Search

OBJECTIVE: This study evaluates the inter-site and intra-site reproducibility of 7 Tesla brain imaging and compares it to literature values for other field strengths.MATERIALS AND METHODS: The same two subjects were imaged at eight different 7 T sites. MP2RAGE, TSE, TOF, SWI, EPI as well as B1 and B0 field maps were analyzed quantitatively to assess inter-site reproducibility. Intra-site reproducibility was measured with rescans at three sites.RESULTS: Quantitative measures of MP2RAGE scans showed high agreement. Inter-site and intra-site reproducibility errors were comparable to 1.5 and 3 T. Other sequences also showed high reproducibility between the sites, but differences were also revealed. The different RF coils used were the main source for systematic differences between the sites.CONCLUSION: Our results show for the first time that multi-center brain imaging studies of the supratentorial brain can be performed at 7 T with high reproducibility and similar reliability as at 3T. This study develops the basis for future large-scale 7 T multi-site studies.

PURPOSE: The quality and precision of post‐mortem MRI microscopy may vary depending on the embedding medium used. To investigate this, our study evaluated the impact of 5 widely used media on: (1) image quality, (2) contrast of high spatial resolution gradient-echo (T(1) and T(2)*-weighted) MR images, (3) effective transverse relaxation rate (R(2)*), and (4) quantitative susceptibility measurements (QSM) of post-mortem brain specimens. METHODS: Five formaldehyde-fixed brain slices were scanned using 7.0T MRI in: (1) formaldehyde solution (formalin), (2) phosphate-buffered saline (PBS), (3) deuterium oxide (D(2)O), (4) perfluoropolyether (Galden), and (5) agarose gel. SNR and contrast-to-noise ratii (SNR/CNR) were calculated for cortex/white matter (WM) and basal ganglia/WM regions. In addition, median R(2)* and QSM values were extracted from caudate nucleus, putamen, globus pallidus, WM, and cortical regions. RESULTS: PBS, Galden, and agarose returned higher SNR/CNR compared to formalin and D(2)O. Formalin fixation, and its use as embedding medium for scanning, increased tissue R(2)*. Imaging with agarose, D(2)O, and Galden returned lower R(2)* values than PBS (and formalin). No major QSM offsets were observed, although spatial variance was increased (with respect to R(2)* behaviors) for formalin and agarose. CONCLUSIONS: Embedding media affect gradient-echo image quality, R(2)*, and QSM in differing ways. In this study, PBS embedding was identified as the most stable experimental setup, although by a small margin. Agarose and Galden were preferred to formalin or D(2)O embedding. Formalin significantly increased R(2)* causing noisier data and increased QSM variance.

BackgroundRecent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance ofNCANvariation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.MethodSixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).ResultsIn patients,NCANrisk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.ConclusionsThis study is the first to describe an effect of theNCANrisk variant on brain structure. Our data show that theNCANrisk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest thatNCANis involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.

Purpose Most approaches for quantitative susceptibility mapping (QSM) are based on a forward model approximation that employs a continuous Fourier transform operator to solve a differential equation system. Such formulation, however, is prone to high-frequency aliasing. The aim of this study was to reduce such errors using an alternative dipole kernel formulation based on the discrete Fourier transform and discrete operators. Methods The impact of such an approach on forward model calculation and susceptibility inversion was evaluated in contrast to the continuous formulation both with synthetic phantoms and in vivo MRI data. Results The discrete kernel demonstrated systematically better fits to analytic field solutions, and showed less over-oscillations and aliasing artifacts while preserving low- and medium-frequency responses relative to those obtained with the continuous kernel. In the context of QSM estimation, the use of the proposed discrete kernel resulted in error reduction and increased sharpness. Conclusion This proof-of-concept study demonstrated that discretizing the dipole kernel is advantageous for QSM. The impact on small or narrow structures such as the venous vasculature might by particularly relevant to high-resolution QSM applications with ultra-high field MRI – a topic for future investigations. The proposed dipole kernel has a straightforward implementation to existing QSM routines.

Through the combined use of (18)F-fallypride positron emission tomography and magnetic resonance imaging this study examined the neural mechanisms underlying the attentional deficits associated with attention deficit/hyperactivity disorder and their potential reversal with a single therapeutic dose of methylphenidate. Sixteen adult patients with attention deficit/hyperactivity disorder and 16 matched healthy control subjects were positron emission tomography and magnetic resonance imaging scanned and tested on a computerized sustained attention task after oral methylphenidate (0.5 mg/kg) and placebo administration in a within-subject, double-blind, cross-over design. Although patients with attention deficit/hyperactivity disorder as a group showed significant attentional deficits and reduced grey matter volume in fronto-striato-cerebellar and limbic networks, they had equivalent D2/D3 receptor availability and equivalent increases in endogenous dopamine after methylphenidate treatment to that observed in healthy control subjects. However, poor attentional performers drawn from both the attention deficit/hyperactivity disorder and the control groups had significantly reduced left caudate dopamine activity. Methylphenidate significantly increased dopamine levels in all nigro-striatal regions, thereby normalizing dopamine levels in the left caudate in low performers. Behaviourally, methylphenidate improved sustained attention in a baseline performance-dependent manner, irrespective of diagnosis. This finding was accompanied by an equally performance-dependent effect of the drug on dopamine release in the midbrain, whereby low performers showed reduced dopamine release in this region. Collectively, these findings support a dimensional model of attentional deficits and underlying nigro-striatal dopaminergic mechanisms of attention deficit/hyperactivity disorder that extends into the healthy population. Moreover, they confer midbrain dopamine autoreceptors a hitherto neglected role in the therapeutic effects of oral methylphenidate in attention deficit/hyperactivity disorder. The absence of significant case-control differences in D2/D3 receptor availability (despite the observed relationships between dopamine activity and attention) suggests that dopamine dysregulation per se is unlikely to be the primary cause underlying attention deficit/hyperactivity disorder pathology in adults. This conclusion is reinforced by evidence of neuroanatomical changes in the same set of patients with attention deficit/hyperactivity disorder.

Parallel transmission (pTx) technology, despite its great potential to mitigate the transmit field inhomogeneity problem in magnetic resonance imaging at ultra-high field (UHF), suffers from a cumbersome calibration procedure, thereby making the approach problematic for routine use. The purpose of this work is to demonstrate on two different 7T systems respectively equipped with 8-transmit-channel RF coils from two different suppliers (Rapid-Biomed and Nova Medical), the benefit of so-called universal pulses (UP), optimized to produce uniform excitations in the brain in a population of adults and making unnecessary the calibration procedures mentioned above. Non-selective and slice-selective UPs were designed to return homogeneous excitation profiles throughout the brain simultaneously on a group of ten subjects, which then were subsequently tested on ten additional volunteers in magnetization prepared rapid gradient echo (MPRAGE) and multi-slice gradient echo (2D GRE) protocols. The results were additionally compared experimentally with the standard non-pTx circularly-polarized (CP) mode, and in simulation with subject-specific tailored excitations. For both pulse types and both coils, the UP mode returned a better signal and contrast homogeneity than the CP mode. Retrospective analysis of the flip angle (FA) suggests that the FA deviation from the nominal FA on average over a healthy adult population does not exceed 11% with the calibration-free parallel-transmit pulses whereas it goes beyond 25% with the CP mode. As a result the universal pulses designed in this work confirm their relevance in 3D and 2D protocols with commercially available equipment. Plug-and-play pTx implementations henceforth become accessible to exploit with more flexibility the potential of UHF for brain imaging.

Implementing new magnetic resonance experiments, or sequences, often involves extensive programming on vendor-specific platforms, which can be time consuming and costly. This situation is exacerbated when research sequences need to be implemented on several platforms simultaneously, for example, at different field strengths. This work presents an alternative programming environment that is hardware-independent, open-source, and promotes rapid sequence prototyping.A novel file format is described to efficiently store the hardware events and timing information required for an MR pulse sequence. Platform-dependent interpreter modules convert the file to appropriate instructions to run the sequence on MR hardware. Sequences can be designed in high-level languages, such as MATLAB, or with a graphical interface. Spin physics simulation tools are incorporated into the framework, allowing for comparison between real and virtual experiments.Minimal effort is required to implement relatively advanced sequences using the tools provided. Sequences are executed on three different MR platforms, demonstrating the flexibility of the approach.A high-level, flexible and hardware-independent approach to sequence programming is ideal for the rapid development of new sequences. The framework is currently not suitable for large patient studies or routine scanning although this would be possible with deeper integration into existing workflows. Magn Reson Med 77:1544-1552, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusion tensor imaging (DTI) detects microstructural changes of the cerebral white matter in Alzheimer's disease (AD). The use of DTI for the diagnosis of AD in a multicenter setting has not yet been investigated. We used voxel-based analysis of fractional anisotropy, mean diffusivity, and grey matter volumes from multimodal magnetic resonance imaging data of 137 AD patients and 143 healthy elderly controls collected across 9 different scanners. We compared different univariate analysis approaches to model the effect of scanner, including a linear model across all scans with a scanner covariate, a random effects model with scanner as a random variable as well as a voxel-based meta-analysis. We found significant reduction of fractional anisotropy and significant increase of mean diffusivity in core areas of AD pathology including corpus callosum, medial and lateral temporal lobes, as well as fornix, cingulate gyrus, precuneus, and prefrontal lobe white matter. Grey matter atrophy was most pronounced in medial and lateral temporal lobe as well as parietal and prefrontal association cortex. The effects of group were spatially more restricted with random effects modeling of scanner effects compared to simple pooled analysis. All three analysis approaches yielded similar accuracy of group separation in block-wise cross-validated logistic regression. Our results suggest similar effects of center on group separation based on different analysis approaches and confirm a typical pattern of cortical and subcortical microstructural changes in AD using a large multimodal multicenter data set.

In the endeavor to understand how our brains enable our multifaceted memories, much controversy surrounds the contributions of the hippocampus and perirhinal cortex (PrC). Here we recorded functional magnetic resonance imaging (fMRI) in healthy controls and intracranial Electroencephalography (EEG) in patients during the same recognition memory paradigm. Although conventional fMRI analysis showed indistinguishable roles of the hippocampus and PrC in familiarity-based item recognition and recollection-based source retrieval, event-related fMRI and EEG time-courses revealed a clear temporal dissociation of memory signals within and across these regions. Whereas an early source retrieval effect was followed by a late, post-decision item novelty effect in hippocampus, an early item novelty effect was followed by a sustained source retrieval effect in PrC. Although factors like memory strength were not experimentally controlled, the temporal pattern across regions suggests that a rapid item recognition signal in PrC triggers a source retrieval process in the hippocampus, which in turn recruits PrC representations/mechanisms – evidenced here by increased hippocampal-PrC coupling during source recognition.

Purpose Relaxation times, transmit homogeneity, signal-to-noise ratio (SNR) and parallel imaging g-factor were determined in the human brain at 3T, 7T, and 9.4T, using standard, tight-fitting coil arrays. Methods The same human subjects were scanned at all three field strengths, using identical sequence parameters and similar 31- or 32-channel receive coil arrays. The SNR of three-dimensional (3D) gradient echo images was determined using a multiple replica approach and corrected with measured flip angle and T2* distributions and the T1 of white matter to obtain the intrinsic SNR. The g-factor maps were derived from 3D gradient echo images with several GRAPPA accelerations. Results As expected, T1 values increased, T2* decreased and the B1-homogeneity deteriorated with increasing field. The SNR showed a distinctly supralinear increase with field strength by a factor of 3.10 ± 0.20 from 3T to 7T, and 1.76 ± 0.13 from 7T to 9.4T over the entire cerebrum. The g-factors did not show the expected decrease, indicating a dominating role of coil design. Conclusion In standard experimental conditions, SNR increased supralinearly with field strength (SNR ∼ B01.65). To take full advantage of this gain, the deteriorating B1-homogeneity and the decreasing T2* have to be overcome. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

PLOS ONE 11(12), e0166647 (2016). doi:10.1371/journal.pone.0166647, Published by PLOS, San Francisco, California, US

Background The European Alzheimer's Disease Consortium and Alzheimer's Disease Neuroimaging Initiative (ADNI) Harmonized Protocol (HarP) is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging (MRI) that can be used as the standard of truth to train new tracers, and to validate automated segmentation algorithms. Training requires large and representative data sets of segmented hippocampi. This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms. Methods Sixty-eight 1.5 T and 67 3 T volumetric structural ADNI scans from different subjects, balanced by age, medial temporal atrophy, and scanner manufacturer, were segmented by five qualified HarP tracers whose absolute interrater intraclass correlation coefficients were 0.953 and 0.975 (left and right). Labels were validated as HarP compliant through centralized quality check and correction. Results Hippocampal volumes (mm 3 ) were as follows: controls: left = 3060 (standard deviation [SD], 502), right = 3120 (SD, 897); mild cognitive impairment (MCI): left = 2596 (SD, 447), right = 2686 (SD, 473); and Alzheimer's disease (AD): left = 2301 (SD, 492), right = 2445 (SD, 525). Volumes significantly correlated with atrophy severity at Scheltens' scale (Spearman's ρ = P = Cerebrospinal fluid spaces (mm 3 ) were as follows: controls: left = 23 (32), right = 25 (25); MCI: left = 15 (13), right = 22 (16); and AD: left = 11 (13), right = 20 (25). Five subjects (3.7%) presented with unusual anatomy. Conclusions This work provides reference hippocampal labels for the training and certification of automated segmentation algorithms. The publicly released labels will allow the widespread implementation of the standard segmentation protocol.

BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P < .001), and physiological variability (49.2%, P < .001).ConclusionsThe HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms. published

To demonstrate the effect of gradient nonlinearity and develop a method for correction of gradient nonlinearity artifacts in prospective motion correction (Mo-Co).Nonlinear gradients can induce geometric distortions in magnetic resonance imaging, leading to pixel shifts with errors of up to several millimeters, thereby interfering with precise localization of anatomical structures. Prospective Mo-Co has been extended by conventional gradient warp correction applied to individual phase encoding steps/groups during the reconstruction. The gradient-related displacements are approximated using spherical harmonic functions. In addition, the combination of this method with a retrospective correction of the changes in the coil sensitivity profiles relative to the object (augmented sensitivity encoding (SENSE) reconstruction) was evaluated in simulation and experimental data.Prospective Mo-Co under gradient fields and coils sensitivity inconsistencies results in residual blurring, spatial distortion, and coil sensitivity mismatch artifacts. These errors can be considerably mitigated by the proposed method. High image quality with very little remaining artifacts was achieved after a few iterations. The relative image errors decreased from 25.7% to below 17.3% after 10 iterations.The combined correction of gradient nonlinearity and sensitivity map variation leads to a pronounced reduction of residual motion artifacts in prospectively motion-corrected data.

The amygdala and the hippocampus are two adjacent structures in the medial temporal lobe that have been broadly investigated in functional and structural neuroimaging due to their central importance in sensory perception, emotion, and memory. Exact demarcation of the amygdalo‐hippocampal border (AHB) is, however, difficult in conventional structural imaging. Recent evidence suggests that, due to this difficulty, functional activation sites with high probability of being located in the hippocampus may erroneously be assigned to the amygdala, and vice versa. In the present study, we investigated the potential of ultra‐high‐field magnetic resonance imaging (MRI) in single sessions for detecting the AHB in humans. We show for the first time the detailed structure of the AHB as it can be visualized in T1‐weighted 7T in vivo images at 0.5‐mm(3) isotropic resolution. Compared to data acquired at 3T, 7T images revealed considerably more structural detail in the AHB region. Thus, we observed a striking inter‐hemispheric and interindividual variability of the exact anatomical configuration of the AHB that points to the necessity of individual imaging of the AHB as a prerequisite for accurate anatomical assignment in this region. The findings of the present study demonstrate the usefulness of ultra‐high‐field structural MRI to resolve anatomical ambiguities of the human AHB. Highly accurate morphometric and functional investigations in this region at 7T may allow addressing such hitherto unexplored issues as whether the structural configuration of the AHB is related to functional differences in amygdalo‐hippocampal interaction. Hum Brain Mapp 35:4316–4329, 2014. © 2014 Wiley Periodicals, Inc.

Prospective motion correction of magnetic resonance (MR) scans commonly uses an external device, such as a camera, to track the pose of the organ of interest. However, in order for external tracking data to be translated into the MR scanner reference frame, the pose of the camera relative to the MR scanner must be known accurately. Here, we describe a fast, accurate, non-iterative technique to determine the position of an external tracking device de novo relative to the MR reference frame.The method relies on imaging a sparse object that allows simultaneous tracking of arbitrary rigid body transformations in the reference frame of the magnetic resonance imaging (MRI) machine and that of the external tracking device.Large motions in the MRI reference frame can be measured using a sparse phantom with an accuracy of 0.2 mm, or approximately 1/10 of the voxel size. By using a dual quaternion algorithm to solve the calibration problem, a good camera calibration can be achieved with fewer than six measurements. Further refinements can be achieved by applying the method iteratively and using motion correction feedback.Independent tracking of a series of movements in two reference frames allows for an analytical solution to the hand-eye-calibration problem for various motion tracking setups in MRI.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti-NMDAR encephalitis.Twenty-four patients with established diagnosis of anti-NMDAR encephalitis and age- and gender-matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel-based morphometry.Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls.Anti-NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti-NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti-NMDAR encephalitis.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a widely used technique for assessing tissue physiology. Spoiled gradient echo (SPGR) pulse sequences are one of the most common methods for acquisition of DCE-MRI data, providing high temporal and spatial resolution with strong T(1)-weighting. Conversion of SPGR signal to concentration is briefly reviewed, and a new closed-form expression for concentration measurement uncertainty for finite signal-to-noise ratio (SNR) and baseline scan time is derived. This result is applicable to arbitrary concentration-dependent relaxation rate and is valid over the same domain as the theoretical SPGR signal equation. Expressions for the lower and upper bounds on measurable concentration are also derived. The existence of a concentration- and tissue-dependent optimal flip angle that minimizes concentration uncertainty is demonstrated and it is shown that, for clinically relevant pulse sequence parameters, this optimal flip angle is significantly larger than the corresponding Ernst angle. Analysis of three pulse sequences from the DCE-MRI literature shows that optimization of flip angle using the methods discussed here leads to potential improvements of 10-1166% in effective SNR over the 0.5-5.0 mM concentration range with minimal or no loss of measurement accuracy down to 0.1 mM. In vivo data from three study patients provide further support for our theoretical expression for concentration measurement uncertainty, with predicted and experimental estimates agreeing to within +/- 30%. Equations for concentration bias resulting from biases in flip angle and from pre-contrast relaxation time and contrast relaxivity (both longitudinal and transverse) are also derived in closed-form. The resulting equations show the potential for significant contributions to bias in concentration measurement arising from even relatively small mis-specification of flip angle and/or pre-contrast longitudinal relaxation time, particularly at high contrast concentrations.

Acoustic noise generated by the MR scanner gradient system during fMRI studies of auditory function is a very significant potential confound. Despite these deleterious effects, fMRI of the auditory cortex has been successful and numerous practitioners have circumvented the problem of acoustic masking noise. In the context of auditory cortex fMRI, the sequence repeat time (TR) has the effect of altering the length of time during which the scanner is quiet. Indeed, the move to whole-brain fMRI makes the problem of acoustic noise more acute and points to the need to examine the role of TR and its influence on the BOLD signal. The aim of this study was to examine the effect of varying the TR time on activation of auditory cortex during presentation and performance of a phonetic discrimination task. The results presented here demonstrate that the influence of sequence repeat time is considerable. For a short repeat time it is likely that the noise from the scanner is a significant mask and hinders accurate task performance. At the other extreme, a repeat time of 9 s is also suboptimal, probably due to attentional effects and lack of concentration and not least because of the longer overall measurement times. The results of this study point to a complicated interplay between psychophysical factors as well as physical parameters; attention, acoustic noise, total duration of the experiment, consideration of the volume of acquisition, and overall difficulty of the task have to be assessed and balanced. For the paradigm used here, the results suggest an optimal TR of around 6 s for a 16-slice acquisition.