August 29, 2018 - This position is closed
PhD title: Methodological developments in metabolic imaging by CEST-MRI for the detection and quantification of glucose - applications to Alzheimer's disease
Glucose is the main source of energy production, particularly in the brain. Compelling evidence indicates a key role of glucose metabolism defects in several neurodegenerative diseases. 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 project are first to push methodological developments of glucoCEST acquisition, 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 may be a relevant biomarker of brain energy metabolism alterations in Alzheimer’s disease using a well characterized mouse model.
In this project, we will strive to offer a new non-invasive tool to the preclinical community to study brain energy dysregulation in the wide variety of mouse models of neurodegenerative diseases. Moreover, this project will improve the CEST imaging method and could speed-up the transfer of the technique for clinical applications for study of neurodegenerative disorders and particularly for Alzheimer’s disease. This thesis will be performed in the Molecular Imaging Research Center MIRCen-CEA located in Fontenay-aux-Roses which is a multidisciplinary center working at the interface between physics and biology. Therefore, the candidate will have to show skills and a strong interest in these two fields. In addition, the candidate will have to be interested in data processing and numerical simulation. In-depth knowledge of software such as Matlab is highly desired.
Possible starting date: January 7, 2019
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