Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T.

Mapping of the longitudinal relaxation time (T1) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T2-dependent variation of the adiabatic inversion efficiency were investigated by single slice T1 mapping with inversion recovery EPI measurements, quantitative T2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T1 estimates at high field, the proposed correction methods resulted in an improved precision, with test-retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%.

Evaluation of transmit efficiency and SAR for a tight fit transceiver human head phased array at 9.4 T.

Ultra-high field (UHF, ≥7 T) tight fit transceiver phased arrays improve transmit (Tx) efficiency (B1+ /√P) in comparison with Tx-only arrays, which are usually larger to fit receive (Rx)-only arrays inside. One of the major problems limiting applications of tight fit arrays at UHFs is the anticipated increase of local tissue heating, which is commonly evaluated by the local specific absorption rate (SAR). To investigate the tradeoff between Tx efficiency and SAR when a tight fit UHF human head transceiver phased array is used instead of a Tx-only/Rx-only RF system, a single-row eight-element prototype of a 400 MHz transceiver head phased array was constructed. The Tx efficiency and SAR of the array were evaluated and compared with that of a larger Tx-only array, which could also be used in combination with an 18-channel Rx-only array. Data were acquired on the Siemens Magnetom whole body 9.4 T human MRI system. Depending on the head size, positioning and the RF shim strategy, the smaller array provides from 11 to 23% higher Tx efficiency. In general, the Tx performance, evaluated as B1+ /√SAR, i.e. the safety excitation efficiency (SEE), is also not compromised. The two arrays provide very similar SEEs evaluated over 1000 random RF shim sets. We demonstrated that, in general, the tight fit transceiver array improves Tx performance without compromising SEE. However, in specific cases, the SEE value may vary, favoring one of the arrays, and therefore must be carefully evaluated.

Combination of a multimode antenna and TIAMO for traveling-wave imaging at 9.4 Tesla.

PURPOSE: To investigate the performance of a multimode antenna combined with time-interleaved acquisition of modes (TIAMO) for improved (1)H image homogeneity as compared to conventional traveling-wave imaging in the human brain at 9.4 Tesla (T). METHODS: An adjustable three-port antenna was built to stimulate the propagation of three basic waveguide modes within a 9.4 T scanner bore. For TIAMO, two time-interleaved acquisitions using different linear combinations of these modes were optimized to achieve a homogeneous rooted sum-of-squares combination of their B1+ patterns ( B1,RSS+). The antenna's transmit and receive performance, as well as local specific absorption rate, were analyzed using experiments and numerical simulations. RESULTS: The optimized TIAMO B1,RSS+ combination was superior to radiofrequency shimming. Across the entire brain, it improved the homogeneity of the excitation field by a factor of two and its maximum-to-minimum ratio by almost a factor of five as compared to the circularly polarized mode. The two-fold increase in "virtual" receive channels enhanced the parallel imaging performance and enabled the use of higher acceleration factors. CONCLUSION: Despite the limited number of channels, a remote three-port antenna combined with TIAMO represents an easily implementable setup to achieve void-free (1)H images from the entire brain at 9.4 T, which can be used for anatomical localization and B0 shimming.

Triple-quantum-filtered sodium imaging at 9.4 Tesla.

PURPOSE: Efficient acquisition of triple-quantum-filtered (TQF) sodium images at ultra-high field (UHF) strength. METHODS: A three-pulse preparation and a stack of double-spirals were used for the acquisition of TQF images at 9.4 Tesla. The flip angles of the TQ preparation were smoothly reduced toward the edge of k-space along the partition-encoding direction. In doing so, the specific absorption rate could be reduced while preserving the maximal signal intensity for the partitions most relevant for image contrast in the center of k-space. Simulations, phantom and in vivo measurements were used to demonstrate the usefulness of the proposed method. RESULTS: A higher sensitivity (∼ 20%) was achieved compared to the standard acquisition without flip angle apodization. Signals from free sodium ions were successfully suppressed irrespective of the amount of apodization used. B0 corrected TQF images with a nominal resolution of 5 × 5 × 5 mm(3) and an acceptable signal-to-noise ratio could be acquired in vivo within 21 min. CONCLUSION: Conventional TQF in combination with flip angle apodization permits to exploit more efficiently the increased sensitivity available at 9.4T.

Quantitative and functional pulsed arterial spin labeling in the human brain at 9.4 T.

PURPOSE: The feasibility of multislice pulsed arterial spin labeling (PASL) of the human brain at 9.4 T was investigated. To demonstrate the potential of arterial spin labeling (ASL) at this field strength, quantitative, functional, and high-resolution (1.05 × 1.05 × 2 mm(3)) ASL experiments were performed. METHODS: PASL was implemented using a numerically optimized adiabatic inversion pulse and presaturation scheme. Quantitative measurements were performed at 3 T and 9.4 T and evaluated on a voxel-by-voxel basis. In a functional experiment, activation maps obtained with a conventional blood-oxygen-level-dependent (BOLD)-weighted sequence were compared with a functional ASL (fASL) measurement. RESULTS: Quantitative measurements revealed a 23% lower perfusion in gray matter and 17% lower perfusion in white matter at 9.4 T compared with 3 T. Furthermore almost identical transit delays and bolus durations were found at both field strengths whereas the calculated voxel volume corrected signal-to-noise ratio was 1.9 times higher at 9.4 T. This result was confirmed by the high-resolution experiment. The functional experiment yielded comparable activation maps for the fASL and BOLD measurements. CONCLUSION: Although PASL at ultrahigh field strengths is limited by high specific absorption rate, functional and quantitative perfusion-weighted images showing a high degree of detail can be obtained.

Three-layered radio frequency coil arrangement for sodium MRI of the human brain at 9.4 Tesla.

PURPOSE: A multinuclei imaging setup with the capability to acquire both sodium ((23) Na) and proton ((1) H) signals at 9.4 Tesla is presented. The main objective was to optimize coil performance at the (23) Na frequency while still having the ability to acquire satisfactory (1) H images. METHODS: The setup consisted of a combination of three radio frequency (RF) coils arranged in three layers: the innermost layer was a 27-channel (23) Na receive helmet which was surrounded by a four-channel (23) Na transceiver array. The outer layer consisted of a four-channel (1) H dipole array for B0 shimming and anatomical localization. Transmit and receive performance of the (23) Na arrays was compared to a single-tuned (23) Na birdcage resonator. RESULTS: While the transmit efficiency of the (23) Na transceiver array was comparable to the birdcage, the (23) Na receive array provided substantial signal-to-noise ratio (SNR) gain near the surface and comparable SNR in the center. The utility of this customized setup was demonstrated by (23) Na images of excellent quality. CONCLUSION: High SNR, efficient transmit excitation and B0 shimming capability can be achieved for (23) Na MRI at 9.4T using novel coil combination. This RF configuration is easily adaptable to other multinuclei applications at ultra high field (≥ 7T).

(17)O relaxation times in the rat brain at 16.4 tesla.

PURPOSE: Measurement of the cerebral metabolic rate of oxygen (CMRO2 ) by means of direct imaging of the (17) O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H2 (17) O measurements. METHODS: Using the improved sensitivity at a field strength of 16.4 Tesla, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. RESULTS: In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2 * = 1.77 ± 0.04 ms. Postmortem H2 (17) O relaxometry at enriched concentrations after inhalation of (17) O2 showed similar T2 * values for gray matter (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than cerebrospinal fluid (2.30 ± 0.16 ms). CONCLUSION: Relaxation times of brain H2 (17) O were measured for the first time in vivo in different types of tissues with high spatial resolution. Because the relaxation times of H2 (17) O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths.

Safety testing and operational procedures for self-developed radiofrequency coils.

The development of novel radiofrequency (RF) coils for human ultrahigh-field (≥7 T), non-proton and body applications is an active field of research in many MR groups. Any RF coil must meet the strict requirements for safe application on humans with respect to mechanical and electrical safety, as well as the specific absorption rate (SAR) limits. For this purpose, regulations such as the International Electrotechnical Commission (IEC) standard for medical electrical equipment, vendor-suggested test specifications for third party coils and custom-developed test procedures exist. However, for higher frequencies and shorter wavelengths in ultrahigh-field MR, the RF fields may become extremely inhomogeneous in biological tissue and the risk of localized areas with elevated power deposition increases, which is usually not considered by existing safety testing and operational procedures. In addition, important aspects, such as risk analysis and comprehensive electrical performance and safety tests, are often neglected. In this article, we describe the guidelines used in our institution for electrical and mechanical safety tests, SAR simulation and verification, risk analysis and operational procedures, including coil documentation, user training and regular quality assurance testing, which help to recognize and eliminate safety issues during coil design and operation. Although the procedure is generally applicable to all field strengths, specific requirements with regard to SAR-related safety and electrical performance at ultrahigh-field are considered. The protocol describes an internal procedure and does not reflect consensus among a large number of research groups, but rather aims to stimulate further discussion related to minimum coil safety standards. Furthermore, it may help other research groups to establish their own procedures. Copyright © 2015 John Wiley & Sons, Ltd.

MR spectroscopy for in vivo assessment of the oncometabolite 2-hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T.

PURPOSE: To examine in vivo metabolic alterations in the isocitrate dehydrogenase (IDH) mutated gliomas using magnetic resonance spectroscopy (MRS) at magnetic field 9.4T. MATERIALS AND METHODS: Spectra were acquired with a 9.4T whole-body scanner with the use of a custom-built head coil (16 channel transmit and 31 channel receive). A modified stimulated echo acquisition mode (STEAM) sequence was used for localization. Eighteen patients with brain tumors of probable glial origin participated in this study. The study was performed in accordance with the guidelines of the local Ethics Committee. RESULTS: The increased spectral resolution allowed us to directly address metabolic alterations caused by the specific pathophysiology of IDH mutations including the presence of the oncometabolite 2-hydroxglutarate (2HG) and a significant decrease of the pooled glutamate and glutamine (20%, P = 0.024), which probably reflects an attempt to replenish α-ketoglutarate lost by conversion to 2HG. We also observed significantly reduced glutathione (GSH) levels (39%, P = 0.019), which could be similarly caused by depletion of dihydronicotinamide-adenine dinucleotide phosphate (NADPH) during this conversion in IDH mutant gliomas. CONCLUSION: We demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations. J. MAGN. RESON. IMAGING 2016;44:823-833.

Efficient generation of T2*-weighted contrast by interslice echo-shifting for human functional and anatomical imaging at 9.4 Tesla.

PURPOSE: Standard gradient-echo sequences are often prohibitively slow for T2*-weighted imaging as long echo times prolong the repetition time of the sequence. Echo-shifting offers a way out of this dilemma by allowing an echo time that exceeds the repetition time. The purpose of this work is to present a gradient-echo sequence that is optimized for multislice T2*-weighted imaging applications by combining echo-shifting with an interleaved slice excitation order. THEORY AND METHODS: This combined approach offers two major advantages: First, it combines the advantages of both concepts, that is, echo time and pulse repetition time can be significantly increased without affecting scan time. Second, there is no echo-shifting related signal loss associated with this concept as only a single radiofrequency pulse is applied per pulse repetition time and slice. RESULTS: A 9.4 Tesla high-resolution T2*-weighted anatomical brain scan of the proposed sequence is compared to a standard gradient-echo. Furthermore, results from 9.4 Tesla blood oxygen level dependent functional magnetic resonance imaging experiments with an in-plane resolution of 0.8 × 0.8 mm(2) are presented. CONCLUSION: The proposed sequence allows for efficient generation of T2*-weighted contrast by combining echo-shifting with an interleaved slice excitation order.

High-resolution quantitative sodium imaging at 9.4 Tesla.

PURPOSE: Investigation of the feasibility to perform high-resolution quantitative sodium imaging at 9.4 Tesla (T). METHODS: A proton patch antenna was combined with a sodium birdcage coil to provide a proton signal without compromising the efficiency of the X-nucleus coil. Sodium density weighted images with a nominal resolution of 1 × 1 × 5 mm(3) were acquired within 30 min with an ultrashort echo time sequence. The methods used for signal calibration as well as for B0, B1, and off-resonance correction were verified on a phantom and five healthy volunteers. RESULTS: An actual voxel volume of roughly 40 µL could be achieved at 9.4T, while maintaining an acceptable signal-to-noise ratio (8 for brain tissue and 35 for cerebrospinal fluid). The measured mean sodium concentrations for gray and white matter were 36 ± 2 and 31 ± 1 mmol/L of wet tissue, which are comparable to values previously reported in the literature. CONCLUSION: The reduction of partial volume effects is essential for accurate measurement of the sodium concentration in the human brain. Ultrahigh field imaging is a viable tool to achieve this goal due to its increased sensitivity.

Ultra-high resolution imaging of the human brain using acquisition-weighted imaging at 9.4T.

One of the main goals of ultra-high field MRI is to increase the spatial resolution reached in structural and functional images. Here, the possibility to obtain in vivo images of the human brain with voxel volumes below 0.02mm(3) is shown at 9.4T. To optimize SNR and suppress ringing artifacts, an acquisition-weighted 3D gradient-echo sequence is used, which acquires more averages in the center than in the outer regions of k-space. The weighting function is adjusted to avoid losses in spatial resolution and scan duration compared to a conventional experiment with an equal number of scans and otherwise identical parameters. Spatial resolution and SNR of the weighted sequence are compared to conventionally acquired images by means of phantom and in vivo measurements, and show improved image quality with unchanged spatial resolution and an SNR increase of up to 36% in phantoms and 20%±5% in vivo. Ultra-high resolution images with a voxel volume of 0.014mm(3) (0.13×0.13×0.8mm(3)) from the human brain have sufficient SNR and show fine intracortical detail, demonstrating the potential of the technique. The combination of acquisition-weighted imaging and highly sensitive array coils at ultra-high fields thus makes it possible to obtain images with ultra-high spatial resolutions within acceptable scan times.

Functional MRI in human subjects with gradient-echo and spin-echo EPI at 9.4 T.

PURPOSE: The increased signal-to-noise ratio and blood oxygen level dependent signal at ultra-high field can only help to boost the resolution in functional MRI studies if the spatial specificity of the activation signal is improved. At a field strength of 9.4 T, both gradient-echo and spin-echo based echo-planar imaging were implemented and applied to investigate the specificity of human functional MRI. A finger tapping paradigm was used to acquire functional MRI data with scan parameters similar to standard neuroscientific applications. METHODS: Spatial resolution, echo, and readout times were varied to determine their influence on the distribution of the blood oxygen level dependent signal. High-resolution co-localized images were used to classify the signal according to its origin in veins or tissue. RESULTS: High-quality activation maps were obtained with both sequences. Signal contributions from tissue were found to be smaller or slightly larger than from veins. Gradient-echo echo-planar imaging yielded lower ratios of micro-/macro-vascular signals of around 0.6 than spin-echo based functional MRI, where this ratio varied between 0.75 and 1.02, with higher values for larger echo and shorter readout time. CONCLUSION: This study demonstrates the feasibility of human functional MRI at 9.4 T with high spatial specificity. Although venous contributions could not be entirely suppressed, venous effects in spin-echo echo-planar imaging are significantly reduced compared with gradient-echo echo-planar imaging.

A 16-channel dual-row transmit array in combination with a 31-element receive array for human brain imaging at 9.4 T.

PURPOSE: Arranging transmit array elements in multiple rows provides an additional degree of freedom to correct B1 (+) field inhomogeneities and to achieve whole-brain excitation at ultrahigh field strengths. Receive arrays shaped to the contours of the anatomy increase the signal-to-noise ratio of the image. In this work, the advantages offered by the transmit and receive array techniques are combined for human brain imaging at 9.4 T. METHODS: A 16-element dual-row transmit array and a 31-element receive array were developed. Based on an accurate numerical model of the transmit array, the deposited power was calculated for different head sizes and positions. The influence of the receive array on the transmit field was characterized. Parallel imaging performance and signal-to-noise ratio of the receive array were evaluated. RESULTS: On average, a two fold increase in signal-to-noise ratio was observed in the whole-brain volume when compared with a 16-channel elliptic microstrip transceiver array. The benefits of combining the two arrays, B1 (+) shimming in three directions and high receive sensitivity, are demonstrated with high-resolution in vivo images. CONCLUSION: The dual-row transmit array provides whole-brain coverage at 9.4 T, which, in combination with the helmet-shaped receive array, is a valuable radio frequency configuration for ultra-high field magnetic resonance imaging of the human brain.

Human brain imaging at 9.4 T using a tunable patch antenna for transmission.

For human brain imaging at ultrahigh fields, the traveling wave concept can provide a more uniform B1+ field over a larger field of view with improved patient comfort compared to conventional volume coils. It suffers, however, from limited transmit efficiency and receive sensitivity and is not readily applicable in systems where the radiofrequency shield is too narrow to allow for unattenuated wave propagation. Here, the near field of a capacitively adjustable patch antenna for excitation is combined with a receive-only array at 9.4 T. The antenna is designed in compact size and placed in close proximity to the subject to improve the transmit efficiency in narrow bores. Experimental and numerical comparisons to conventional microstrip arrays reveal improved B1+ homogeneity and longitudinal coverage, but at the cost of elevated local specific absorption rate. High-resolution functional and anatomical images demonstrate the use of this setup for in vivo human brain imaging at 9.4 T.

Rat brain MRI at 16.4T using a capacitively tunable patch antenna in combination with a receive array.

For MRI at 16.4T, with a proton Larmor frequency of 698 MHz, one of the principal RF engineering challenges is to generate a spatially homogeneous transmit field over a larger volume of interest for spin excitation. Constructing volume coils large enough to house a receive array along with the subject and to maintain the quadrature symmetry for different loading conditions is difficult at this frequency. This calls for new approaches to RF coil design for ultra-high field MR systems. A remotely placed capacitively tunable patch antenna, which can easily be adjusted to different loading conditions, was used to generate a relatively homogeneous excitation field covering a large imaging volume with a transversal profile similar to that of a birdcage coil. Since it was placed in front of the animal, this created valuable free space in the narrow magnet bore around the subject for additional hardware. To enhance the reception sensitivity, the patch antenna was combined with an actively detunable 3-channel receive coil array. In addition to increased SNR compared to a quadrature transceive surface coil, we were able to get high quality gradient echo and spin-echo images covering the whole rat brain.

Contrast at high field: relaxation times, magnetization transfer and phase in the rat brain at 16.4 T.

As field strength increases, the magnetic resonance imaging contrast parameters like relaxation times, magnetization transfer or image phase change, causing variations in contrast and signal-to-noise ratio. To obtain reliable data for these parameters at 16.4 T, high-resolution measurements of the relaxation times T(1), T(2) and T(2)*, as well as of the magnetization transfer ratio and the local frequency in the rat brain were performed. Tissue-specific values were obtained for up to 17 brain structures to assess image contrast. The measured parameters were compared to those found at different field strengths to estimate contrast and signal behavior at increasing field. T(1) values were relatively long with (2272 ± 113) ms in cortex and (2073 ± 97) ms in white matter, but did not show a tendency to converge, leading to an almost linear increase in signal-to-noise ratio and still growing contrast-to-noise ratio. T(2) was short with (25 ± 2) ms in cortex and (20 ± 1) ms in white matter. Magnetization transfer effects increase by around 25% compared to published 4.7 T data, which leads to improved contrast. The image phase, as novel and high-field specific contrast mechanism, is shown to obtain good contrast in deep brain regions with increasing signal-to-noise ratio up to high field strengths.

Human imaging at 9.4 T using T(2) *-, phase-, and susceptibility-weighted contrast.

The effect of susceptibility differences on an MR image is known to increase with field strength. Magnetic field inhomogeneities within the voxels influence the apparent transverse relaxation time T(2) *, while effects due to different precession frequencies between voxels caused by local field variations are evident in the image phase, and susceptibility-weighted imaging highlights the veins and deep brain structures. Here, these three contrast mechanisms are examined at a field strength of 9.4 T. The T(2) * maps generated allow the identification of white matter structures not visible in conventional images. Phase images with in-plane resolutions down to 130 µm were obtained, showing high gray/white matter contrast and allowing the identification of internal cortical structures. The susceptibility-weighted images yield excellent visibility of small venous structures and attain an in-plane resolution of 175 µm.

Enhanced neurochemical profile of the rat brain using in vivo (1)H NMR spectroscopy at 16.4 T.

Single voxel magnetic resonance spectroscopy with ultrashort echo time was implemented at 16.4 T to enhance the neurochemical profile of the rat brain in vivo. A TE of 1.7 msec was achieved by sequence optimization and by using short-duration asymmetric pulses. Macromolecular signal components were parameterized individually and included in the quantitative analysis, replacing the use of a metabolite-nulled spectrum. Because of the high spectral dispersion, several signals close to the water line could be detected, and adjacent peaks could be resolved. All 20 metabolites detected in this study were quantified with Cramér-Rao lower bounds below 20%, implying reliable quantification accuracy. The signal of acetate was detected for the first time in rat brain in vivo with Cramér-Rao lower bounds of 16% and a concentration of 0.52 µmol/g. The absolute concentrations of most metabolites showed close agreement with values previously measured using in vivo (1)H NMR spectroscopy and in vitro biochemical assay.

Design and evaluation of an RF front-end for 9.4 T human MRI.

At the field strength of 9.4 T, the highest field currently available for human MRI, the wavelength of the MR signals is significantly shorter than the size of the examined structures. Even more than at 7 T, constructive and destructive interferences cause strong inhomogeneities of the B1 field produced by a volume coil, causing shading over large parts of the image. Specialized radio frequency hardware and B1 management methods are required to obtain high-quality images that take full advantage of the high field strength. Here, the design and characteristics of a radio frequency front-end especially developed for proton imaging at 9.4 T are presented. In addition to a 16-channel transceiver array coil, capable of volume transmit mode and independent signal reception, it consists of custom built low noise preamplifiers and TR switches. Destructive interference patterns were eliminated, in virtually the entire brain, using a simple in situ radio frequency phase shimming technique. After mapping the B1+ profile of each transmit channel, a numerical algorithm was used to calculate the appropriate transmit phase offsets needed to obtain a homogeneous excitation field over a user defined region. Between two and three phase settings are necessary to obtain homogeneous images over the entire brain.