Study of energy metabolism in vivo using glucose CEST-MRI – nrjCEST

Glucose is the main source of energy production, particularly in brain. Compelling evidence indicate a key role of glucose metabolism defects in several neurodegenerative diseases. Positron emission tomography is the reference exam to non-invasively assess glucose uptake, but this technique suffers from an intrinsic lack of spatial resolution. This limits its applications, particularly for the study of neurodegenerative diseases in mouse models.
A new magnetic resonance imaging modality (chemical exchange saturation transfer or CEST), has been proposed to image glucose non-invasively with high spatial and temporal resolutions. This magnetic resonance imaging (MRI) method called glucoCEST could offer a new tool to map energy metabolism in healthy and pathological mouse brain. However, this method is currently limited by the lack of specificity. Indeed, only relative changes in glucoCEST signal are reported but such measurements provide little information about absolute variations of glucose concentration and its degradation products through glycolytic pathway into the brain. In addition to the methodological aspect of the CEST acquisitions, the quantitative aspect is currently one of the major limitations of CEST imaging which prevents the transfer of the technique for clinical applications.
In this context, the goals of this ambitious project are first to push methodological developments of glucoCEST imaging, then to develop innovative tools to quantify the glucoCEST signal in order to establish quantitative maps of glucose utilization in vivo using pharmacokinetics models, and finally, to demonstrate that our method can constitute a relevant biomarker of brain energy metabolism alterations in Alzheimer’s disease using a well characterized mouse model.
With the nrjCEST project, we strive to offer a new non-invasive tool to the preclinical community to study brain energy dysregulation using the wide variety of mouse models of neurodegenerative diseases. Moreover, this project will tremendously improve the CEST imaging method and will speed-up the transfer of the technique for clinical applications for study of neurodegenerative disorders and particularly for Alzheimer’s disease.