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.

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.