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

The cerebral metabolic rate of oxygen consumption (CMRO) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO can be measured by direct O magnetic resonance imaging (O-MRI) of HO signal changes during inhalation of 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 in the APP/PS1 mouse model of amyloidosis. We found that CMRO was significantly lower in the APP/PS1 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 observed in APP/PS1 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the 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 values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.