Détection de la maladie d'Alzheimer par la technique d'élastographie par IRM – MAN

RESUME PROJET – Contexte scientifique et objectifs Alzheimer's disease (AD) is characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms. It is the most common cause of dementia. It is recognized that the production and maintenance of myelin is essential for normal brain function. Aging-related breakdown of myelin negatively impacts the cognitive performances with the neurofibrilary tangles and amyloid plaques being the hallmarks of the disease. Nowadays, the only definite way to diagnose AD is to find out whether there are plaques and tangles in brain tissue. This requires histopathlogical examination of brain tissue. Therefore, doctors can only make a diagnosis of 'possible' or 'probable' AD. Previous researches on AD using MRI mainly focus on direct amyloid plaque imaging. The work in MRI has taken several directions such as ex vivo imaging with long scan time and imaging of plaques after administration of exogenous plaque-labeling contrast media.RESUME PROJET – Description This study aims to further validate the hypothesis that AD alters the viscoelastic properties of the axons in the region between hippocampus and cortex, i.e. within the Corpus Callosum (CC) which is the area most strongly affected by demyelination. Initial results together with Hong Kong University on genetically altered mice did already show that the elasticity within the brain changes due to the presence of AD. This study would establish for the first time a link between alterations of the myelin sheath around the axons occurring on the microscopic level due to disease progression and modulations of macroscopic properties such as the elasticity. Since the CC represents a highly ordered structure with axon fibers bundled together it is mandatory to consider an anisotropic model for elasticity reconstruction. We are proposing to utilize a novel MR based imaging technology (MR-Elastography) for the assessment of the viscoelastic properties of different structures within the brain. Here, mechanical waves are coupled into the brain via an external driver. The propagation of the mechanical waves inside the brain can be followed by motion-sensitized MRI sequences. Those images contain the required information to calculate afterwards locally the viscoelastic properties of the material. Initially, this technique shall be applied and validated on mice models. Here, it is proposed to perform longitudinal studies on double transgenetic mice carrying Alzheimers in order to study the effect of disease progression. Mice are particularly well suited for such an approach since one week of disease progression for mice translates into years for humans. In a second step, this technique shall be applied to humans. We propose to design a dedicated device to generate mechanical waves inside the human brain. This transducer could be based on classical mechanics leading to vibrations. Another approach would be to use pulsed ultrasound in order to generate waves inside the brain.RESUME PROJET – Resultats attendus The feasibility to measure the mechanical properties of the human brain using MR-Elastography study has already been shown. Here, we expect to demonstrate that disease progression of AD correlates with changes of viscoelastic properties for mice. In particular, we are capable to extract anisotropic mechanical information regarding the fibre structure inside the brain. These novel information might indicate the degree of the disease since it is expected that normal brain tissue obtains similar values among healthy subjects. This is different to for instance liver tissue which has already for healthy volunteers a certain variability. Establishing this novel link between AD and mechanical properties would help to examine the effect of drug therapy for Alzheimer's disease. It would also represent a milestone concerning the early detection of AD for people being at risk due to familial predisposition.