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The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31 P-MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31 P-MRSI was performed in 12 breast cancer patients treated with NAC. 31 P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in-organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki-67 levels was determined using linear regression. Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki-67 index was found (P = 0.03). We demonstrated that it is possible to detect subtle changes in 31 P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.

The differentiation grade of cervical cancer is histologically assessed by examining biopsies or surgical specimens. MRS is a highly sensitive technique that images tissue metabolism and can be used to increase the specificity of tissue characterization in a non-invasive manner. We aim to explore the feasibility of using in vivo 1 H-MRS at 7 T in women with cervical cancer to study tissue fatty acid composition. 10 women with histologically proven Stage IB1-IIB cervical cancer were scanned with a whole-body 7 T MR system with a multi-transmit system and an internal receive only monopole antenna. A STEAM sequence was used to obtain 1 H-MRS data. Fatty acid resonances were fitted with Lorentzian curves and the 2.1 ppm/1.3 ppm ratios were calculated. 1 H-MRS data showed fatty acid signals resonating at 2.1 ppm, 1.9 ppm, 1.5 ppm, 1.3 ppm and 0.9 ppm. Mean 2.1/1.3 ppm ratios were 0.019 ± 0.01, 0.021 ± 0.006, 0.12 ± 0.089 and 0.39 ± 0.27 for normal, Grade I, Grade II and Grade III groups respectively. Poorly differentiated tumor tissue (Grade III) showed elevated fatty acid ratios when compared with the well differentiated tumor (Grade I) or normal tissue. 1 H-MRS in cervical cancer at 7 T is feasible and individual fatty acid signals were detected. In addition, poorly differentiated tumors show more fatty acid unsaturation. The 2.1 ppm/1.3 ppm ratio has potential for tumor characterization in a non-invasive manner for uterine cervical cancer.

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1-weighted image, and a T2-weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1-weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2-weighted spin echo images with uniformly weighted contrast.

The inhibitory gamma-aminobutyric acid (GABA) system is involved in the etiology of most psychiatric disorders, including schizophrenia, autism spectrum disorder (ASD) and major depressive disorder (MDD). It is therefore not surprising that proton magnetic resonance spectroscopy ((1) H-MRS) is increasingly used to investigate in vivo brain GABA levels. However, integration of the evidence for altered in vivo GABA levels across psychiatric disorders is lacking. We therefore systematically searched the clinical (1) H-MRS literature and performed a meta-analysis. A total of 40 studies (N = 1,591) in seven different psychiatric disorders were included in the meta-analysis: MDD (N = 437), schizophrenia (N = 517), ASD (N = 150), bipolar disorder (N = 129), panic disorder (N = 81), posttraumatic stress disorder (PTSD) (N = 104), and attention deficit/hyperactivity disorder (ADHD) (N = 173). Brain GABA levels were lower in ASD (standardized mean difference [SMD] = -0.74, P = 0.001) and in depressed MDD patients (SMD = -0.52, P = 0.005), but not in remitted MDD patients (SMD = -0.24, P = 0.310) compared with controls. In schizophrenia this finding did not reach statistical significance (SMD = -0.23, P = 0.089). No significant differences in GABA levels were found in bipolar disorder, panic disorder, PTSD, and ADHD compared with controls. In conclusion, this meta-analysis provided evidence for lower brain GABA levels in ASD and in depressed (but not remitted) MDD patients compared with healthy controls. Findings in schizophrenia were more equivocal. Even though future (1) H-MRS studies could greatly benefit from a longitudinal design and consensus on the preferred analytical approach, it is apparent that (1) H-MRS studies have great potential in advancing our understanding of the role of the GABA system in the pathogenesis of psychiatric disorders. Hum Brain Mapp 37:3337-3352, 2016. © 2016 Wiley Periodicals, Inc.

Widespread use of ultrahigh-field (31) P 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 (1) H body coil integrated at the MR system. Finally, we demonstrate high-quality three-dimensional (31) P 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.

The purpose of this article was to compare the sensitivity of proton observed phosphorus editing (POPE) with direct (31) P MRS with Ernst angle excitation for (1) H-(31) P coupled metabolites at 7 T. POPE sequences were developed for detecting phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) on the (1) H channel, thereby using the enhanced sensitivity of the (1) H nuclei over (31) P detection. Five healthy volunteers were examined with POPE and (31) P-MRS. POPE editing showed a more than doubled sensitivity in an ideal phantom experiment as compared with direct (31) P MRS with Ernst angle excitation. In vivo, despite increased relaxation losses, significant gains in signal-to-noise ratio (SNR) of 30-40% were shown for PE and GPE + PC levels in the human brain. The SNR of GPC was lower in the POPE measurement compared with the (31) P-MRS measurement. Furthermore, selective narrowband editing on the (31) P channel showed the ability to separate the overlapping GPE and PE signals in the (1) H spectrum. POPE can be used for enhanced detection of (1) H-(31) P coupled metabolites in vivo. Copyright © 2015 John Wiley & Sons, Ltd.

Summary Energy metabolism of the human visual cortex was investigated by performing 31P functional MRS. Introduction The human brain is known to be the main glucose demanding organ of the human body and neuronal activity can increase this energy demand. In this study we investigate whether alterations in pH during activation of the brain can be observed with MRS, focusing on the mitochondrial inorganic phosphate (Pi) pool as potential marker of energy demand. Methods Six participants were scanned with 16 consecutive 31P‐MRSI scans, which were divided in 4 blocks of 8:36 minutes of either rest or visual stimulation. Since the signals from the mitochondrial compartments of Pi are low, multiple approaches to achieve high SNR 31P measurements were combined. This included: a close fitting 31P RF coil, a 7 T‐field strength, Ernst angle acquisitions and a stimulus with a large visual angle allowing large spectroscopy volumes containing activated tissue. Results The targeted resonance downfield of the main Pi peak could be distinguished, indicating the high SNR of the 31P spectra. The peak downfield of the main Pi peak is believed to be connected to mitochondrial performance. In addition, a BOLD effect in the PCr signal was observed as a signal increase of 2–3% during visual stimulation as compared to rest. When averaging data over multiple volunteers, a small subtle shift of about 0.1 ppm of the downfield Pi peak towards the main Pi peak could be observed in the first 4 minutes of visual stimulation, but no longer in the 4 to 8 minute scan window. Indications of a subtle shift during visual stimulation were found, but this effect remains small and should be further validated. Conclusion Overall, the downfield peak of Pi could be observed, revealing opportunities and considerations to measure specific acidity (pH) effects in the human visual cortex., Energy metabolism of the human visual cortex was investigated by performing 31P functional MRS, focused on mitochondrial inorganic phosphate (Pimi/ex) as potential marker of energy demand. Since the concentration is low, multiple approaches to acquire high SNR 31P measurements were combined. Results show that the mitochondrial Pi resonance could be detected. During visual stimulation a small subtle shift was observed, especially in the first 4 minutes. Overall, this reveals opportunities and considerations to measure pH effects in the visual cortex.

PURPOSE: The design and performance of a novel head coil setup for (31)P spectroscopy at ultra high field strengths (7T) is presented. The described system supports measurements at both the (1)H and (31)P resonance frequencies. METHODS: The novel coil consists of two, actively detunable, coaxial birdcage coils to give homogeneous transmit, combined with a double resonant 30 channel receive array. This allows for anatomical imaging combined with (31)P acquisitions over the whole head, without changing coils or disturbing the subject. A phosphate buffer phantom and three healthy volunteers were scanned with a pulse acquire CSI sequence using both the novel array coil and a conventional transceiver birdcage. Four different methods of combining the array channels were compared at three different levels of SNR. RESULTS: The novel coil setup delivers significantly increased (31)P SNR in the peripheral regions of the brain, reaching up to factor 8, while maintaining comparable performance relative to the birdcage in the center. CONCLUSIONS: The new system offers the potential to acquire whole brain (31)P MRSI with superior signal relative to the standard options.

Trifluridine/tipiracil (TAS-102) has shown a significant overall survival benefit in patients with heavily pre-treated metastatic colorectal cancer. However, predicting treatment response and toxicity in individual patients remains challenging. Fluorine (19F)-containing drugs can be detected with magnetic resonance spectroscopy (MRS) to determine the metabolic rates and the biodistribution of the drug in normal and tumour tissue, which are related to treatment efficacy and toxicity. This is the first study to investigate the potential of 7-T 19F-MRS to detect TAS-102 metabolites in humans. We demonstrate that, with the used setup, TAS-102 is not detectable in liver metastases of metastatic colorectal cancer patients on a normal treatment schedule. Therefore, 19F-MRS TAS-102 metabolite detection is not yet useful for the clinical early prediction of treatment response. As 19F-MRS is able to detect TAS-102 in phantom and murine models, the use of 19F-MRS remains a potential tool to noninvasively detect and possibly monitor the metabolism when higher dosages of TAS-102 are administered, for example in organoid and animal studies.

Dynamic contrast‐enhanced MRI is the workhorse of breast MRI, where the diagnosis of lesions is largely based on the enhancement curve shape. However, this curve shape is biased by RF transmit (B1⁺) field inhomogeneities. B1⁺ field information is required in order to correct these. The use of a generic, coil‐specific B1⁺ template is proposed and tested. Finite‐difference time‐domain simulations for B1⁺ were performed for healthy female volunteers with a wide range of breast anatomies. A generic B1⁺ template was constructed by averaging simulations based on four volunteers. Three‐dimensional B1⁺ maps were acquired in 15 other volunteers. Root mean square error (RMSE) metrics were calculated between individual simulations and the template, and between individual measurements and the template. The agreement between the proposed template approach and a B1⁺ mapping method was compared against the agreement between acquisition and reacquisition using the same mapping protocol. RMSE values (% of nominal flip angle) comparing individual simulations with the template were in the range 2.00‐4.01%, with mean 2.68%. RMSE values comparing individual measurements with the template were in the range8.1‐16%, with mean 11.7%. The agreement between the proposed template approach and a B1⁺ mapping method was only slightly worse than the agreement between two consecutive acquisitions using the same mapping protocol in one volunteer: the range of agreement increased from ±16% of the nominal angle for repeated measurement to ±22% for the B1⁺ template. With local RF transmit coils, intersubject differences in B1⁺ fields of the breast are comparable to the accuracy of B1⁺ mapping methods, even at 7 T. Consequently, a single generic B1⁺ template suits subjects over a wide range of breast anatomies, eliminating the need for a time‐consuming B1⁺ mapping protocol.

Objective To demonstrate imaging performance for cardiac MR imaging at 7 T using a coil array of 8 transmit/receive dipole antennas and 16 receive loops. Materials and methods An 8-channel dipole array was extended by adding 16 receive-only loops. Average power constraints were determined by electromagnetic simulations. Cine imaging was performed on eight healthy subjects. Geometrical factor (g-factor) maps were calculated to assess acceleration performance. Signal-to-noise ratio (SNR)-scaled images were reconstructed for different combinations of receive channels, to demonstrate the SNR benefits of combining loops and dipoles. Results The overall image quality of the cardiac functional images was rated a 2.6 on a 4-point scale by two experienced radiologists. Imaging results at different acceleration factors demonstrate that acceleration factors up to 6 could be obtained while keeping the average g-factor below 1.27. SNR maps demonstrate that combining loops and dipoles provides a more than 50% enhancement of the SNR in the heart, compared to a situation where only loops or dipoles are used. Conclusion This work demonstrates the performance of a combined loop/dipole array for cardiac imaging at 7 T. With this array, acceleration factors of 6 are possible without increasing the average g-factor in the heart beyond 1.27. Combining loops and dipoles in receive mode enhances the SNR compared to receiving with loops or dipoles only. Electronic supplementary material The online version of this article (10.1007/s10334-017-0665-5) contains supplementary material, which is available to authorized users.

PURPOSE: The design of RF coils for MRI transmit becomes increasingly challenging at high frequencies required for MRI at 7T and above. Our goal is to show a proof of principle of a new type of transmit coil for higher field strengths. METHOD: We demonstrate an alternative transmit coil design based on dielectric waveguide principles which transfers energy via evanescent wave coupling. The operating principles and conditions are explored by simulations. The waveguide is applied for in vivo imaging at 7T. RESULTS: The waveguide can be an efficient transmit coil when four conditions are fulfilled: (1) the waveguide should be operated just above the cutoff frequency of the lowest order transverse electric mode, (2) the waveguide should not operate at a frequency where the wavelength fits an integer number of times in the waveguide length and standing wave patterns become very prominent, (3) for homogeneous excitation, the waveguide should be bent around the object, and (4) there should be an air gap between the waveguide and the object. CONCLUSIONS: By choosing the dielectric and the dimensions adequately, the dielectric waveguide couples the magnetic field efficiently into the body. The waveguide can be redesigned for higher frequencies by simple adaptations and may be a promising transmit alternative. Magn Reson Med 76:1314-1324, 2016. © 2015 Wiley Periodicals, Inc.

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 (1)H (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 (1)H 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.

Purpose Fluctuations of the background magnetic field (B0) due to body and breathing motion can lead to significant artifacts in brain imaging at ultrahigh field. Corrections based on real-time sensing using external field probes show great potential. This study evaluates different aspects of field interpolation from these probes into the brain which is implicit in such methods. Measurements and simulations were performed to quantify how well B0-fluctuations in the brain due to body and breathing motion are reflected in external field probe measurements. Methods Field probe measurements were compared with scanner acquired B0-maps from experiments with breathing and shoulder movements. A realistic simulation of B0-fluctuations caused by breathing was performed, and used for testing different sets of field probe positions. Results The B0-fluctuations were well reflected in the field probe measurements in the shoulder experiments, while the breathing experiments showed only moderate correspondence. The simulations showed the importance of the probe positions, and that performing full 3rd order corrections based on 16 field probes is not recommended. Conclusion Methods for quantitative assessment of the field interpolation problem were developed and demonstrated. Field corrections based on external field measurements show great potential, although potential pitfalls were identified. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

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, σw 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.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS (H-1-MRS) at 7T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations (subject', institute' and random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T-1, T-2, magnetization transfer effects and partial volume effects, were obtained with mean Cramer-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with H-1-MRS at ultra-high magnetic field. Copyright (c) 2015 John Wiley & Sons, Ltd.

INTRODUCTIONBreast cancer is the most common form of cancer amongwomen (1). In addition to x-ray mammography, theAmerican Cancer Society advises the performance ofbreast MRI in women with suspected breast cancerbecause of its relatively high sensitivity (2). Dynamiccontrast-enhanced (DCE) MRI scans are primarily used toassess the size and grade of breast cancer by combiningmorphological and kinetic information. In the most opti-mal case, these scans have high spatial resolution todetermine the morphology of the tumor, as well as ahigh temporal resolution to determine the uptake andwashout curve of the gadolinium (3–6).While sensitivity of DCE-MRI in the diagnosis of breastcancer is over 90%, the specificity is only 70% (7).Therefore, studies are being designed to improve thespecificity of breast MRI. For instance, it was shown thatultrafast DCE and diffusion-weighted imaging (DWI) canbe used to improve differentiation between benign andmalignant tumors (3,5,8,9).At higher field strength, like 7T, the signal-to-noiseratio (SNR) increases, facilitating the use of

Objectives The objective of this study was to assess the feasibility of carotid vessel wall imaging at 7.0 for T magnetic resonance imaging (MRI) in a series of patients with a symptomatic greater than 70% stenosis of the internal carotid artery. Materials and methods First, a series of 6 healthy volunteers were scanned at 3.0 T and 7.0 T MRI to perform a signal-to-noise ratio comparison between these 2 field strengths. Second, in patients with a greater than 70% stenosed carotid artery, a 7.0 T MRI protocol, consisting of a dual-echo turbo spin echo sequence (echo times of 45 and 150 milliseconds) and a T1-weighted turbo spin echo sequence, was obtained. Lumen and vessel wall were delineated for interobserver and intraobserver reproducibility, and signal intensity distribution in the most severely stenosed part of the internal carotid artery was correlated with different plaque components on histopathologic findings. Results The mean (SD) signal-to-noise ratio in the vessel wall was 42 (12) at 7.0 T and 24 (4) at 3.0 T. Nineteen patients were included, but technical issues yielded carotid MRI data of 14 patients available for the final analysis. Of these patients, 4 were diagnosed with stroke, 7 were diagnosed with a transient ischemic attack, and 3 were diagnosed with amaurosis fugax. Intraclass correlation coefficient of the agreements of lumen and vessel wall determination between 2 observers and between the repeated measures of 1 observer were above 0.80 in both 3.0 T and 7.0 T data sets of the healthy volunteers and also in the 7.0 T data set of the patients. Signal hyperintensity in the 7.0 T magnetic resonance images was inversely proportional to calcification. Other correlations between plaque components and signal intensity could not be confirmed. Conclusions This first series of patients with carotid atherosclerotic plaque who were scanned at 7.0 T MRI shows that 7.0 T MRI enables to adequately determine lumen and vessel wall areas. Signal hyperintensity in these 7.0 T magnetic resonance images was inversely proportional to calcification. However, at this stage, no other correlations between histologic findings and vessel wall contrast were found. Implementation of in vivo high-resolution 7.0 T MRI of plaque components for risk stratification remains challenging. Future development of hardware and software is still needed to attain a more robust setup and to enable complete plaque characterization, similar to what is currently possible with multiple MRI sequences at 1.5 T and 3.0 T MRI.

PURPOSE: Hypoxia is an important marker for resistance to therapy. In this study, we quantify the macroscopic effects of R2* mapping in prostate cancer patients incorporating susceptibility matching and field strengths effects. MATERIALS AND METHODS: 91 patients were scanned without endorectal coil (ERC) at 3T. Only when rectal gas was absent, data was included for analysis. Another group of 10 patients was scanned using a susceptibility matched ERC. To assess the residual contamination of R2 and macroscopic field non-uniformities, a group of 10 patients underwent ultra-high resolution 7T MRI. RESULTS: Of the patients scanned at 3T 60% presented rectal gas and were excluded, due to susceptibility artifacts. At 3T the tumor was significantly different (P

Intelligence is a measure of general cognitive functioning capturing a wide variety of different cognitive functions. It has been hypothesized that the brain works to minimize the resources allocated toward higher cognitive functioning. Thus, for the intelligent brain, it may be that not simply more is better, but rather, more efficient is better. Energy metabolism supports both inhibitory and excitatory neurotransmission processes. Indeed, in glutamatergic and GABAergic neurons, the primary energetic costs are associated with neurotransmission. We tested the hypothesis that minimizing resources through the excitation–inhibition balance encompassing gamma-aminobutyric acid (GABA) and glutamate may be beneficial to general cognitive functioning using 7 T 1H-MRS in 23 healthy individuals (male/female = 16/7, 27.7 ± 5.3 years). We find that a higher working memory index is significantly correlated with a lower GABA to glutamate ratio in the frontal cortex and with a lower glutamate level in the occipital cortex. Thus, it seems that working memory performance is associated with the excitation–inhibition balance in the brain.

The aim of this study was to investigate the signal-to-noise ratio (SNR) gain in early-stage cervical cancer at ultrahigh-field MRI (e.g. 7 T) using a combination of multiple external antennas and a single endorectal antenna. In particular, we used an endorectal monopole antenna to increase the SNR in cervical magnetic resonance imaging (MRI). This should allow high-resolution, T2 -weighted imaging and magnetic resonance spectroscopy (MRS) for metabolic staging, which could facilitate the local tumor status assessment. In a prospective feasibility study, five healthy female volunteers and six patients with histologically proven stage IB1-IIB cervical cancer were scanned at 7 T. We used seven external fractionated dipole antennas for transmit-receive (transceive) and an endorectally placed monopole antenna for reception only. A region of interest, containing both normal cervix and tumor tissue, was selected for the SNR measurement. Separated signal and noise measurements were obtained in the region of the cervix for each element and in the near field of the monopole antenna (radius < 30 mm) to calculate the SNR gain of the endorectal antenna in each patient. We obtained high-resolution, T2 -weighted images with a voxel size of 0.7 × 0.8 × 3.0 mm3 . In four cases with optimal placement of the endorectal antenna (verified on the T2 -weighted images), a mean gain of 2.2 in SNR was obtained at the overall cervix and tumor tissue area. Within a radius of 30 mm from the monopole antenna, a mean SNR gain of 3.7 was achieved in the four optimal cases. Overlap between the two different regions of the SNR calculations was around 24%. We have demonstrated that the use of an endorectal monopole antenna substantially increases the SNR of 7-T MRI at the cervical anatomy. Combined with the intrinsically high SNR of ultrahigh-field MRI, this gain may be employed to obtain metabolic information using MRS and to enhance spatial resolutions to assess tumor invasion.

PURPOSE: (13)C magnetic resonance spectroscopy (MRS) in combination with infusion of (13)C-labeled substrates has led to unique insights into human brain metabolism and neurotransmitter cycling. However, the low sensitivity of direct (13)C MRS and high radiofrequency (RF) power requirements has limited (13)C MRS studies to predominantly data acquisition in large volumes of the occipital cortex. The purpose of this study is to develop an MRS technique for localized detection of (13)C-labeling of glutamate and glutamine in the human frontal lobe. METHODS: We used an indirect ((1)H-[(13)C]), proton-observed, carbon-edited MRS sequence (selPOCE) for detection of (13)C-labeled metabolites in relatively small volumes located in the frontal lobe at 4 Tesla. SelPOCE allows for selective and separate detection of glutamate and glutamine resonances, which significantly overlap at magnetic field strengths used for clinical MRI. RESULTS: Phantom data illustrate how selPOCE can be tuned to selectively detect (13)C labeling in different metabolites. 3D specific absorption rates (SAR) simulations of RF power deposition show that the selPOCE method operates comfortably within the global and local FDA SAR guidelines. In vivo selPOCE data are presented acquired from a 45 mL volume in the frontal lobe of healthy subjects. The in vivo data show the time-dependent (13)C-labeling of glutamate and glutamine during intravenous infusion of [1-(13)C]-glucose. Metrics describing spectral fitting quality of the glutamate and glutamine resonances are reported. CONCLUSION: SelPOCE allows the detection of (13)C-labeling in glutamate and glutamine from a relatively small volume in the human frontal lobe at low RF power requirements.

Dynamic contrast‐enhanced MRI is the workhorse of breast MRI, where the diagnosis of lesions is largely based on the enhancement curve shape. However, this curve shape is biased by RF transmit (B 1 +) field inhomogeneities. B 1 + field information is required in order to correct these. The use of a generic, coil‐specific B 1 + template is proposed and tested. Finite‐difference time‐domain simulations for B 1 + were performed for healthy female volunteers with a wide range of breast anatomies. A generic B 1 + template was constructed by averaging simulations based on four volunteers. Three‐dimensional B 1 + maps were acquired in 15 other volunteers. Root mean square error (RMSE) metrics were calculated between individual simulations and the template, and between individual measurements and the template. The agreement between the proposed template approach and a B 1 + mapping method was compared against the agreement between acquisition and reacquisition using the same mapping protocol. RMSE values (% of nominal flip angle) comparing individual simulations with the template were in the range 2.00‐4.01%, with mean 2.68%. RMSE values comparing individual measurements with the template were in the range8.1‐16%, with mean 11.7%. The agreement between the proposed template approach and a B 1 + mapping method was only slightly worse than the agreement between two consecutive acquisitions using the same mapping protocol in one volunteer: the range of agreement increased from ±16% of the nominal angle for repeated measurement to ±22% for the B 1 + template. With local RF transmit coils, intersubject differences in B 1 + fields of the breast are comparable to the accuracy of B 1 + mapping methods, even at 7 T. Consequently, a single generic B 1 + template suits subjects over a wide range of breast anatomies, eliminating the need for a time‐consuming B 1 + mapping protocol.

Purpose To detect neuronal activity–evoked pH changes by amide proton transfer–chemical exchange saturation transfer (APT‐CEST) MRI at 7 T. Methods Three healthy subjects participated in the study. A low‐power 3‐dimensional APT‐CEST sequence was optimized through the Bloch‐McConnell equations. pH sensitivity of the sequence was estimated both in phantoms and in vivo. The feasibility of pH–functional MRI was tested in Bloch‐McConnell‐simulated data using the optimized sequence. In healthy subjects, the visual stimuli were used to evoke transient pH changes in the visual cortex, and a 3‐dimensional APT‐CEST volume was acquired at the pH‐sensitive frequency offset of 3.5 ppm every 12.6 s. Results In theory, a three‐component general linear model was capable of separating the effects of blood oxygenation level–dependent contrast and pH. The Bloch‐McConnell equations indicated that a change in pH of 0.03 should be measurable at the experimentally determined temporal signal‐to‐noise ratio of 108. However, only a blood oxygenation level–dependent effect in the visual cortex could be discerned during the visual stimuli experiments performed in the healthy subjects. Conclusions The results of this study suggest that if indeed there are any transient brain pH changes in response to visual stimuli, those are under 0.03 units pH change, which is extremely difficult to detect using the existent techniques. Magn Reson Med 80:126–136, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PURPOSE: To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) (1)H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths. A sLASER sequence has been developed for 7 T, using field focusing at short TE, resulting in twice as much signal as can be obtained using STEAM and improved localization accuracy due to a decreased chemical shift artifact. MATERIALS AND METHODS: Eight subjects were scanned twice using both STEAM and sLASER. Data were acquired from the frontal and occipital brain region. Subsequently, intraclass correlations were computed for the estimated metabolite concentrations. RESULTS: sLASER has higher ICC's for glutamate concentration as compared to STEAM in both the frontal and occipital VOI, which is probably due to the higher sensitivity and localization accuracy. CONCLUSION: We conclude that sLASER (1)H-MRS at 7 T is a reliable method to obtain reproducible measures of glutamate levels in the human brain at such high accuracy that individual variability, even between age-matched subjects, is measured.

Background: Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. Schizophrenia is also characterized by cognitive impairments. A possible mechanism in schizophrenia is hypofunction of the NMDA-type of the glutamate receptor in the medial prefrontal cortex, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. Methods: We measured GABA–creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T (Marsman et al, 2014). In addition, general cognitive functioning was measured using the Wechsler Adult Intelligence Test. Measurements were available in 17 patients with schizophrenia and 23 healthy controls. Results: Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls. Moreover, GABA–Cr ratios in the prefrontal cortex were inversely correlated with cognitive functioning in the patients. No significant differences in metabolite concentrations in the parieto-occipital cortex were found between the groups. Conclusion: Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. In a second study, including siblings of patients with schizophrenia we are currently assessing whether altered GABA levels are related to causes or consequences of the disease.

We studied the feasibility of high-resolution T2-weighted cervical cancer imaging on an ultra-high-field 7.0-T magnetic resonance imaging (MRI) system using an endorectal antenna of 4.7-mm thickness. A feasibility study on 20 stage IB1–IIB cervical cancer patients was conducted. All underwent pre-treatment 1.5-T MRI. At 7.0-T MRI, an external transmit/receive array with seven dipole antennae and a single endorectal monopole receive antenna were used. Discomfort levels were assessed. Following individualised phase-based B1 + shimming, T2-weighted turbo spin echo sequences were completed. Patients had stage IB1 (n = 9), IB2 (n = 4), IIA1 (n = 1) or IIB (n = 6) cervical cancer. Discomfort (ten-point scale) was minimal at placement and removal of the endorectal antenna with a median score of 1 (range, 0–5) and 0 (range, 0–2) respectively. Its use did not result in adverse events or pre-term session discontinuation. To demonstrate feasibility, T2-weighted acquisitions from 7.0-T MRI are presented in comparison to 1.5-T MRI. Artefacts on 7.0-T MRI were due to motion, locally destructive B1 interference, excessive B1 under the external antennae and SENSE reconstruction. High-resolution T2-weighted 7.0-T MRI of stage IB1–IIB cervical cancer is feasible. The addition of an endorectal antenna is well tolerated by patients. • High resolution T 2 -weighted 7.0-T MRI of the inner female pelvis is challenging • We demonstrate a feasible approach for T 2 -weighted 7.0-T MRI of cervical cancer • An endorectal monopole receive antenna is well tolerated by participants • The endorectal antenna did not lead to adverse events or session discontinuation

Background The N -methyl-D-aspartate receptor hypofunction model of schizophrenia predicts dysfunction in both glutamatergic and gamma-aminobutyric acidergic (GABAergic) transmission. We addressed this hypothesis by measuring GABA, glutamate, glutamine, and the sum of glutamine plus glutamate concentrations in vivo in patients with schizophrenia using proton magnetic resonance spectroscopy at 7T, which allows separation of metabolites that would otherwise overlap at lower field strengths. In addition, we investigated whether altered levels of GABA, glutamate, glutamine, and the sum of glutamine plus glutamate reflect genetic vulnerability to schizophrenia by including healthy first-degree relatives. Methods Proton magnetic resonance spectroscopy at 7T was performed in 21 patients with chronic schizophrenia who were taking medication, 23 healthy first-degree relatives of patients with schizophrenia, and 24 healthy nonrelatives. Glutamate, glutamine, and GABA were measured cortically and subcortically in bilateral basal ganglia and occipital cortex. Results Patients with schizophrenia had reduced cortical GABA compared with healthy relatives and the combined sample of healthy relatives and healthy nonrelatives, suggesting that altered GABAergic systems in schizophrenia are associated with either disease state or medication effects. Reduced cortical glutamine relative to healthy control subjects was observed in patients with schizophrenia and the combined sample of healthy relatives and patients with schizophrenia, suggesting that altered glutamatergic metabolite levels are associated with illness liability. No group differences were found in the basal ganglia. Conclusions Taken together, these findings are consistent with alterations in GABAergic and glutamatergic systems in patients with schizophrenia and provide novel insights into these systems in healthy relatives.

Purpose To assess reproducibility of glutamate measurement in the human brain by two short echo time (TE) 1H-MRS sequences [stimulated echo acquisition mode (STEAM) and semi-localized by adiabatic selective refocusing (sLASER)] at 7 T. Reliable assessment of glutamate is important when studying a variety of neurological and neuropsychiatric disorders. At 7 T, the glutamate signal can be separated from the glutamine signal and hence more accurately measured as compared to lower field strengths. A sLASER sequence has been developed for 7 T, using field focusing at short TE, resulting in twice as much signal as can be obtained using STEAM and improved localization accuracy due to a decreased chemical shift artifact. Materials and methods Eight subjects were scanned twice using both STEAM and sLASER. Data were acquired from the frontal and occipital brain region. Subsequently, intraclass correlations were computed for the estimated metabolite concentrations. Results sLASER has higher ICC’s for glutamate concentration as compared to STEAM in both the frontal and occipital VOI, which is probably due to the higher sensitivity and localization accuracy. Conclusion We conclude that sLASER 1H-MRS at 7 T is a reliable method to obtain reproducible measures of glutamate levels in the human brain at such high accuracy that individual variability, even between age-matched subjects, is measured.

Item does not contain fulltext Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, gamma-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification. It is currently unknown to what extent variations in the analysis pipeline used to quantify (1) H-MRS data affect outcomes. The purpose of this study was to evaluate whether the quantification of identical (1) H-MRS scans across independent and experienced research groups would yield comparable results. We investigated the influence of model parameters and spectral quantification software on fitted metabolite concentration values. Sixty spectra in 30 individuals (repeated measures) were acquired using a 7-T MRI scanner. Data were processed by four independent research groups with the freedom to choose their own individualized and optimal parameter settings using LCModel software. Data were processed a second time in one group using an independent software package (NMRWizard) for an additional comparison with a different post-processing platform. Correlations across research groups of the ratio between the highest and, arguably, the most relevant resonances for neurotransmission [N-acetyl aspartate (NAA), N-acetyl aspartyl glutamate (NAAG) and Glu] over the total creatine [creatine (Cr) + phosphocreatine (PCr)] concentration, using Pearson's product-moment correlation coefficient (r), were calculated. Mean inter-group correlations using LCModel software were 0.87, 0.88 and 0.77 for NAA/Cr + PCr, NAA + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. The mean correlations when comparing NMRWizard results with LCModel fitting results at University Medical Center Utrecht (UMCU) were 0.87, 0.89 and 0.71 for NAA/Cr + PCr, NAA + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results reinforce the notion that standard practices should be established to regularize outcomes of (1) H-MRS studies, and that basis sets used for processing should be made available to the scientific community.

Purpose To establish a preoperative decision model for accurate indication of systemic therapy in early-stage breast cancer using multiparametric MRI at 7-tesla field strength. Materials and methods Patients eligible for breast-conserving therapy were consecutively included. Patients underwent conventional diagnostic workup and one preoperative multiparametric 7-tesla breast MRI. The postoperative (gold standard) indication for systemic therapy was established from resected tumor and lymph-node tissue, based on 10-year risk-estimates of breast cancer mortality and relapse using Adjuvant! Online. Preoperative indication was estimated using similar guidelines, but from conventional diagnostic workup. Agreement was established between preoperative and postoperative indication, and MRI-characteristics used to improve agreement. MRI-characteristics included phospomonoester/phosphodiester (PME/PDE) ratio on 31-phosphorus spectroscopy (31P-MRS), apparent diffusion coefficients on diffusion-weighted imaging, and tumor size on dynamic contrast-enhanced (DCE)-MRI. A decision model was built to estimate the postoperative indication from preoperatively available data. Results We included 46 women (age: 43-74yrs) with 48 invasive carcinomas. Postoperatively, 20 patients (43%) had positive, and 26 patients (57%) negative indication for systemic therapy. Using conventional workup, positive preoperative indication agreed excellently with positive postoperative indication (N = 8/8; 100%). Negative preoperative indication was correct in only 26/38 (68%) patients. However, 31P-MRS score (p = 0.030) and tumor size (p = 0.002) were associated with the postoperative indication. The decision model shows that negative indication is correct in 21/22 (96%) patients when exempting tumors larger than 2.0cm on DCE-MRI or with PME>PDE ratios at 31P-MRS. Conclusions Preoperatively, positive indication for systemic therapy is highly accurate. Negative indication is highly accurate (96%) for tumors sized ≤2,0cm on DCE-MRI and with PME≤PDE ratios on 31P-MRS.

Spectral degradations as a result of temporal field variations are observed in MRSI of the human prostate. Moving organs generate substantial temporal and spatial field fluctuations as a result of susceptibility mismatch with the surrounding tissue (i.e. periodic breathing, cardiac motion or random bowel motion). Nine patients with prostate cancer were scanned with an endorectal coil (ERC) on a 7-T MR scanner. Temporal B0 field variations were observed with fast dynamic B0 mapping in these patients. Simulations of dynamic B0 corrections were performed using zero- to second-order shim terms. In addition, the temporal B0 variations were applied to simulated MR spectra causing, on average, 15% underestimation of the choline/citrate ratio. Linewidth distortions and frequency shifts (up to 30 and 8 Hz, respectively) were observed. To demonstrate the concept of observing local field fluctuations in real time during MRSI data acquisition, a field probe (FP) tuned and matched for the 19 F frequency was incorporated into the housing of the ERC. The data acquired with the FP were compared with the B0 field map data and used to correct the MRSI datasets retrospectively. The dynamic B0 mapping data showed variations of up to 30 Hz (0.1 ppm) over 72 s at 7 T. The simulated zero-order corrections, calculated as the root mean square, reduced the standard deviation (SD) of the dynamic variations by an average of 41%. When using second-order corrections, the reduction in the SD was, on average, 56%. The FP data showed the same variation range as the dynamic B0 data and the variation patterns corresponded. After retrospective correction, the MRSI data showed artifact reduction and improved spectral resolution. B0 variations can degrade the MRSI substantially. The simple incorporation of an FP into an ERC can improve prostate cancer MRSI without prior knowledge of the origin of the dynamic field distortions. Copyright © 2014 John Wiley & Sons, Ltd.

Purpose: Going to ultrahigh field MRI (e. g., 7 Tesla [ T]), the nonuniformity of the B_1 field and the increased radiofrequency (RF) power deposition become challenging. While surface coils improve the power efficiency in B_1, its field remains nonuniform. In this work, an RF pulse was designed that uses the slab selection to compensate the inhomogeneous B_1 field of a surface coil without a substantial increase in specific absorption rate (SAR). Theory and Methods: A breast surface coil was used with a decaying B_1 field in the anterior- posterior direction of the human breast. Slab selective RF pulses were designed and compared with adiabatic and spokes RF pulses. Proof of principle was demonstrated with FFE and B_1 maps of the human breast. ResultsIn vivo measurements obtained with the breast surface coil show that the tilt optimized flip uniformity (TOFU) RF pulses can improve the flip angle homogeneity by 31%, while the SAR will be lower compared with BIR-4 and spokes RF pulses. ConclusionBy applying TOFU RF pulses to the breast surface coil, we are able to compensate the inhomogeneous field, while keeping the SAR low. Therefore stronger T-1-weighting in FFE sequences can be obtained, while pulse durations can remain short, as shown in the human breast at 7T. Magn Reson Med 74:482-488, 2015. (c) 2014 Wiley Periodicals, Inc.

PURPOSE: Lipid suppression in MR brain imaging and spectroscopy has been a long-standing problem for which various techniques have been developed. Most methods are based on inversion recovery or spatially or spectrally selective excitation of the lipid signal followed by dephasing. All techniques require additional RF pulses, gradient crushers and delays, which increase the duration and complexity of sequences. In addition, the lipid signal is poorly shimmed, and is composed of different resonance frequencies that have different relaxation properties. METHODS: In this work, a novel approach for suppression of extra cranial lipids is presented, by means of an outer volume crusher coil. It is based on the principle of surface spoiling gradients, which generate a very local and inhomogeneous magnetic field in the outer layer of the head, and thereby destroys the phase coherence of the extra cranial signals. RESULTS: Dephasing of the signal can be incorporated in almost any sequence because it requires only a short pulse of the coil, and does not require additional RF pulses or delays. Examples of lipid suppression are shown in both gradient echo imaging and spectroscopic imaging. CONCLUSION: Outer volume crushing allows for simple fat suppression and boosts scanning efficiency, which is particularly beneficial at ultra-high field strengths.

PurposeNeoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high-field (7T) P-31 magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes. MethodA dual-tuned quadrature coil that is a P-31 (120 MHz) transceiver and a H-1 (300 MHz) receiver was designed using a novel detune circuit. The transceiver/receiver coil in the axilla is used with a fractionated dipole antenna on the back of the subject and the conventional breast coil for transmit. ResultsThe novel circuit detuned the H-1 resonance without disturbing the P-31 resonance. In vivo demonstrations included: >80% homogeneous B-1(+) for H-1 over the axilla, identification of a small (3-mm diameter) lymph node, and P-31 MR spectra from a single healthy lymph node. The setup can detect ConclusionsThe first P-31 MR spectrum from an in vivo lymph node indicates that the presented design may be sufficiently sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of the lymph nodes at 7T is possible through combining lightweight antenna elements with dual-tuned transceiver/receive-only coils. Magn Reson Med 73:2038-2046, 2015. (c) 2014 Wiley Periodicals, Inc.

Purpose: To evaluate the 7 Tesla (T) MRI of the carotid arteries, as quantitatively compared with 3T. Materials and Methods: The 7T MRI of the carotid arteries was performed in six healthy subjects and in two patients with carotid stenosis. The healthy group was scanned at 3T and at 7T, using current coil setups at both field strengths. T1 and T2 values of the normal carotid vessel wall were assessed at both field strengths. B1+ maps and signal to noise ratio (SNR) maps were obtained, as well as T1 weighted images with a resolution as high as 0.4 × 0.4 × 1.5 mm3. Results: The T1 of the normal carotid vessel wall was found to be 1227 ± 47 ms at 3T and 1628 ± 130 ms at 7T, while a T2 of 55 ± 11 ms at 3T and 46 ± 4 ms at 7T was found. A twofold average gain in SNR at the carotid arteries was found with 7T. T1 weighted images showed an increased SNR at 7T for all subjects. Conclusion: Evaluation between 3T and 7T carotid MRI with optimized setups at both field strengths showed improved SNR at 7T, an increase in vessel wall T1 and a decrease in vessel wall T2.

The increased magnetic susceptibility effects at higher magnetic fields increase the demands for shimming of the B0 field for in vivo MRI and MRS. Both static and dynamic techniques have been developed to compensate for susceptibility-induced field inhomogeneities. In this study, we investigate the impact of and need for both static and dynamic higher order B0 shimming of magnetic field homogeneities in clinical breast MRI at 7 T. Both global and local field variations at lipid–tissue interfaces were observed in the magnetic field using TE-optimized B0 mapping at 7 T. With static B0 shimming, a field homogeneity of 39 ± 11 Hz (n = 48) was reached in a single breast using second-order shimming. Further compensation of the residual local field inhomogeneities caused by lipid–tissue interfaces does not seem to be feasible with shallow spherical harmonic fields. For bilateral shimming, the shimming quality was significantly less at 62 ± 15 Hz (n = 22) over both breasts, even after (simulated) fourth-order shimming. In addition, a substantial time-dependent field instability of 30 Hz peak to peak, with significant higher order field contributions, was observed during regular breathing. In conclusion, TE-optimized B0 field mapping reveals substantial field variations in the lipid-rich environment of the human breast, in both space and time. The static field variations could be partially minimized by third-order B0 shimming, providing sufficient lipid suppression. However, in order to fully benefit from the increased spectral dispersion at high fields, the significant magnetic field variations during breathing need to be considered. Copyright © 2014 John Wiley & Sons, Ltd.

The aim of this study was to detect microcalcifications in human whole breast specimens using high-field MRI. Four mastectomy specimens, obtained with approval of the institutional review board, were subjected to gradient-echo MRI acquisitions on a high-field MR scanner. The phase derivative was used to detect microcalcifications. The echo time and imaging resolution were varied to study the sensitivity of the proposed method. Computed tomography images of the mastectomy specimens and prior acquired mammography images were used to validate the results. A template matching algorithm was designed to detect microcalcifications automatically. The three spatial derivatives of the signal phase surrounding a field-perturbing object allowed three-dimensional localization, as well as the discrimination of diamagnetic field-perturbing objects, such as calcifications, and paramagnetic field-perturbing structures, e.g. blood. A longer echo time enabled smaller disturbances to be detected, but also resulted in shading as a result of other field-disturbing materials. A higher imaging resolution increased the detection sensitivity. Microcalcifications in a linear branching configuration that spanned over 8 mm in length were detected. After manual correction, the automatic detection tool identified up to 18 microcalcifications within the samples, which was in close agreement with the number of microcalcifications found on previously acquired in vivo mammography images. Microcalcifications can be detected by MRI in human whole breast specimens by the application of phase derivative imaging.

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity.In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

PURPOSE: Assess the potential gain in acceleration performance of a 256-channel versus 32-channel receive coil array at 7 T in combination with a 2D CAIPIRINHA sequence for 3D data sets. METHODS: A 256-channel receive setup was simulated by placing 2 small 16-channel high-density receive arrays at 2 × 8 different locations on the head of healthy participants. Multiple consecutive measurements were performed and coil sensitivity maps were combined to form a complete 256-channel data set. This setup was compared with a standard 32-channel head coil, in terms of SNR, noise correlation, and acceleration performance (g-factor). RESULTS: In the periphery of the brain, the receive SNR was on average a factor 1.5 higher (ranging up to a factor 2.7 higher) than the 32-channel coil; in the center of the brain the SNR was comparable or lower, depending on the size of the region of interest, with a factor 1.0 on average (ranging from 0.7 up to a factor of 1.6). The average noise correlation between coil elements was 3% for the 256-channel coil, and 5% for the 32-channel coil. At acceptable g-factors (< 2), the achievable acceleration factor using SENSE and 2D CAIPIRINHA was 24 and 28, respectively, versus 9 and 12 for the 32-channel coil. CONCLUSION: The receive performance of the simulated 256 channel array was better than the 32-channel reference. Combined with 2D CAIPIRINHA, a peak acceleration factor of 28 was assessed, showing great potential for high-density receive arrays.

Loss-of-function mutations in glutaminase (GLS), the enzyme converting glutamine into glutamate, and the counteracting enzyme glutamine synthetase (GS) cause disturbed glutamate homeostasis and severe neonatal encephalopathy. We report a de novo Ser482Cys gain-of-function variant in GLS encoding GLS associated with profound developmental delay and infantile cataract. Functional analysis demonstrated that this variant causes hyperactivity and compensatory downregulation of GLS expression combined with upregulation of the counteracting enzyme GS, supporting pathogenicity. Ser482Cys-GLS likely improves the electrostatic environment of the GLS catalytic site, thereby intrinsically inducing hyperactivity. Alignment of +/−12.000 GLS protein sequences from >1000 genera revealed extreme conservation of Ser482 to the same degree as catalytic residues. Together with the hyperactivity, this indicates that Ser482 is evolutionarily preserved to achieve optimal—but submaximal—GLS activity. In line with GLS hyperactivity, increased glutamate and decreased glutamine concentrations were measured in urine and fibroblasts. In the brain (both grey and white matter), glutamate was also extremely high and glutamine was almost undetectable, demonstrated with magnetic resonance spectroscopic imaging at clinical field strength and subsequently supported at ultra-high field strength. Considering the neurotoxicity of glutamate when present in excess, the strikingly high glutamate concentrations measured in the brain provide an explanation for the developmental delay. Cataract, a known consequence of oxidative stress, was evoked in zebrafish expressing the hypermorphic Ser482Cys-GLS and could be alleviated by inhibition of GLS. The capacity to detoxify reactive oxygen species was reduced upon Ser482Cys-GLS expression, providing an explanation for cataract formation. In conclusion, we describe an inborn error of glutamate metabolism caused by a GLS hyperactivity variant, illustrating the importance of balanced GLS activity.

Dynamic magnetic field shimming is gaining interest for field sensitive MRI acquisitions. Using slice based or real-time shim updating, significant improvements in static field (B0) uniformity can be obtained. While the ability to rapidly switch shim fields can improve overall B0 homogeneity, it induces eddy current fields that must be characterized and compensated for. Methods used to achieve this have thus far been based on linear projection spin echo sequences or field probe assemblies. Here, a novel image-based method is presented to measure and characterize eddy current fields without the need for field probes or projection based measurements. This technique can be extended to characterize very high order spherical harmonic fields, making it a useful tool to calibrate next-generation shim systems implementing dynamic field steering with greater than third order shim terms. Results are used to calibrate a Dynamic Shim Updating unit for pre-emphasis and eddy current compensation. Three-dimensional datasets are acquired at multiple MR facilities containing complete spatiotemporal field information to compensate eddy current field self- and cross-terms for up to third order. Furthermore, simulation studies are performed to investigate the effect of scan resolution and phantom size with respect to accurate eddy current field characterization. © 2014 Wiley Periodicals, Inc. Concepts Magn Reson Part A 42A: 245–260, 2013.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and has been associated with several cognitive functions that are known to change with age. In rodents and humans age-related glutamate changes have been found in several brain areas. In this cross-sectional study the presence and extent of age-associated glutamate changes in the medial frontal cortex of healthy young adults were measured. Proton magnetic resonance spectroscopy (1H-MRS) and brain imaging were performed at 7T in a 2×2×2cm3 voxel in 33 participants between 18 and 31 years old. Glutamate concentrations and grey and white matter volume could be successfully determined at an ultra-high magnetic field strength. Glutamate concentrations were lower in older individuals (0.33mM/year). This decline is in line with grey matter thinning in the medial frontal cortex, but could not be explained by cortical thinning alone. Therefore, the decrease in glutamate in young adulthood may be due to physiological changes rather than anatomical changes.

Purpose To evaluate the feasibility and reproducibility of free fatty acid (FFA) measurement for diagnosing adipose tissue dysfunction by 1H-magnetic resonance spectroscopy (1H-MRS) in different abdominal adipose tissue depots in healthy obese and lean subjects. Materials and Methods Polyunsaturated fatty acids (PUFA), total unsaturated fatty acids (TUFA), triglycerides (TG), and their ratios were determined in three adipose tissue depots of 12 obese and 13 lean subjects. Subjects underwent two separate examinations to assess reproducibility. Results In lean subjects, 44% of measurements failed due to inclusion of nonadipose tissue in the spectroscopy voxel, as opposed to 23% in obese subjects. Reproducibility of PUFA, TUFA, and TG was moderate to good in obese subjects (intraclass correlation coefficients [ICCs] 0.18–0.75), and poor to moderate in lean subjects (ICCs −1.04–0.55) in subcutaneous and omental adipose tissue. In the perirenal adipose tissue, ICCs were poor in both lean and obese subjects (−0.794–0.013). PUFA/TUFA and PUFA/TG were higher in omental adipose tissue in obese vs. lean subjects (35*10−3 vs. 0.16*10−3, P = 0.01 and 2.05*10−3 vs. 0.01*10−3, P = 0.02, respectively). Conclusion 1H-MRS is a feasible and reproducible method for FFA profiling in abdominal adipose tissue in abdominally obese individuals. 1H-MRS has potential as diagnostic tool for noninvasive identification of adipose tissue dysfunction. J. Magn. Reson. Imaging 2014;40:423–431. © 2013 Wiley Periodicals, Inc.

To assess the feasibility of 7-T contrast-enhanced breast MRI in patients with suspicious masses.Twenty patients with 23 suspicious breast masses on conventional imaging (mean size 13 mm, range 5-27 mm) were examined at 7 T. The MRI protocol included a dynamic series with injection of 0.1 mmol/kg gadobutrol (seven consecutive 3D T1-weighted gradient echo sequences, resolution 1 × 1 × 2 mm(3), temporal resolution 63 s) and ultra-high-resolution imaging (T1-weighted 3D gradient echo sequence, resolution 0.45 × 0.57 × 0.45 mm(3)). Two observers (R1 and R2) independently judged the examinations on image quality and classified lesions according to BI-RADS. The added value of ultra-high-resolution imaging was assessed.The image quality was deemed excellent in 1 and 0, good in 10 and 12, sufficient in 8 and 8, and insufficient in 1 and 0 for R1 and R2 respectively. Twenty of the 23 lesions were identified at 7-T MRI by both observers. All histopathologically proven malignant lesions (n = 19) were identified and classified as BI-RADS-MRI 4 or 5. Ultra-high-resolution imaging increased reader confidence in 88 % (R1) and 59 % (R2) of acquisitions.The study shows the feasibility of dynamic contrast-enhanced 7-T breast MRI, where all malignant mass lesions were identified by two observers.• Magnetic resonance imaging is important in the evaluation of breast cancer. • Recently, 7-T MRI has become available. • The 7-T dynamic contrast-enhanced breast MRI is feasible in patients. • The 7-T breast examinations are amenable to evaluation according to BI-RADS.

γ-Aminobutyric acid (GABA) and lactate are metabolites which are present in the brain. These metabolites can be indicators of psychiatric disorders or tumor hypoxia, respectively. The measurement of these weakly coupled spin systems can be performed using MRS editing techniques; however, at high field strength, this can be challenging. This is due to the low available B1 (+) field at high fields, which results in narrow-bandwidth refocusing pulses and, consequently, in large chemical shift displacement artifacts. In addition, as a result of the increased chemical shift displacement artifacts and chemical shift dispersion, the efficiency of the MRS method is reduced, even when using adiabatic refocusing pulses. To overcome this limitation, frequency offset corrected inversion (FOCI) pulses have been suggested as a mean to substantially increase the bandwidth of adiabatic pulses. In this study, a Mescher-Garwood semi-localization by adiabatic selection and refocusing (MEGA-sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA-sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths.

Purpose Intramolecular zero-quantum-coherences (ZQCs) are intrinsically insensitive toward magnetic field inhomogeneity. This fact is used to quantify and characterize lipid signals in the human breast at 7 T despite the presence of severe magnetic field inhomogeneity caused by water–lipid susceptibility boundaries. Methods A novel 3D localized 2D ZQC method is presented. The combination of cardiac/respiratory triggering and post-acquisition navigator echo correction provides high-quality 2D NMR spectra in vivo. Results The lipid profile of the human breast could be quantified by 2D ZQC NMR in 100% of the subjects despite a wide range of magnetic field homogeneity. With conventional 1D 1H MRS, the magnetic field homogeneity was only adequate in 60% of the subjects. The results from 2D ZQC NMR and 1D NMR are in good correspondence, both in vitro and in vivo. Conclusion It has been demonstrated that high quality and quantitative 2D ZQC NMR spectra can be acquired from human breast tissue at 7 T. While the simplicity and sensitivity of 1D MRS are preferable when the magnetic field homogeneity is adequate, the 2D ZQC method provides a viable alternative in cases where this requirement cannot be met. Magn Reson Med 71:451–457, 2014. © 2013 Wiley Periodicals, Inc.

Robust fat suppression is essential in bilateral breast MRI at 7 Tesla. The lack of good fat suppression can result in errors when calculating the enhancement curve from dynamic contrast-enhanced acquisitions. In this work we propose discretized frequency shimming to improve the quality of fat suppression by exploiting the capabilities of a parallel transmit setup.With discretized frequency shimming, different resonance frequencies are used for the different transmitters of the radiofrequency coil. This can be particularly useful for frequency-selective radiofrequency pulses, such as water excitation. The potential of this method has been investigated by simulations on seven acquired BSimulations show a decrease in off-resonance excitation for all subjects when discretized frequency shimming is used. This decrease is highly subject-dependent, but can result in up to 30% better fat suppression, as observed in phantom and volunteer experiments.Discretized frequency shimming improves fat suppression in bilateral breast MRI at 7 Tesla. Magn Reson Med 79:593-599, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The aim of this study is to compare the current state of lesion identification, the BI-RADS classification and the contrast-enhancement behavior at 7T and 3T breast MRI in the same patient group. Twenty-seven patients with thirty suspicious lesions were selected for this prospective study and underwent both 7T and 3T MRI. All examinations were rated by two radiologists (R1 and R2) independently on image quality, lesion identification and BI-RADS classification. We assessed sensitivity, specificity, NPV and PPV, observer agreement, lesion sizes, and contrast-enhancement-to-noise ratios (CENRs) of mass lesions. Fifteen of seventeen histopathological proven malignant lesions were detected at both field strengths. Image quality of the dynamic series was good at 7T, and excellent at 3T (P = 0.001 for R1 and P = 0.88 for R2). R1 found higher rates of specificity, NPV and PPV at 7T when compared to 3T, while R2 found the same results for sensitivity, specificity, NPV and PPV for both field strengths. The observers showed excellent agreement for BI-RADS categories at 7T (κ = 0.86) and 3T (κ = 0.93). CENRs were higher at 7T (P = 0.015). Lesion sizes were bigger at 7T according to R2 (P = 0.039). Our comparison study shows that 7T MRI allows BI-RADS conform analysis. Technical improvements, such as acquisition of T2w sequences and adjustment of B1+ field inhomogeneity, are still necessary to allow clinical use of 7T breast MRI.

Magnetic resonance spectroscopy (MRS) is a noninvasive technique that provides in vivo information about tissue metabolism. This article briefly describes the physical mechanisms of this powerful technique that enables imaging of endogenous markers for disease. Some examples are given of its current application in clinical use, thereby pointing out some pearls and pitfalls. In addition, new techniques for MRS and their potential for and impact on clinical use are discussed.