The SNR of time-of-flight positron emission tomography data for joint reconstruction of the activity and attenuation images.

Objective.Measurement of the time-of-flight (TOF) difference of each coincident pair of photons increases the effective sensitivity of positron emission tomography (PET). Many authors have analyzed the benefit of TOF for quantification and hot spot detection in the reconstructed activity images. However, TOF not only improves the effective sensitivity, it also enables the joint reconstruction of the tracer concentration and attenuation images. This can be used to correct for errors in CT- or MR-derived attenuation maps, or to apply attenuation correction without the help of a second modality. This paper presents an analysis of the effect of TOF on the variance of the jointly reconstructed attenuation and (attenuation corrected) tracer concentration images.Approach.The analysis is performed for PET systems that have a distribution of possibly non-Gaussian TOF-kernels, and includes the conventional Gaussian TOF-kernel as a special case. Non-Gaussian TOF-kernels are often observed in novel detector designs, which make use of two (or more) different mechanisms to convert the incoming 511 keV photon to optical photons. The analytical result is validated with a simple 2D simulation.Main results.We show that if two different TOF-kernels are equivalent for image reconstruction with known attenuation, then they are also equivalent for joint reconstruction of the activity and the attenuation images. The variance increase in the activity, caused by also jointly reconstructing the attenuation image, vanishes when the TOF-resolution approaches perfection.Significance.These results are of interest for PET detector development and for the development of stand-alone PET systems.

The SNR of Positron Emission Data With Gaussian and Non-Gaussian Time-of-Flight Kernels, With Application to Prompt Photon Coincidence.

It is well known that measurement of the time-of-flight (TOF) increases the information provided by coincident events in positron emission tomography (PET). This information increase propagates through the reconstruction and improves the signal-to-noise ratio in the reconstructed images. Takehiro Tomitani has analytically computed the gain in variance in the reconstructed image, provided by a particular TOF resolution, for the center of a uniform disk and for a Gaussian TOF kernel. In this paper we extend this result, by computing the signal-to-noise ratio (SNR) contributed by individual coincidence events for two different tasks. One task is the detection of a hot spot in the center of a uniform cylinder. The second one is the same as that considered by Tomitani, i.e. the reconstruction of the central voxel in the image of a uniform cylinder. In addition, we extend the computation to non-Gaussian TOF kernels. It is found that a modification of the TOF-kernel changes the SNR for both tasks in almost exactly the same way. The proposed method can be used to compare TOF-systems with different and possibly event-dependent TOF-kernels, as encountered when prompt photons, such as Cherenkov photons are present, or when the detector is composed of different scintillators. The method is validated with simple 2D simulations and illustrated by applying it to PET detectors producing optical photons with event-dependent timing characteristics.

DOI estimation through signal arrival time distribution: a theoretical description including proof of concept measurements.

The challenge to reach 10 ps coincidence time resolution (CTR) in time-of-flight positron emission tomography (TOF-PET) is triggering major efforts worldwide, but timing improvements of scintillation detectors will remain elusive without depth-of-interaction (DOI) correction in long crystals. Nonetheless, this momentum opportunely brings up the prospect of a fully time-based DOI estimation since fast timing signals intrinsically carry DOI information, even with a traditional single-ended readout. Consequently, extracting features of the detected signal time distribution could uncover the spatial origin of the interaction and in return, provide enhancement on the timing precision of detectors. We demonstrate the validity of a time-based DOI estimation concept in two steps. First, experimental measurements were carried out with current LSO:Ce:Ca crystals coupled to FBK NUV-HD SiPMs read out by fast high-frequency electronics to provide new evidence of a distinct DOI effect on CTR not observable before with slower electronics. Using this detector, a DOI discrimination using a double-threshold scheme on the analog timing signal together with the signal intensity information was also developed without any complex readout or detector modification. As a second step, we explored by simulation the anticipated performance requirements of future detectors to efficiently estimate the DOI and we proposed four estimators that exploit either more generic or more precise features of the DOI-dependent timestamp distribution. A simple estimator using the time difference between two timestamps provided enhanced CTR. Additional improvements were achieved with estimators using multiple timestamps (e.g. kernel density estimation and neural network) converging to the Cramér-Rao lower bound developed in this work for a time-based DOI estimation. This two-step study provides insights on current and future possibilities in exploiting the timing signal features for DOI estimation aiming at ultra-fast CTR while maintaining detection efficiency for TOF PET.

Roadmap toward the 10 ps time-of-flight PET challenge.

Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with x-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting cancer in complete remission. Moreover, there is an increasing demand for reducing the radioactive doses injected to the patients without impairing image quality. There are three ways to improve PET scanner sensitivity: improving detector efficiency, increasing geometrical acceptance of the imaging device and pushing the timing performance of the detectors. Currently, some pre-localization of the electron-positron annihilation along a line-of-response (LOR) given by the detection of a pair of annihilation photons is provided by the detection of the time difference between the two photons, also known as the time-of-flight (TOF) difference of the photons, whose accuracy is given by the coincidence time resolution (CTR). A CTR of about 10 picoseconds FWHM will ultimately allow to obtain a direct 3D volume representation of the activity distribution of a positron emitting radiopharmaceutical, at the millimetre level, thus introducing a quantum leap in PET imaging and quantification and fostering more frequent use of 11C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.

Pushing Cherenkov PET with BGO via coincidence time resolution classification and correction.

Bismuth germanate (BGO) shows good properties for positron emission tomography (PET) applications, but was substituted by the development of faster crystals like lutetium oxyorthosilicate (LSO) for time-of-flight PET (TOF-PET). Recent improvements in silicon photomultipliers (SiPMs) and fast readout electronics make it possible to access the Cherenkov photon signal produced upon 511 keV interaction, which makes BGO a cost-effective candidate for TOF-PET. Tails in the time-delay distribution, however, remain a challenge. These are mainly caused by the high statistical fluctuation on the Cherenkov photons detected. To select fast events with a high detected Cherenkov photon number, the signal rise time of the SiPM was used for discrimination. The charge, time delay and signal rise time was measured for two different lengths of BGO crystals coupled to FBK NUV-HD SiPMs and high frequency readout in a coincidence time resolution setup. The recorded events were divided into 5 × 5 categories based on the signal rise time, and time resolutions of 200 ± 3 ps for 2 × 2 × 20 mm3 and 117 ± 3 ps for 2 × 2 × 3 mm3 were measured for the fastest 20% of the events (4% in coincidence). These good timing events can provide additional information for the image reconstruction in order to increase the SNR significantly, without spoiling the detector sensitivity. Putting all photopeak events together and correcting for the time bias introduced by different numbers of Cherenkov photons detected, time resolutions of 259 ± 3 ps for 20 mm long and 151 ± 3 ps for 3 mm long crystals were measured. For a small fraction of events sub-100 ps coincidence time resolution with BGO was reached for a 3 mm short pixel.

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

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.

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

Core-shell ZnO:Ga-SiO2 nanocrystals: limiting particle agglomeration and increasing luminescence via surface defect passivation.

Heat treatment is needed to increase the luminescence intensity of ZnO:Ga particles, but it comes at the cost of higher particle agglomeration. Higher agglomeration results in low transparency of scintillating powder when embedded in a matrix and constitutes one of the biggest disadvantages, besides low light yield and low stopping power, of ZnO:Ga powder. Limiting ZnO:Ga particle size is therefore a key step in order to prepare highly luminescent and transparent composites with prospects for optical applications. In this work, SiO2 coating was successfully used to improve luminescence intensity or limitation of crystallite size growth during further annealing. Furthermore, ZnO:Ga and ZnO:Ga-SiO2 core-shells were embedded in a polystyrene matrix.

Improved single photon time resolution for analog SiPMs with front end readout that reduces influence of electronic noise.

A key step to improve the coincidence time resolution of positron emission tomography detectors that exploit small populations of promptly emitted photons is improving the single photon time resolution (SPTR) of silicon photomultipliers (SiPMs). The influence of electronic noise has previously been identified as the dominant factor affecting SPTR for large area, analog SiPMs. In this work, we measure the achievable SPTR with front end electronic readout that minimizes the influence of electronic noise. With this readout circuit, the SPTR measured for one FBK NUV single avalanche photodiode (SPAD) was also achieved with a [Formula: see text] mm2 FBK NUV SiPM. SPTR for large area devices was also significantly improved. The measured SPTRs for [Formula: see text] mm2 Hamamatsu and SensL SiPMs were [Formula: see text]150 ps FWHM, and SPTR [Formula: see text]100 ps FWHM was measured for [Formula: see text] mm2 and [Formula: see text] mm2 FBK NUV and NUV-HD SiPMs. We also explore additional factors affecting the achievable SPTR for large area, analog SiPMs when the contribution of electronic noise is minimized and pinpoint potential areas of improvement to further reduce the SPTR of large area sensors towards that achievable for a single SPAD.

Preparation and luminescence properties of ZnO:Ga - polystyrene composite scintillator.

Highly luminescent ZnO:Ga-polystyrene composite (ZnO:Ga-PS) with ultrafast subnanosecond decay was prepared by homogeneous embedding the ZnO:Ga scintillating powder into the scintillating organic matrix. The powder was prepared by photo-induced precipitation with subsequent calcination in air and Ar/H2 atmospheres. The composite was subsequently prepared by mixing the ZnO:Ga powder into the polystyrene (10 wt% fraction of ZnO:Ga) and press compacted to the 1 mm thick pellet. Luminescent spectral and kinetic characteristics of ZnO:Ga were preserved. Radioluminescence spectra corresponded purely to the ZnO:Ga scintillating phase and emission of polystyrene at 300-350 nm was absent. These features suggest the presence of non-radiative energy transfer from polystyrene host towards the ZnO:Ga scintillating phase which is confirmed by the measurement of X-ray excited scintillation decay with picosecond time resolution. It shows an ultrafast rise time below the time resolution of the experiment (18 ps) and a single-exponential decay with the decay time around 500 ps.

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.

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.

Conical photonic crystals for enhancing light extraction efficiency from high refractive index materials.

We propose, analyze and optimize a two-dimensional conical photonic crystal geometry to enhance light extraction from a high refractive index material, such as an inorganic scintillator. The conical geometry suppresses Fresnel reflections at an optical interface due to adiabatic impedance matching from a gradient index effect. The periodic array of cone structures with a pitch larger than the wavelength of light diffracts light into higher-order modes with different propagating angles, enabling certain photons to overcome total internal reflection (TIR). The numerical simulation shows simultaneous light yield gains relative to a flat surface both below and above the critical angle and how key parameters affect the light extraction efficiency. Our optimized design provides a 46% gain in light yield when the conical photonic crystals are coated on an LSO (cerium-doped lutetium oxyorthosilicate) scintillator.

Sub-100 ps coincidence time resolution for positron emission tomography with LSO:Ce codoped with Ca.

The coincidence time resolution (CTR) becomes a key parameter of 511 keV gamma detection in time of flight positron emission tomography (TOF-PET). This is because additional information obtained through timing leads to a better noise suppression and therefore a better signal to noise ratio in the reconstructed image. In this paper we present the results of CTR measurements on two different SiPM technologies from FBK coupled to LSO:Ce codoped 0.4%Ca crystals. We compare the measurements performed at two separate test setups, i.e. at CERN and at FBK, showing that the obtained results agree within a few percent. We achieve a best CTR value of 85 ± 4 ps FWHM for 2 × 2 × 3 mm(3) LSO:Ce codoped 0.4%Ca crystals, thus breaking the 100 ps barrier with scintillators similar to LSO:Ce or LYSO:Ce. We also demonstrate that a CTR of 140 ± 5 ps can be achieved for longer 2 × 2 × 20 mm(3) crystals, which can readily be implemented in the current generation PET systems to achieve the desired increase in the signal to noise ratio.

Influence of depth of interaction upon the performance of scintillator detectors.

The uncertainty in time of particle detection within a scintillator detector, characterised by the coincidence time resolution (CTR), is explored with respect to the interaction position within the scintillator crystal itself. Electronic collimation between two scintillator detectors is utilised to determine the CTR with depth of interaction (DOI) for different materials, geometries and wrappings. Significantly, no relationship between the CTR and DOI is observed within experimental error. Confinement of the interaction position is seen to degrade the CTR in long scintillator crystals by 10%.