Whole-brain 3D mapping of oxygen metabolism using constrained quantitative BOLD

Quantitative BOLD (qBOLD) MRI permits noninvasive evaluation of hemodynamic and metabolic states of the brain by quantifying parametric maps of deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Y_v), and along with a measurement of cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO₂). The method, thus should have potential to provide important information on many neurological disorders as well as normal cerebral physiology. One major challenge in qBOLD is to separate deoxyhemoglobin's contribution to R₂' from other sources modulating the voxel signal, for instance, R₂, R₂' from non-heme iron (R'_2,nh), and macroscopic magnetic field variations. Further, even with successful separation of the several confounders, it is still challenging to extract DBV and Y_v from the heme-originated R₂' because of limited sensitivity of the qBOLD model. These issues, which have not been fully addressed in currently practiced qBOLD methods, have so far precluded 3D whole-brain implementation of qBOLD. Thus, the purpose of this work was to develop a new 3D MRI oximetry technique that enables robust qBOLD parameter mapping across the entire brain. To achieve this goal, we employed a rapid, R₂'-sensitive, steady-state 3D pulse sequence (termed 'AUSFIDE') for data acquisition, and implemented a prior-constrained qBOLD processing pipeline that exploits a plurality of preliminary parameters obtained via AUSFIDE, along with additionally measured cerebral venous blood volume. Numerical simulations and in vivo studies at 3 T were performed to evaluate the performance of the proposed, constrained qBOLD mapping in comparison to the parent qBOLD method. Measured parameters (Y_v, DBV, R'_2,nh, nonblood magnetic susceptibility) in ten healthy subjects demonstrate the expected contrast across brain territories, while yielding group-averages of 64.0 ± 2.3 % and 62.2 ± 3.1 % for Y_v and 2.8 ± 0.5 % and 1.8 ± 0.4 % for DBV in cortical gray and white matter, respectively. Given the Y_v measurements, additionally quantified CBF in seven of the ten study subjects enabled whole-brain 3D CMRO₂ mapping, yielding group averages of 134.2 ± 21.1 and 79.4 ± 12.6 μmol/100 g/min for cortical gray and white matter, in good agreement with literature values. The results suggest feasibility of the proposed method as a practical and reliable means for measuring neurometabolic parameters over an extended brain coverage.