Repeatability of 31P MRSI in the human brain at 7 T with and without the nuclear Overhauser effect

An often‐employed strategy to enhance signals in ³¹P MRS is the generation of the nuclear Overhauser effect (NOE) by saturation of the water resonance. However, NOE allegedly increases the variability of the ³¹P data, because variation is reported in NOE enhancements. This would negate the signal‐to‐noise (SNR) gain it generates. We hypothesized that the variation in NOE enhancement values is not caused by the variability in NOE itself, but is attributable to measurement uncertainties in the values used to calculate the enhancement. If true, the expected increase in SNR with NOE would improve the repeatability of ³¹P MRS measurements. To verify this hypothesis, a repeatability study of native and NOE‐enhanced ³¹P MRSI was performed in the brains of seven healthy volunteers at 7 T. The repeatability coefficient (RC) and the coefficient of variation in repeated measurements (CoV_repeat) were determined for each method, and the 95% limits of agreement (LoAs) between native and NOE‐enhanced signals were calculated. The variation between the methods, defined by the LoA, is at least as great as that predicted by the RC of each method. The sources of variation in NOE enhancements were determined using variance component analysis. In the seven metabolites with a positive NOE enhancement (nine metabolite resonances assessed), CoV_repeat improved, on average, by 15%. The LoAs could be explained by the RCs of the individual methods for the majority of the metabolites, generally confirming our hypothesis. Variation in NOE enhancement was mainly attributable to the factor repeat, but between‐voxel effects were also present for phosphoethanolamine and (glycero)phosphocholine. CoV_repeat and fitting error were strongly correlated and improved with positive NOE. Our findings generally indicate that NOE enhances the signal of metabolites, improving the repeatability of metabolite measurements. Additional variability as a result of NOE was minimal. These findings encourage the use of NOE‐enhanced ³¹P MRSI. Copyright © 2015 John Wiley & Sons, Ltd.     

Feasibility and reproducibility of neurochemical profile quantification in the human hippocampus at 3 T

Hippocampal dysfunction is known to be associated with several neurological and neuropsychiatric disorders such as Alzheimer's disease, epilepsy, schizophrenia and depression; therefore, there has been significant clinical interest in studying hippocampal neurochemistry. However, the hippocampus is a challenging region to study using ¹H MRS, hence the use of MRS for clinical research in this region has been limited. Our goal was therefore to investigate the feasibility of obtaining high‐quality hippocampal spectra that allow reliable quantification of a neurochemical profile and to establish inter‐session reproducibility of hippocampal MRS, including reproducibility of voxel placement, spectral quality and neurochemical concentrations. Ten healthy volunteers were scanned in two consecutive sessions using a standard clinical 3 T MR scanner. Neurochemical profiles were obtained with a short‐echo (T_E = 28 ms) semi‐LASER localization sequence from a relatively small (~4 mL) voxel that covered about 62% of the hippocampal volume as calculated from segmentation of T₁‐weighted images. Voxel composition was highly reproducible between sessions, with test–retest coefficients of variation (CVs) of 3.5% and 7.5% for gray and white matter volume fraction, respectively. Excellent signal‐to‐noise ratio (~54 based on the N‐acetylaspartate (NAA) methyl peak in non‐apodized spectra) and linewidths (~9 Hz for water) were achieved reproducibly in all subjects. The spectral quality allowed quantification of NAA, total choline, total creatine, myo‐inositol and glutamate with high scan–rescan reproducibility (CV ≤ 6%) and quantification precision (Cramér–Rao lower bound, CRLB < 9%). Four other metabolites, including glutathione and glucose, were quantified with scan–rescan CV below 20%. Therefore, the highly optimized, short‐echo semi‐LASER sequence together with FASTMAP shimming substantially improved the reproducibility and number of quantifiable metabolites relative to prior reports. In addition, the between‐session variation in metabolite concentrations, as well as CRLB, was lower than the between‐subject variation of the concentrations for most metabolites, indicating that the method has the sensitivity to detect inter‐individual differences in the healthy brain. Copyright © 2015 John Wiley & Sons, Ltd.     

Optimized 31P MRS in the human brain at 7 T with a dedicated RF coil setup

The design and construction of a dedicated RF coil setup for human brain imaging (¹H) and spectroscopy (³¹P) at ultra‐high magnetic field strength (7 T) is presented. The setup is optimized for signal handling at the resonance frequencies for ¹H (297.2 MHz) and ³¹P (120.3 MHz). It consists of an eight‐channel ¹H transmit–receive head coil with multi‐transmit capabilities, and an insertable, actively detunable ³¹P birdcage (transmit–receive and transmit only), which can be combined with a seven‐channel receive‐only ³¹P array. The setup enables anatomical imaging and ³¹P studies without removal of the coil or the patient. By separating transmit and receive channels and by optimized addition of array signals with whitened singular value decomposition we can obtain a sevenfold increase in SNR of ³¹P signals in the occipital lobe of the human brain compared with the birdcage alone. These signals can be further enhanced by 30 ± 9% using the nuclear Overhauser effect by B₁‐shimmed low‐power irradiation of water protons. Together, these features enable acquisition of ³¹P MRSI at high spatial resolutions (3.0 cm³ voxel) in the occipital lobe of the human brain in clinically acceptable scan times (~15 min). © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Noninvasive quantification of human brain ascorbate concentration using 1H NMR spectroscopy at 7 T

Ascorbate (Asc, vitamin C) was quantified in the human brain noninvasively using two different ¹H NMR spectroscopy methods: short‐echo time STEAM and MEGA‐PRESS homonuclear editing. Taking advantage of increased sensitivity and chemical shift dispersion at 7 T, Asc was quantified with increased reliability relative to our previous study accomplished at 4 T. Asc concentration quantified from short‐echo time spectra measured from the occipital lobe of eight healthy subjects ([Asc] = 1.1 ± 0.3 µmol/g, mean ± SD) was in excellent agreement with Asc concentration quantified from the same volume of interest using homonuclear editing ([Asc] = 1.2 ± 0.2 µmol/g). This agreement indicates that at 7 T, Asc can be reliably quantified in the human brain simultaneously with 15 other metabolites. Additional advantages of the short‐echo time approach were: shorter measurement time than homonuclear editing and minimal effect of T₂ relaxation on Asc quantification. High magnetic field was also beneficial for Asc quantification with MEGA‐PRESS because increased chemical shift dispersion enabled editing with full efficiency, which resulted in a supra‐linear gain in signal‐to‐noise ratio relative to 4 T. Copyright © 2009 John Wiley & Sons, Ltd.     

Detection of lactate in the striatum without contamination of macromolecules by J‐difference editing MRS at 7 T

Lactate levels are measurable by MRS and are related to neural activity. Therefore, it is of interest to accurately measure lactate levels in the basal ganglia networks. If sufficiently stable, lactate measurements may be used to investigate alterations in dopaminergic signalling in the striatum, facilitating the detection and diagnosis of metabolic deficits. The aim of this study is to provide a J‐difference editing MRS technique for the selective editing of lactate only, thus allowing the detection of lactate without contamination of overlapping macromolecules. As a validation procedure, macromolecule nulling was combined with J‐difference editing, and this was compared with J‐difference editing with a new highly selective editing pulse. The use of a high‐field (7T) MR scanner enables the application of editing pulses with very narrow bandwidth, which are selective for lactate. We show that, despite the sensitivity to B₀ offsets, the use of a highly selective editing pulse is more efficient for the detection of lactate than the combination of a broad‐band editing pulse with macromolecule nulling. Although the signal‐to‐noise ratio of uncontaminated lactate detection in healthy subjects is relatively low, this article describes the test–retest performance of lactate detection in the striatum when using highly selective J‐difference editing MRS at 7 T. The coefficient of variation, σ_w and intraclass correlation coefficients for within‐ and between‐subject differences of lactate were determined. Lactate levels in the left and right striatum were determined twice in 10 healthy volunteers. Despite the fact that the test–retest performance of lactate detection is moderate with a coefficient of variation of about 20% for lactate, these values can be used for the design of new studies comparing, for example, patient populations with healthy controls. Copyright © 2015 John Wiley & Sons, Ltd.     

Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

Feasibility and repeatability of localized 31P‐MRS four‐angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T

Phosphorus (³¹P) MRS, combined with saturation transfer (ST), provides non‐invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T₁^app measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four‐angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra‐high‐field MR system, to accelerate the measurement of both P_i‐to‐ATP and PCr‐to‐ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth‐resolved surface coil MRS (DRESS)‐localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, P_i‐to‐ATP and PCr‐to‐ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS‐localized FAST method. The repeatability of PCr‐to‐ATP and P_i‐to‐ATP exchange rate constants, determined by the slab‐selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr‐to‐ATP metabolic flux decreased (from F_CK = 8.21 ± 1.15 mM s^?1 to F_CK = 3.86 ± 1.38 mM s^?1) and the P_i‐to‐ATP flux increased (from F_ATP = 0.43 ± 0.14 mM s^?1 to F_ATP = 0.74 ± 0.13 mM s^?1). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS‐localized FAST method at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Regional neurochemical profiles in the human brain measured by 1H MRS at 7 T using local B1 shimming

Increased sensitivity and chemical shift dispersion at ultra‐high magnetic fields enable the precise quantification of an extended range of brain metabolites from ¹H MRS. However, all previous neurochemical profiling studies using single‐voxel MRS at 7 T have been limited to data acquired from the occipital lobe with half‐volume coils. The challenges of ¹H MRS of the human brain at 7 T include short T₂ and complex B₁ distribution that imposes limitations on the maximum achievable B₁ strength. In this study, the feasibility of acquiring and quantifying short‐echo (TE = 8 ms), single‐voxel ¹H MR spectra from multiple brain regions was demonstrated by utilizing a 16‐channel transceiver array coil with 16 independent transmit channels, allowing local transmit B₁ (B₁⁺) shimming. Spectra were acquired from volumes of interest of 1–8 mL in brain regions that are of interest for various neurological disorders: frontal white matter, posterior cingulate, putamen, substantia nigra, pons and cerebellar vermis. Local B₁⁺ shimming substantially increased the transmit efficiency, especially in the peripheral and ventral brain regions. By optimizing a STEAM sequence for utilization with a 16‐channel coil, artifact‐free spectra were acquired with a small chemical shift displacement error (<5% /ppm/direction) from all regions. The high signal‐to‐noise ratio enabled the quantification of neurochemical profiles consisting of at least nine metabolites, including γ‐aminobutyric acid, glutamate and glutathione, in all brain regions. Significant differences in neurochemical profiles were observed between brain regions. For example, γ‐aminobutyric acid levels were highest in the substantia nigra, total creatine was highest in the cerebellar vermis and total choline was highest in the pons, consistent with the known biochemistry of these regions. These findings demonstrate that single‐voxel ¹H MRS at ultra‐high field can reliably detect region‐specific neurochemical patterns in the human brain, and has the potential to objectively detect alterations in neurochemical profiles associated with neurological diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D‐GRAPPA‐accelerated MRSI of the brain at 7 T

This work presents a new approach for high‐resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)‐MRSI with a short acquisition delay and acceleration via in‐plane two‐dimensional generalised autocalibrating partially parallel acquisition (2D‐GRAPPA) with adiabatic double inversion recovery (IR)‐based lipid suppression to allow robust high‐resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2–25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold‐in of transcranial lipids were suppressed via double IR, with a non‐selective symmetric frequency sweep. The use of long, low‐power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal‐to‐noise ratio (SNR), compared with conventional IR suppression (52–70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D‐GRAPPA provided acceleration up to a factor of nine for in vivo FID‐MRSI without a substantial increase in g‐factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D‐GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Whole‐body radiofrequency coil for 31P MRSI at 7 T

Widespread use of ultrahigh‐field ³¹P MRSI in clinical studies is hindered by the limited field of view and non‐uniform radiofrequency (RF) field obtained from surface transceivers. The non‐uniform RF field necessitates the use of high specific absorption rate (SAR)‐demanding adiabatic RF pulses, limiting the signal‐to‐noise ratio (SNR) per unit of time. Here, we demonstrate the feasibility of using a body‐sized volume RF coil at 7 T, which enables uniform excitation and ultrafast power calibration by pick‐up probes. The performance of the body coil is examined by bench tests, and phantom and in vivo measurements in a 7‐T MRI scanner. The accuracy of power calibration with pick‐up probes is analyzed at a clinical 3‐T MR system with a close to identical ¹H body coil integrated at the MR system. Finally, we demonstrate high‐quality three‐dimensional ³¹P MRSI of the human body at 7 T within 5 min of data acquisition that includes RF power calibration. Copyright © 2016 John Wiley & Sons, Ltd.     

Depth‐resolved surface coil MRS (DRESS)‐localized dynamic 31P‐MRS of the exercising human gastrocnemius muscle at 7 T

Dynamic ³¹P‐MRS with sufficiently high temporal resolution enables the non‐invasive evaluation of oxidative muscle metabolism through the measurement of phosphocreatine (PCr) recovery after exercise. Recently, single‐voxel localized ³¹P‐MRS was compared with surface coil localization in a dynamic fashion, and was shown to provide higher anatomical and physiological specificity. However, the relatively long TE needed for the single‐voxel localization scheme with adiabatic pulses limits the quantification of J‐coupled spin systems [e.g. adenosine triphosphate (ATP)]. Therefore, the aim of this study was to evaluate depth‐resolved surface coil MRS (DRESS) as an alternative localization method capable of free induction decay (FID) acquisition for dynamic ³¹P‐MRS at 7 T. The localization performance of the DRESS sequence was tested in a phantom. Subsequently, two dynamic examinations of plantar flexions at 25% of maximum voluntary contraction were conducted in 10 volunteers, one examination with and one without spatial localization. The DRESS slab was positioned obliquely over the gastrocnemius medialis muscle, avoiding other calf muscles. Under the same load, significant differences in PCr signal drop (31.2 ± 16.0% versus 43.3 ± 23.4%), end exercise pH (7.06 ± 0.02 versus 6.96 ± 0.11), initial recovery rate (0.24 ± 0.13 mm /s versus 0.35 ± 0.18 mm /s) and maximum oxidative flux (0.41 ± 0.14 mm /s versus 0.54 ± 0.16 mm /s) were found between the non‐localized and DRESS‐localized data, respectively. Splitting of the inorganic phosphate (Pi) signal was observed in several non‐localized datasets, but in none of the DRESS‐localized datasets. Our results suggest that the application of the DRESS localization scheme yielded good spatial selection, and provided muscle‐specific insight into oxidative metabolism, even at a relatively low exercise load. In addition, the non‐echo‐based FID acquisition allowed for reliable detection of ATP resonances, and therefore calculation of the specific maximum oxidative flux, in the gastrocnemius medialis using standard assumptions about resting ATP concentration in skeletal muscle. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo MRI analysis of depth‐dependent ultrastructure in human knee cartilage at 7 T

Signal intensities of T₂‐weighted magnetic resonance images depend on the local fiber arrangement in hyaline cartilage. The aims of this study were to determine whether angle‐sensitive MRI at 7 T can be used to quantify the cartilage ultrastructure of the knee in vivo and to assess potential differences with age. Ten younger (21–30) and ten older (55–76 years old) healthy volunteers were imaged with a T₂‐weighted spin‐echo sequence in a 7 T whole‐body MRI. A “fascicle” model was assumed to describe the depth‐dependent fiber arrangement of cartilage. The R/T boundary positions between radial and transitional zones were assessed from intensity profiles in small regions of interest in the femur and tibia, and normalized to cartilage thickness using logistic curve fits. The quality of our highly resolved (0.3 × 0.3 × 1.0 mm³) MR cartilage images were high enough for quantitative analysis (goodness of fit R² = 0.91 ± 0.09). Between younger and older subjects, normalized positions of the R/T boundary, with value 0 at the bone–cartilage interface and 1 at the cartilage surface, were significantly (p < 0.05) different in femoral (0.51 ± 0.12 versus 0.41 ± 0.10), but not in tibial cartilage (0.65 ± 0.11 versus 0.57 ± 0.09, p = 0.119). Within both age groups, differences between femoral and tibial R/T boundaries were significant. Using a fascicle model and angle‐sensitive MRI, the depth‐dependent anisotropic fiber arrangement of knee cartilage could be assessed in vivo from a single 7 T MR image. The derived quantitative parameter, thickness of the radial zone, may serve as an indicator of the structural integrity of cartilage. This method may potentially be suitable to detect and monitor early osteoarthritis because the progressive disintegration of the anisotropic network is also indicative of arthritic changes in cartilage. Copyright © 2013 John Wiley & Sons, Ltd.     

Two‐voxel spectroscopy with dynamic B0 shimming and flip angle adjustment at 7 T in the human motor cortex

The aim of this study was to acquire high‐quality in vivo ¹H spectra concurrently from two voxels at ultra‐high field (7 T) without specialized hardware. To this end, an acquisition scheme was developed in which first‐order shims and flip angles are dynamically updated to acquire spectra from both of the brain's motor cortices in an alternating fashion. To validate this acquisition scheme, separate, static, single‐voxel acquisitions were also performed for comparison. Six subjects were examined using semi‐LASER spectroscopy at 7 T. Barium titanate pads were used to increase the extent of the effective transmit field (B₁⁺). Spectra were obtained from the hand area of both motor cortices for both acquisition schemes. LCModel was used to determine neurochemical profiles in order to examine variations between acquisition schemes and volumes of interest. The dynamic two‐voxel acquisition protocol produced water linewidths (full width at half‐maximum between 11.6 and 12.8 Hz) and signal‐to‐noise ratios similar to those from static single‐voxel measurements. The concentrations of 13 individual and 3 combined metabolites with Cramér–Rao lower bounds below 30% were reliably detected for both acquisition schemes, and agreed well with previous postmortem assay and spectroscopy studies. The results show that high spectral quality from two voxels can be acquired concurrently without specialized hardware. This practical technique can be applied to many neuroscience applications. Copyright © 2015 John Wiley & Sons, Ltd.     

1H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors

Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used ¹H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A T_E =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N‐acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.     

Measurement of brain lactate during visual stimulation using a long TE semi‐LASER sequence at 7 T

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long (144 ms) semi‐LASER sequence at 7 T. spectra were acquired on healthy volunteers ( ) during a paradigm with 15 min of visual stimulation. Outer‐volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér‐Rao lower bound of 8%. Statistically significant ( , one‐tailed ‐test) increases in lactate ( 10%) and glutamate ( 3%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non‐contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non‐oxidative reaction pathways.     

39K and 23Na relaxation times and MRI of rat head at 21.1 T

At ultrahigh magnetic field strengths (B₀ ≥ 7.0 T), potassium (³⁹K) MRI might evolve into an interesting tool for biomedical research. However, ³⁹K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of ³⁹K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared ³⁹K and sodium (²³Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. ³⁹K relaxation times were markedly shorter than those of ²³Na. Compared with the lower field strength, ³⁹K relaxation times were up to 1.9‐ (T₁), 1.4‐ (T_2S) and 1.9‐fold (T_2L) longer at 21.1 T. The increase in the ²³Na relaxation times was less pronounced (up to 1.2‐fold). Mono‐exponential fits of the ³⁹K longitudinal relaxation time at 21.1 T revealed T₁ = 14.2 ± 0.1 ms for the healthy rat head. The ³⁹K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T_2S) and long (T_2L) components, respectively. ²³Na relaxation times were markedly longer (T₁ = 41.6 ± 0.4 ms; T_2S = 4.9 ± 0.2 ms; T_2L = 33.2 ± 0.2 ms). ³⁹K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm³ within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for ²³Na and ³⁹K MRI at ultrahigh magnetic field strength. Our results demonstrate that ³⁹K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.     

Quantification of human high‐energy phosphate metabolite concentrations at 3 T with partial volume and sensitivity corrections

Practical noninvasive methods for the measurement of absolute metabolite concentrations are key to the assessment of the depletion of myocardial metabolite pools which occurs with several cardiac diseases, including infarction and heart failure. Localized MRS offers unique noninvasive access to many metabolites, but is often confounded by nonuniform sensitivity and partial volume effects in the large, poorly defined voxels commonly used for the detection of low‐concentration metabolites with surface coils. These problems are exacerbated at higher magnetic field strengths by greater radiofrequency (RF) field inhomogeneity and differences in RF penetration with heteronuclear concentration referencing. An example is the ³¹P measurement of cardiac adenosine triphosphate (ATP) and phosphocreatine (PCr) concentrations, which, although central to cardiac energetics, have not been measured at field strengths above 1.5 T. Here, practical acquisition and analysis protocols are presented for the quantification of [PCr] and [ATP] with one‐dimensionally resolved surface coil spectra and concentration referencing at 3 T. The effects of nonuniform sensitivity and partial tissue volumes are addressed at 3 T by the application of MRI‐based three‐dimensional sensitivity weighting and tissue segmentation. The method is validated in phantoms of different sizes and concentrations, and used to measure [PCr] and [ATP] in healthy subjects. In calf muscle (n = 8), [PCr] = 24.7 ± 3.4 and [ATP] = 5.7 ± 1.3 µmol/g wet weight, whereas, in heart (n = 18), [PCr] = 10.4 ± 1.5 and [ATP] = 6.0 ± 1.1 µmol/g wet weight (all mean ± SD), consistent with previous reports at lower fields. The method enables, for the first time, the efficient, semi‐automated quantification of high‐energy phosphate metabolites in humans at 3 T with nonuniform excitation and detection. Copyright © 2013 John Wiley & Sons, Ltd.     

19 F MRSI of capecitabine in the liver at 7 T using broadband transmit–receive antennas and dual‐band RF pulses

Capecitabine (Cap) is an often prescribed chemotherapeutic agent, successfully used to cure some patients from cancer or reduce tumor burden for palliative care. However, the efficacy of the drug is limited, it is not known in advance who will respond to the drug and it can come with severe toxicity. ¹⁹ F Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) have been used to non‐invasively study Cap metabolism in vivo to find a marker for personalized treatment. In vivo detection, however, is hampered by low concentrations and the use of radiofrequency (RF) surface coils limiting spatial coverage. In this work, the use of a 7T MR system with radiative multi‐channel transmit–receive antennas was investigated with the aim of maximizing the sensitivity and spatial coverage of ¹⁹ F detection protocols. The antennas were broadband optimized to facilitate both the ¹H (298 MHz) and ¹⁹ F (280 MHz) frequencies for accurate shimming, imaging and signal combination. B₁⁺ simulations, phantom and noise measurements showed that more than 90% of the theoretical maximum sensitivity could be obtained when using B₁⁺ and B₁^? information provided at the ¹H frequency for the optimization of B₁⁺ and B₁^? at the ¹⁹ F frequency. Furthermore, to overcome the limits in maximum available RF power, whilst ensuring simultaneous excitation of all detectable conversion products of Cap, a dual‐band RF pulse was designed and evaluated. Finally, ¹⁹ F MRS(I) measurements were performed to detect ¹⁹ F metabolites in vitro and in vivo. In two patients, at 10 h (patient 1) and 1 h (patient 2) after Cap intake, ¹⁹ F metabolites were detected in the liver and the surrounding organs, illustrating the potential of the set‐up for in vivo detection of metabolic rates and drug distribution in the body. Copyright © 2015 John Wiley & Sons, Ltd.