Quantification of oxygen metabolic rates in Human brain with dynamic ¹⁷ O 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 direct ¹⁷ O MRI.

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.

Prior knowledge about only one α-related parameter was sufficient to resolve the CMRO₂ nonidentifiability, and CMRO₂ rates (0.72-0.99 µmol/g_tissue /min in white matter, 1.02-1.78 µmol/g_tissue /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.

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.