Evaluation of whole-brain oxygen metabolism in Alzheimer's disease using QSM and quantitative BOLD

The objective of this study was to evaluate the whole-brain pattern of oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂) perturbation in Alzheimer's disease (AD) and investigate the relationship between regional cerebral oxygen metabolism and global cognition.

Twenty-six AD patients and 25 age-matched healthy controls (HC) were prospectively recruited in this study. Mini-Mental State Examination (MMSE) was used to evaluate cognitive status. We applied the QQ-CCTV algorithm which combines quantitative susceptibility mapping and quantitative blood oxygen level-dependent models (QQ) for OEF calculation. CBF map was computed from arterial spin labeling and CMRO₂ was generated based on Fick's principle. Whole-brain and regional OEF, CBF, and CMRO₂ analyses were performed. The associations between these measures in substructures of deep brain gray matter and MMSE scores were assessed.

Whole brain voxel-wise analysis showed that CBF and CMRO₂ values significantly decreased in AD predominantly in the bilateral angular gyrus, precuneus gyrus and parieto-temporal regions. Regional analysis showed that CBF value decreased in the bilateral caudal hippocampus and left rostral hippocampus and CMRO₂ value decreased in left caudal and rostral hippocampus in AD patients. Considering all subjects in the AD and HC groups combined, the mean CBF and CMRO₂ values in the bilateral hippocampus positively correlated with the MMSE score.

CMRO₂ mapping with the QQ-CCTV method - which is readily available in MR systems for clinical practice - can be a potential biomarker for AD. In addition, CMRO₂ in the hippocampus may be a useful tool for monitoring cognitive impairment.