Direct estimation of 17 O MR images (DIESIS) for quantification of oxygen metabolism in the human brain with partial volume correction.

PURPOSE: To provide a data post-processing method that corrects for partial volume effects (PVE) and fast T 2 * decay in dynamic 17 O MRI for the mapping of cerebral metabolic rates of oxygen consumption (CMRO2 ). METHODS: CMRO2 is altered in neurodegenerative diseases and tumors and can be measured after 17 O gas inhalation using dynamic 17 O MRI. CMRO2 quantification is difficult because of PVE. To correct for PVE, a direct estimation of the MR images (DIESIS) method is proposed and used in 4 dynamic 17 O MRI data sets of a healthy volunteer acquired on a 3T MRI system. With DIESIS, 17 O MR signal time curves in selected regions were directly estimated based on parcellation of a coregistered 1 H MPRAGE image. RESULTS: Profile likelihood analysis of the DIESIS method showed identifiability of CMRO2 . In white matter (WM), DIESES reduced CMRO2 from 0.97 ± 0.25 µmol/gtissue /min with Kaiser-Bessel gridding reconstruction to 0.85 ± 0.21 µmol/gtissue /min, whereas in gray matter (GM) it increases from 1.3 ± 0.31 µmol/gtissue /min to 1.86 ± 0.36 µmol/gtissue /min; both values are closer to the literature values from the 15 O-PET studies. CONCLUSION: DIESIS provided an increased separation of CMRO2 values in GM and WM brain regions and corrected for partial volume effects in 17 O-MRI inhalation experiments. DIESIS could also be applied to more heterogeneous tissues such as glioblastomas if subregions of the tumor can be represented as additional parcels.

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.

3D CMRO2 mapping in human brain with direct 17O MRI: Comparison of conventional and proton-constrained reconstructions.

Oxygen metabolism is altered in brain tumor regions and is quantified by the cerebral metabolic rate of oxygen consumption (CMRO2). Direct dynamic 17O MRI with inhalation of isotopically enriched 17O2 gas can be used to quantify CMRO2; however, pixel-wise CMRO2 quantification in human brain is challenging due to low natural abundance of 17O isotope and, thus, the low signal-to-noise ratio (SNR) of 17O MR images. To test the feasibility CMRO2 mapping at a clinical 3 T MRI system, a new iterative reconstruction was proposed, which uses the edge information contained in a co-registered 1H gradient image to construct a non-homogeneous anisotropic diffusion (AD) filter. AD-constrained reconstruction of 17O MR images was compared to conventional Kaiser-Bessel gridding without and with Hanning filtering, and to iterative reconstruction with a total variation (TV) constraint. For numerical brain phantom and in two in vivo data sets of one healthy volunteer, AD-constrained reconstruction provided 17O images with improved resolution of fine brain structures and resulted in higher SNR. CMRO2 values of 0.78 - 1.55µmol/gtissue/min (white brain matter) and 1.03 - 2.01µmol/gtissue/min (gray brain matter) as well as the CMRO2 maps are in a good agreement with the results of 15O-PET and 17O MRI at 7 T and at 9.4 T. In conclusion, the proposed AD-constrained reconstruction enabled calculation of 3D CMRO2 maps at 3 T MRI system, which is an essential step towards clinical translation of 17O MRI for non-invasive CMRO2 quantification in tumor patients.

Quantification of oxygen metabolic rates in Human brain with dynamic 17 O MRI: Profile likelihood analysis.

PURPOSE: Parameter identifiability and confidence intervals were determined using a profile likelihood (PL) analysis method in a quantification model of the cerebral metabolic rate of oxygen consumption (CMRO2 ) with direct 17 O MRI. METHODS: Three-dimensional dynamic 17 O MRI datasets of the human brain were acquired after inhalation of 17 O2 gas with the help of a rebreathing system, and CMRO2 was quantified with a pharmacokinetic model. To analyze the influence of the different model parameters on the identifiability of CMRO2 , PLs were calculated for different settings of the model parameters. In particular, the 17 O enrichment fraction of the inhaled 17 O2 gas, α, was investigated assuming a constant and a linearly varying model. Identifiability was analyzed for white and gray matter, and the dependency on different priors was studied. RESULTS: Prior knowledge about only one α-related parameter was sufficient to resolve the CMRO2 nonidentifiability, and CMRO2 rates (0.72-0.99 µmol/gtissue /min in white matter, 1.02-1.78 µmol/gtissue /min in gray matter) are in a good agreement with the results of 15 O positron emission tomography studies. Nonconstant α values significantly improved model fitting. CONCLUSION: The profile likelihood analysis shows that CMRO2 can be measured reliably in 17 O gas MRI experiment if the 17 O enrichment fraction is used as prior information for the model calculations. Magn Reson Med 78:1157-1167, 2017. © 2016 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.

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

At ultrahigh magnetic field strengths (B0 ≥ 7.0 T), potassium ((39) K) MRI might evolve into an interesting tool for biomedical research. However, (39) K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of (39) K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared (39) K and sodium ((23) Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. (39) K relaxation times were markedly shorter than those of (23) Na. Compared with the lower field strength, (39) K relaxation times were up to 1.9- (T1 ), 1.4- (T2S ) and 1.9-fold (T2L ) longer at 21.1 T. The increase in the (23) Na relaxation times was less pronounced (up to 1.2-fold). Mono-exponential fits of the (39) K longitudinal relaxation time at 21.1 T revealed T1 = 14.2 ± 0.1 ms for the healthy rat head. The (39) K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T2S ) and long (T2L ) components, respectively. (23) Na relaxation times were markedly longer (T1 = 41.6 ± 0.4 ms; T2S = 4.9 ± 0.2 ms; T2L = 33.2 ± 0.2 ms). (39) K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm(3) within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for (23) Na and (39) K MRI at ultrahigh magnetic field strength. Our results demonstrate that (39) K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.

Anatomically weighted second-order total variation reconstruction of 23Na MRI using prior information from 1H MRI.

Sodium ((23)Na) MRI is a noninvasive tool to assess cell viability, which is linked to the total tissue sodium concentration (TSC). However, due to low in vivo concentrations, (23)Na MRI suffers from low signal-to-noise ratio (SNR) and limited spatial resolution. As a result, image quality is compromised by Gibbs ringing artifacts and partial volume effects. An iterative reconstruction algorithm that incorporates prior information from (1)H MRI is developed to reduce partial volume effects and to increase the SNR in non-proton MRI. Anatomically weighted second-order total variation (AnaWeTV) is proposed as a constraint for compressed sensing reconstruction of 3D projection reconstruction (3DPR) data. The method is evaluated in simulations and a MR measurement of a multiple sclerosis (MS) patient by comparing it to gridding and other reconstruction techniques. AnaWeTV increases resolution of known structures and reduces partial volume effects. In simulated MR brain data (nominal resolution Δx(3) = 3 × 3 × 3 mm(3)), the intensity error of four small MS lesions was reduced from (6.9 ± 3.8)% (gridding) to (2.8 ± 1.4)% (AnaWeTV with T2-weighted reference images). Compared to gridding, a substantial SNR increase of 130% was found in the white matter of the MS patient. The algorithm is robust against misalignment of the prior information on the order of the (23)Na image resolution. Features without prior information are still reconstructed with high contrast. AnaWeTV allows a more precise quantification of TSC in structures with prior knowledge. Thus, the AnaWeTV algorithm is in particular beneficial for the assessment of tissue structures that are visible in both (23)Na and (1)H 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.

Iterative 3D projection reconstruction of (23) Na data with an (1) H MRI constraint.

PURPOSE: To increase the signal-to-noise ratio (SNR) and to reduce artifacts in non-proton magnetic resonance imaging (MRI) by incorporation of a priori information from (1) H MR data in an iterative reconstruction. METHODS: An iterative reconstruction algorithm for 3D projection reconstruction (3DPR) is presented that combines prior anatomical knowledge and image sparsity under a total variation (TV) constraint. A binary mask (BM) is used as an anatomical constraint to penalize non-zero signal intensities outside the object. The BM&TV method is evaluated in simulations and in MR measurements in volunteers. RESULTS: In simulated BM&TV brain data, the artifact level was reduced by 20% while structures were well preserved compared to gridding. SNR maps showed a spatially dependent SNR gain over gridding reconstruction, which was up to 100% for simulated data. Undersampled 3DPR (23) Na MRI of the human brain revealed an SNR increase of 29 ± 7%. Small anatomical structures were reproduced with a mean contrast loss of 14%, whereas in TV-regularized iterative reconstructions a loss of 66% was found. CONCLUSION: The BM&TV algorithm allows reconstructing images with increased SNR and reduced artifact level compared to gridding and performs superior to an iterative reconstruction using an unspecific TV constraint only.

Quantification of regional CMRO2 in human brain using dynamic 17O-MRI at 3T.

OBJECTIVE: To investigate the feasibility of cerebral metabolic rate of oxygen consumption (CMRO2) measurements with MRI at 3 Tesla in different brain regions. METHODS: CMRO2 represents a key indicator of the physiological state of brain tissue. Dynamic 17O-MRI with inhalation of isotopically enriched 17O gas has been used to quantify global CMRO2 in brain white (WM) and gray matter (GM). However, global CMRO2 can only reflect the overall oxygen metabolism of the brain and cannot provide enough information on local tissue oxygen metabolism. To investigate the feasibility of determination of regional CMRO2 at a clinical 3 T MRI system, CMRO2 values in frontal, parietal and occipital WM and GM were determined in 5 healthy volunteers and compared to evaluate the regional differences of oxygen metabolism in WM and GM. Additionally, regional CMRO2 values were determined in deep brain structures including thalamus, dorsal striatum, caudate nucleus and insula cortex and in the cerebella, and compared with literature values from 15O-PET studies. RESULTS: In cortical GM the determined CMRO2 values were in good agreement with the literature, whereas values in WM were about 32-48% higher than literature values. Regional analysis revealed a significantly higher CMRO2 in the occipital GM compared to the frontal and parietal GM. By contrast, no significant difference of CMRO2 was observed across the WM. In addition, CMRO2 in deep brain structures was lower compared to literature values and in the cerebella a good hemispheric symmetry of the tissue oxygen metabolism was found. CONCLUSION: Dynamic 17O-MRI enables direct, non-invasive determination of regional CMRO2 in brain structures in healthy volunteers at 3T.

Simultaneous multi-parametric mapping of total sodium concentration, T1, T2 and ADC at 7 T using a multi-contrast unbalanced SSFP.

PURPOSE: Quantifying multiple NMR properties of sodium could be of benefit to assess changes in cellular viability in biological tissues. A proof of concept of Quantitative Imaging using Configuration States (QuICS) based on a SSFP sequence with multiple contrasts was implemented to extract simultaneously 3D maps of applied flip angle (FA), total sodium concentration, T1, T2, and Apparent Diffusion Coefficient (ADC). METHODS: A 3D Cartesian Gradient Recalled Echo (GRE) sequence was used to acquire 11 non-balanced SSFP contrasts at a 6 × 6 × 6 mm3 isotropic resolution with carefully-chosen gradient spoiling area, RF amplitude and phase cycling, with TR/TE = 20/3.2 ms and 25 averages, leading to a total acquisition time of 1 h 18 min. A least-squares fit between the measured and the analytical complex signals was performed to extract quantitative maps from a mono-exponential model. Multiple sodium phantoms with different compositions were studied to validate the ability of the method to measure sodium NMR properties in various conditions. RESULTS: Flip angle maps were retrieved. Relaxation times, ADC and sodium concentrations were estimated with controlled precision below 15%, and were in accordance with measurements from established methods and literature. CONCLUSION: The results illustrate the ability to retrieve sodium NMR properties maps, which is a first step toward the estimation of FA, T1, T2, concentration and ADC of 23Na for clinical research. With further optimization of the acquired QuICS contrasts, scan time could be reduced to be suitable with in vivo applications.