We propose to advance time-of-flight (ToF) positron emission tomography (PET) detector instrumentation that, if successful, will further enhance abilities to visualize and quantify molecular signatures of disease in the clinic. ToF PET uses the arrival time difference of detected coincidence photons to better estimate the position of the positron annihilation along the response line between any two detector elements in the PET system. Accurate ToF event positioning requires sub- nanosecond coincidence time resolution to reduce the uncertainty in annihilation photon emission location along a response line. For state-of-the-art clinical ToF PET systems, which achieve ~600-900 ps full-width-at-half-maximum (FWHM) coincidence time resolution [using photomultiplier tubes (PMTs)], the photon depth of interaction (DoI) uncertainty within the e2 cm length detector crystals does not significantly affect ToF position uncertainty. For the proposed d300 ps coincidence time resolution, the ToF uncertainty due to photon DoI within e2 cm length crystals cannot be ignored. Thus, our goal in this proposal is to create a PET detector with d300 ps FWHM coincidence time resolution that also measures photon DoI within the scintillation crystal. In addition to enhancing photon arrival time information, the capability for photon DoI resolution also promotes spatial resolution uniformity across the field of view (FoV). Furthermore, the proposed design has the unique capability to measure the 3D position and energy of each individual interaction of multi-interaction photon events, which can be exploited to further improve spatial resolution and contrast resolution. To achieve these design goals, we propose to explore a new detector design based on single ended readout of e2 cm length scintillation crystals coupled one-to-one to arrays of fast, high-gain silicon photomultiplier (SiPM) photodetectors. The full detector signal waveforms will be digitized by novel, commercially available sampling architectures, and DoI (and 3D positioning) information is determined by correlation with various parameters of the digitized detector pulse shape for each event, such as pulse height, rise and falling edge frequency patterns. In a PET system, DoI information leads to more accurate ToF event positioning along a response line that can impact reconstructed image performance, but in this work we focus on studying dependence of photon arrival time and coincidence time resolution on photon DoI. If the proposed design does not meet the time and DoI resolution specifications, as a backup plan, an alternative detector architecture based on layers of short scintillation detectors will be studied. Impact: If successful, a PET system built with the proposed detectors will increase image signal-to-noise ratio (SNR) three-fold compared to a non-ToF system for a 40 cm diameter patient, and provide enhancement of spatial resolution and contrast resolution that together will substantially enhance the ability to visualiz and quantify molecular signatures of disease residing in diffuse background activity. Alternatively the substantial SNR boost can be exploited to reduce injected dose or scan time.

Public Health Relevance

We propose to develop an advanced, yet practical photon detector technology appropriate for a new-generation clinical time-of-flight positron emission tomography (PET) system that has better than 300 pico-seconds coincidence (two-photon) time resolution and 5 mm photon interaction depth resolution within the entire detector volume. If successful, such an advance would enable substantial enhancements to image quality and quantitative accuracy over current PET system technology that would translate into benefits such as (1) improved visualization and quantification of subtle molecular and cellular-based signatures of disease residing in a diffuse background, or (2) substantially reduced injected radiation dose and/or scan duration. These features would both help to promote more widespread use of PET as well as expand its role in the clinical management of disease.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BMIT-J (01))
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Sastre, Antonio
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Stanford University
Schools of Medicine
United States
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Bieniosek, M F; Cates, J W; Levin, C S (2016) A multiplexed TOF and DOI capable PET detector using a binary position sensitive network. Phys Med Biol 61:7639-7651
Bieniosek, M F; Cates, J W; Grant, A M et al. (2016) Analog filtering methods improve leading edge timing performance of multiplexed SiPMs. Phys Med Biol 61:N427-40
Bieniosek, M F; Cates, J W; Levin, C S (2016) Achieving fast timing performance with multiplexed SiPMs. Phys Med Biol 61:2879-92
Vinke, Ruud; Yeom, Jung Yeol; Levin, Craig S (2015) Electrical delay line multiplexing for pulsed mode radiation detectors. Phys Med Biol 60:2785-802
Cates, Joshua W; Vinke, Ruud; Levin, Craig S (2015) Analytical calculation of the lower bound on timing resolution for PET scintillation detectors comprising high-aspect-ratio crystal elements. Phys Med Biol 60:5141-61
Yeom, Jung Yeol; Vinke, Ruud; Levin, Craig S (2014) Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET. Med Phys 41:122501
Vinke, Ruud; Olcott, Peter D; Cates, Joshua W et al. (2014) The lower timing resolution bound for scintillators with non-negligible optical photon transport time in time-of-flight PET. Phys Med Biol 59:6215-29
Yeom, Jung Yeol; Vinke, Ruud; Levin, Craig S (2013) Optimizing timing performance of silicon photomultiplier-based scintillation detectors. Phys Med Biol 58:1207-20
Chinn, Garry; Olcott, Peter D; Levin, Craig S (2013) Sparse signal recovery methods for multiplexing PET detector readout. IEEE Trans Med Imaging 32:932-42
Levin, Craig S (2012) Promising new photon detection concepts for high-resolution clinical and preclinical PET. J Nucl Med 53:167-70

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