The performance of available small animal PET scanners continues to be detector rather than physics limited. Significant improvements in the sensitivity and spatial resolution of a small animal PET scanner would not only improve the quantification of signals that we are currently able to visualize (by reducing partial volume effects and increasing signal-to-noise) but would also open up important new applications that are beyond the reach of contemporary animal PET systems. The goal of the original application was to develop depth-encoding PET detectors that simultaneously exhibit high spatial resolution and high efficiency by using dual-ended readout of high-efficiency and finely pixelated scintillator arrays with position sensitive avalanche photodiodes (PSAPDs). During the fourth year of the current grant, we have successfully developed both rectangular and tapered lutetium oxyorthosilicate (LSO) arrays with crystal sizes down to 0.5 mm, very high efficiency (20 mm thick detectors) and a depth of interaction (DOI) resolution of ~ 2 mm. A prototype PET scanner was developed using these depth encoding detectors and it was shown that detector efficiency, spatial resolution and spatial resolution uniformity can be greatly improved by using our new detectors compared with the detectors used in commercial small-animal PET systems.
The aims of this renewal are to apply this detector technology and develop a high spatial resolution (~0.5 mm) and high sensitivity (~20%) preclinical PET scanner designed for molecular imaging studies in the mouse brain. The proposed research plan will also involve developing novel data correction and image reconstruction algorithms to fully utilize the high spatial and DOI capabilities of these detectors and to apply the scanner for selected proof-of-concept mouse brain imaging studies. The goals of this proposal are 1) to develop electronics and data acquisition for the proposed scanner;2) to develop depth encoding detectors with even smaller crystal size;3) to measure the contributions of positron range and photon acolinearity to the spatial resolution of a PET scanner;4) to simulate whether gantry rotation and continuous bed motion will improve the image quality of the proposed scanner;5) to construct the proposed PET scanner;6) to develop reconstruction and correction algorithms for the scanner;7) to evaluate the performance of the scanner;8) to perform selected in-vivo mouse brain imaging studies. The overall impact of this proposal is that it will lead to a preclinical PET scanner based on novel depth- encoding solid state detectors and tapered scintillator arrays that provides an unprecedented combination of spatial resolution and sensitivity for molecular imaging of the mouse brain. This will open up new opportunities for quantitative molecular imaging studies of development and aging, studies of murine disease models (Alzheimer's disease, Parkinson's disease, stroke, and neurodevelopmental disorders to name but a few), and monitoring of novel therapeutic strategies based on small molecules, peptides, nanoparticles, gene therapies or cellular therapies.

Public Health Relevance

This proposal seeks to develop a positron emission tomography (PET) scanner that has an unprecedented combination of spatial resolution and sensitivity for imaging the mouse brain. The innovation in this scanner is the use of thick depth-encoding detectors arranged in a small ring diameter to increase the sensitivity and the use of tapered scintillator arrays to further increase the sensitivity. High spatial resolution is achieved by using arrays with very small crystal size and high depth-of-interaction resolution. This scanner will drastically improve the capability of PET to aid in the understanding and treatment of major neurological disorders and diseases such as Alzheimer's disease, Parkinson's disease, stroke and epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB006109-08
Application #
8484221
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Sastre, Antonio
Project Start
2006-04-01
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
8
Fiscal Year
2013
Total Cost
$283,660
Indirect Cost
$94,177
Name
University of California Davis
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Rodriguez-Villafuerte, Mercedes; Yang, Yongfeng; Cherry, Simon R (2014) A Monte Carlo investigation of the spatial resolution performance of a small-animal PET scanner designed for mouse brain imaging studies. Phys Med 30:76-85
Ren, Silin; Yang, Yongfeng; Cherry, Simon R (2014) Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout. Med Phys 41:072503
Yang, Yongfeng; Wu, Yibao; Farrell, Richard et al. (2011) Signal and noise properties of position-sensitive avalanche photodiodes. Phys Med Biol 56:6327-36
Yang, Yongfeng; James, Sara St; Wu, Yibao et al. (2011) Tapered LSO arrays for small animal PET. Phys Med Biol 56:139-53
St James, Sara; Yang, Yongfeng; Bowen, Spencer L et al. (2010) Simulation study of spatial resolution and sensitivity for the tapered depth of interaction PET detectors for small animal imaging. Phys Med Biol 55:N63-74
Wu, Yibao; Ng, Thomas S C; Yang, Yongfeng et al. (2009) A study of the timing properties of position-sensitive avalanche photodiodes. Phys Med Biol 54:5155-72
Yang, Yongfeng; Wu, Yibao; Cherry, Simon R (2009) Investigation of Depth of Interaction Encoding for a Pixelated LSO Array with a Single Multi-Channel PMT. IEEE Trans Nucl Sci 56:2594-2599
James, Sara St; Yang, Yongfeng; Wu, Yibao et al. (2009) Experimental characterization and system simulations of depth of interaction PET detectors using 0.5 mm and 0.7 mm LSO arrays. Phys Med Biol 54:4605-19
Yang, Yongfeng; Qi, Jinyi; Wu, Yibao et al. (2009) Depth of interaction calibration for PET detectors with dual-ended readout by PSAPDs. Phys Med Biol 54:433-45
Yang, Yongfeng; Wu, Yibao; Qi, Jinyi et al. (2008) A prototype PET scanner with DOI-encoding detectors. J Nucl Med 49:1132-40