8C-6 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 demyelination. As a unique tool to study non-invasively those properties, we use 3D MR-elastography operating at 1000 Hz 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 mu and viscosity eta. The displacement fields are measured at an isotropic resolution of 300 mum. 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 (mupar- muperp) characterizing the transversal isotropic mechanical properties of this white matter region. The AD group shows a decr-
ease in both mupar and muperp. 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.
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ABSTRACT: A combination of radiation force and ultrafast ultrasound imaging is used to both generate and track the propagation of a shear wave in the brain whose local speed is directly related to stiffness, characterized by the dynamic shear modulus G*. When performed on trepanated rats, this approach called shear wave imaging (SWI) provides 3-D brain elasticity maps reaching a spatial resolution of 0.7 mm×1 mm×0.4 mm with a good reproducibility (<13%). The dynamic shear modulus of brain tissues exhibits values in the 2-25 kPa range with a mean value of 12 kPa and is quantified for different anatomical regions. The anisotropy of the shear wave propagation is studied and the first in vivo anisotropy map of brain elasticity is provided. The propagation is found to be isotropic in three gray matter regions but highly anisotropic in two white matter regions. The good temporal resolution (~10 ms per acquisition) of SWI also allows a dynamic estimation of brain elasticity to within a single cardiac cycle, showing that brain pulsatility does not transiently modify local elasticity. SWI proves its potential for the study of pathological modifications of brain elasticity both in small animal models and in clinical intra-operative imaging.IEEE transactions on medical imaging. 09/2010; 30(3):550-8.
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ABSTRACT: The imaging problem of elastography is an inverse problem. The nature of an inverse problem is that it is ill-conditioned. We consider properties of the mathematical map which describes how the elastic properties of the tissue being reconstructed vary with the field measured by magnetic resonance imaging (MRI). This map is a nonlinear mapping, and our interest is in proving certain conditioning and regularity results for this operator which occurs implicitly in this problem of imaging in elastography. In this treatment we consider the tissue to be linearly elastic, isotropic, and spatially heterogeneous. We determine the conditioning of this problem of function reconstruction, in particular for the stiffness function. We further examine the conditioning when determining both stiffness and density. We examine the Fréchet derivative of the nonlinear mapping, which enables us to describe the properties of how the field affects the individual maps to the stiffness and density functions. We illustrate how use of the implicit function theorem can considerably simplify the analysis of Fréchet differentiability and regularity properties of this underlying operator. We present new results which show that the stiffness map is mildly ill-posed, whereas the density map suffers from medium ill-conditioning. Computational work has been done previously to study the sensitivity of these maps, but our work here is analytical. The validity of the Newton—Kantorovich and optimization methods for the computational solution of this inverse problem is directly linked to the Fréchet differentiability of the appropriate nonlinear operator, which we justify.SIAM Journal on Applied Mathematics 01/2011; 71:1578-1605. · 1.58 Impact Factor
Chapter: Brain Tissue Mechanical Properties[show abstract] [hide abstract]
ABSTRACT: The human brain is soft highly metabolically active tissue, floating in cerebrospinal fluid (CSF) within the rigid cranium. This environment acts to isolate the brain from the majority of external mechanical loads experienced by the head during normal daily life. The brain does experience a range of mechanical loads directly, as a result of blood and CSF flow, and to some extent, body posture. The dynamic balance of pulsatile hydrodynamic forces in the skull is maintained by blood and CSF flow into and out of the skull throughout the cardiac cycle (the Monroe-Kelly hypothesis), since the internal volume of the skull is constant. Reflex responses maintain blood flow during changes in posture and activity, so as to stabilize the mechanical and biochemical environment of the brain.07/2011: pages 69-89;