The overall goal of the proposed research is-to develop novel in vivo imaging methods for A(3 plaque detection and classification in transgenic mice using positron emission tomography (PET). The reduction of amyloid beta plaques is among the main therapeutic objectives for the treatment of Alzheimer's disease (AD). Ap imaging with PET has now entered the realm of the revised criteria for diagnosis of AD. In vivo imaging of Ap in mouse brain would facilitate the study of the AD pathology and testing of drugs that could stop or decelerate the disease progress. However, the heterogeneous microstructure of the plaques makes an in vivo approach to detecting and quantifying the plaque burden challenging due to insufficient resolution. Also, current image reconstruction techniques are not well adapted to the reconstruction of heterogeneous microstructures. The candidate is proposing a method that takes advantage of a stochastic object model of AP to improve in vivo imaging. The parameters of this model are sampled from distributions that contain information about the size and number of plaques in different brain regions as well as their variations among animals and changes overtime. These parameters are obtained from in vitro data using advanced stereological analysis methods. The stochastic object model will be incorporated into an optimization method, such as simulated annealing. The objective of this process is to search for a random realization of the object model that provides the best fit between the estimated and the measured data from the imaging system by minimizing a target function. The candidate's training in the K99 phase has provided the required skills to establish herself in this interdisciplinary field. It is also a logical extension of her past experience in PET/SPECT instrumentation and image reconstruction.
The specific aims of the ROO phase outline studies to explore the feasibility of this technique with animal scans. The candidate's long-term goal is to develop signal detection and pattern recognition tools to overcome the practical limitations of iri vivo imaging systems while maintaining her focus on their implementation in AD research.

Public Health Relevance

The studies outlined in the Research Strategy propose new compoutational techiques for conducting preclinical molecular imaging of Alzheimer's disease (AD) and can be implemented to study new radiotracers and treatment monitoring. There is a potential for translating these techniques into human AD imaging using PET or PET/MRl.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Transition Award (R00)
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No Study Section (in-house review) (NSS)
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Sastre, Antonio
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Vanderbilt University Medical Center
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Lin, Alexander; Kupinski, Matthew A; Peterson, Todd E et al. (2018) Task-based design of a synthetic-collimator SPECT system used for small animal imaging. Med Phys 45:2952-2963
Campbell, Desmond L; Kang, Hakmook; Shokouhi, Sepideh (2017) Application of Haralick texture features in brain [18F]-florbetapir positron emission tomography without reference region normalization. Clin Interv Aging 12:2077-2086
Shokouhi, Sepideh; Riddle, William R; Kang, Hakmook (2017) A new data analysis approach for measuring longitudinal changes of metabolism in cognitively normal elderly adults. Clin Interv Aging 12:2123-2130
Shokouhi, Sepideh; Mckay, John W; Baker, Suzanne L et al. (2016) Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment. Alzheimers Res Ther 8:2
Shokouhi, Sepideh; Campbell, Desmond; Brill, Aaron B et al. (2016) Longitudinal Positron Emission Tomography in Preventive Alzheimer's Disease Drug Trials, Critical Barriers from Imaging Science Perspective. Brain Pathol 26:664-71
Johnson, Lindsay C; Ovchinnikov, Oleg; Shokouhi, Sepideh et al. (2015) Development of a Germanium Small-Animal SPECT System. IEEE Trans Nucl Sci 2015:2036-2042
Shokouhi, Sepideh; Rogers, Baxter P; Kang, Hakmook et al. (2015) Modeling clustered activity increase in amyloid-beta positron emission tomographic images with statistical descriptors. Clin Interv Aging 10:759-70
Johnson, Lindsay C; Shokouhi, Sepideh; Peterson, Todd E (2014) Reducing multiplexing artifacts in multi-pinhole SPECT with a stacked silicon-germanium system: a simulation study. IEEE Trans Med Imaging 33:2342-51
Shokouhi, S; Claassen, D; Riddle, Wr (2014) Imaging Brain Metabolism and Pathology in Alzheimer's Disease with Positron Emission Tomography. J Alzheimers Dis Parkinsonism 4:
Shokouhi, Sepideh; Claassen, Daniel; Kang, Hakmook et al. (2013) Longitudinal progression of cognitive decline correlates with changes in the spatial pattern of brain 18F-FDG PET. J Nucl Med 54:1564-9

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