In this project a three-dimensional 19F ultrashort TE (UTE) MRI methodology will be developed for quantitative imaging of fluorinated compounds designed to bind amyloid beta (Ab) deposits. The 19F UTE method will be developed on a 7T small animal MRI instrument and evaluated in experiments on phantoms and on the brains of PS1/APP double transgenic mice, a common mouse model of Alzheimer's Disease. Results on mouse brains will be quantitatively compared to histological staining for Ab and imaging agent.
Alzheimer's disease (AD) remains a progressive, incurable disease, resulting in the erosion of an individual's intellect and personality. The disease prevalence and impact will be increasing as a large segment of the population ages. One of the main pathological hallmarks of the disease is the abnormal accumulation of amyloid b protein (Ab) into extracellular toxic plaques that could be responsible for the clinical expression of AD and represents an important molecular target in treating AD. Agents that can prevent its formation and accumulation, or stimulate its clearance, are being developed as potential new therapies. Transgenic mice, which express human Ab are being utilized in this important research area. At the present time, however, there is no non-invasive imaging method that allows the distribution of Ab to be adequately measured in these mouse models. In this project we propose to develop and evaluate a 19F 3D ultrashort TE (UTE) MRI methodology to image fluorine-labeled amyloidiphilic agents in vivo. Because there is no appreciable naturally occurring 19F signal in the body, these agents have potential to provide very specific markers of the presence of Ab. Because of their high sensitivity and ability to obtain signal from very short T2 signal, UTE techniques should provide the optimal way of imaging small amounts of bound 19F agent. The 19F 3D UTE sequence will be evaluated in phantoms, in ex vivo fixed brains of AD mice, and in mice brains in vivo. All MRI imaging will be quantitatively compared to histological sections of mice brains that have been stained for Ab.
|Yoshimaru, Eriko; Totenhagen, John; Alexander, Gene E et al. (2014) Design, manufacture, and analysis of customized phantoms for enhanced quality control in small animal MRI systems. Magn Reson Med 71:880-4|