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.

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.

Initial investigation of glucose metabolism in mouse brain using enriched 17 O-glucose and dynamic 17 O-MRS.

In this initial work, the in vivo degradation of 17 O-labeled glucose was studied during cellular glycolysis. To monitor cellular glucose metabolism, direct 17 O-magnetic resonance spectroscopy (MRS) was used in the mouse brain at 9.4 T. Non-localized spectra were acquired with a custom-built transmit/receive (Tx/Rx) two-turn surface coil and a free induction decay (FID) sequence with a short TR of 5.4 ms. The dynamics of labeled oxygen in the anomeric 1-OH and 6-CH2 OH groups was detected using a Hankel-Lanczos singular value decomposition (HLSVD) algorithm for water suppression. Time-resolved 17 O-MRS (temporal resolution, 42/10.5 s) was performed in 10 anesthetized (1.25% isoflurane) mice after injection of a 2.2 M solution containing 2.5 mg/g body weight of differently labeled 17 O-glucose dissolved in 0.9% physiological saline. From a pharmacokinetic model fit of the H217 O concentration-time course, a mean apparent cerebral metabolic rate of 17 O-labeled glucose in mouse brain of CMRGlc  = 0.07 ± 0.02 µmol/g/min was extracted, which is of the same order of magnitude as a literature value of 0.26 ± 0.06 µmol/g/min reported by 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET). In addition, we studied the chemical exchange kinetics of aqueous solutions of 17 O-labeled glucose at the C1 and C6 positions with dynamic 17 O-MRS. In conclusion, the results of the exchange and in vivo experiments demonstrate that the C6-17 OH label in the 6-CH2 OH group is transformed only glycolytically by the enzyme enolase into the metabolic end-product H217 O, whereas C1-17 OH ends up in water via direct hydrolysis as well as glycolysis. Therefore, dynamic 17 O-MRS of highly labeled 17 O-glucose could provide a valuable non-radioactive alternative to FDG PET in order to investigate glucose metabolism.

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.