Indirect 1H-[13C] MRS of the human brain at 7 T using a 13C-birdcage coil and eight transmit-receive 1H-dipole antennas with a 32-channel 1H-receive array.

The neuronal tricarboxylic acid and glutamate/glutamine (Glu/Gln) cycles play important roles in brain function. These processes can be measured in vivo using dynamic 1H-[13C] MRS during administration of 13C-labeled glucose. Proton-observed carbon-edited (POCE) MRS enhances the signal-to-noise ratio (SNR) compared with direct 13C-MRS. Ultra-high field further boosts the SNR and increases spectral dispersion; however, even at 7 T, Glu and Gln 1H-resonances may overlap. Further gain can be obtained with selective POCE (selPOCE). Our aim was to create a setup for indirect dynamic 1H-[13C] MRS in the human brain at 7 T. A home-built non-shielded transmit-receive 13C-birdcage head coil with eight transmit-receive 1H-dipole antennas was used together with a 32-channel 1H-receive array. Electromagnetic simulations were carried out to ensure that acquisitions remained within local and global head SAR limits. POCE-MRS was performed using slice-selective excitation with semi-localization by adiabatic selective refocusing (sLASER) and stimulated echo acquisition mode (STEAM) localization, and selPOCE-MRS using STEAM. Sequences were tested in a phantom containing non-enriched Glu and Gln, and in three healthy volunteers during uniformly labeled 13C-glucose infusions. In one subject the voxel position was alternated between bi-frontal and bi-occipital placement within one session. [4-13C]Glu-H4 and [4-13C]Gln-H4 signals could be separately detected using both STEAM-POCE and STEAM-selPOCE in the phantom. In vivo, [4,5-13C]Glx could be detected using both sLASER-POCE and STEAM-POCE, with similar sensitivities, but [4,5-13C]Glu and [4,5-13C]Gln signals could not be completely resolved. STEAM-POCE was alternately performed bi-frontal and bi-occipital within a single session without repositioning of the subject, yielding similar results. With STEAM-selPOCE, [4,5-13C]Glu and [4,5-13C]Gln could be clearly separated. We have shown that with our setup indirect dynamic 1H-[13C] MRS at 7 T is feasible in different locations in the brain within one session, and by using STEAM-selPOCE it is possible to separate Glu from Gln in vivo while obtaining high quality spectra.

Measurement of metabolite levels and treatment-induced changes in hepatic metastases of gastro-esophageal cancer using 7-T phosphorus magnetic resonance spectroscopic imaging.

Methods for early treatment response evaluation to systemic therapy of liver metastases are lacking. Tumor tissue often exhibits an increased ratio of phosphomonoesters to phosphodiesters (PME/PDE), which can be noninvasively measured by phosphorus magnetic resonance spectroscopy (31P MRS), and may be a marker for early therapy response assessment in liver metastases. However, with commonly used 31P surface coils for liver 31P MRS, the liver is not fully covered, and metastases may be missed. The objective of this study was to demonstrate the feasibility of 31P MRS imaging (31P MRSI) with full liver coverage to assess 31P metabolite levels and chemotherapy-induced changes in liver metastases of gastro-esophageal cancer, using a 31P whole-body birdcage transmit coil in combination with a 31P body receive array at 7 T. 3D 31P MRSI data were acquired in two patients with hepatic metastases of esophageal cancer, before the start of chemotherapy and after 2 (and 9 in patient 2) weeks of chemotherapy. 3D 31P MRSI acquisitions were performed using an integrated 31P whole-body transmit coil in combination with a 16-channel body receive array at 7 T, with a field of view covering the full abdomen and a nominal voxel size of 20-mm isotropic. From the 31P MRSI data, 12 31P metabolite signals were quantified. Prior to chemotherapy initiation, both PMEs, that is, phosphocholine (PC) and phosphoethanolamine (PE), were significantly higher in all metastases compared with the levels previously determined in the liver of healthy volunteers. After 2 weeks of chemotherapy, PC and PE levels remained high or even increased further, resulting in increased PME/PDE ratios compared with healthy liver tissue, in correspondence with the clinical assessment of progressive disease after 2 months of chemotherapy. The suggested approach may present a viable tool for early therapy (non)response assessment of tumor metabolism in patients with liver metastases.

Human Brain Deuterium Metabolic Imaging at 7 T: Impact of Different [6,6'-2H2]Glucose Doses.

BACKGROUND: Deuterium metabolic imaging (DMI) is an innovative, noninvasive metabolic MR imaging method conducted after administration of 2H-labeled substrates. DMI after [6,6'-2H2]glucose consumption has been used to investigate brain metabolic processes, but the impact of different [6,6'-2H2]glucose doses on DMI brain data is not well known. PURPOSE: To investigate three different [6,6'-2H2]glucose doses for DMI in the human brain at 7 T. STUDY TYPE: Prospective. POPULATION: Six healthy participants (age: 28 ± 8 years, male/female: 3/3). FIELD STRENGTH/SEQUENCE: 7 T, 3D 2H free-induction-decay (FID)-magnetic resonance spectroscopic imaging (MRSI) sequence. ASSESSMENT: Three subjects received two different doses (0.25 g/kg, 0.50 g/kg or 0.75 g/kg body weight) of [6,6'-2H2]glucose on two occasions and underwent consecutive 2H-MRSI scans for 120 minutes. Blood was sampled every 10 minutes during the scan, to determine plasma glucose levels and plasma 2H-Glucose atom percent excess (APE) (part-1). Three subjects underwent the same protocol once after receiving 0.50 g/kg [6,6'-2H2]glucose (part-2). STATISTICAL TEST: Mean plasma 2H-Glucose APE and glucose plasma concentrations were compared using one-way ANOVA. Brain 2H-Glc and brain 2H-Glx (part-1) were analyzed with a two-level Linear Mixed Model. In part-2, a General Linear Model was used to compare brain metabolite signals. Statistical significance was set at P < 0.05. RESULTS: Between 60 and 100 minutes after ingesting [6,6'-2H2]glucose, plasma 2H-Glc APE did not differ between 0.50 g/kg and 0.75 g/kg doses (P = 0.961), but was significantly lower for 0.25 g/kg. Time and doses significantly affected brain 2H-Glucose levels (estimate ± standard error [SE]: 0.89 ± 0.01, 1.09 ± 0.01, and 1.27 ± 0.01, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively) and brain 2H-Glutamate/Glutamine levels (estimate ± SE: 1.91 ± 0.03, 2.27 ± 0.03, and 2.46 ± 0.03, for 0.25 g/kg, 0.50 g/kg, and 0.75 g/kg, respectively). Plasma 2H-Glc APE, brain 2H-Glc, and brain 2H-Glx levels were comparable among subjects receiving 0.50 g/kg [6,6'-2H2]glucose. DATA CONCLUSION: Brain 2H-Glucose and brain 2H-Glutamate/Glutamine showed to be [6,6'-2H2]glucose dose dependent. A dose of 0.50 g/kg demonstrated comparable, and well-detectable, 2H-Glucose and 2H-Glutamate/Glutamine signals in the brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

31 P MR Spectroscopy in the Pancreas: Repeatability, Comparison With Liver, and Pilot Pancreatic Cancer Data.

BACKGROUND: Non-invasive evaluation of phosphomonoesters (PMEs) and phosphodiesters (PDEs) by 31-phosphorus MR spectroscopy (31 P MRS) may have potential for early therapy (non-)response assessment in cancer. However, 31 P MRS has not yet been applied to investigate the human pancreas in vivo. PURPOSE: To assess the technical feasibility and repeatability of 31 P MR spectroscopic imaging (MRSI) of the pancreas, compare 31 P metabolite levels between pancreas and liver, and determine the feasibility of 31 P MRSI in pancreatic cancer. STUDY TYPE: Prospective cohort study. POPULATION: 10 healthy subjects (age 34 ± 12 years, four females) and one patient (73-year-old female) with pancreatic ductal adenocarcinoma. FIELD STRENGTH/SEQUENCE: 7-T, 31 P FID-MRSI, 1 H gradient-echo MRI. ASSESSMENT: 31 P FID-MRSI of the abdomen (including the pancreas and liver) was performed with a nominal voxel size of 20 mm (isotropic). For repeatability measurements, healthy subjects were scanned twice on the same day. The patient was only scanned once. Test-retest 31 P MRSI data of pancreas and liver voxels (segmented on 1 H MRI) of healthy subjects were quantified by fitting in the time domain and signal amplitudes were normalized to γ-adenosine triphosphate. In addition, the PME/PDE ratio was calculated. Metabolite levels were averaged over all voxels within the pancreas, right liver lobe and left liver lobe, respectively. STATISTICAL TESTS: Repeatability of test-retest data from healthy pancreas was assessed by paired t-tests, Bland-Altman analyses, and calculation of the intrasubject coefficients of variation (CoVs). Significant differences between healthy pancreas and right and left liver lobes were assessed with a two-way analysis of variance (ANOVA) for repeated measures. A P-value <0.05 was considered statistically significant. RESULTS: The intrasubject CoVs for PME, PDE, and PME/PDE in healthy pancreas were below 20%. Furthermore, PME and PME/PDE were significantly higher in pancreas compared to liver. In the patient with pancreatic cancer, qualitatively, elevated relative PME signals were observed in comparison with healthy pancreas. DATA CONCLUSION: In vivo 31 P MRSI of the human healthy pancreas and in pancreatic cancer may be feasible at 7 T. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

An RF coil design to enable quintuple nuclear whole-brain MRI.

PURPOSE: To bring metabolic imaging based on multi-NMR toward practical use from the RF hardware perspective. METHODS: A highly integrated RF coil is designed for whole-brain MRI and MRS targeted to five nuclear species: 1 H, 19 F, 31 P, 23 Na, and 13 C. Dipole antennas and closely loaded local receiver loops are combined in this setup. RESULTS: High-quality in vivo scan results of 1 H, 31 P, 23 Na, and 13 C on healthy volunteers have been achieved. For 1 H, the transmit efficiency is 77% of a single-tuned commercial head coil (NOVA 8-transmit [Tx]/32-receive [Rx]; NOVA Medical, Wilmington, MA, USA). For 31 P, 110% SNR of a dual-tuned close-fit head-birdcage was achieved at the center of the subject, based on MR experiments on a phantom. For 31 P, 23 Na, and 13 C, bench measurements indicate SNR loss of 15%, 27%, and 30% compared with single-tuned conditions. 19 F performance has been proven to be similar to that of 1 H through bench tests and electromagnetic simulations. CONCLUSION: With this device, 1 H-based anatomic images that are expected to meet clinical requirements, as well as high-quality multi-NMR images and spectra, can be acquired within one scan session without hardware replacement or patient repositioning, enabling morphologic and metabolic MRI within acceptable scan time.

In vivo phosphorus magnetic resonance spectroscopic imaging of the whole human liver at 7 T using a phosphorus whole-body transmit coil and 16-channel receive array: Repeatability and effects of principal component analysis-based denoising.

Quantitative three-dimensional (3D) imaging of phosphorus (31 P) metabolites is potentially a promising technique with which to assess the progression of liver disease and monitor therapy response. However, 31 P magnetic resonance spectroscopy has a low sensitivity and commonly used 31 P surface coils do not provide full coverage of the liver. This study aimed to overcome these limitations by using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T. Using this setup, we determined the repeatability of whole-liver 31 P magnetic resonance spectroscopic imaging (31 P MRSI) in healthy subjects and assessed the effects of principal component analysis (PCA)-based denoising on the repeatability parameters. In addition, spatial variations of 31 P metabolites within the liver were analyzed. 3D 31 P MRSI data of the liver were acquired with a nominal voxel size of 20 mm isotropic in 10 healthy volunteers twice on the same day. Data were reconstructed without denoising, and with PCA-based denoising before or after channel combination. From the test-retest data, repeatability parameters for metabolite level quantification were determined for 12 31 P metabolite signals. On average, 31 P MR spectra from 100 ± 25 voxels in the liver were analyzed. Only voxels with contamination from skeletal muscle or the gall bladder were excluded and no voxels were discarded based on (low) signal-to-noise ratio (SNR). Repeatability for most quantified 31 P metabolite levels in the liver was good to excellent, with an intrasubject variability below 10%. PCA-based denoising increased the SNR ~ 3-fold, but did not improve the repeatability for mean liver 31 P metabolite quantification with the fitting constraints used. Significant spatial heterogeneity of various 31 P metabolite levels within the liver was observed, with marked differences for the phosphomonoester and phosphodiester metabolites between the left and right lobe. In conclusion, using a 31 P whole-body transmit coil in combination with a 16-channel 31 P receive array at 7 T allowed 31 P MRSI acquisitions with full liver coverage and good to excellent repeatability.

No need to detune transmitters in 32-channel receiver arrays at 7 T.

Ultrahigh field magnetic resonance imaging facilitates high spatiotemporal resolution that benefits from increasing the number of receiver elements. Because high-density receiver arrays have a relatively small element size compared with the transmitter, a side effect is that such setups cause low flux coupling between the transmitter and receiver. Moreover, when transmitters are designed in a multitransmit configuration, their relative size is much smaller than the sample, reducing coupling to the sample and thereby potentially also the coupling to the receivers. Transmitters are traditionally detuned during reception. In this study, we investigate, for a 32-channel receiver head array at 7 T, if transmitter detuning of a quadrature birdcage or of an eight-channel transmit coil can be omitted without substantially sacrificing signal-to-noise ratio (SNR). The transmit elements are operated once with and once without detuning and, in the latter, the received signals are either merged with the array or excluded for image reconstruction. For each of the three measurements, SNR and 1/g-factor maps are investigated. The tuning of the quadrature and eight-channel transmit coils during signal reception introduced a 10.1% and 6.5% penalty in SNR, respectively, relative to the SNR received with detuned transmitters. When also incorporating the signal of the transmit coils, the SNR was regained to 98.5% or 101.4% for the quadrature and eight-channel coil, respectively, relative to the detuned transmitters, while the 1/g-factor maps improved slightly. For the 32-channel receive coil used the SNR penalty can become negligible when omitting detuning of the transmit coils. This not only simplifies transmit coil designs, potentially increasing their efficiency, but also enables the transmitters to be used as receivers in parallel to the receiver array, thus increasing parallel imaging performance.

Maximizing sensitivity for fast GABA edited spectroscopy in the visual cortex at 7 T.

The combination of functional MRI (fMRI) and MRS is a promising approach to relate BOLD imaging to neuronal metabolism, especially at high field strength. However, typical scan times for GABA edited spectroscopy are of the order of 6-30 min, which is long compared with functional changes observed with fMRI. The aim of this study is to reduce scan time and increase GABA sensitivity for edited spectroscopy in the human visual cortex, by enlarging the volume of activated tissue in the primary visual cortex. A dedicated setup at 7 T for combined fMRI and GABA MRS is developed. This setup consists of a half volume multi-transmit coil with a large screen for visual cortex activation, two high density receive arrays and an optimized single-voxel MEGA-sLASER sequence with macromolecular suppression for signal acquisition. The coil setup performance as well as the GABA measurement speed, SNR, and stability were evaluated. A 2.2-fold gain of the average SNR for GABA detection was obtained, as compared with a conventional 7 T setup. This was achieved by increasing the viewing angle of the participant with respect to the visual stimulus, thereby activating almost the entire primary visual cortex, allowing larger spectroscopy measurement volumes and resulting in an improved GABA SNR. Fewer than 16 signal averages, lasting 1 min 23 s in total, were needed for the GABA fit method to become stable, as demonstrated in three participants. The stability of the measurement setup was sufficient to detect GABA with an accuracy of 5%, as determined with a GABA phantom. In vivo, larger variations in GABA concentration are found: 14-25%. Overall, the results bring functional GABA detections at a temporal resolution closer to the physiological time scale of BOLD cortex activation.

A 3-slice cardiac quantitative native and post-contrast T1 and T2 MRI protocol requiring only four BHs using a 72-channel receive array coil.

Introduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel-imaging approach with a 72-channel receive-array to reduce BHs and demonstrate this in healthy subjects and hypertrophic cardiomyopathy (HCM) patients. Methods: A T1/T2 phantom was scanned at 3 T using a 16-channel and a novel 72-channel coil to assess the impact of different coils and acceleration factors on relaxation times. 16-18 healthy participants (8 female, age 28.4 ± 5.1 years) and 3 HCM patients (3 male, age 55.3 ± 4.2 years) underwent cardiac-MRI with the 72-channel coil, using a Modified Look-Locker scan with a shared inversion pulse across 3 slices and a Gradient-Spin-Echo scan. Acceleration was done by sensitivity encoding (SENSE) with accelerations 2, 4, and 6. LV T1 and T2 values were analyzed globally, per slice, and in 16 segments, with SENSE = 2 as the reference. Results: The phantom scans revealed no bias between coils and acceleration factors for T1 or T2, except for T2 with SENSE = 2, which resulted in a bias of 8.0 ± 6.7 ms (p < 0.001) between coils. SENSE = 4 and 6 enabled T1 mapping of three slices in a single BH, and T2 mapping of three slices within two BHs. In healthy subjects, T1 and T2 values varied. We found an average overestimation of T1 in 3 slices of 25 ± 87 ms for SENSE = 4 and 30 ± 103 ms using SENSE = 6, as compared to SENSE = 2. Acceleration resulted in decreased signal-to-noise; however, visually insignificant and without increased incidence of SENSE-artifacts. T2 was overestimated by 2.1 ± 5.0 ms for SENSE = 4 and 6.4 ± 9.7 ms using SENSE = 6, as compared to SENSE = 2. Native and post-contrast T1 measurements with SENSE = 4 and ECV quantification in HCM patients was successful. Conclusion: The 72-channel receiver-array coil with SENSE = 4 and 6, enabled LV-tissue characterization in three slices. Pre- and post-contrast T1 maps were obtained in a single BH, while T2 required two BHs.

A 72-channel receive array coil allows whole-heart cine MRI in two breath holds.

BACKGROUND: A new 72-channel receive array coil and sensitivity encoding, compressed (C-SENSE) and noncompressed (SENSE), were investigated to decrease the number of breath-holds (BHs) for cardiac magnetic resonance (CMR). METHODS: Three-T CMRs were performed using the 72-channel coil with SENSE-2/4/6 and C-SENSE-2/4/6 accelerated short-axis cine two-dimensional balanced steady-state free precession sequences. A 16-channel coil with SENSE-2 served as reference. Ten healthy subjects were included. BH-time was kept under 15 s. Data were compared in terms of image quality, biventricular function, number of BHs, and scan times. RESULTS: BHs decreased from 7 with C-SENSE-2 (scan time 70 s, 2 slices/BH) to 3 with C-SENSE-4 (scan time 42 s, 4-5 slices/BH) and 2 with C-SENSE-6 (scan time 28 s, 7 slices/BH). Compared to reference, image sharpness was similar for SENSE-2/4/6, slightly inferior for C-SENSE-2/4/6. Blood-to-myocardium contrast was unaffected. C-SENSE-4/6 was given lower qualitative median scores, but images were considered diagnostically adequate to excellent, with C-SENSE-6 suboptimal. Biventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes, ejection fractions (EF), cardiac outputs, and left ventricle (LV)-mass were similar for SENSE-2/4/6 with no systematic bias and clinically appropriate limits of agreements. C-SENSE slightly underestimated LV-EDV (-6.38 ± 6.0 mL, p < 0.047), LV-ESV (-7.94 ± 6.0 mL, p < 0.030) and overestimated LV-EF (3.16 ± 3.10%; p < 0.047) with C-SENSE-4. Bland-Altman analyses revealed minor systematic biases in these variables with C-SENSE-2/4/6 and for LV-mass with C-SENSE-6. CONCLUSIONS: Using the 72-channel coil, short-axis CMR for quantifying biventricular function was feasible in two BHs where SENSE slightly outperformed C-SENSE.

A mask-compatible, radiolucent, 8-channel head and neck receive array for MRI-guided radiotherapy treatments and pre-treatment simulation.

Immobilization masks are used to prevent patient movement during head and neck (H&N) radiotherapy. Motion restriction is beneficial both during treatment, as well as in the pre-treatment simulation phase, where magnetic resonance imaging (MRI) is often used for target definition. However, the shape and size of the immobilization masks hinder the use of regular, close-fitting MRI receive arrays. In this work, we developed a mask-compatible 8-channel H&N array that consists of a single-channel baseplate, on which the mask can be secured, and a flexible 7-channel anterior element that follows the shape of the mask. The latter uses high impedance coils to achieve its flexibility and radiolucency. A fully-functional prototype was manufactured, its radiolucency was characterized, and the gain in imaging performance with respect to current clinical setups was quantified. Dosimetry measurements showed an overall dose change of -0.3%. Small, local deviations were up to -2.7% but had no clinically significant impact on a full treatment plan, as gamma pass rates (3%/3 mm) only slightly reduced from 97.9% to 97.6% (clinical acceptance criterion: ≥95%). The proposed H&N array improved the imaging performance with respect to three clinical setups. The H&N array more than doubled (+123%) and tripled (+246%) the signal-to-noise ratio with respect to the clinical MRI-simulation and MR-linac setups, respectively.G-factors were also lower with the proposed H&N array. The improved imaging performance resulted in a clearly visible signal-to-noise ratio improvement of clinically used TSE and DWI acquisitions. In conclusion, the 8-channel H&N array improves the imaging performance of MRI-simulation and MR-linac acquisitions, while dosimetry suggests that no clinically significant dose changes are induced.

Confirmatory factor analysis including MRI-derived adipose tissues quantification improves associations of metabolic dysregulation to diastolic dysfunction.

AIMS: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. METHODS: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. RESULTS: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolic-load factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. CONCLUSION: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased left-ventricular diastolic function, more apparent in females than in males.