High-resolution time-of-flight PET detector with 100 ps coincidence time resolution using a side-coupled phoswich configuration.

Photon time-of-flight (TOF) capability in positron emission tomography (PET) enables reconstructed image signal-to-noise ratio (SNR) improvement. With the coincidence time resolution (CTR) of 100 picosecond (ps), a five-fold SNR improvement can be achieved with a 40 cm diameter imaging subject, relative to a system without TOF capability. This 100 ps CTR can be achieved for aclinically relevantdetector design (crystal element length ≥20 mm with reasonably high crystal packing fraction) using a side-readout PET detector configuration that enables 511 keV photon interaction depth-independent light collection efficiency and lower variance in scintillation photon transit time to the silicon photomultiplier (SiPM). In this study, we propose a new concept of TOF-PET detector to achieve high (<2 mm) resolution, using a 'side-coupled phoswich' configuration, where two crystals with different decay times (τd) are coupled in a side-readout configuration to a common row of photosensors. The proposed design was validated and optimized with GATE Monte Carlo simulation studies to determine an efficient detector design. Based on the simulation results, a proof-of-concept side-coupled phoswich detector design was developed comprising two LSO crystals with the size of 1.9 × 1.9 × 10 mm3with decay times of 34.39 and 43.07 ns, respectively. The phoswich crystals were side-coupled to the same three 4 × 4 mm2SiPMs and detector performances were evaluated. As a result of the experimental evaluation, the side-coupled phoswich configuration achieved CTR of 107 ± 3 ps, energy resolution of 10.5% ± 1.21% at 511 keV and >95% accuracy in identifying interactions in the two adjacent 1.9 × 1.9 × 10 mm3crystal elements using the time-over-threshold technique. Based on our results, we can achieve excellent spatial and energy resolution in addition to ∼100 ps CTR with this novel detector design.

Gray: a ray tracing-based Monte Carlo simulator for PET.

Monte Carlo simulation software plays a critical role in PET system design. Performing complex, repeated Monte Carlo simulations can be computationally prohibitive, as even a single simulation can require a large amount of time and a computing cluster to complete. Here we introduce Gray, a Monte Carlo simulation software for PET systems. Gray exploits ray tracing methods used in the computer graphics community to greatly accelerate simulations of PET systems with complex geometries. We demonstrate the implementation of models for positron range, annihilation acolinearity, photoelectric absorption, Compton scatter, and Rayleigh scatter. For validation, we simulate the GATE PET benchmark, and compare energy, distribution of hits, coincidences, and run time. We show a [Formula: see text] speedup using Gray, compared to GATE for the same simulation, while demonstrating nearly identical results. We additionally simulate the Siemens Biograph mCT system with both the NEMA NU-2 scatter phantom and sensitivity phantom. We estimate the total sensitivity within [Formula: see text]% when accounting for differences in peak NECR. We also estimate the peak NECR to be [Formula: see text] kcps, or within [Formula: see text]% of published experimental data. The activity concentration of the peak is also estimated within 1.3%.

A promising new mechanism of ionizing radiation detection for positron emission tomography: modulation of optical properties.

Using conventional scintillation detection, the fundamental limit in positron emission tomography (PET) time resolution is strongly dependent on the inherent temporal variances generated during the scintillation process, yielding an intrinsic physical limit for the coincidence time resolution of around 100 ps. On the other hand, modulation mechanisms of the optical properties of a material exploited in the optical telecommunications industry can be orders of magnitude faster. In this paper we borrow from the concept of optics pump-probe measurement to for the first time study whether ionizing radiation can produce modulations of optical properties, which can be utilized as a novel method for radiation detection. We show that a refractive index modulation of approximately [Formula: see text] is induced by interactions in a cadmium telluride (CdTe) crystal from a 511 keV photon source. Furthermore, using additional radionuclide sources, we show that the amplitude of the optical modulation signal varies linearly with both the detected event rate and average photon energy of the radiation source.

Analytical calculation of the lower bound on timing resolution for PET scintillation detectors comprising high-aspect-ratio crystal elements.

Excellent timing resolution is required to enhance the signal-to-noise ratio (SNR) gain available from the incorporation of time-of-flight (ToF) information in image reconstruction for positron emission tomography (PET). As the detector's timing resolution improves, so does SNR, reconstructed image quality, and accuracy. This directly impacts the challenging detection and quantification tasks in the clinic. The recognition of these benefits has spurred efforts within the molecular imaging community to determine to what extent the timing resolution of scintillation detectors can be improved and develop near-term solutions for advancing ToF-PET. Presented in this work, is a method for calculating the Cramér-Rao lower bound (CRLB) on timing resolution for scintillation detectors with long crystal elements, where the influence of the variation in optical path length of scintillation light on achievable timing resolution is non-negligible. The presented formalism incorporates an accurate, analytical probability density function (PDF) of optical transit time within the crystal to obtain a purely mathematical expression of the CRLB with high-aspect-ratio (HAR) scintillation detectors. This approach enables the statistical limit on timing resolution performance to be analytically expressed for clinically-relevant PET scintillation detectors without requiring Monte Carlo simulation-generated photon transport time distributions. The analytically calculated optical transport PDF was compared with detailed light transport simulations, and excellent agreement was found between the two. The coincidence timing resolution (CTR) between two 3 × 3 × 20 mm(3) LYSO:Ce crystals coupled to analogue SiPMs was experimentally measured to be 162 ± 1 ps FWHM, approaching the analytically calculated lower bound within 6.5%.

Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality.

PURPOSE: The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF. MATERIALS AND METHODS: We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality. RESULTS: Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed. CONCLUSION: The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

A method to achieve spatial linearity and uniform resolution at the edges of monolithic scintillation crystal detectors.

We have performed Monte Carlo simulations of the scintillation light transport between adjacent monolithic LYSO crystals that are optically coupled together using coupling media of varying refractive index. The scintillation light from the crystals was read out by SiPM arrays from the large crystal face. Scintillation event positioning results show that this optical coupling technique preserves the shape of the light spread function near and across the interface between the two crystals in order to substantially reduce the edge-artifacts observed in monolithic scintillation crystals, while not degrading the timing performance.

Study of PET intrinsic spatial resolution and contrast recovery improvement for PET/MRI systems.

This paper studied PET intrinsic spatial resolution and contrast recovery improvement for PET/MRI dual modality systems. A Monte Carlo simulation tool was developed to study positron diffusion in tissues with and without a magnetic field for six commonly used isotopes ((18)F, (11)C, (13)N, (15)O, (68)Ga and (82)Rb). A convolution process was implemented to investigate PET intrinsic spatial resolution, taking into account three factors: positron diffusion range, collinear photon annihilation and finite detector element width. The resolution improvement was studied quantitatively as a function of magnetic field strength for three PET system configurations (whole-body, brain-dedicated and small-animal PET). When the magnetic field strength increases up to 10 T, the system spatial resolution in directions orthogonal to the field for (15)O, (68)Ga and (82)Rb is comparable to that of (18)F without the magnetic field. Beyond 10 T, no significant improvement of spatial resolution was observed. In addition, the modulation transfer function was studied to predict the intrinsic contrast recovery improvement for several existing and promising PET/MRI configurations.

A maximum NEC criterion for Compton collimation to accurately identify true coincidences in PET.

In this work, we propose a new method to increase the accuracy of identifying true coincidence events for positron emission tomography (PET). This approach requires 3-D detectors with the ability to position each photon interaction in multi-interaction photon events. When multiple interactions occur in the detector, the incident direction of the photon can be estimated using the Compton scatter kinematics (Compton Collimation). If the difference between the estimated incident direction of the photon relative to a second, coincident photon lies within a certain angular range around colinearity, the line of response between the two photons is identified as a true coincidence and used for image reconstruction. We present an algorithm for choosing the incident photon direction window threshold that maximizes the noise equivalent counts of the PET system. For simulated data, the direction window removed 56%-67% of random coincidences while retaining > 94% of true coincidences from image reconstruction as well as accurately extracted 70% of true coincidences from multiple coincidences.

Effects of multiple-interaction photon events in a high-resolution PET system that uses 3-D positioning detectors.

PURPOSE: The authors' laboratory is developing a dual-panel, breast-dedicated PET system. The detector panels are built from dual-LSO-position-sensitive avalanche photodiode (PSAPD) modules-units holding two 8 x 8 arrays of 1 mm3 LSO crystals, where each array is coupled to a PSAPD. When stacked to form an imaging volume, these modules are capable of recording the 3-D coordinates of individual interactions of a multiple-interaction photon event (MIPE). The small size of the scintillation crystal elements used increases the likelihood of photon scattering between crystal arrays. In this article, the authors investigate how MIPEs impact the system photon sensitivity, the data acquisition scheme, and the quality and quantitative accuracy of reconstructed PET images. METHODS: A Monte Carlo simulated PET scan using the dual-panel system was performed on a uniformly radioactive phantom for the photon sensitivity study. To establish the impact of MIPEs on a proposed PSAPD multiplexing scheme, experimental data were collected from a dual-LSO-PSAPD module edge-irradiated with a 22Na point source, the data were compared against simulation data based on an identical setup. To assess the impact of MIPEs on the dual-panel PET images, a simulated PET of a phantom comprising a matrix of hot spherical radiation sources of varying diameters immersed in a warm background was performed. The list-mode output data were used for image reconstruction, where various methods were used for estimating the location of the first photon interaction in MIPEs for more accurate line of response positioning. The contrast recovery coefficient (CRC), contrast to noise ratio (CNR), and the full width at half maximum spatial resolution of the spheres in the reconstructed images were used as figures of merit to facilitate comparison. RESULTS: Compared to image reconstruction employing only events with interactions confined to one LSO array, a potential single photon sensitivity gain of > 46.9% (> 115.7% for coincidence) was noted for a uniform phantom when MIPEs with summed-energy falling within a +/- 12% window around the photopeak were also included. Both experimental and simulation data demonstrate that < 0.4% of the events whose summed-energy deposition falling within that energy window interacted with both crystal arrays within the same dual-LSO-PSAPD module. This result establishes the feasibility of a proposed multiplexed readout of analog output signals of the two PSAPDs within each module. Using MIPEs with summed-energy deposition within the 511 keV +/- 12% photopeak window and a new method for estimating the location of the first photon interaction in MIPEs, the corresponding reconstructed image exhibited a peak CNR of 7.23 for the 8 mm diameter phantom spheres versus a CNR of 6.69 from images based solely on single LSO array interaction events. The improved system photon sensitivity could be exploited to reduce the scan time by up to approximately 10%, while still maintaining image quality comparable to that achieved if MIPEs were excluded. CONCLUSIONS: MIPE distribution in the detectors allows the proposed photodetector multiplexing arrangement without significant information loss. Furthermore, acquiring MIPEs can enhance system photon sensitivity and improve PET image CNR and CRC. The system under development can therefore competently acquire and analyze MIPEs and produce high-resolution PET images.

Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors.

We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 x 15 cm(2) area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve approximately 32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be approximately 94.2 kcts s(-1) (breast volume: 720 cm(3) and activity concentration: 3.7 kBq cm(-3)) for a approximately 10% energy window around 511 keV and approximately 8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (sigma(rms)/mean) < or = 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within roughly 7 min imaging time. Furthermore, we observe that the degree of spatial resolution degradation along the direction orthogonal to the two panels that is typical of a limited angle tomography configuration is mitigated by having high-resolution DOI capabilities that enable more accurate positioning of oblique response lines.

Count rate studies of a box-shaped PET breast imaging system comprised of position sensitive avalanche photodiodes utilizing monte carlo simulation.

We are investigating a high-sensitivity, high-resolution positron emission tomography (PET) system for clinical use in the detection, diagnosis and staging of breast cancer. Using conventional figures of merit, design parameters were evaluated for count rate performance, module dead time, and construction complexity. The detector system modeled comprises extremely thin position-sensitive avalanche photodiodes coupled to lutetium oxy-orthosilicate scintillation crystals. Previous investigations of detector geometries with Monte Carlo indicated that one of the largest impacts on sensitivity is local scintillation crystal density when considering systems having the same average scintillation crystal densities (same crystal packing fraction and system solid-angle coverage). Our results show the system has very good scatter and randoms rejection at clinical activity ranges ( approximately 200 muCi).

Primer on molecular imaging technology.

A wide range of technologies is available for in vivo, ex vivo, and in vitro molecular and cellular imaging. This article focuses on three key in vivo imaging system instrumentation technologies used in the molecular imaging research described in this special issue of Eur J Nucl Med Mol Imaging: positron emission tomography, single-photon emission computed tomography, and bioluminescence imaging. For each modality, the basics of how it works, important performance parameters, and the state-of-the-art instrumentation are described. Comparisons and integration of multiple modalities are also discussed. The principles discussed in this article apply to both human and small animal imaging.