First implementation of dynamic oxygen-17 (17O) magnetic resonance imaging at 7 Tesla during neuronal stimulation in the human brain.

OBJECTIVE: First implementation of dynamic oxygen-17 (17O) MRI at 7 Tesla (T) during neuronal stimulation in the human brain. METHODS: Five healthy volunteers underwent a three-phase 17O gas (17O2) inhalation experiment. Combined right-side visual stimulus and right-hand finger tapping were used to achieve neuronal stimulation in the left cerebral hemisphere. Data analysis included the evaluation of the relative partial volume (PV)-corrected time evolution of absolute 17O water (H217O) concentration and of the relative signal evolution without PV correction. Statistical analysis was performed using a one-tailed paired t test. Blood oxygen level-dependent (BOLD) experiments were performed to validate the stimulation paradigm. RESULTS: The BOLD maps showed significant activity in the stimulated left visual and sensorimotor cortex compared to the non-stimulated right side. PV correction of 17O MR data resulted in high signal fluctuations with a noise level of 10% due to small regions of interest (ROI), impeding further quantitative analysis. Statistical evaluation of the relative H217O signal with PV correction (p = 0.168) and without (p = 0.382) did not show significant difference between the stimulated left and non-stimulated right sensorimotor ROI. DISCUSSION: The change of cerebral oxygen metabolism induced by sensorimotor and visual stimulation is not large enough to be reliably detected with the current setup and methodology of dynamic 17O MRI at 7 T.

First application of dynamic oxygen-17 magnetic resonance imaging at 7 Tesla in a patient with early subacute stroke.

Dynamic oxygen-17 (17O) magnetic resonance imaging (MRI) is an imaging method that enables a direct and non-invasive assessment of cerebral oxygen metabolism and thus potentially the distinction between viable and non-viable tissue employing a three-phase inhalation experiment. The purpose of this investigation was the first application of dynamic 17O MRI at 7 Tesla (T) in a patient with stroke. In this proof-of-concept experiment, dynamic 17O MRI was applied during 17O inhalation in a patient with early subacute stroke. The analysis of the relative 17O water (H217O) signal for the affected stroke region compared to the healthy contralateral side revealed no significant difference. However, the technical feasibility of 17O MRI has been demonstrated paving the way for future investigations in neurovascular diseases.

Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma.

Background Altered metabolism is a characteristic of cancer. Because of a shift in glucose metabolism from oxidative phosphorylation to lactate production for energy generation, malignant tumors are characterized by increased glycolysis followed by lactic acid fermentation, even in the presence of abundant oxygen (the Warburg effect). Purpose To quantitatively investigate dynamic oxygen 17 (17O) MRI in healthy participants and participants with untreated glioma to understand altered cerebral oxygen metabolism in glioma. Materials and Methods In this prospective study conducted from September 2016 to June 2018, individuals with newly diagnosed previously untreated glioma (World Health Organization grade II-IV) and healthy volunteers were included. Dynamic 17O MRI was performed with a 7.0-T whole-body system. 17O2 gas inhalation enabled dynamic measurement of the cerebral metabolic rate of oxygen (CMRO2) consumption. In healthy volunteers and participants with glioma, CMRO2 values in gray matter and white matter volumes were compared by using Wilcoxon signed rank tests. In participants with glioma, the tumor volume and tumor subcompartments were compared with normal-appearing gray matter and white matter by using Friedman test followed by Holm-Sidak post hoc tests. Results Ten participants (mean age, 42 years ± 18 [standard deviation]; nine men) with glioma and three healthy volunteers (mean age, 44 years ± 21; all men) were evaluated. CMRO2 was higher in normal-appearing gray matter compared with white matter in both participants with glioma (2.36 µmol/g/min ± 0.22 vs 0.75 µmol/g/min ± 0.10, respectively) and healthy volunteers (2.38 µmol/g/min ± 0.15 vs 0.63 µmol/g/min ± 0.05, respectively) (P < .001 and P = .03, respectively). In the tumor region, CMRO2 was reduced (high-grade tumor CMRO2, 0.23 µmol/g/min ± 0.07; low-grade tumor CMRO2, 0.39 µmol/g/min ± 0.16; overall CMRO2, 0.34 µmol/g/min ± 0.16) compared with normal-appearing gray matter (P < .001) and normal-appearing white matter (P < .001) in accordance with the Warburg theorem. Conclusion Dynamic oxygen 17 MRI method at 7.0 T as a direct metabolic imaging technique in glioma enabled quantitative visualization of the Warburg effect. A general reduction in oxidative glycolysis was observed in accordance with the Warburg theorem. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Rapalino in this issue.

Comparison of optimized intensity correction methods for 23Na MRI of the human brain using a 32-channel phased array coil at 7 Tesla.

PURPOSE: To correct for the non-homogeneous receive profile of a phased array head coil in sodium magnetic resonance imaging (23Na MRI). METHODS: 23Na MRI of the human brain (n = 8) was conducted on a 7T MR system using a dual-tuned quadrature 1H/23Na transmit/receive birdcage coil, equipped with a 32-channel receive-only array. To correct the inhomogeneous receive profile four different methods were applied: (1) the uncorrected phased array image and an additionally acquired birdcage image as reference image were low-pass filtered and divided by each other. (2) The second method substituted the reference image by a support region. (3) By averaging the individually calculated receive profiles, a universal sensitivity map was obtained and applied. (4) The receive profile was determined by a pre-scanned large uniform phantom. The calculation of the sensitivity maps was optimized in a simulation study using the normalized root-mean-square error (NRMSE). All methods were evaluated in phantom measurements and finally applied to in vivo 23Na MRI data sets. The in vivo measurements were partial volume corrected and for further evaluation the signal ratio between the outer and inner cerebrospinal fluid compartments (CSFout:CSFin) was calculated. RESULTS: Phantom measurements show the correction of the intensity profile applying the given methods. Compared to the uncorrected phased array image (NRMSE = 0.46, CSFout:CSFin = 1.71), the quantitative evaluation of simulated and measured intensity corrected human brain data sets indicates the best performance utilizing the birdcage image (NRMSE = 0.39, CSFout:CSFin = 1.00). However, employing a support region (NRMSE = 0.40, CSFout:CSFin = 1.17), a universal sensitivity map (NRMSE = 0.41, CSFout:CSFin = 1.05) or a pre-scanned sensitivity map (NRMSE = 0.42, CSFout:CSFin = 1.07) shows only slightly worse results. CONCLUSION: Acquiring a birdcage image as reference image to correct for the receive profile demonstrates the best performance. However, when aiming to reduce acquisition time or for measurements without existing birdcage coil, methods that use a support region as reference image, a universal or a pre-scanned sensitivity map provide good alternatives for correction of the receive profile.

Multinuclear MRI at Ultrahigh Fields.

In this article, an overview of the current developments and research applications for non-proton magnetic resonance imaging (MRI) at ultrahigh magnetic fields (UHFs) is given. Due to technical and methodical advances, efficient MRI of physiologically relevant nuclei, such as Na, Cl, Cl, K, O, or P has become feasible and is of interest to obtain spatially and temporally resolved information that can be used for biomedical and diagnostic applications. Sodium (Na) MRI is the most widespread multinuclear imaging method with applications ranging over all regions of the human body. Na MRI yields the second largest in vivo NMR signal after the clinically used proton signal (H). However, other nuclei such as O and P (energy metabolism) or Cl and K (cell viability) are used in an increasing number of MRI studies at UHF. One major advancement has been the increased availability of whole-body MR scanners with UHFs (B0 ≥7T) expanding the range of detectable nuclei. Nevertheless, efforts in terms of pulse sequence and post-processing developments as well as hardware designs must be made to obtain valuable information in clinically feasible measurement times. This review summarizes the available methods in the field of non-proton UHF MRI, especially for Na MRI, as well as introduces potential applications in clinical research.

Corrections of myocardial tissue sodium concentration measurements in human cardiac 23 Na MRI at 7 Tesla.

PURPOSE: To quantify the tissue sodium concentration (TSC) in cardiac 23 Na MRI. To evaluate the influence of different correction methods on the measured myocardial TSC. METHODS: 23 Na MRI of four healthy subjects was conducted at a whole-body 7T MRI system using an oval-shaped 23 Na birdcage coil. Data acquisition was performed with a density-adapted 3D radial pulse sequence using a golden angle projection scheme. 1 H MRI data were acquired at a 3T MRI system to generate a myocardial mask. Retrospective cardiac and respiratory gating were used to reconstruct 23 Na MRI data in the diastolic phase and exhaled state. B0 and B1 inhomogeneity and partial volume (PV) effects were corrected. Relaxation times and TSC of ex vivo blood samples and calf muscle were determined. These values were used in the PV correction to estimate myocardial TSC, which was compared with the measured TSC of calf muscle. RESULTS: Without any correction the measured myocardial TSC was (54 ± 5) mM. The applied correction methods reduced these values by (48 ± 5)% to (29 ± 3) mM, where PV correction had the largest effect (reduction of (34 ± 1)%). Respiratory and cardiac motion gating decreased the concentrations by (11 ± 1)%. With the applied setup, the corrections of B0 and B1 inhomogeneity (reduction of (3 ± 2)%) had negligible influences on TSC values. The resulting myocardial TSC was approximately 1.4-fold higher than the measured TSC of calf muscle tissue of the same healthy subjects ((20 ± 3) mM). CONCLUSION: For quantitative human cardiac 23 Na MRI several corrections are needed and ranked for our setup: PV correction, respiratory and cardiac gating, correction for B1 inhomogeneity effects.

Reproducibility of CMRO2 determination using dynamic 17 O MRI.

PURPOSE: To assess the reproducibility of 17 O MRI-based determination of the cerebral metabolic rate of oxygen consumption (CMRO2 ) in healthy volunteers. To assess the influence of image acquisition and reconstruction parameters on dynamic quantification of functional parameters such as CMRO2 . METHODS: Dynamic 17 O MRI data were simulated and used to investigate influences of temporal resolution (Δt) and partial volume correction (PVC) on the determination of CMRO2 . Three healthy volunteers were examined in two separate examinations. In vivo 17 O MRI measurements were conducted with a nominal spatial resolution of (7.5 mm)3 using a density-adapted radial sequence with golden angle acquisition scheme. In each measurement, 4.0 ± 0.1 L of 70%-enriched 17 O gas were administered using a rebreathing system. Data were corrected with a PVC algorithm, and CMRO2 was determined in gray matter (GM) and white matter (WM) compartments using a three-phase metabolic model (baseline, 17 O inhalation, decay phase). RESULTS: Comparison with the ground truth of simulations revealed improved CMRO2 determination after application of PVC and with Δt ≤ 2:00 min. Evaluation of in vivo data yields to CMRO2,GM = 2.31 ± 0.1 µmol/g/min and to CMRO2,WM = 0.69 ± 0.04 µmol/g/min with coefficients of variation (CoV) of 0.3-5.5% and 4.3-5.0% for intra-volunteer and inter-volunteer data, respectively. CONCLUSION: This in vivo 17 O inhalation study demonstrated that the proposed experimental setup enables reproducible determination of CMRO2 in healthy volunteers. Magn Reson Med 79:2923-2934, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Improved T*2 determination in 23Na, 35Cl, and 17O MRI using iterative partial volume correction based on 1H MRI segmentation.

OBJECTIVE: Functional parameters can be measured with the help of quantitative non-proton MRI where exact relaxometry parameters are needed. Investigation of [Formula: see text] is often biased by strong partial volume (PV) effects. Hence, in this work a PV correction algorithm approach was evaluated that uses iteratively adapted [Formula: see text]-values and high-resolution structural 1H data to determine transverse relaxation in non-proton MRI more accurately. MATERIALS AND METHODS: Simulations, a phantom study and in vivo 23Na, 17O and 35Cl MRI measurements of five healthy volunteers were performed to evaluate the algorithm. [Formula: see text] values of grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) were obtained. Data were acquired at B 0  = 7T with nominal spatial resolutions of (4-7 mm)3 using a density-adapted radial sequence. The resulting transverse relaxation times were used for quantification of 17O data. RESULTS: The conducted simulations and phantom study verified the correction performance of the algorithm. For in vivo measured [Formula: see text] values, the correction of PV effects leads to an increase in CSF and to a decrease in GM/WM (23Na MRI: long/short GM, WM [Formula: see text]: 36.4 ± 3.1/5.4 ± 0.2, 23.3 ± 2.6/3.5 ± 0.1 ms; 35Cl MRI: 8.9 ± 1.4/1.0 ± 0.4, 5.9 ± 0.3/0.4 ± 0.1 ms; 17O MRI: 2.5 ± 0.1, 2.8 ± 0.1 ms). Iteratively corrected in vivo [Formula: see text] values of the 17O study resulted in improved water content quantification. CONCLUSION: The proposed iterative algorithm for PV correction leads to more accurate [Formula: see text] values and, thus, can improve accuracy in quantitative non-proton MRI.

Partial volume correction for in vivo (23)Na-MRI data of the human brain.

The concentration of sodium is a functional cell parameter and absolute quantification can be interesting for diagnostical purposes. The accuracy of sodium magnetic resonance imaging ((23)Na-MRI) is strongly biased by partial volume effects (PVEs). Hence our purpose was to establish a partial volume correction (PVC) method for (23)Na-MRI. The existing geometric transfer matrix (GTM) correction method was transferred from positron emission tomography (PET) to (23)Na-MRI and tested in a phantom study. Different parameters, as well as accuracy of registration and segmentation were evaluated prior to first in vivo measurements. In vivo sodium data-sets of the human brain were obtained at B0=7T with a nominal spatial resolution of (3mm)(3) using a density adapted radial pulse sequence. A volunteer study with four healthy subjects was performed to measure partial volume (PV) corrected tissue sodium concentration (TSC) which was verified by means of an intrinsic correction control. In the phantom study the PVC algorithm yielded a good correction performance and reduced the discrepancy between the measured sodium concentration value and the expected value in the smallest compartments of the phantom by 11% to a mean PVE induced discrepancy of 5.7% after correction. The corrected in vivo data showed a reduction of PVE bias for the investigated compartments for all volunteers, resulting in a mean reduction of discrepancy between two separate CSF compartments from 36% to 7.6%. The absolute TSC for two separate CSF compartments (sulci, lateral ventricles), gray and white brain matter after correction were 129±8mmol/L, 138±4mmol/L, 48±1mmol/L and 43±3mmol/L, respectively. The applied PVC algorithm reduces the PV-bias in quantitative (23)Na-MRI. Accurate, high-resolution anatomical data is required to enable appropriate PVC. The algorithm and segmentation approach is robust and leads to reproducible results.