Preclinical positron emission tomography (PET) has become a widely used tool in biomedical research, particularly in the evaluation of new therapeutics. Hundreds of scanners are installed across the world in major medical research centers and within pharmaceutical companies. For a variety of reasons, however, the performance of these systems falls well short of what can theoretically be achieved. This has two important consequences. Firstly, the quantitative potential of current studies of radiopharmaceutical kinetics and uptake is undermined by limited spatial resolution (reducing accuracy) and limited sensitivity (reducing precision). Secondly, important applications for preclinical PET, for example metabolic imaging in gray matter structures in the mouse brain or studies of low abundance protein targets, such as TSPO receptor expression in chronic inflammation, are just out of the reach of current instruments. The goal of this proposal is to develop a pathway towards small-animal PET scanners that can come as close as possible to the theoretical limits of spatial resolution and sensitivity imposed by fundamental physics and the properties of available detector materials. Building on 15 years of development of increasingly high resolution detectors for small-animal PET, recent advances in realizing dual-ended detectors that can also simultaneously provide high sensitivity and combining these with highly innovative silicon photomultiplier (SiPM) photodetectors, we propose a design that will lead to detector modules with unprecedented performance for small-animal PET applications. Specifically, we will develop fully-engineered detector modules suitable for close packing in a preclinical PET scanner geometry that will support better than 0.6 mm reconstructed spatial resolution, an average sensitivity of >10% across the whole body of a mouse, depth-of-interaction resolution < 3 mm, timing resolution < 3 ns and energy resolution < 30%. We will develop the electronics and software to efficiently read out these modules with no significant degradation in performance and integrate them into the open source OpenPET libraries for access by the entire nuclear medical imaging community. Lastly, we will use experimental data from fully-engineered detector modules combined with advanced simulation tools to design and predict the performance of a preclinical scanner using our new technology. The outcome of this proposal will be detector modules and a scanner design that advance preclinical PET to new levels of spatial resolution and sensitivity together with the comprehensive set of experimental and simulation data that will be needed to justify moving to the next stage of developing a prototype small-animal PET scanner. There also will be a broader impact in that the detector technology and electronics developed will be applicable to other PET systems, especially dedicated organ imaging (e.g. brain, breast) scanners and PET/MR systems.

Public Health Relevance

Positron emission tomography (PET) is a non-invasive and quantitative imaging technique that allows molecular targets and pathways to be imaged in living subjects. It is widely used for preclinical studies aimed at determining the biological properties of new drugs and treatments to aid in identifying promising candidates to move forwards into clinical trials. The performance of current preclinical PET technology, however, does not come close to reaching the theoretical limits in terms of spatial resolution or sensitivit. In this proposal we use innovative silicon photomultiplier light sensors as the basis for detectors that can advance preclinical PET to a new level, improving performance for all current applications and opening the window on new applications that are beyond the range of current instruments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB019439-01A1
Application #
8963350
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Sastre, Antonio
Project Start
2015-07-01
Project End
2019-04-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of California Davis
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Peng, Peng; Liu, Chih-Chieh; Du, Junwei et al. (2018) Improving Edge Crystal Identification in Flood Histograms Using Triangular Shape Crystals. Biomed Phys Eng Express 4:
Du, Junwei; Peng, Peng; Bai, Xiaowei et al. (2018) Shared-photodetector readout to improve the sensitivity of positron emission tomography. Phys Med Biol 63:205002
Du, Junwei; Bai, Xiaowei; Gola, Alberto et al. (2018) Performance of a high-resolution depth-encoding PET detector module using linearly-graded SiPM arrays. Phys Med Biol 63:035035
Berg, Eric; Cherry, Simon R (2018) Innovations in Instrumentation for Positron Emission Tomography. Semin Nucl Med 48:311-331
Du, Junwei; Schmall, Jeffrey P; Di, Kun et al. (2017) Performance Comparison of Different Readouts for Position-Sensitive Solid-State Photomultiplier Arrays. Biomed Phys Eng Express 3:
Du, Junwei; Schmall, Jeffrey P; Judenhofer, Martin S et al. (2017) A Time-Walk Correction Method for PET Detectors Based on Leading Edge Discriminators. IEEE Trans Radiat Plasma Med Sci 1:385-390
Kwon, Sun Il; Ferri, Alessandro; Gola, Alberto et al. (2016) Reaching 200-ps timing resolution in a time-of-flight and depth-of-interaction positron emission tomography detector using phosphor-coated crystals and high-density silicon photomultipliers. J Med Imaging (Bellingham) 3:043501
Du, Junwei; Yang, Yongfeng; Bai, Xiaowei et al. (2016) Characterization of Large-Area SiPM Array for PET Applications. IEEE Trans Nucl Sci 63:8-16
Kwon, Sun Il; Gola, Alberto; Ferri, Alessandro et al. (2016) Bismuth germanate coupled to near ultraviolet silicon photomultipliers for time-of-flight PET. Phys Med Biol 61:L38-L47