Zero echo time $^{17}$O-MRI reveals decreased cerebral metabolic rate of oxygen consumption in a murine model of amyloidosis

International audienceThe 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