Zero Echo Time (17)O-MRI Reveals Decreased Cerebral Metabolic Rate of Oxygen Consumption in a Murine Model of Amyloidosis

The cerebral metabolic rate of oxygen consumption (CMRO(2)) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO(2) can be measured by direct (17)O magnetic resonance imaging ((17)O-MRI) of H(2)(17)O signal changes during inhalation of (17)O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.7 T to measure CMRO(2) in the APP(swe)/PS1(dE9) mouse model of amyloidosis. We found that CMRO(2) was significantly lower in the APP(swe)/PS1(dE9) brain than in wild-type at 12–14 months. We also estimated cerebral blood flow (CBF) from the post-inhalation washout curve and found no difference between groups. These results suggest that the lower CMRO(2) observed in APP(swe)/PS1(dE9) is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the (17)O-MRI data using different quantification models (linear and 3-phase model) showed that the choice of the model does not affect group comparison results. However, the simplified linear model significantly underestimated the absolute CMRO(2) values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.