cortex), activation decreased linearly in relation to alfentanil concentrations, which was significantly less pronounced in OPRM1 118G carriers. In contrast, in brain regions known to process the affective dimension of pain (parahippocampal gyrus, amygdala, anterior insula), pain-related activation disappeared at the lowest alfentanil dose, without genotype differences.

Right hemispheric language dominance in a right-handed male with a right frontal tumor shown by functional transcranial Doppler sonography.

BACKGROUND: A 38-year-old, right-handed man with late-onset right frontal epilepsy due to a ganglioglioma and atypical right hemispheric language dominance is described. METHODS: Language dominance was investigated with functional transcranial Doppler sonography (fTCD), and language localization with functional magnetic resonance imaging (fMRI). RESULTS: During a word generation task, fTCD showed atypical right hemispheric language dominance, which was confirmed by fMRI using a semantic word comparison and a word stem completion task. This information helped to guide the resective procedure, which left the patient seizure-free and did not induce new deficits. CONCLUSION: Functional TCD appears to be a useful and reliable screening tool for determining hemispheric language dominance, even in patients with atypical language representation. Functional MRI may be used to confirm fTCD results and further localize eloquent cortex.

Contributions of sensory input, auditory search and verbal comprehension to cortical activity during speech processing.

We studied eight normal subjects in an fMRI experiment where they listened to natural speech sentences and to matched simple or complex speech envelope noises. Neither of the noises (simple or complex) were understood initially, but after the corresponding natural speech sentences had been heard, comprehension was close to perfect for the complex but still absent for the simple speech envelope noises. This setting thus involved identical stimuli that were understood or not and permitted to identify (i) a neural substrate of speech comprehension unconfounded by stimulus acoustic properties (common to natural speech and complex noises), (ii) putative correlates of auditory search for phonetic cues in noisy stimuli (common to simple and complex noises once the matching natural speech had been heard) and (iii) the cortical regions where speech comprehension and auditory search interact. We found correlates of speech comprehension in bilateral medial (BA21) and inferior (BA38 and BA38/21) temporal regions, whereas acoustic feature processing occurred in more dorsal temporal regions. The left posterior superior temporal cortex (Wernicke's area) responded to the acoustic complexity of the stimuli but was additionally sensitive to auditory search and speech comprehension. Attention was associated with recruitment of the dorsal part of Broca's area (BA44) and interaction of auditory attention and comprehension occurred in bilateral insulae, the anterior cingulate and the right medial frontal cortex. In combination, these results delineate a neuroanatomical framework for the functional components at work during natural speech processing, i.e. when comprehension results from concurrent acoustic processing and effortful auditory search.

EEG-correlated fMRI of human alpha activity.

Electroencephalography-correlated functional magnetic resonance imaging (EEG/fMRI) can be used to identify blood oxygen level-dependent (BOLD) signal changes associated with both physiological and pathological EEG events. Here, we implemented continuous and simultaneous EEG/fMRI to identify BOLD signal changes related to spontaneous power fluctuations in the alpha rhythm (8-12 Hz), the dominant EEG pattern during relaxed wakefulness. Thirty-two channels of EEG were recorded in 10 subjects during eyes-closed rest inside a 1.5-T magnet resonance (MR) scanner using an MR-compatible EEG recording system. Functional scanning by echoplanar imaging covered almost the entire cerebrum every 4 s. Off-line MRI artifact subtraction software was applied to obtain continuous EEG data during fMRI acquisition. The average alpha power over 1-s epochs was derived at several electrode positions using a Fast Fourier Transform. The power time course was then convolved with a canonical hemodynamic response function, down-sampled, and used for statistical parametric mapping of associated signal changes in the image time series. At all electrode positions studied, a strong negative correlation of parietal and frontal cortical activity with alpha power was found. Conversely, only sparse and nonsystematic positive correlation was detected. The relevance of these findings is discussed in view of the current theories on the generation and significance of the alpha rhythm and the related functional neuroimaging findings.

Fast three-dimensional sodium imaging of human brain.

A three-dimensional sodium imaging technique with a minimum echo time of 0.9 ms is described in a 2.0 Tesla whole-body system. The relaxation behaviour in vivo of sodium was analysed: a fast T(2)(*) relaxation component between 1.2 and 1.6 ms and a slow T(2)(*) relaxation component between 7.1 ms and 8.4 ms were quantified in brain tissue of three volunteers. Three-dimensional sodium images of the human brain were acquired in 8.5 min with a resolution of 4.7 x 4.7 x 10 mm (0.2 cc voxel size) and a signal-to-noise ratio of 20 in brain tissue and 30 in cerebrospinal fluid.

Perfusion imaging using spin-labeling methods: contrast-to-noise comparison in functional MRI applications.

In this study the performance of FLASH imaging with selective inversion preparation for functional perfusion studies was investigated. In addition to the absolute quantification of perfusion by measurement of the longitudinal relaxation times with global (T(1glob)) and selective (T(1sel)) inversion, the measurement of absolute (BASE) and relative (FAIR) perfusion increases by subtraction of appropriately weighted images was also considered. The subject averages of absolute perfusion obtained by the quantitative method were 70.7 +/- 4.0 ml/100g/min in gray matter, 10.2 +/- 3.4 ml/100g/min in white matter, and 89.0 +/- 3.1 ml/100g/min in visual cortex. These values, as well as the average increase of perfusion due to visual stimulation (44.4 +/- 3.7 ml/100g/min), agree well with respective data reported by PET and other MRI studies. However, for individual subjects the standard deviations over single ROIs inside the visual cortex lay around 100% which prevented the detection of significant activation. BASE and FAIR, on the other hand, were able to detect significant activation in single subjects. The measured average perfusion increases were 51.7 +/- 6.6 ml/100g/min and 56.5 +/- 13.8%, respectively. Magn Reson Med 46:172-182, 2001.

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study.

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multislice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to cocontractions and dystonic postures.

Cerebral activation pattern in primary writing tremor.

OBJECTIVE: To compare the cerebral activation pattern during writing of patients with writing tremor with healthy controls using functional MRI METHODS: Three patients with writing tremor and 10 healthy controls were examined using a 1.5 Tesla scanner. All subjects performed a paradigm of alternating 30 second periods of rest or writing. For functional imaging 60 EPI multislice data sets were acquired. All images were analyzed using SPM96 software. Data were analyzed for the group of patients with writing tremor and compared with those of the control group. RESULTS: Both patients with writing tremor and controls showed a significant activation of the contralateral primary sensorimotor cortex, SMA, and area 44. By contrast, motor cortex activation in writing tremor also included the contralateral premotor area (area 6) and ipsilateral prefrontal area (inferior frontal gyrus; areas 10, 44, and 47). Only patients with writing tremor showed a bilateral activation of the parietal lobule (area 40) with a more pronounced activation on the contralateral side. Furthermore, there was a bilateral activation of the cerebellum with a more pronounced area of activation on the ipsilateral side. CONCLUSIONS: Brain areas activated in writing tremor included activation patterns otherwise typical for both essential tremor and writer's cramp. Therefore a distinct category for writing tremor integrating hallmarks of essential tremor and writer's cramp is proposed.

Noninvasive direct stimulation of the cochlear nerve for functional MR imaging of the auditory cortex.

We herein present our preliminary experience with functional MR imaging of the direct electrical stimulation of the cochlear nerve using an MR imaging-compatible electrode placed in the external auditory meatus of five patients with binaural sensorineural hearing loss. The stimulator was placed outside the imager's bore, and the electrode produced virtually no susceptibility artifacts. In three of five patients, it was possible to activate the superior temporal gyrus during functional MR imaging. No side effects were observed.