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

Celine Baligand,Marie-Claude Gaillard,Géraldine Liot,Olivier Barret,Jean-Baptiste Pérot,Marc Dhenain,Julien Valette,Amélie Tourais,Didier Thenadey,Julien Flament,Fanny Petit

doi:10.3390/metabo11050263

Abstract

The cerebral metabolic rate of oxygen consumption (CMRO2) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO2 can be measured by direct 17O magnetic resonance imaging (17O-MRI) of H217O signal changes during inhalation of 17O-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 CMRO2 in the APPswe/PS1dE9 mouse model of amyloidosis. We found that CMRO2 was significantly lower in the APPswe/PS1dE9 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 CMRO2 observed in APPswe/PS1dE9 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the 17O-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 CMRO2 values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.

Highlights

Oxidative metabolism is essential to sustain brain’s varying energy needs at rest and during neuronal activation
We used 3D free induction decay (FID) chemical shift imaging (CSI) with the shortest achievable echo time (TE = 0.3 ms) as a reference to evaluate the performances of the zero echo time (ZTE) approach in a 17 O natural abundance free water sample and in vivo in the mouse brain
Using identical flip angles and repetition times optimized to maximize signal, we compared the sequences in terms of their signal-to-noise ratio (SNR)

Summary

Introduction

Oxidative metabolism is essential to sustain brain’s varying energy needs at rest and during neuronal activation. Whether the defect in oxidative metabolism is the cause the pathological manifestation or rather results from disease progression is still unclear. The half-life of 15 O is very short (~2 min) and direct access to a cyclotron is required. While it has been used in small animals [3,4], an important constraint remains that the actual spatial resolution is intrinsically limited by the disintegration properties of 15 O, i.e., the distance that the positron travels prior to annihilation (maximum free path of 8 mm [5]) which, in practice, often limits rodent studies to whole brain measurements [6]

Methods

Results

Conclusion