Imagerie de la compartimentation et de la pharmacologie du lithium par IRM du Lithium-7 in vivo at très haut champ magnétique.

At ultra-high magnetic field, increased polarization opens the way for the NMR imaging and spectroscopy of exotic nuclei such as Lithium-7 (7Li) and Sodium-23 (23Na) with unprecedented sensitivities.
During this PhD thesis, the goal will be to develop, validate and apply 23Na and 7Li preclinical imaging protocols in the context of the new 11.7T Iseult MRI scanner of NeuroSpin (CEA/DRF/JOLIOT) as well as on its 17.2 T preclinical scanner. The PhD student will continue the work realized these last years on 23Na and 7Li imaging and will push for better and more significant NRM data. Our focus will be to use these methods to study the pharmacology and biophysical properties of Lithium in the brain. In particular, we aim at investigating the transport kinetics of Li+ through the Blood-Brain-Barrier, its compartmentation and its competition with Na+ ions.

Imaging disease associated astrogliosis by Positron Emission Tomography in Alzheimer’s disease

This PhD fellowship focuses on the assessment of astrocytic reactivity induced by tauopathy, associated with Alzheimer's disease, using PET imaging or 3D-autoradiography using the radioligand [11C]BU99008 or [3H]BU99008 specific for I2-BS receptors, target of astrocytic reactivity. The main objectives of this research project are: 1- to validate the specificity of the [11C]/[3H]BU99008 ligand binding in different models of tauopathy; 2- to characterise the signature of reactive astrocytes detected by BU99008; and 3- to assess the specific binding of [11C]/[3H]BU99008 as well as gene expression following a therapeutic strategy targeting I2-BS receptors in one of the tauopathy models. Our methodological approach adopts a multiscale perspective, combining PET imaging with microscopic and transcriptomic analyses, thus enabling a multiscale analysis ranging from macro (in vivo) to micro (in vitro). These studies not only provide a fundamental understanding of astrocytic reactivity, but also open important perspectives for the development of therapeutic strategies targeting astrocytic reactivity in the context of neurodegenerative diseases.

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