Quantification of oxygen metabolic rates in Human brain with dynamic17O MRI: Profile likelihood analysis.
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 direct17O MRI.



Three-dimensional dynamic17O MRI datasets of the human brain were acquired after inhalation of17O2gas with the help of a rebreathing system, and CMRO2was 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, the17O enrichment fraction of the inhaled17O2gas, 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.



Prior knowledge about only one α-related parameter was sufficient to resolve the CMRO2nonidentifiability, and CMRO2rates (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 of15O positron emission tomography studies. Nonconstant α values significantly improved model fitting.



The profile likelihood analysis shows that CMRO2can be measured reliably in17O gas MRI experiment if the17O 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.
Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Dmitry
D
Kurzhunov
Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Freiburg, Germany.|German Cancer Consortium, Heidelberg, Germany.|German Cancer Research Center, Heidelberg, Germany.
Robert
R
Borowiak
Institute of Physics, University of Freiburg, Freiburg, Germany.
Helge
H
Hass
Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Philipp
P
Wagner
Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Freiburg, Germany.|German Cancer Consortium, Heidelberg, Germany.|German Cancer Research Center, Heidelberg, Germany.
Axel Joachim
AJ
Krafft
Institute of Physics, University of Freiburg, Freiburg, Germany.|BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
Jens
J
Timmer
Department of Radiology, Medical Physics, University Medical Center Freiburg, Freiburg, Germany.|Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Michael
M
Bock
D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010103:Oxygen Isotopes / Q000097:blood / Q000378:metabolism*
D010103:Oxygen Isotopes; C000615258:Oxygen-17
cerebral metabolic rate of oxygen consumption (CMRO2); direct 17O MRI; identifiability analysis; non-proton MRI; oxygen metabolism; profile likelihood