Description of the thesis topic

The identification of reliable, sensitive, and specific biomarkers for the early detection of individuals at risk of developing Alzheimer's disease (AD) represents a key public health issue. Furthermore, these early biomarkers are essential for better understanding the initial phases of the disease. At the cellular level, the p-Tau pathology that causes neurodegeneration occurs well before the first cognitive symptoms, but in vivo imaging markers capable of detecting initial neuronal loss during this silent phase are currently lacking.
This doctoral project proposes to implement an innovative methodology using diffusion MRI imaging combined with a post-processing tool for the optimized calculation of a diffusion orientation function at each voxel. The objective is to develop an in vivo marker of initial neuronal degeneration in the anterior temporal lobe, characteristic of early AD in the silent phase. To this end, we will draw on data from the Prédicog clinical study, ancillary to the Toulouse INSPIRE cohort. The longitudinal study is currently ongoing and we already have imaging data acquired on 100 elderly volunteers without cognitive impairment.
References:
D. Tuch (2004) Q-ball imaging. Magn Res Med 52 (6) 1358-1372.
F. Rémy, N. Vayssiere, L. Saint-Aubert, E. Barbeau, J. Pariente (2015) White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance. Neuroimage Clin 7 () 482-92
Maréchal P, Navarrete Y, Davis S. On the foundations of the maximum entropy principle using Fenchel duality for Shannon and Tsallis entropies. Physica Scripta. 2024 Jun 21;99(7):075265

Work Context

The interdisciplinary scientific supervision of the thesis will be provided by Florence Rémy (Prof Neuroscience, CerCo) and Pierre Maréchal (Prof Mathematics, IMT).
The MRI data are acquired in the Prédicog clinical study, funded by the Occitanie Region and the Fondation de l'Avenir, and coordinated by the Gérontopôle of Toulouse University Hospital (ClinicalTrials.gov ID: NCT06058897). As a member of CerCo, the doctoral student will have access to the 3T MRI platform at the Baudot Pavilion (Purpan University Hospital) as well as to the computing server. As a member of IMT, he/she will benefit from an environment expert in mathematical methods for analyzing and solving inverse problems, particularly in medical imaging. Technical support for image acquisition and analysis will be provided by the MRI platform engineers, the CerCo calculation engineer and the Philips company (industrial partner) in charge of MRI quality control.

Constraints and risks

The doctoral student will be required to work near intense magnetic fields, on a 3 Tesla MRI platform.