PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET.

https://jnm.snmjournals.org/content/jnumed/early/2017/09/21/jnumed.116.184028.full.pdf

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care.

This paper presents new developments in inorganic scintillators widely used for radiation detection. It addresses major emerging research topics outlining current needs for applications and material sciences issues with the overall aim to provide an up-to-date picture of the field. While the traditional forms of scintillators have been crystals and ceramics, new research on films, nanoparticles, and microstructured materials is discussed as these material forms can bring new functionality and therefore find applications in radiation detection. The last part of the contribution reports on the very recent evolutions of the most advanced theories, methods, and analyses to describe the scintillation mechanisms.

/pdf/needs-trends-and-advances-in-inorganic-scintillators-2t027dfpaq.pdf

Needs, Trends, and Advances in Inorganic Scintillators

There is an increasing demand for high sensitivity multiparametric medical imaging approaches. High precision time-of-flight positron emission tomography (TOFPET) scanners have a very high potential in this context, providing an improvement in the signal-to-noise ratio of the reconstructed image and the possibility to further increase the already very high sensitivity (at the pico-molar level) of PET scanners. If the present state-of-the art coincidence time resolution of about 500 ps can be improved, it will open the way in particular to a significant reduction of the dose injected to the patient, and consequently, to the possibility to extend the use of PET scans to new categories of patients. This paper will describe the systematic approach followed by a number of researchers worldwide to push the limits of TOFPET imaging to the sub-100 ps level. It will be shown that the possibility to reach 10 ps, although extremely challenging, is not limited by physical barriers and that a number of disruptive technologies are presently being investigated at the level of all the components of the detection chain to gain at least a factor of 10 as compared to the present state-of-the-art.

Pushing the Limits in Time-of-Flight PET Imaging

The urgency for affordable and reliable detectors for ionizing radiation in medical diagnostics, nuclear control and particle physics is generating growing demand for scintillator devices combining efficient scintillation, fast emission lifetime, high interaction probability with ionizing radiation and mitigated reabsorption losses in large-volume/high-density detectors. To date, the simultaneous achievement of all such features is still an open challenge. Here we realize this regime with poly(methyl methacrylate) nanocomposites embedding CsPbBr3 perovskite nanocrystals as sensitizers for a conjugated organic dye featuring a large Stokes shift and a fast emission lifetime in the red spectral region. Complete energy transfer from the nanocrystals to the dye under both X-rays and α-particle excitation results in highly stable radioluminescence with an efficiency comparable to that of commercial-grade inorganic and plastic scintillators; an ~3.4 ns emission lifetime, competitive with fast lanthanide scintillators; and reabsorption-free waveguiding for long optical distances. Poly(methyl methacrylate) nanocomposites embedding CsPbBr3 perovskite nanocrystals can be used to simultaneously achieve optimized parameters in scintillator devices.

Efficient, fast and reabsorption-free perovskite nanocrystal-based sensitized plastic scintillators

The silicon-photomultiplier (SiPM) is becoming the device of choice for different applications, for example in fast timing like in time of flight positron emission tomography (TOF-PET) and in high energy physics (HEP). It is also becoming a choice in many single-photon or few-photon based applications, like for spectroscopy, quantum experiments and distance measurements (LIDAR). In order to fully benefit from the good performance of the SiPM, in particular its sensitivity, the dynamic range and its intrinsically fast timing properties it is necessary to understand, quantitatively describe and simulate the various parameters concerned. These analyses consider the structure and the electrical model of a single photon avalanche diode (SPAD), i.e. the SiPM microcell, and the integration in an array, i.e. the SiPM. Additionally, for several applications a more phenomenological and complete view on SiPMs has to be done, e.g. photon detection efficiency, single photon time resolution, SiPM signal response, gain fluctuation, dark count rate, afterpulse, prompt and delayed optical crosstalk. These quantities of SiPMs can strongly influence the time and energy resolution, for example in PET and HEP. Having a complete overview on all of these parameters allows to draw conclusions on how best performances can be achieved for the various needs of different applications.

http://cds.cern.ch/record/2692477/files/10.1016_j.nima.2018.11.118.pdf

Understanding and simulating SiPMs

Solid state photodetectors like silicon photomultipliers (SiPMs) are playing an important role in several fields of medical imaging, life sciences and high energy physics. They are able to sense optical photons with a single photon detection time precision below 100 ps, making them ideal candidates to read the photons generated by fast scintillators in time of flight positron emission tomography (TOF-PET). By implementing novel high-frequency readout electronics, it is possible to perform a completely new evaluation of the best timing performance achievable with state-of-the-art analog-SiPMs and scintillation materials. The intrinsic SiPM single photon time resolution (SPTR) was measured with Ketek, HPK, FBK, SensL and Broadcom devices. Also, the best achieved coincidence time resolution (CTR) for these devices was measured with LSO:Ce:Ca of [Formula: see text] mm3 and [Formula: see text] mm3 size crystals. The intrinsic SPTR for all devices ranges between 70 ps and 135 ps FWHM when illuminating the entire [Formula: see text] mm2 or [Formula: see text] mm2 area. The obtained CTR with LSO:Ce:Ca of [Formula: see text] mm3 size ranges between 58 ps and 76 ps FWHM for the SiPMs evaluated. Bismuth Germanate (BGO), read out with state of-the-art NUV-HD SiPMs from FBK, achieved a CTR of 158 [Formula: see text] ps and 277 [Formula: see text] ps FWHM for [Formula: see text] mm3 and [Formula: see text] mm3 crystals, respectively. Other BGO geometries yielded 167 [Formula: see text] 3 ps FWHM for [Formula: see text] mm3 and 235 [Formula: see text] 5 ps FWHM for [Formula: see text] mm3 also coupled with Meltmount (n  =  1.582) and wrapped in Teflon. Additionally, the average number of Cherenkov photons produced by BGO in each 511 keV event was measured to be 17 [Formula: see text] 3 photons. Based on this measurement, we predict the limits of BGO for ultrafast timing in TOF-PET with Monte Carlo simulations. Plastic scintillators (BC422, BC418), BaF2, GAGG:Ce codoped with Mg and CsI:undoped were also tested for TOF performance. Indeed, BC422 can achieve a CTR of 35 [Formula: see text] 2 ps FWHM using only Compton interactions in the detector with a maximum deposited energy of 340 keV. BaF2 with its fast cross-luminescence enables a CTR of 51 [Formula: see text] 5 ps FWHM when coupled to VUV-HD SiPMs from FBK, with only  ∼22% photon detection efficiency (PDE). We summarize the measured CTR of the various scintillators and discuss their intrinsic timing performance.

https://iopscience.iop.org/article/10.1088/1361-6560/ab63b4/pdf

Experimental time resolution limits of modern SiPMs and TOF-PET detectors exploring different scintillators and Cherenkov emission.

Time of flight (TOF) in positron emission tomography (PET) has experienced a revival of interest after its first introduction in the eighties. This is due to a significant progress in solid state photodetectors (SiPMs) and newly developed scintillators (LSO and its derivatives). Latest developments at Fondazione Bruno Kessler (FBK) lead to the NUV-HD SiPM with a very high photon detection efficiency of around 55%. Despite the large area of 4×4 mm2 it achieves a good single photon time resolution (SPTR) of 180±5ps FWHM. Coincidence time resolution (CTR) measurements using LSO:Ce codoped with Ca scintillators yield best values of 73±2ps FWHM for 2×2×3 mm3 and 117±3ps for 2×2×20 mm3 crystal sizes. Increasing the crystal cross-section from 2×2 mm2 to 3×3 mm2 a non negligible CTR deterioration of approximately 7ps FWHM is observed. Measurements with LSO:Ce codoped Ca and LYSO:Ce scintillators with various cross-sections (1×1 mm2 - 4×4 mm2) and lengths (3mm - 30mm) will be a basis for discussing on how the crystal geometry affects timing in TOF-PET. Special attention is given to SiPM parameters, e.g. SPTR and optical crosstalk, and their measured dependency on the crystal cross-section. Additionally, CTR measurements with LuAG:Ce, LuAG:Pr and GGAG:Ce samples are presented and the results are interpreted in terms of their scintillation properties, e.g. rise time, decay time, light yield and emission spectra.

https://iopscience.iop.org/article/10.1088/1748-0221/11/08/P08008/pdf

State of the art timing in TOF-PET detectors with LuAG, GAGG and L(Y)SO scintillators of various sizes coupled to FBK-SiPMs

The coincidence time resolution (CTR) of scintillator based detectors commonly used in positron emission tomography is well known to be dependent on the scintillation decay time (τd) and the number of photons detected (n'), i.e. CTR proportional variant √τd/n'. However, it is still an open question to what extent the scintillation rise time (τr) and other fast or prompt photons, e.g. Cherenkov photons, at the beginning of the scintillation process influence the CTR. This paper presents measurements of the scintillation emission rate for different LSO type crystals, i.e. LSO:Ce, LYSO:Ce, LSO:Ce codoped Ca and LGSO:Ce. For the various LSO-type samples measured we find an average value of 70 ps for the scintillation rise time, although some crystals like LSO:Ce codoped Ca seem to have a much faster rise time in the order of 20 ps. Additional measurements for LuAG:Ce and LuAG:Pr show a rise time of 535 ps and 251 ps, respectively. For these crystals, prompt photons (Cherenkov) can be observed at the beginning of the scintillation event. Furthermore a significantly lower rise time value is observed when codoping with calcium. To quantitatively investigate the influence of the rise time to the time resolution we measured the CTR with the same L(Y)SO samples and compared the values to Monte Carlo simulations. Using the measured relative light yields, rise- and decay times of the scintillators we are able to quantitatively understand the measured CTRs in our simulations. Although the rise time is important to fully explain the CTR variation for the different samples tested we determined its influence on the CTR to be in the order of a few percent only. This result is surprising because, if only photonstatistics of the scintillation process is considered, the CTR would be proportional to the square root of the rise time. The unexpected small rise time influence on the CTR can be explained by the convolution of the scintillation rate with the single photon time resolution (SPTR) of the photodetector and the photon travel spread (PTS) in the crystal. The timing benefits of prompt photons at the beginning of the scintillation process (Cherenkov etc) are further studied, which leads to the conclusion that the scintillation rise time, SPTR and PTS have to be lowered simultaneously to fully profit from these fast photons in order to improve the CTR significantly.

https://iopscience.iop.org/article/10.1088/0031-9155/61/7/2802/pdf

Measurement of intrinsic rise times for various L(Y)SO and LuAG scintillators with a general study of prompt photons to achieve 10 ps in TOF-PET.

Scintillator based radiation detectors readout by SiPMs successively break records in their reached time resolution. Nevertheless, new challenges in time of flight positron emission tomography (TOF-PET) and high energy physics are setting unmatched goals in the 10 ps range. Recently it was shown that high frequency (HF) readout of SiPMs significantly improves the measured single photon time resolution (SPTR), allowing to evaluate the intrinsic performance of large area devices; e.g. FBK NUV-HD SiPMs of [Formula: see text] mm2 area and 40 [Formula: see text]m single photon avalanche diode (SPAD) size achieve 90 ps FWHM. In TOF-PET such readout allows to lower the leading edge detection threshold, so that the fastest photons produced in the crystal can be utilized. This is of utmost importance if a high SPTR and prompt Cherenkov light generated by the hot-recoil electron upon 511 keV photo-absorption should improve timing. This paper shows that high-frequency bipolar transistor readout of state-of-the-art SiPMs coupled to high-performance scintillators can substantially improve the best achievable coincidence time resolution (CTR) in TOF-PET. In this context a CTR of 158 [Formula: see text] 3 ps FWHM with [Formula: see text] mm3 BGO crystals coupled to FBK SiPMs is achieved. This faint Cherenkov signal is as well present in standard LSO scintillators, which together with low SPTR values (<90 ps FWHM) improves the CTR of [Formula: see text] mm3 LSO:Ce:Ca coupled to FBK NUV-HD [Formula: see text] mm2 with 25 [Formula: see text]m SPAD size to 61 [Formula: see text] 2 ps FWHM using HF-electronics, as compared to 73 [Formula: see text] 2 ps when readout by the NINO front-end ASIC. When coupling the LSO:Ce:Ca crystals to FBK NUV-HD SiPMs of [Formula: see text] mm2 and 40 [Formula: see text]m SPAD size, using HF-electronics, a CTR of even 58 [Formula: see text] 3 ps for [Formula: see text] mm3 and 98 [Formula: see text] 3 ps for [Formula: see text] mm3 is achieved. This new experimental data will allow to further discuss the timing limits in scintillator-based detectors.

https://iopscience.iop.org/article/10.1088/1361-6560/aafd52/pdf

Stefan Gundacker

Papers

Understanding and simulating SiPMs

Experimental time resolution limits of modern SiPMs and TOF-PET detectors exploring different scintillators and Cherenkov emission.

State of the art timing in TOF-PET detectors with LuAG, GAGG and L(Y)SO scintillators of various sizes coupled to FBK-SiPMs

Measurement of intrinsic rise times for various L(Y)SO and LuAG scintillators with a general study of prompt photons to achieve 10 ps in TOF-PET.

High-frequency SiPM readout advances measured coincidence time resolution limits in TOF-PET.