TOF Information Research Articles

Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity

Objective. Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed. Novel research demonstrated significant improvements in the reachable timing resolutions when combining conventional calibration approaches with machine learning, with the disadvantage of extensive calibration times infeasible for a clinical application. In this work, we made the first steps towards an in-system application and analyzed the effects of varying data sparsity on a machine learning timing calibration, aiming to accelerate the calibration time. Furthermore, we demonstrated the versatility of our calibration concept by applying the procedure for the first time to analog readout technology. Approach. We modified experimentally acquired calibration data used for training regarding their statistical and spatial sparsity, mimicking reduced measurement time and variability of the training data. Trained models were tested on unseen test data, characterized by fine spatial sampling and rich statistics. In total, 80 decision tree models with the same hyperparameter settings, were trained and holistically evaluated regarding data scientific, physics-based, and PET-based quality criteria. Main results. The calibration procedure can be heavily reduced from several days to some minutes without sacrificing quality and still significantly improving the timing resolution from (304±5)ps to (216±1)ps compared to conventionally used analytical calibration methods.Significance. This work serves as the first step in making the developed machine learning-based calibration suitable for an in-system application to profit from the method’s capabilities on the system level. Furthermore, this work demonstrates the functionality of the methodology on detectors using analog readout technology. The proposed holistic evaluation criteria here serve as a guideline for future evaluations of machine learning-based calibration approaches.

Characterization of the partial volume effect along the axial field-of-view of the Biograph Vision Quadra total-body PET/CT system for multiple isotopes

BackgroundTotal-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers).Materials and MethodsCylindrical phantoms equipped with three different sphere sizes (inner diameters 7.86 mm, 28 and 37 mm) were utilized for the PVE evaluation. The 7.86 mm sphere was filled with F-18 (8:1 and 4:1), Ga-68 (8:1) and Zr-89 (8:1). The 28 mm and 37 mm spheres were filled with F-18 (8:1). Background concentration in the respective phantoms was of ~ 3 kBq/ml. The phantoms were measured at multiple positions in the FOV (axial: 0, 10, 20, 30, 40 and 50 cm, transaxial: 0, 10, 20 cm). The data were reconstructed with the standard clinical protocol, including PSF correction and TOF information with up to 10 iterations for maximum ring differences (MRDs) of 85 and 322; CRCs, as well as voxel noise levels, were determined for each position.ResultsF-18 CRCs (SBR 8:1 and 4:1) of the 7.86 mm sphere decreased up to 18% from the center FOV (cFOV) toward the transaxial edge and increased up to 17% toward the axial edge. Noise levels were below 15% for the default clinical reconstruction parameters. The larger spheres exhibited a similar pattern. Zr-89 revealed ~ 10% lower CRCs than F-18 but larger noise (9.1% (F-18), 19.1% (Zr-89); iteration 4, cFOV) for the default reconstruction. Zr-89 noise levels in the cFOV significantly decreased (~ 28%) when reconstructing the data with MRD322 compared with MRD85 along with a slight decrease in CRC values. Ga-68 exhibited the lowest CRCs for the three isotopes and noise characteristics comparable to those of F-18.ConclusionsDistinct differences in the PVE within the FOV were detected for clinically relevant isotopes F-18, Ga-68 and Zr-89, as well as for different sphere sizes. Depending on the positions inside the FOV, the sphere-to-background ratios, count statistics and isotope used, this can result in an up to 50% difference between CRCs. Hence, these changes in PVE can significantly affect the quantitative analysis of patient data. MRD322 resulted in slightly lower CRC values, especially in the center FOV, whereas the voxel noise significantly decreased compared with MRD85.

A concise perspective on the effect of interpreting the double layer capacitance data over the intrinsic evaluation parameters in oxygen evolution reaction

Electrochemical active surface area (ECSA) normalized polarization information of an electrocatalyst provide an insightful information of specific activity. ECSA values of a catalyst are directly related to the double-layer capacitance (Cdl) value of the catalyst. Here in this report, we have highlighted the effective ways of calculating Cdl values for the determination specific OER activity in detail. Various electrochemical analysis shows that selection of proper ways of calculating Cdl values can direct us to get real and error-free specific activity information. From the experimental verification, it is observed that linear fitting (LF) method can be a best practice for providing much more reliable data as compare to normal slope calculation (NSC) to get Cdl value of a catalyst. Obviously, it is common to expect that the Cdl value obtained from both methods should provide same value. But adopted internal unit conversion during the calculation of Cdl by NSC method could bring a severe error. Using our critical valuations of Cdl data followed by the specific activity, per-site TOF, surface area and surface coverage information researchers can ensure precision and correctness when presenting their data regarding the activity of an electrocatalyst.

Determination of 19 polyphenolic compounds in tea by ultra-high performance liquid chromatography combined with quadrupole-time of flight mass spectrometry

A rapid method was presented for the determination of 19 polyphenols in tea by ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF MS). Tea samples were extracted by 50% (V/V) ethanol, then separated by Waters Acquity BEH C18 column using a binary solvent system composed of acetonitrile and water (0.1% formic acid) by gradient elution. The analytes were determined by Q-TOF MS in TOF MS and information dependent acquisition (IDA)-MS/MS mode. The results showed that mass accuracy error of the 19 polyphenols were lower than 5.0 × 10–6, good linear relationship was got in range of 0.2–500 μg/L and correlation coefficient was higher than 0.9990. The LOD was in the range of 0.002–0.100 mg/kg and the LOQ was in the range of 0.004–0.200 mg/kg. Recovery of the method was in range of 78.4%–109.2% with spike levels of 0.004–2.000 mg/kg, relative standard deviations were lower than 10%. The method was simple, rapid and accurate. It could be used for the rapid screening and quantitative analysis of 19 polyphenols in tea.

A backprojection kernel (KRNL3D) for very-wide-aperture 3D tomography applied to PET with Multigrid for precise use of time-of-flight data

In ‘KRNL3D’ we derive a kernel function K(y 1, y 2, φ) whose backprojections from all directions (θ, φ) in the spherical band on the celestial sphere, when integrated with respect to solid angle, yield ρ, the 3D Gaussian point response function (PRF) of radius 1. This K, when convolved against line integral data from an unknown density function f, yields an integral formula for the ‘mollification’ ff = ρ ∗ f, which is a slightly blurred version of f, and which stabilizes the mild ill-posedness. Applied to positron emission tomography that backprojection reconstruction occurs stochastically and one emission event at a time, after needed data corrections. We describe Octave (≈Matlab) codes to tabulate K and to test its use with a large aperture or π/6. ‘KRNL3D- TOF’ truncates backprojection to a cylindrical patch about the TOF approximate location of each event. These ‘backplacements’ decrease the computational cost and limit noise and streaking in one region from contaminating the reconstruction in more distant regions. They also retain the ability to count emission events in an isolated blob despite very low event counts, a valuable feature for dynamic studies of metabolic processes. ‘Multigrid’ allows further reduction in the radius and lengths of the cylinders, thereby enabling even more precise use of the TOF information. This precision should be especially important as researchers decrease the TOF uncertainty in newer generation scanners. Finally, we discuss ‘further work’ that needs to be done. Our codes are being made freely available at https://github.com/keithmillerberkeley/PET-codes.

Time of Flight in Perspective: Instrumental and Computational Aspects of Time Resolution in Positron Emission Tomography.

The first time-of-flight positron emission tomography (TOF-PET) scanners were developed as early as in the 1980s. However, the poor light output and low detection efficiency of TOF-capable detectors available at the time limited any gain in image quality achieved with these TOF-PET scanners over the traditional non-TOF PET scanners. The discovery of LSO and other Lu-based scintillators revived interest in TOF-PET and led to the development of a second generation of scanners with high sensitivity and spatial resolution in the mid-2000s. The introduction of the silicon photomultiplier (SiPM) has recently yielded a third generation of TOF-PET systems with unprecedented imaging performance. Parallel to these instrumentation developments, much progress has been made in the development of image reconstruction algorithms that better utilize the additional information provided by TOF. Overall, the benefits range from a reduction in image variance (SNR increase), through allowing joint estimation of activity and attenuation, to better reconstructing data from limited angle systems. In this work, we review these developments, focusing on three broad areas: 1) timing theory and factors affecting the time resolution of a TOF-PET system; 2) utilization of TOF information for improved image reconstruction; and 3) quantification of the benefits of TOF compared to non-TOF PET. Finally, we offer a brief outlook on the TOF-PET developments anticipated in the short and longer term. Throughout this work, we aim to maintain a clinically driven perspective, treating TOF as one of multiple (and sometimes competitive) factors that can aid in the optimization of PET imaging performance.

Determination of 8 Endogenous Alkaloid Components inBoletusUsing Ultrahigh-Performance Liquid Chromatography Combined with Quadrupole-Time of Flight Mass Spectrometry

A ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) method was developed for simultaneous determination of 8 endogenous alkaloid compounds inBoletus.Boletussamples were extracted by 50% (V/V) methanol-water solution, then separated by CORTECS UPLC HILIC column using a binary solvent system by gradient elution. The analytes were determined by Q-TOF/MS in TOF MS and information dependent acquisition (IDA)-MS/MS mode. The results showed that mass accuracy error of the 8 endogenous alkaloids were lower than 5.0 × 10−6, good linear relationship was got in range of 0.2–500 μg/L, and correlation coefficient was higher than 0.9990. The limit of detection was in the range of 0.002–0.100 mg/kg and the limit of quantification was in the range of 0.004–0.200 mg/kg. Recovery of the method was in range of 80.1%–101.5% with spike levels of 0.004–2.00 mg/kg, relative standard deviations were lower than 10%. The method was simple, specific, and reliable. It could be used for the rapid screening and quantitative analysis of 8 endogenous alkaloids inBoletus.

Robustness of post-reconstruction and direct kinetic parameter estimates under rigid head motion in dynamic brain PET imaging

ObjectiveDynamic PET imaging is extensively used in brain imaging to estimate parametric maps. Inter-frame motion can substantially disrupt the voxel-wise time-activity curves (TACs), leading to erroneous maps during kinetic modelling. Therefore, it is important to characterize the robustness of kinetic parameters under various motion and kinetic model related factors. MethodsFully 4D brain simulations ([15O]H2O and [18F]FDG dynamic datasets) were performed using a variety of clinically observed motion patterns. Increasing levels of head motion were investigated as well as varying temporal frames of motion initiation. Kinetic parameter estimation was performed using both post-reconstruction kinetic analysis and direct 4D image reconstruction to assess bias from inter-frame emission blurring and emission/attenuation mismatch. ResultsKinetic parameter bias heavily depends on the time point of motion initiation. Motion initiated towards the end of the scan results in the most biased parameters. For the [18F]FDG data, k4 is the more sensitive parameter to positional changes, while K1 and blood volume were proven to be relatively robust to motion. Direct 4D image reconstruction appeared more sensitive to changes in TACs due to motion, with parameter bias spatially propagating and depending on the level of motion. ConclusionKinetic parameter bias highly depends upon the time frame at which motion occurred, with late frame motion-induced TAC discontinuities resulting in the least accurate parameters. This is of importance during prolonged data acquisition as is often the case in neuro-receptor imaging studies. In the absence of a motion correction, use of TOF information within 4D image reconstruction could limit the error propagation.

An integrated targeted and untargeted approach for the analysis of ergot alkaloids in cereals using UHPLC – hybrid quadrupole time-of-flight mass spectrometry

An ultra-high performance liquid chromatography hybrid quadrupole – time of flight (Q-TOF) mass spectrometry (MS) method is described for the simultaneous quantitative determination of common ergot alkaloids and the screening, detection and identification of unexpected (less studied or novel) members of this class of toxic fungal secondary metabolites. The employed analytical strategy involves an untargeted data acquisition (consisting of full scan TOF MS survey and information dependent acquisition MS/MS scans) and the processing of data using both targeted and untargeted approaches. Method performance characteristics for the quantitative analysis of 6 common ergot alkaloids i.e. ergometrine, ergosine, ergotamine, ergocornine, ergocristine, ergokryptine and their corresponding epimers in rye were comparable to those previously reported for triple-quadrupole (QqQ) MS/MS. The method limits of quantification (LOQ) were in the range from 3 to 19 μg/kg, and good linearity was observed for the different ergot alkaloids in the range from LOQ to 1000 μg/kg. Furthermore, the method demonstrated good precision (relative standard deviations at 50 μg/kg not higher than 14.6 and 16.2% for the intra-day and inter-day precision, respectively), and the trueness values at different concentration levels were all between 89 and 115%. The method was applied for the analysis of a set of 17 rye samples and demonstrated the presence of these ergot alkaloids in the range from <LOQ to 2,811 μg/kg. Further mining of the same data based on a ‘non-targeted peak finding’ algorithm and the use of full MS and MS/MS accurate mass data allowed the detection and identification of 19 ergot alkaloids that are commonly not included in most analytical methods using QqQ instruments. Some of these alkaloids are reported for the first time in naturally contaminated samples.

Whole-Body Single-Bed Time-of-Flight RPC-PET: Simulation of Axial and Planar Sensitivities With NEMA and Anthropomorphic Phantoms

A single-bed, whole-body positron emission tomograph based on resistive plate chambers has been proposed (RPC-PET). An RPC-PET system with an axial field-of-view (AFOV) of 2.4 m has been shown in simulation to have higher system sensitivity using the NEMA NU2-1994 protocol than commercial PET scanners. However, that protocol does not correlate directly with lesion detectability. The latter is better correlated with the planar (slice) sensitivity, obtained with a NEMA NU2-2001 line-source phantom. After validation with published data for the GE Advance, Siemens TruePoint and TrueV, we study by simulation their axial sensitivity profiles, comparing results with RPC-PET. Planar sensitivities indicate that RPC-PET is expected to outperform 16-cm (22-cm) AFOV scanners by a factor 5.8 (3.0) for 70-cm-long scans. For 1.5-m scans (head to mid-legs), the sensitivity gain increases to 11.7 (6.7). Yet, PET systems with large AFOV provide larger coverage but also larger attenuation in the object. We studied these competing effects with both spherical- and line-sources immersed in a 27-cm-diameter water cylinder. For 1.5-m-long scans, the planar sensitivity drops one order of magnitude in all scanners, with RPC-PET outperforming 16-cm (22-cm) AFOV scanners by a factor 9.2 (5.3) without considering the TOF benefit. A gain in the effective sensitivity is expected with TOF iterative reconstruction. Finally, object scatter in an anthropomorphic phantom is similar for RPC-PET and modern, scintillator-based scanners, although RPC-PET benefits further if its TOF information is utilized to exclude scatter events occurring outside the anthropomorphic phantom.

A TOF-PET prototype with position sensitive PMT readout

A prototype of time-of-flight positron emission computed tomography (TOF-PET) has been developed for acquiring the coincident detection of 511 keV γ-rays produced from positron annihilation. It consists of two 80.5 mm×80.5 mm LYSO scintillator arrays (composed of 35 ×35 pixel finger crystals) with the position sensitive photomultiplier tubes R2487 as the readout. Each array is composed of 2 mm ×2 mm×15 mm finger crystals and the average pixel pitch is 2.30 mm. The measured results indicate that the TOF information has the potential to significantly enhance the image quality by improving the noise variance in the image reconstruction. The best spatial resolution (FWHM) of the prototype for the pairs of 511 keV γ-rays is 1.98 mm and 2.16 mm in the x and y directions, respectively, which are smaller than the average pixel pitch of 2.30 mm.

Photo-Detectors for Time of Flight Positron Emission Tomography (ToF-PET)

We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector. ToF information provides better localization of the annihilation event along the line formed by each detector pair, resulting in an overall improvement in signal to noise ratio (SNR) of the reconstructed image. Apart from the demand for high luminosity and fast decay time of the scintillation crystal, proper design and selection of the photo-detector and methods for arrival time pick-off are a prerequisite for achieving excellent time resolution required for ToF-PET. We review the two types of photo-detectors used in ToF-PET: photomultiplier tubes (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs.

Exact and approximate Fourier rebinning of PET data from time-of-flight to non time-of-flight

The image reconstruction problem for fully 3D TOF PET is challenging because of the large data sizes involved. One approach to this problem is to first rebin the data into one of the following lower dimensional formats: 2D TOF, 3D non TOF or 2D non TOF. Here we present a unified framework based on a generalized projection slice theorem for TOF data that can be used to compute each of these mappings. We use this framework to develop approaches for rebinning into non TOF formats without significant loss of information. We first derive the exact mappings and then describe approximations which address the missing data problem for oblique sinograms. We evaluate the performance of approximate rebinning using Monte Carlo simulations. Our results show that rebinning into non TOF sinograms retains significant SNR advantages over sinograms collected without TOF information.

Applying Bayesian neural networks to identify pion, kaon and proton in BESII**Supported by National Natural Science Foundation of China (10605014)

The Monte-Carlo samples of pion, kaon and proton generated from 0.3 GeV/c to 1.2 GeV/c by the `tester' generator from SIMBES which are used to simulate the detector of BESII are identified with the Bayesian neural networks (BNN). The pion identification and misidentification efficiencies are obviously better at high momentum region using BNN than the methods of χ2 analysis of dE/dX and TOF information. The kaon identification and misidentification efficiencies are obviously better from 0.3 GeV/c to 1.2 GeV/c using BNN than the methods of χ2 analysis. The proton identification and misidentification efficiencies using BNN are basically consistent with the ones of χ2 analysis. The anti-proton identification and misidentification efficiencies are better below 0.6 GeV/c using BNN than the methods of χ2 analysis.

Development of TOF-PET using Cherenkov Radiation

We proposed a new concept of TOF-PET (Time-of-Flight Positron Emission Tomography) using Cherenkov radiation. Basic experiments revealed a timing resolution of 170ps, but the detection efficiency was less than those of the conventional BaF2 scintillators. Through simulation studies, we confirmed that the spatial resolution and the S/N ratio of the images reconstructed with TOF information were 1.5 and 3 times better, respectively, than they were without TOF information, when we adopted the FP (Forward Projection) method combined with the ML-EM (Maximum Likelihood Expectation Maximization) algorithm as an image reconstruction algorithm. Consequently, we concluded that TOF-PET using Cherenkov radiation is a promising candidate for next-generation PET. We concluded that PWO (PbWO4) is the best Cherenkov radiator from the viewpoint of detection efficiency. Additionally, we found that the Monte Carlo algorithm was able to generate images having error bars and thus to make quantitative diagnoses possible.

Development of TOF-PET using Cherenkov Radiation

We proposed a new concept of TOF-PET (Time-of-Flight Positron Emission Tomography) using Cherenkov radiation. Basic experiments revealed a timing resolution of 170ps, but the detection efficiency was less than those of the conventional BaF2 scintillators. Through simulation studies, we confirmed that the spatial resolution and the S/N ratio of the images reconstructed with TOF information were 1.5 and 3 times better, respectively, than they were without TOF information, when we adopted the FP (Forward Projection) method combined with the ML-EM (Maximum Likelihood Expectation Maximization) algorithm as an image reconstruction algorithm. Consequently, we concluded that TOF-PET using Cherenkov radiation is a promising candidate for next-generation PET. We concluded that PWO (PbWO4) is the best Cherenkov radiator from the viewpoint of detection efficiency. Additionally, we found that the Monte Carlo algorithm was able to generate images having error bars and thus to make quantitative diagnoses possible.

Synthesis and properties of α,ω-phenyl-capped bithiophene derivatives

Download options Please wait... Supplementary files Experimental details, detailed synthesis, characterisation, POM photographs, DSC, TOF and FET measurements PDF (448K) Article information DOI https://doi.org/10.1039/B608441A Article type Paper Submitted 14 Jun 2006 Accepted 24 Aug 2006 First published 18 Sep 2006 Download Citation J. Mater. Chem., 2006,16, 4335-4342 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Synthesis and properties of α,ω-phenyl-capped bithiophene derivatives P. G. A. Janssen, M. Pouderoijen, A. J. J. M. van Breemen, P. T. Herwig, G. Koeckelberghs, A. R. Popa-Merticaru, S. C. J. Meskers, J. J. P. Valeton, E. W. Meijer and A. P. H. J. Schenning, J. Mater. Chem., 2006, 16, 4335 DOI: 10.1039/B608441A To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Pim G. A. Janssen Maarten Pouderoijen Albert J. J. M. van Breemen Peter T. Herwig Guy Koeckelberghs Andreea R. Popa-Merticaru Stefan C. J. Meskers Josué J. P. Valeton E. W. Meijer Albertus P. H. J. Schenning

High-resolution image reconstruction method for time-of-flight positronemission tomography

We present a new image reconstruction method for time-of-flight positronemission tomography (TOF-PET). The TOF-PET measurement system is modelled usingthe continuous-discrete mapping model, and images are reconstructed using analgebraic technique. The proposed method can produce images with better spatialresolution than conventional methods based on the filtered backprojectionmethod. Numerical simulation results show that accurate modelling of themeasurement system improves the spatial resolution and the contrast recovery,while the utilization of TOF information improves the signal-to-noise ratios ofimages.

Velocity quantification in magnetic resonance imaging

A variety of methods has been developed for quantitating flow in vivo. These are usually based on the principles of velocity-phase or TOF information. The former allows a point-by-point 2D image of velocity, but also has other manifestations involving real-time 1D projections or 1D projections with 1D velocity information (flow zeugmatography). The TOF methods use the in-flow of unsaturated spins into a saturated region (for example) to estimate flow. The concepts, features, and clinical applications of these and other techniques are reviewed in this article.

The PEP Quark Search Proportional Chambers

Proportional chambers are used in the PEP Free Quark Search to identify and remove possible background sources such as particles traversing the edges of counters, to permit geometric corrections to the dE/dx and TOF information from the scintillator and Cerenkov counters, and to look for possible high cross section quarks. The present beam pipe has a thickness of 0.007 interaction lengths (λi) and is followed in both arms (each with 45° ⩽ θ ⩽ 135°. Δϕ = 90°) by 5 proportional chambers, each 0.0008 λi thick with 32 channels of pulse height readout, and by 3 thin scintillator planes, each 0.003 λi thick. Following this thin front end, each arm of the detector has 8 layers of scintillator (one with scintillating light pipes) interspersed with 4 proportional chambers and a layer of lucite Cerenkov counters. Both the calculated ion statistics and measurements using He-CH4 gas in a test chamber indicate that the chamber efficiencies should be > 98% for q = 1/3. The Landau spread measured in the test was equal to that observed for normal q = 1 traversals. One scintillator plane and thin chamber in each arm will have an extra set of ADC's with a wide gate bracketing the normal one so timing errors and tails of earlier pulses should not produce fake quarks.