Anisotropic viscoelastic properties of the corpus callosum - Application of high-resolution 3D MR-elastography to an Alzheimer mouse model

Abstract

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 histopathological examination of brain tissue. Previous researches on AD using MRI mainly focus on direct plaque imaging. This study aims to validate the hypothesis that AD alters the mechanical properties of the axons in the region between hippocampus and cortex, i.e. within the Corpus Callosum (CC) which is an area strongly affected by demvelination. As a unique tool to study non-invasively those properties, we use 3D MR-elastography operating at 1000Hz mechanical excitation frequency. Post-processing of the complex-valued displacement field provides the local fiber direction (determined by two Euler angles) and two complex shear moduli: one perpendicular to the local fiber direction and one parallel to it. Each modulus is a complex number giving access to both the anisotropic elasticity μ and viscosity η. The displacement fields are measured at an isotropic resolution of 300μm. Four transgenic female mice expressing mutant human APP/PS1 genes and three wild-type (WT) control mice were studied over several weeks. We observe locally enhanced elasticity and viscosity in the corpus callosum compared to the rest of the brain. As expected from normal anatomy, this region also shows a significantly higher anisotropy (μ ∥- μ ⊥ characterizing the transversal isotropic mechanical properties of this white matter region. The AD group shows a decrease in both μ ∥ and μ ⊥. It also seems to have a decreased value of perpendicular viscosity suggesting easier wave propagation in the transverse direction due to demyelination. Those preliminary results indicate that AD alters the mechanical properties of the white matter. Those differences were not detectable when utilizing an isotropic model for the reconstruction of the viscoelastic properties. © 2007 IEEE.