ABSTRACT Purpose To enable sodium SWIFT imaging, which is a zero‐echo time imaging technique, at ultra‐high magnetic fields through the development of custom electronics hardware, and to showcase this capability with in vivo imaging results. Methods The custom hardware developed consists of a high‐speed optical trigger with 10 ns resolution, an in‐bore PIN diode driver capable of sourcing high current, and RF switches (both an in‐line switchable attenuator and transmit/receive switch) optimized to achieve sub‐microsecond switching speeds while also producing isolation between the transmitter and receiver. Results Practical switching speeds of 0.6 μs (receive to transmit) and 1.7 μs (transmit to receive) are achieved on the RF switches, limited by transient‐induced spurious emissions from the low noise amplifier. Transmit to receive isolation of 115 dB is achieved over a 1 MHz bandwidth, with 120 dB of isolation at the Larmor frequency. This was crucial to suppress unblanked RFPA noise. SWIFT images of the human wrist with 1.5 mm isotropic resolution were acquired in less than 5 min to demonstrate the utility of sodium SWIFT imaging at ultra‐high field. SWIFT imaging signal‐to‐noise ratio in a reference phantom with heterogeneous sodium concentrations was comparable to ultra‐short echo time imaging, which provided assurance that hardware had achieved the necessary specifications. Conclusions The feasibility of sodium SWIFT imaging at ultra‐high field was established, and a musculoskeletal imaging application was demonstrated. The success of this work enables further development of SWIFT at high and ultra‐high fields for imaging of sodium, proton, and other nuclei.
PURPOSE:To demonstrate mesoscale whole-brain T2*-weighted (T2*w) MRI at 10.5 T, quantify R2* relaxation rate and magnetic susceptibility (χ), and evaluate T2*w contrast at such high field strength. METHODS:Multi-echo GRE (ME-GRE) data were collected in healthy adults at 0.5 mm isotropic resolution at 10.5 T. Whole-brain images were reconstructed with navigator-guided joint motion and field correction and were used for quantitative R2* and χ mapping. Regional R2* and χ values and R2* contrast were analyzed in volumetric regions of interest (ROIs) and intra-cortical surface-based ROIs. For comparison, ME-GRE data from the same subjects were acquired using a similar protocol at 7 T. RESULTS:High-quality whole-brain T2*w images were obtained, enabling R2* and χ mapping with delineation of fine-scale brain structures. Regional R2* analysis revealed a linear relationship between 10.5 T and 7 T R2* values with a slope of 1.52, in agreement with previously reported linear field dependency of R2*. Estimated χ values were field-independent in most brain regions under consideration except for the basal ganglia where χ was observed to be lower at 10.5 T than at 7 T. The normalized R2* contrast that is, the R2* difference normalized by the mean R2*, increased by about 3% between brain regions and 12% between cortical depths from 7 to 10.5 T. CONCLUSION:It is feasible to achieve high-quality mesoscale whole-brain T2*w MRI at 10.5 T and associated quantitative R2* and χ mapping. Our results may aid future optimization of anatomic T2*w brain MRI at ultrahigh field beyond 7 T.
PURPOSE:To enable sodium SWIFT imaging, which is a zero-echo time imaging technique, at ultra-high magnetic fields through the development of custom electronics hardware, and to showcase this capability with in vivo imaging results. METHODS:The custom hardware developed consists of a high-speed optical trigger with 10 ns resolution, an in-bore PIN diode driver capable of sourcing high current, and RF switches (both an in-line switchable attenuator and transmit/receive switch) optimized to achieve sub-microsecond switching speeds while also producing isolation between the transmitter and receiver. RESULTS:Practical switching speeds of 0.6 μs (receive to transmit) and 1.7 μs (transmit to receive) are achieved on the RF switches, limited by transient-induced spurious emissions from the low noise amplifier. Transmit to receive isolation of 115 dB is achieved over a 1 MHz bandwidth, with 120 dB of isolation at the Larmor frequency. This was crucial to suppress unblanked RFPA noise. SWIFT images of the human wrist with 1.5 mm isotropic resolution were acquired in less than 5 min to demonstrate the utility of sodium SWIFT imaging at ultra-high field. SWIFT imaging signal-to-noise ratio in a reference phantom with heterogeneous sodium concentrations was comparable to ultra-short echo time imaging, which provided assurance that hardware had achieved the necessary specifications. CONCLUSIONS:The feasibility of sodium SWIFT imaging at ultra-high field was established, and a musculoskeletal imaging application was demonstrated. The success of this work enables further development of SWIFT at high and ultra-high fields for imaging of sodium, proton, and other nuclei.
Introduction: Ultra-high-field magnetic resonance (MR) systems (7 T and 9.4 T) offer the ability to probe human brain metabolism with enhanced precision. Here, we present the preliminary findings from 3D MR spectroscopic imaging (MRSI) of the human brain conducted with the world's first 10.5 T whole-body MR system. Methods: Employing a custom-built 16-channel transmit and 80-channel receive MR coil at 10.5 T, we conducted MRSI acquisitions in six healthy volunteers to map metabolic compounds in the human cerebrum in vivo. Three MRSI protocols with different matrix sizes and scan times (4.4 × 4.4 × 4.4 mm³: 10 min, 3.4 × 3.4 × 3.4 mm³: 15 min, and 2.75×2.75×2.75 mm³: 25 min) were tested. Concentric ring trajectories were utilized for time-efficient encoding of a spherical 3D k-space with ∼4 kHz spectral bandwidth. B0/B1 shimming was performed based on respective field mapping sequences and anatomical T1-weighted MRI were obtained. Results: By combining the benefits of an ultra-high-field system with the advantages of free-induction-decay (FID-)MRSI, we present the first metabolic maps acquired at 10.5 T in the healthy human brain at both high (voxel size of 4.4³ mm³) and ultra-high (voxel size of 2.75³ mm³) isotropic spatial resolutions. Maps of 13 metabolic compounds (aspartate, choline compounds and creatine + phosphocreatine, γ-aminobutyric acid (GABA), glucose, glutamine, glutamate, glutathione, myo-inositol, scyllo-inositol, N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), taurine) and macromolecules were obtained individually. The spectral quality was outstanding in the parietal and occipital lobes, but lower in other brain regions such as the temporal and frontal lobes. The average total NAA (tNAA = NAA + NAAG) signal-to-noise ratio over the whole volume of interest was 12.1± 8.9 and the full width at half maximum of tNAA was 24.7± 9.6 Hz for the 2.75 × 2.75 × 2.75 mm³ resolution. The need for an increased spectral bandwidth in combination with spatio-spectral encoding imposed significant challenges on the gradient system, but the FID approach proved very robust to field inhomogeneities of ∆B0 = 45 ± 38 Hz (frequency offset ± spatial STD) and B1+ = 65 ± 11° within the MRSI volume of interest. Discussion: These preliminary findings highlight the potential of 10.5 T MRSI as a powerful imaging tool for probing cerebral metabolism. By providing unprecedented spatial and spectral resolution, this technology could offer a unique view into the metabolic intricacies of the human brain, but further technical developments will be necessary to optimize data quality and fully leverage the capabilities of 10.5 T MRSI.
Mapping brain connectivity in primates remains a major challenge due to difficulties in resolving microscopic white matter architecture, while maintaining whole-brain coverage. Increasing imaging spatial resolution is key for disambiguating fiber configurations within smaller anatomical volumes. Here, we present developments that allow high-resolution diffusion MRI of the macaque brain, both in vivo and ex vivo, using one of the world's highest-field human MRI scanners operating at 10.5 Tesla. Our approach achieves data of highest reported resolutions for this field strength and scanner type, (750 μm)3 in vivo and (400 μm)3 ex vivo, with diffusion weighting up to b = 6000 s/mm2. We detail methodological advances in data acquisition, image reconstruction, processing and whole-brain tractography that overcome critical challenges associated with ultra-high-field imaging. This work establishes a new benchmark for high-resolution neuroimaging at 10.5T, paving the way for comparable human studies and enabling analyses of brain connectivity across species and tissue states at unprecedented detail. The dataset, along with all processing pipelines, containerised workflows, and reusable web services, is openly shared to support reproducibility and future integration with microscopy for studying white matter microstructure and connections at the mesoscale. ### Competing Interest Statement The authors have declared no competing interest. NIH Common Fund, UM1NS132207 European Research Council, 101000969 Sir Henry
Diffusion MRI provides a non-invasive probe of local fibre bundles and long-range anatomical connections to characterise the structural connectome. One way to achieve very high spatial resolution diffusion MRI data for connectivity investigations is to scan ex-vivo brains over many hours or days, ideally at ultra-high field strength to boost signal levels. However, conventional diffusion MRI acquisition techniques do not generally deliver good data quality for the challenging conditions of ex-vivo tissue, characterised by reduced diffusivities and relaxation times when compared to in vivo. In this work, we investigate the potential of the diffusion-weighted steady-state free precession (DW-SSFP) sequence for ex vivo diffusion imaging of the macaque brain using a 10.5 T human MRI scanner with a conventional ( G max = 70 mT/m ) gradient set. SNR-efficiency optimisations incorporating experimental relaxation times demonstrate that the DW-SSFP sequence is predicted to achieve improved or similar SNR efficiency compared to a diffusion-weighted spin- and stimulated-echo sequence. Importantly, DW-SSFP can achieve this with the additional benefit of negligible geometric distortions, unlike conventional diffusion MRI using an echo-planar imaging readout. Using optimised DW-SSFP sequence parameters, we propose a protocol at 0.4 mm isotropic resolution using a two-shell multi-orientation protocol (effective b-values of 3200 s/mm2 and 5600 s/mm2). We fit the data using Tensor, Ball and 3-Sticks and Constrained Spherical Deconvolution signal representations. The results demonstrate high-quality diffusivity estimates across the entire brain with the ability to resolve multiple fibre populations in challenging crossing-fibre regions. The data will be made fully open source and multimodal as part of the Center for Mesoscale Connectomics, providing a resource for future connectivity investigations.
Personalized functional brain developmental trajectories can be studied with Precision Functional Mapping (PFM). Our previous work has demonstrated that PFM can be achieved in infants despite rapid brain growth. However, even with extensive data collection (up to 1 hour of fMRI), the reliability and precision of these maps remain lower than those observed in youth and adults - particularly within subcortical structures. In this work we demonstrate the utility of high-field 7T MRI compared to 3T MRI for facilitating PFM in infants. We showcase data from multi-echo fMRI acquisitions in the same infants at both 7T and 3T and demonstrate that 7T imaging in infants is safe and feasible with our subject-specific safety workflow. Moreover, we demonstrate that the use of a higher magnetic field strength affords a spatial resolution more appropriately matched to infants' smaller head and brain sizes, yielding notable improvements in data quality, especially for PFM. The increase in both spatial precision and reliability also suggests that 7T MRI can reduce the amount of data required for PFM. Last, we show how ultra-high field imaging can help us study the development of subcortical-to-cortical connectivity patterns, crucial for understanding brain development during this developmental window. 7T MRI is a promising new avenue for developmental cognitive neuroscience.
PURPOSE:To develop and characterize a 128-channel head array for brain imaging at 10.5 T, evaluate signal-to-noise ratio (SNR) relative to ultimate intrinsic SNR (uiSNR) and lower field strengths, and demonstrate human brain anatomical and functional imaging with this unique magnetic field and high-channel-count array. METHODS:The coil consists of a 16-channel self-decoupled loop transmit/receive (16Tx/Rx) array with a 112-loop receive-only (Rx) insert. Interactions between the 16Tx/Rx array and the 112Rx insert were mitigated using coaxial cable traps placed every 1/16 of a wavelength on each feed cable, locating most preamplifier boards outside the transmitter field, and miniaturizing those placed directly on individual coils. RESULTS:The effect of the 112Rx insert on the circumscribing 16Tx/Rx array was minimized, leading to similar transmit field maps obtained experimentally with and without the 112Rx array in place and by electromagnetic simulations of the 16Tx/Rx array alone. The 128-channel array captured 77% of uiSNR centrally. Significantly higher 1/g-factor values across the whole brain was achieved compared with 7 T. Excellent SNR, high parallel-imaging performance, and minimal Tx-Rx interactions collectively facilitated acquisition of high-quality, high-resolution, proof-of-concept functional and anatomical images, including with power-demanding sequences in the human brain. CONCLUSIONS:Counterintuitive to expectations based on magnetic fields less than or equal to 7 T, the higher channel counts provided SNR gains centrally, capturing about 80% uiSNR. The fraction of uiSNR achieved centrally in 64Rx, 80Rx, and 128Rx arrays suggested that a plateau was being reached at 80%. At this plateau, B0-dependent SNR gains for 10.5 T relative to 7 T were approximately linear to quadratic for the periphery and the center, respectively.
PURPOSE:Toward pushing the boundaries of ultrahigh fields for human brain imaging, we wish to evaluate experimentally achievable SNR relative to ultimate intrinsic SNR (uiSNR) at 10.5T, develop design strategies toward approaching the latter, quantify magnetic field-dependent SNR gains, and demonstrate the feasibility of whole-brain, high-resolution human brain imaging at this uniquely high field strength. METHODS:A dual row 16-channel self-decoupled transmit (Tx) and receive (Rx) array was developed for 10.5T using custom Tx/Rx switches. A 64-channel receive-only array was built to fit into the 16-channel Tx/Rx array. Electromagnetic modeling and experiments were used to define safe operational power limits. Experimental SNR was evaluated relative to uiSNR at 10.5T and 7T. RESULTS:The 64-channel Rx array alone captured approximately 50% of the central uiSNR at 10.5T, while an identical array developed for 7T captured about 76% of uiSNR at 7T. The 16-channel Tx/80-channel Rx configuration brought the fraction of uiSNR captured at 10.5T to levels comparable to the 64-channel Rx array at 7T. SNR data displayed an approximate B 0 2 $$ {\mathrm{B}}_0^2 $$ dependence over a large central region when evaluated in the context of uiSNR. Whole-brain, high-resolution T 2 * $$ {\mathrm{T}}_2^{\ast } $$ -weighted and T1-weighted anatomical and gradient-recalled-echo BOLD-EPI functional MRI images were obtained at 10.5T for the first time with such an advanced array. CONCLUSION:We demonstrated the ability to approach the uiSNR at 10.5T over the human brain, achieving large SNR gains over 7T, currently the most commonly used ultrahigh-field platform. Whole-brain, high-resolution anatomical and EPI-based functional MRI data were obtained at 10.5T, illustrating the promise of greater than 10T fields in studying the human brain.
Purpose: Toward pushing the boundaries of ultrahigh fields for human brain imaging, we wish to evaluate experimentally achievable SNR relative to ultimate intrinsic SNR (uiSNR) at 10.5T, develop design strategies toward approaching the latter, quantify magnetic field-dependent SNR gains, and demonstrate the feasibility of whole-brain, high-resolution human brain imaging at this uniquely high field strength. Methods: A dual row 16-channel self-decoupled transmit (Tx) and receive (Rx) array was developed for 10.5T using custom Tx/Rx switches. A 64-channel receive-only array was built to fit into the 16-channel Tx/Rx array. Electromagnetic modeling and experiments were used to define safe operational power limits. Experimental SNR was evaluated relative to uiSNR at 10.5T and 7T. Results: The 64-channel Rx array alone captured approximately 50% of the central uiSNR at 10.5T, while an identical array developed for 7T captured about 76% of uiSNR at 7T. The 16-channel Tx/80-channel Rx configuration brought the fraction of uiSNR captured at 10.5T to levels comparable to the 64-channel Rx array at 7T. SNR data displayed an approximate B-0 (2) dependence over a large central region when evaluated in the context of uiSNR. Whole-brain, high-resolution T-2(& lowast;)-weighted and T- 1-weighted anatomical and gradient-recalled-echo BOLD-EPI functional MRI images were obtained at 10.5T for the first time with such an advanced array. Conclusion: We demonstrated the ability to approach the uiSNR at 10.5T over the human brain, achieving large SNR gains over 7T, currently the most commonly used ultrahigh-field platform. Whole-brain, high-resolution anatomical and EPI-based functional MRI data were obtained at 10.5T, illustrating the promise of greater than 10T fields in studying the human brain.
One of the most important new frontiers in the effort to improve the spatial resolution and accuracy of imaging of human brain activity is the recent development of greater than 10 Tesla magnetic fields. Here we present initial results for 10.5 Tesla Blood Oxygenation Level Dependent (BOLD) based functional brain imaging (fMRI) of the human brain acquired with previously unavailable or difficult to attain spatial resolutions and functional contrast. We present data obtained with nominal isotropic resolutions ranging from 0.65 to 0.35 mm for partial brain coverage for stimulus evoked responses, and 0.75 mm for whole brain coverage to capture the spontaneous fluctuations that are the source of functional connectivity measures. The increasingly higher nominal resolutions (i.e. smaller voxel volumes and dimensions) employed in image acquisition were shown to correspond to real gains in resolution using image reconstruction methods developed to minimize blurring. Existence of supralinear gains in stimulus-evoked percent signal change and major improvements in statistical significance were evident relative to 7 Tesla, the most advanced commercially available ultrahigh magnetic field platform currently employed in human brain studies. These results were feasible due to gains in intrinsic signal-to-noise ratio, BOLD contrast, and image acceleration provided by the uniquely high magnetic field of 10.5 Tesla, and the use of novel high channel count arrays to capture these gains. The results provide a preview of the potential that will be available in the new era of greater than 10 Tesla human functional imaging, particularly for mesoscale functional organizations and connectivity. ### Competing Interest Statement The authors have declared no competing interest.
Purpose:To develop and characterize the performance of a 128-channel head array for brain imaging at 10.5 tesla and evaluate the potential of brain imaging at this unique, >10 tesla magnetic field. Methods:The coil is composed of a 16-channel self-decoupled loop transmit/receive array with a 112-loop receive-only (Rx) insert. Interactions between the outer transmitter and the inner 112Rx insert were mitigated using coaxial cable traps placed every 1/16 of a wavelength on each feed cable, locating most preamplifier boards outside the transmitter field and miniaturizing those placed directly on individual coils. Results:The 128-channel array described herein achieved 77% of ultimate intrinsic SNR in the center of the brain. Transmit field maps obtained experimentally on a phantom with and without the receive array were similar and matched EM simulations, leading to FDA approval for human imaging. Anatomical and functional data, including with power demanding sequences, were acquired successfully on human volunteers. Conclusions:Counterintuitive to expectations based on magnetic fields ≤7T, the higher channel counts provided SNR gains centrally, capturing ∼80% uiSNR. Fraction of uiSNR achieved centrally in 64Rx, 80Rx, and 128Rx arrays suggested that a plateau was being reached at 80%. At this plateau, linear to approximately quadratic B 0 dependent SNR gains for the periphery and the center, respectively, were observed for 10.5T relative 7T.
Multichannel transmit (Tx) arrays are essential for ultra-high fields. In the absence of commercial options, such arrays must be built in-house. Prior to human imaging, however, safe operations limits for specific absorption rate (SAR) must be established. This is done using EM simulations, the accuracy of which has to be verified by comparing measured and simulated data. Unfortunately, EM simulations may not fully represent experimental conditions, especially for complex transmitter designs. In this work, we propose a numerical approach to determine uncertainties encountered in EM modeling that allows the determination of safe operation limits despite EM modeling errors.
With the development of accelerated acquisition protocols, it is possible to achieve functional brain mapping with submillimeter resolution. This permits studying the human brain at the mesoscopic scale. Typical submillimeter images measure 0.8 mm. isotropic voxels, barely enough to study human functional mesoscopic responses. Here we acquire functional images at 10.5 T with the unprecedented spatial resolution of 0.4 mm. isotropic voxels. Using NORDIC to suppress thermal noise, we demonstrate the feasibility of achieving meaningful brain mapping at these ultra-high resolutions, where single voxels contains but a few thousand cells, further bridging the gap between fMRI and optical imaging
Susceptibility-weighted imaging (SWI) and quantitative susceptibility mapping (QSM) have been shown to provide unique contrasts that can be used to study pathophysiologic changes of tissue magnetic susceptibility in various brain diseases. As magnetic susceptibility effects increase with the main field strength, there has been a rapidly growing interest in performing SWI and QSM at ultrahigh field (UHF) (7 Tesla and above). The aim of this study was to demonstrate how the use of the UHF of 10.5 Tesla may promote SWI and QSM of the human brain.
There has been an increasing interest to acquire high-resolution diffusion MRI at ultrahigh field (≥7 Tesla) due to the increased SNR and improved parallel imaging performance. To fully capitalize on the benefit of ultrahigh field, it is desirable to image with many receiver coils. In this study, we acquired slice-accelerated whole-brain 1.05-mm isotropic diffusion images on an FDA-approved 7 Tesla scanner (Siemens Terra) using a homemade 63-channel head RF array with various slice and in-plane accelerations. We found that the use of 63 channels can achieve higher acceleration factors (up to 9-fold acceleration in total) while maintaining the image quality.
Purpose: To combine a new two-stage N/2 ghost correction and an adapted L1-SPIRiT method for reconstruction of 7T highly accelerated whole-brain diffusion MRI (dMRI) using only autocalibration scans (ACS) without the need of additional single-band reference (SBref) scans. Methods: The proposed ghost correction consisted of a 3-line reference approach in stage 1 and the reference-free entropy method in stage 2. The adapted L1-SPIRiT method was formulated within the 3D k-space framework. Its efficacy was examined by acquiring two dMRI data sets at 1.05-mm isotropic resolutions with a total acceleration of 6 or 9 (i.e., 2-fold or 3-fold slice and 3-fold in-plane acceleration). Diffusion analysis was performed to derive DTI metrics and estimate fiber orientation distribution functions (fODFs). The results were compared with those of 3D k-space GRAPPA using only ACS, all in reference to 3D k-space GRAPPA using both ACS and SBref (serving as a reference). Results: The proposed ghost correction eliminated artifacts more robustly than conventional approaches. Our adapted L1-SPIRiT method outperformed 3D k-space GRAPPA when using only ACS, improving image quality to what was achievable with 3D k-space GRAPPA using both ACS and SBref scans. The improvement in image quality further resulted in an improvement in estimation performances for DTI and fODFs. Conclusion: The combination of our new ghost correction and adapted L1-SPIRiT method can reliably reconstruct 7T highly accelerated whole-brain dMRI without the need of SBref scans, increasing acquisition efficiency and reducing motion sensitivity.
The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3 T. Twenty-nine young adults (age 21 ± 1 years) and 24 older adults (age 74 ± 3 years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3 T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.
Diffusion-weighted MRI (DWI) suffers from the intrinsic low SNR, especially for high-resolution and/or high b-value acquisitions. Thus, denoising methods are critical for diffusion images. Recently, increasing attention has been paid to complex DWI image denoising. Here, we propose a 2-step non-local low-rank joint denoising method to process complex-valued DWI images. Simulation data and in-vivo brain data were used to test the proposed method. The results showed that the proposed method may further improve the image quality.
PurposeThe aim of the study is to optimize the performance of localized 1H MRS sequences at 3T, using the entire spin system of N‐acetyl aspartate (NAA) as an example of the large chemical shift spread of all the metabolites routinely detected in vivo, including the amide region. We specifically focus on the design of the suitable broadband excitation radiofrequency (RF) pulses to minimize chemical shift artifacts.MethodsThe performance of the excitation and refocusing pulse shapes is evaluated with respect to NAA localization. Two new excitation RF pulses are developed to achieve optimized performance in the brain using single‐voxel 1H MRS at 3T. Numerical simulations and in vivo experiments are carried out to demonstrate the performance of the RF pulses.ResultsNew excitation RF pulses with the same B1 requirements but larger excitation bandwidth (up to a factor of 2) are shown to significantly reduce localization artifacts. The large frequency spread of the entire NAA spin system necessitates the use of broadband excitation and refocusing pulses for MRS at 3T.ConclusionTo minimize chemical shift artifacts of metabolic compounds with spins in the amide area (>5 ppm) at 3T it is important to use broadband excitation and refocusing pulses.