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Élastographie par résonance magnétique multifréquence in vitro et ex vivo pour la caractérisation d’agrégats fibrillaires cérébraux

Abstract : Among several biological processes involved in dementia, fibrillar aggregation of endogenous proteins with altered conformation is an early characteristic of neurodegenerative diseases. Magnetic resonance elastography (MRE), an imaging technique that maps the mechanical properties of tissues, has recently been applied in neurodegenerative diseases. Although mechanical changes associated with these diseases have been detected, the mechanical effect of fibril has not yet been isolated in clinical or preclinical studies. This thesis work aims to exploit the fractal properties of fibrils to differentiate them from non-aggregated proteins. The exponent of the power law, obtained by adjusting multi-frequency MRE data acquired on phantom and rat brain ex vivo, could reveal at the macroscopic scale the presence of these fibrillar aggregates at the microscopic scale. During this thesis, an MRI elastography bench for imaging in vitro and ex vivo samples was developed. This device made it possible to implement a series of multi-frequency MRE measurements (400 to 1200Hz) on agarose samples containing two types of fibrils, α-Syn and Aβ, and a non-aggregated protein used as a control. The same device has made it possible to characterize with multi-frequency MRE (800 to 1200Hz) rat brains ex vivo previously injected with α-Syn in the striatum. For each rat, the contralateral striatum was injected with saline solution and used as a control. All MRE data were acquired on a 4.7T preclinical system using a modified RARE sequence. After a direct 3D inversion, the storage modulus, phase angle and wave velocity were extracted from the elastograms. The power law exponent is obtained by adjusting to the multi-frequency data. In inclusions containing fibrils, y was significantly higher than in those containing nonaggregated protein. This result is all the more interesting because the mono-frequency parameters were not affected much by the presence of fibrils: multi-frequency MRE provides information on the microstructure of tissues and makes it possible to characterize fibrillar proteins, however small they may be (a few μm). In rats, storage and loss modules decrease significantly over all frequencies studied compared to contralateral striatum. The parameters y and ϕ on the other hand do not allow discriminating between fibril injection and control injection. Further experiments would be needed to understand the absence of ex vivo detection. This thesis constitutes an original methodological contribution in the field of MRE, by isolating for the first time the biomechanical effect of fibrillar structures involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease
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Mathilde Bigot. Élastographie par résonance magnétique multifréquence in vitro et ex vivo pour la caractérisation d’agrégats fibrillaires cérébraux. Biotechnologie. Université de Lyon, 2019. Français. ⟨NNT : 2019LYSE1207⟩. ⟨tel-02475585⟩

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