Magnetic resonance imaging at 9.4 T: the Maastricht journey.

The 9.4 T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4 T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7 T. This article reviews some of the 9.4 T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4 T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4 T. Our experience shows that, while considerable effort was required compared to our 7 T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Ultra-high resolution blood volume fMRI and BOLD fMRI in humans at 9.4 T: Capabilities and challenges.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

Estimating and eliminating the excitation errors in bipolar gradient composite excitations caused by radiofrequency-gradient delay: Example of bipolar spokes pulses in parallel transmission.

PURPOSE: To eliminate a slice-position-dependent excitation error commonly observed in bipolar-gradient composite excitations such as spokes pulses in parallel transmission. THEORY AND METHODS: An undesired timing delay between subpulses in the composite pulse and their bipolar slice-selective gradient is hypothesized to cause the error. A mathematical model is presented here to relate this mismatch to an induced slice-position-dependent phase difference between the subpulses. A new navigator method is proposed to measure the timing mismatch and eliminate the error. This is demonstrated at 7 Tesla with flip-angle maps measured by a presaturation turbo-flash sequence and in vivo images acquired by a simultaneous multislice/echo-planar imaging (SMS-EPI) sequence. RESULTS: Error-free flip-angle maps were obtained in two ways: 1) by correcting the time delay directly and 2) by applying the corresponding slice-position-dependent phase differences to the subpulses. This confirms the validity of the mathematical description. The radiofrequency (RF)-gradient delay measured by the navigator method was of 6.3 µs, which agreed well with the estimate from flip-angle maps at different delay times. By applying the timing correction, accurately excited EPI images were acquired with bipolar dual-spokes SMS-2 excitations. CONCLUSION: An effective correction is proposed to mitigate slice-position-dependent errors in bipolar composite excitations caused by undesired RF-gradient timing delays. Magn Reson Med 78:1883-1890, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High-resolution gradient-recalled echo imaging at 9.4T using 16-channel parallel transmit simultaneous multislice spokes excitations with slice-by-slice flip angle homogenization.

PURPOSE: In order to fully benefit from the improved signal-to-noise and contrast-to-noise ratios at 9.4T, the challenges of B1+ inhomogeneity and the long acquisition time of high-resolution 2D gradient-recalled echo (GRE) imaging were addressed. THEORY AND METHODS: Flip angle homogenized excitations were achieved by parallel transmission (pTx) of 3-spoke pulses, designed by magnitude least-squares optimization in a slice-by-slice fashion; the acquisition time reduction was achieved by simultaneous multislice (SMS) pulses. The slice-specific spokes complex radiofrequency scaling factors were applied to sinc waveforms on a per-channel basis and combined with the other pulses in an SMS slice group to form the final SMS-pTX pulse. Optimal spokes locations were derived from simulations. RESULTS: Flip angle maps from presaturation TurboFLASH showed improvement of flip angle homogenization with 3-spoke pulses over CP-mode excitation (normalized root-mean-square error [NRMSE] 0.357) as well as comparable excitation homogeneity across the single-band (NRMSE 0.119), SMS-2 (NRMSE 0.137), and SMS-3 (NRMSE 0.132) 3-spoke pulses. The application of the 3-spoke SMS-3 pulses in a 48-slice GRE protocol, which has an in-plane resolution of 0.28 × 0.28 mm, resulted in a 50% reduction of scan duration (total acquisition time 6:52 min including reference scans). CONCLUSION: Time-efficient flip angle homogenized high-resolution GRE imaging at 9.4T was accomplished by using slice-specific SMS-pTx spokes excitations. Magn Reson Med 78:1050-1058, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Volumetric imaging with homogenised excitation and static field at 9.4 T.

OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner. MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively. RESULTS: Over six in vivo acquisitions, the B0-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 ± 0.9 to 9.2 ± 0.7 % with all B 1 (+)  voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image. CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.

Technical feasibility of integrating 7 T anatomical MRI in image-guided radiotherapy of glioblastoma: a preparatory study.

OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. MATERIALS AND METHODS: The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. RESULTS: The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was ≤2 mm. CONCLUSION: Integration of high-quality and geometrically-reliable 7 T MR images into neurosurgical navigation and RTP software is technically feasible and safe.

Thermal simulations in the human head for high field MRI using parallel transmission.

PURPOSE: To investigate, via numerical simulations, the compliance of the specific absorption rate (SAR) versus temperature guidelines for the human head in magnetic resonance imaging procedures utilizing parallel transmission at high field. MATERIALS AND METHODS: A combination of finite element and finite-difference time-domain methods was used to calculate the evolution of the temperature distribution in the human head for a large number of parallel transmission scenarios. The computations were performed on a new model containing 20 anatomical structures. RESULTS: Among all the radiofrequency field exposure schemes simulated, the recommended 39°C maximum local temperature was never exceeded when the local 10-g average SAR threshold was reached. On the other hand, the maximum temperature barely complied with its guideline when the global SAR reached 3.2 W/kg. The maximal temperature in the eye could very well rise by more than 1°C in both cases. CONCLUSION: Considering parallel transmission, the recommended values of local 10-g SAR may remain a relevant metric to ensure that the local temperature inside the human head never exceeds 39°C, although it can lead to rises larger than 1°C in the eye. Monitoring temperature instead of SAR can provide increased flexibility in pulse design for parallel transmission.

Ultra-high field spinal cord MRI in multiple sclerosis: Where are we standing? A literature review.

Magnetic resonance imaging (MRI) is a cornerstone in multiple sclerosis (MS) diagnostics and monitoring. Ultra-high field (UHF) MRI is being increasingly used and becoming more accessible. Due to the small diameter and mobility of the spinal cord, imaging this structure at ultra-high fields poses additional challenges compared to brain imaging. Here we review the potential benefits for the MS field by providing a literature overview of the use UHF spinal cord MRI in MS research and we elaborate on the challenges that are faced. Benefits include increased signal- and contrast-to-noise, enabling for higher spatial resolutions, which can improve MS lesion sensitivity in both the spinal white matter as well as grey matter. Additionally, these benefits can aid imaging of microstructural abnormalities in the spinal cord in MS using advanced MRI techniques like functional imaging, MR spectroscopy and diffusion-based techniques. Technical challenges include increased magnetic field inhomogeneities, distortions from physiological motion and optimalisation of sequences. Approaches including parallel imaging techniques, real time shimming and retrospective compensation of physiological motion are making it increasingly possible to unravel the potential of spinal cord UHF MRI in the context of MS research.

Direct visualization of non-human primate subcortical nuclei with contrast-enhanced high field MRI.

Subcortical nuclei are increasingly targeted for deep brain stimulation (DBS) and for gene transfer to treat neurological and psychiatric disorders. For a successful outcome in patients, it is critical to place DBS electrodes or infuse viral vectors accurately within targeted nuclei. However current MRI approaches are still limited to localize brainstem and basal ganglia nuclei accurately. By combining ultra-high resolution structural MRI and contrast-enhanced MRI using iron oxide nanoparticles at high field (3T and 7T), we could precisely locate the subcortical nuclei, in particular the subthalamic nucleus in macaques, and validate this location by intracranial electrophysiological mapping. The present data pave the way to a clinical application.

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage. METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2* degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack. RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue. CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice.

Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.

Characterizing geometrical accuracy in clinically optimised 7T and 3T magnetic resonance images for high-precision radiation treatment of brain tumours.

BACKGROUND AND PURPOSE: In neuro-oncology, high spatial accuracy is needed for clinically acceptable high-precision radiation treatment planning (RTP). In this study, the clinical applicability of anatomically optimised 7-Tesla (7T) MR images for reliable RTP is assessed with respect to standard clinical imaging modalities. MATERIALS AND METHODS: System- and phantom-related geometrical distortion (GD) were quantified on clinically-relevant MR sequences at 7T and 3T, and on CT images using a dedicated anthropomorphic head phantom incorporating a 3D grid-structure, creating 436 points-of-interest. Global GD was assessed by mean absolute deviation (MADGlobal). Local GD relative to the magnetic isocentre was assessed by MADLocal. Using 3D displacement vectors of individual points-of-interest, GD maps were created. For clinically acceptable radiotherapy, 7T images need to meet the criteria for accurate dose delivery (GD < 1 mm) and present comparable GD as tolerated in clinically standard 3T MR/CT-based RTP. RESULTS: MADGlobal in 7T and 3T images ranged from 0.3 to 2.2 mm and 0.2-0.8 mm, respectively. MADLocal increased with increasing distance from the isocentre, showed an anisotropic distribution, and was significantly larger in 7T MR sequences (MADLocal = 0.2-1.2 mm) than in 3T (MADLocal = 0.1-0.7 mm) (p < 0.05). Significant differences in GD were detected between 7T images (p < 0.001). However, maximum MADLocal remained ≤1 mm within 68.7 mm diameter spherical volume. No significant differences in GD were found between 7T and 3T protocols near the isocentre. CONCLUSIONS: System- and phantom-related GD remained ≤1 mm in central brain regions, suggesting that 7T MR images could be implemented in radiotherapy with clinically acceptable spatial accuracy and equally tolerated GD as in 3T MR/CT-based RTP. For peripheral regions, GD should be incorporated in safety margins for treatment uncertainties. Moreover, the effects of sequence-related factors on GD needs further investigation to obtain RTP-specific MR protocols.

After over 200 years, 7 T magnetic resonance imaging reveals the foliate structure of the human corpus callosum in vivo.

OBJECTIVE: A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T. METHODS: 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined. RESULTS: The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC. CONCLUSION: The separate sets of data-the atlas of Klingler, anatomical images and second eigenvector images-all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.

Gadolinium-staining reveals amyloid plaques in the brain of Alzheimer's transgenic mice.

Detection of amyloid plaques in the brain by in vivo neuroimaging is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD) and evaluation of therapeutic efficacy. Here we describe a new method to detect amyloid plaques by in vivo magnetic resonance imaging (MRI) based on the intracerebroventricular injection of a nontargeted gadolinium (Gd)-based contrast agent, which rapidly diffuses throughout the brain and increases the signal and contrast of magnetic resonance (MR) images by shortening the T1 relaxation time. This gain in image sensitivity after in vitro and in vivo Gd staining significantly improves the detection and resolution of individual amyloid plaques in the cortex and hippocampus of AD transgenic mice. The improved image resolution is sensitive enough to demonstrate an age-dependent increase of amyloid plaque load and a good correlation between the amyloid load measured by µMRI and histology. These results provide the first demonstration that nontargeted Gd staining can enhance the detection of amyloid plaques to follow the progression of AD and to evaluate the activity of amyloid-lowering therapeutic strategies in longitudinal studies.

Signal and noise characteristics of SSFP FMRI: a comparison with GRE at multiple field strengths.

Recent work has proposed the use of steady-state free precession (SSFP) as an alternative to the conventional methods for obtaining functional MRI (FMRI) data. The contrast mechanism in SSFP is likely to be related to conventional FMRI signals, but the details of the signal changes may differ in important ways. Functional contrast in SSFP has been proposed to result from several different mechanisms, which are likely to contribute in varying degrees depending on the specific parameters used in the experiment. In particular, the signal dynamics are likely to differ depending on whether the sequence is configured to scan in the SSFP transition band or passband. This work describes experiments that explore the source of SSFP FMRI signal changes by comparing SSFP data to conventional gradient-recalled echo (GRE) data. Data were acquired at a range of magnetic field strengths and repetition times, for both transition band and passband methods. The signal properties of SSFP and GRE differ significantly, confirming a different source of functional contrast in SSFP. In addition, the temporal noise properties are significantly different, with important implications for SSFP FMRI sequence optimisation.

Strategies for improving the detection of fMRI activation in trigeminal pathways with cardiac gating.

Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI.

Detection of entorhinal layer II using 7Tesla [corrected] magnetic resonance imaging.

The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 microm isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease.