Physics and technology of time-of-flight PET detectors

The imaging performance of clinical positron emission tomography (PET) systems has evolved impressively during the last ∼15 years. A main driver of these improvements has been the introduction of time-of-flight (TOF) detectors with high spatial resolution and detection efficiency, initially based on photomultiplier tubes, later silicon photomultipliers. This review aims to offer insight into the challenges encountered, solutions developed, and lessons learned during this period. Detectors based on fast, bright, inorganic scintillators form the scope of this work, as these are used in essentially all clinical TOF-PET systems today. The improvement of the coincidence resolving time (CRT) requires the optimization of the entire detection chain and a sound understanding of the physics involved facilitates this effort greatly. Therefore, the theory of scintillation detector timing is reviewed first. Once the fundamentals have been set forth, the principal detector components are discussed: the scintillator and the photosensor. The parameters that influence the CRT are examined and the history, state-of-the-art, and ongoing developments are reviewed. Finally, the interplay between these components and the optimization of the overall detector design are considered. Based on the knowledge gained to date, it appears feasible to improve the CRT from the values of 200-400 ps achieved by current state-of-the-art TOF-PET systems to about 100 ps or less, even though this may require the implementation of advanced methods such as time resolution recovery. At the same time, it appears unlikely that a system-level CRT in the order of ∼10 ps can be reached with conventional scintillation detectors. Such a CRT could eliminate the need for conventional tomographic image reconstruction and a search for new approaches to timestamp annihilation photons with ultra-high precision is therefore warranted. While the focus of this review is on timing performance, it attempts to approach the topic from a clinically driven perspective, i.e. bearing in mind that the ultimate goal is to optimize the value of PET in research and (personalized) medicine. RST/Medical Physics & Technolog

Sealed catheter-based beta sources for intravascular brachytherapy: Novel designs and dosimetric characterization

Abstract not availableApplied Science

Improving the Time Resolution of TOF-PET Detectors by Double-Sided Readout

State-of-the-art scintillation detectors for time-of-flight positron emission tomography (TOF-PET) typically employ scintillation crystals with a high aspect ratio (e.g. 4 ×4 ×22 mm3) read out on one of the small crystal surfaces. This single-sided readout (SSR) geometry may be unfavorable in terms of the coincidence resolving time (CRT) that can be achieved because of its effect on the light collection efficiency; the spread in the scintillation photon propagation times; and depth-of-interaction (DOI) related, variable detection delays. In this work it is investigated to which extent these effects can be mitigated by applying a fast photosensor on each of the small crystal surfaces. Such double-sided readout (DSR) has been introduced previously to counter the issue of DOI-related parallax errors. For the present purpose, we used Hamamatsu MPPC-S10362-33-050 C silicon photomultipliers (SiPMs) optically coupled to LSO:Ce,Ca scintillators. For polished 3 ×3 ×20 mm3 crystals with SSR, CRT values of 184 ±6 ps FWHM and 215 ±6 ps FWHM were determined for irradiation head-on and from the side, respectively. In this case, DSR improved the CRT measured under side irradiation to 174 ±6 ps FWHM. A much more substantial improvement was observed for equally sized crystals having etched side surfaces. For these crystals the CRT changed from 358 ±5 ps FWHM (head-on irradiation) and 343 ±6 FWHM (side irradiation) with SSR to 180 ±5 ps FWHM with DSR (side irradiation). These values are compared with the time resolution of detectors employing LSO:Ce,Ca crystals with a size of 3 ×3 ×5 mm3 ( CRT = 121 ±2 ps FWHM) and 3 ×3 ×10 mm3 ( CRT = 162 ±9 ps FWHM and CRT = 183 ±3 ps for polished and etched crystals, respectively).RST/Radiation, Science and TechnologyApplied Science

BGO as a hybrid scintillator / Cherenkov radiator for cost-effective time-of-flight PET

Due to detector developments in the last decade, the time-of-flight (TOF) method is now commonly used to improve the quality of positron emission tomography (PET) images. Clinical TOF-PET systems based on L(Y)SO:Ce crystals and silicon photomultipliers (SiPMs) with coincidence resolving times (CRT) between 325 ps and 400 ps FWHM have recently been developed. Before the introduction of L(Y)SO:Ce, BGO was used in many PET systems. In addition to a lower price, BGO offers a superior attenuation coefficient and a higher photoelectric fraction than L(Y)SO:Ce. However, BGO is generally considered an inferior TOF-PET scintillator. In recent years, TOF-PET detectors based on the Cherenkov effect have been proposed. However, the low Cherenkov photon yield in the order of ∼10 photons per event complicates energy discrimination-a severe disadvantage in clinical PET. The optical characteristics of BGO, in particular its high transparency down to 310 nm and its high refractive index of ∼2.15, are expected to make it a good Cherenkov radiator. Here, we study the feasibility of combining event timing based on Cherenkov emission with energy discrimination based on scintillation in BGO, as a potential approach towards a cost-effective TOF-PET detector. Rise time measurements were performed using a time-correlated single photon counting (TCSPC) setup implemented on a digital photon counter (DPC) array, revealing a prompt luminescent component likely to be due to Cherenkov emission. Coincidence timing measurements were performed using BGO crystals with a cross-section of 3 mm × 3 mm and five different lengths between 3 mm and 20 mm, coupled to DPC arrays. Non-Gaussian coincidence spectra with a FWHM of 200 ps were obtained with the 27 mm3 BGO cubes, while FWHM values as good as 330 ps were achieved with the 20 mm long crystals. The FWHM value was found to improve with decreasing temperature, while the FWTM value showed the opposite trend.RST/Radiation, Science and TechnologyRST/Applied Radiation & Isotope

Achieving 10 ps coincidence time resolution in TOF-PET is an impossible dream

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.RST/Radiation, Science and TechnologyRST/Medical Physics & Technolog

Towards monolithic scintillator based TOF-PET systems: Practical methods for detector calibration and operation

Gamma-ray detectors based on thick monolithic scintillator crystals can achieve spatial resolutions <2 mm full-width-at-half-maximum (FWHM) and coincidence resolving times (CRTs) better than 200 ps FWHM. Moreover, they provide high sensitivity and depth-of-interaction (DOI) information. While these are excellent characteristics for clinical time-of-flight (TOF) positron emission tomography (PET), the application of monolithic scintillators has so far been hampered by the lengthy and complex procedures needed for position- and time-of-interaction estimation. Here, the algorithms previously developed in our group are revised to make the calibration and operation of a large number of monolithic scintillator detectors in a TOF-PET system practical. In particular, the k-nearest neighbor (k-NN) classification method for x,y-position estimation is accelerated with an algorithm that quickly preselects only the most useful reference events, reducing the computation time for position estimation by a factor of ∼200 compared to the previously published k-NN 1D method. Also, the procedures for estimating the DOI and time of interaction are revised to enable full detector calibration by means of fan-beam or flood irradiations only. Moreover, a new technique is presented to allow the use of events in which some of the photosensor pixel values and/or timestamps are missing (e.g. due to dead time), so as to further increase system sensitivity. The accelerated methods were tested on a monolithic scintillator detector specifically developed for clinical PET applications, consisting of a 32 mm × 32 mm × 22 mm LYSO : Ce crystal coupled to a digital photon counter (DPC) array. This resulted in a spatial resolution of 1.7 mm FWHM, an average DOI resolution of 3.7 mm FWHM, and a CRT of 214 ps. Moreover, the possibility of using events missing the information of up to 16 out of 64 photosensor pixels is shown. This results in only a small deterioration of the detector performance.RST/Radiation, Science and TechnologyRST/Applied Radiation & Isotope

Time-based position estimation in monolithic scintillator detectors

Gamma-ray detectors based on bright monolithic scintillation crystals coupled to pixelated photodetectors are currently being considered for several applications in the medical imaging field. In a typical monolithic detector, both the light intensity and the time of arrival of the earliest scintillation photons can be recorded by each of the photosensor pixels every time a gamma interaction occurs. Generally, the time stamps are used to determine the gamma interaction time while the light intensities are used to estimate the 3D position of the interaction point. In this work we show that the spatio-temporal distribution of the time stamps also carries information on the location of the gamma interaction point and thus the time stamps can be used as explanatory variables for position estimation. We present a model for the spatial resolution obtainable when the interaction position is estimated using exclusively the time stamp of the first photon detected on each of the photosensor pixels. The model is shown to be in agreement with experimental measurements on a 16 mm × 16 mm × 10 mm LSO : Ce,0.2%Ca crystal coupled to a digital photon counter (DPC) array where a spatial resolution of 3 mm (root mean squared error) is obtained. Finally we discuss the effects of the main parameters such as scintillator rise and decay time, light output and photosensor single photon time resolution and pixel size.Radiation, Science and TechnologyApplied Science

A High Count-Rate and Depth-of-Interaction Resolving Single-Layered One-Side Readout Pixelated Scintillator Crystal Array for PET Applications

Organ-specific, targeted field-of-view (FoV) positron emission tomography (PET)/magnetic resonance imaging (MRI) inserts are viable solutions for a number of imaging tasks where whole-body PET/MRI systems lack the necessary sensitivity and resolution. To meet the required PET detector performance of these systems, high count-rates and effective spatial resolutions on the order of a few mm, a novel two-axis patterned reflector foil pixelated scintillator crystal array design is developed and its proof-of-concept illustrated in-silico with the Monte Carlo radiation transport modeling toolkit Geant4. It is shown that the crystal surface roughness and phased open reflector cross-sectional patterns could be optimized to maximize either the PET radiation detector's effective spatial resolution, or count rate before event pile up. In addition, it was illustrated that these two parameters had minimal impact on the energy and time resolution of the proposed PET radiation detector design. Finally, it is shown that a PET radiation detector with balance performance could be constructed using ground crystals and phased open reflector cross-sectional pattern corresponding to the middle of the tested range.RST/Medical Physics & Technolog

An Approach for Optimizing Prompt Gamma Photon-Based Range Estimation in Proton Therapy Using Cramér-Rao Theory

Various methods for in vivo range estimation during proton therapy based on the measurement of prompt gamma (PG) photons have been proposed. However, optimizing the method of detection by trial-and-error is a tedious endeavor. Here, we investigate the feasibility of using the Cramér-Rao lower bound (CRLB) to more quickly arrive at an optimum detector design. The CRLB provides the smallest possible variance on the proton range obtained from any unbiased estimator, given a statistical model of the observations. We simulated clinical proton pencil beams targeting a cylindrical, soft-tissue equivalent phantom and scored the PG photons around the phantom. Spatially, temporally and spectrally resolved PG emission profiles corresponding to different proton ranges were generated. We calculated the proton range estimation uncertainty as a function of several detector setup parameters such as detector size, bin size, and photon acceptance angle. We found a minimum uncertainty for the proton range estimation based on either spatial, spectral, or temporal information of 2.13 mm, 1.97 mm and 2.05 mm, respectively, if the detection parameters were optimized for each case. We conclude that the CRLB is a promising tool for the optimization of the detector setup for PG based range estimation in particle therapy.RST/Medical Physics & Technolog

Scintillation properties of Ca co-doped L(Y)SO:Ce between 193 K and 373 K for TOF-PET/MRI

RST/Radiation, Science and TechnologyApplied Science