| Magnetic resonance elastography (MRE) is an MRI technique to noninvasively measure tissue stiffness. Shear waves are introduced into the tissue of interest by an external vibration source, imaged with a phase-contrast MRI pulse sequence with motion encoding gradients that are synchronized to the external motion, and finally mathematically inverted to calculate tissue stiffness. The hypothesis of this thesis is that MRE can be used to detect in vivo a change in brain stiffness due to Alzheimer's disease (AD). The first part of the thesis is devoted to minimizing acquisition time of MRE of the brain. Due to the relatively long wavelength per field of view and low amplitude of motion typical of shear waves in the brain, the spectral width of a shear wave image in k-space is small. The necessary extent of k-space to reconstruct the shear wave images can be sampled in a single shot with an MRE EPI pulse sequence. Next, MRE was performed in the APP-PS1 mouse model of AD. Five transgenic mice had significantly decreased brain stiffness compared to a group of eight age-matched wild-type mice. These results motivated a human pilot study to use MRE to measure the effects of AD on brain stiffness. The reproducibility of the 3D brain MRE exam was assessed in 10 volunteers without known neurological disorders. Each volunteer underwent 4 MRE exams over 2 days. The maximum coefficient of variation determined from the volunteer studies was just over 3%, indicating high reproducibility of the exam. To study the effects of AD, 7 subjects with probable AD were recruited along with 14 age- and gender-matched PIB-negative cognitively normal controls and 7 age- and gender-matched PIB-positive cognitively normal controls. MRE measured decreased brain stiffness in the AD subjects compared to cognitively normal controls both with and without significant brain amyloid load. The results likely reflect a loss of normal cytoarchitecture of the brain due to AD. Brain stiffness determined by MRE demonstrates potential as a new biomarker of AD, which in the future may work in conjunction with existing biomarkers to improve the sensitivity or specificity of AD diagnosis. |
