Effect of cerebral protein aggregates on tissue mechanical properties measured by Magnetic Resonance Elastography

Mathilde Bigot (1) , Fabien Chauveau (2) , Celine Mandon (3) , Olivier Beuf (1) , Simon Lambert (1)

1 RMN et optique : De la mesure au biomarqueur
2 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
3 GEMBAS - Génie Enzymatique, Membrane Biomimétique et Assemblages Supramoléculaires

In several cases of neurodegenerative diseases, cerebral proteins can agglomerate and form fibrils as from the early stages of the illness [1]. The endogenous proteins involved are different depending on the disease (β-amyloid for Alzheimer’s disease, α-synuclein for Parkinson’s disease and Tau protein frontotemporal dementia), but the structure remains the same: β-sheets. Those aggregates can be detected in vivo with TEP-scan and radiotracers, but the exam is irradiating, and the response is only qualitative yet [2]. The tracers are also only designed to identify one type of aggregate at the time, which is too specific for a screening test. MRI only permits a late detection of the illness, based on a diminution of the brain volume, direct detection of the aggregates showing little sensitivity [3]. The need for a simple test that could attest the presence of a neurodegenerative illness at an early stage is thus still very strong. We propose to develop an in vivo imaging technique based on the link between the microscopic structure of the aggregates and macroscopic observables collected with an MRI device. Magnetic Resonance Elastography (MRE) consists of the study of shear wave propagation in the matter, using an MRI signal. The wave observed is produced by an exterior shaker synchronized with the MRE signal. Images are taken at different steps of the wave propagation. After appropriate reconstruction, the wave speed is obtained. It leads to the viscoelastic properties of the matter. The relation between the wave speed and the input frequency reflects the multiple diffraction in the microscopic scale [4,5], and we expect to determine the link between the fibrillary structure of the protein aggregates and the MRI signal thanks to this relation. Developments will be required to obtain an adequate image resolution. Development of 3D-printed phantoms with fibril inclusions is ongoing. Those phantoms are, in the meantime, characterized with MRE. After a full study of the received signal and characterization of the fibrils, ex vivo, and in vivo studies are scheduled. Their aim is to determine if the “micro/macro” link observed in phantoms persist in vivo, where the environment is more complex. Our study is still at the beginning of its implementation, but MRE appears like a promising way to characetrize small objects with a specific structure. We hope to develop it enough to make the idea of its clinical use practicable.

Domaines: Imagerie médicale; Imagerie

Mathilde Bigot, Fabien Chauveau, Celine Mandon, Olivier Beuf, Simon Lambert. Effect of cerebral protein aggregates on tissue mechanical properties measured by Magnetic Resonance Elastography. Journée Santé@labex, Dec 2016, Lyon, France. ⟨hal-01881078⟩