Investigation of Electronic Signal Processing Chains for a Prototype TOF-PET System With 100-ps Coincidence Time Resolution.

We have evaluated CTR performance of four different mixed-signal front-end electronic readout configurations with the goal to achieve 100 picoseconds (ps) coincidence time resolution (CTR). The proposed TOF-PET detector elements are based on two 3 × 3 × 10 mm3 "fast LGSO" crystal segments, side-coupled to linear arrays of 3 × 3 mm2 silicon photomultipliers (SiPMs), to form a total crystal length of 20 mm. We studied multiple configurations and components for the front-end readout: 1) high speed radio frequency (RF) amplifiers; 2) an ASIC-based discriminator; 3) combination of RF amplifier, balun transformer, and discriminator ASIC; and 4) combination of balun transformer, and discriminator ASIC. Using two 3 × 3 × 10 mm3 fast LGSO crystals side coupled to a linear array of three SiPMs, coincidence data were experimentally acquired for each readout configuration in combination with a low jitter field programmable gate array (FPGA)-based time to digital converter (TDC). After evaluating timing performance of the three readout schemes, the best CTR value of 99.4 ± 1.9 ps FWHM was achieved for configuration (3), which is more than 20 ps better than the results achieved using configurations (1) and (2).

Advances in Detector Instrumentation for PET.

During the last 3 decades, PET has become a standard-of-care imaging technique used in the management of cancer and in the characterization of neurologic disorders and cardiovascular disease. It has also emerged as a prominent molecular imaging method to study the basic biologic pathways of disease in rodent models. This review describes the basics of PET detectors, including a detailed description of indirect and direct 511-keV photon detection methods. We will also cover key detector performance parameters and describe detector instrumentation advances during the last decade.

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

Performance evaluation of side-by-side optically coupled monolithic LYSO crystals.

BACKGROUND: Significant interest has been recently shown for using monolithic scintillation crystals in molecular imaging systems, such as positron emission tomography (PET) scanners. Monolithic-based PET scanners result in a lower cost and higher sensitivity, in contrast to systems based on the more conventional pixellated configuration. The monolithic design allows one to retrieve depth-of-interaction information of the impinging 511 keV photons without the need for additional hardware materials or complex positioning algorithms. However, the so-called edge-effect inherent to monolithic-based approaches worsens the detector performance toward the crystal borders due to the truncation of the light distribution, thus decreasing positioning accuracy. PURPOSE: The main goal of this work is to experimentally demonstrate the detector performance improvement when machine-learning artificial neural-network (NN) techniques are applied for positioning estimation in multiple monolithic scintillators optically coupled side-by-side. METHODS: In this work, we show the performance evaluation of two LYSO crystals of 33 × 25.4 × 10 mm3 optically coupled by means of a high refractive index adhesive compound (Meltmount, refractive index n = 1.70). A 12 × 12 silicon photomultiplier array has been used as photosensor. For comparison, the same detector configuration was tested for two additional coupling cases: (1) optical grease (n = 1.46) in between crystals, and (2) isolated crystals using black paint with an air gap at the interface (named standard configuration). Regarding 2D photon positioning (XY plane), we have tested two different methods: (1) a machine-learning artificial NN algorithm and (2) a squared-charge (SC) centroid technique. RESULTS: At the interface region of the detector, the SC method achieved spatial resolutions of 1.7 ± 0.3, 2.4 ± 0.3, and 2.6 ± 0.4 mm full-width at half-maximum (FWHM) for the Meltmount, grease, and standard configurations, respectively. These values improve to 1.0 ± 0.2, 1.2 ± 0.2, and 1.2 ± 0.3 mm FWHM when the NN algorithm was employed. Regarding energy performance, resolutions of 18 ± 2%, 20 ± 2%, and 23 ± 3% were obtained at the interface region of the detector for Meltmount, grease, and standard configurations, respectively. CONCLUSIONS: The results suggest that optically coupling together scintillators with a high refractive index adhesive, in combination with an NN algorithm, reduces edge-effects and makes it possible to build scanners with almost no gaps in between detectors.

Nuclear-medicine probes: Where we are and where we are going.

Nuclear medicine probes turned into the key for the identification and precise location of sentinel lymph nodes and other occult lesions (i.e., tumors) by using the systemic administration of radiotracers. Intraoperative nuclear probes are key in the surgical management of some malignancies as well as in the determination of positive surgical margins, thus reducing the extent and potential surgery morbidity. Depending on their application, nuclear probes are classified into two main categories, namely, counting and imaging. Although counting probes present a simple design, are handheld (to be moved rapidly), and provide only acoustic signals when detecting radiation, imaging probes, also known as cameras, are more hardware-complex and also able to provide images but at the cost of an increased intervention time as displacing the camera has to be done slowly. This review article begins with an introductory section to highlight the relevance of nuclear-based probes and their components as well as the main differences between ionization- (semiconductor) and scintillation-based probes. Then, the most significant performance parameters of the probe are reviewed (i.e., sensitivity, contrast, count rate capabilities, shielding, energy, and spatial resolution), as well as the different types of probes based on the target radiation nature, namely: gamma (γ), beta (ß) (positron and electron), and Cherenkov. Various available intraoperative nuclear probes are finally compared in terms of performance to discuss the state-of-the-art of nuclear medicine probes. The manuscript concludes by discussing the ideal probe design and the aspects to be considered when selecting nuclear-medicine probes.

Reducing Calibration Time in PET Systems Based on Monolithic Crystals.

In the past years, the gamma-ray detector designs based on the monolithic crystals have demonstrated to be excellent candidates for the design of high-performance PET systems. The monolithic crystals allow to achieve the intrinsic detector resolutions well below state-of-the-art; to increase packing fraction thus, increasing the system sensitivity; and to improve lesion detectability at the edges of the scanner field of view (FOV) because of their intrinsic depth of interaction (DOI) capabilities. The bottleneck to translate to the clinical PET systems based on a large number of monolithic detectors is eventually the requirement of mechanically complex and time-consuming calibration processes. To mitigate this drawback, several methods have been already proposed, such as using non-physically collimated radioactive sources or implementing the neuronal networks (NN) algorithms trained with simulated data. In this work, we aimed to simplify and fasten a calibration process of the monolithic based systems. The Normal procedure consists of individually acquiring a 11 × 11 22Na source array for all the detectors composing the PET system and obtaining the calibration map for each module using a method based on the Voronoi diagrams. Two reducing time methodologies are presented: (i) TEST1, where the calibration map of one detector is estimated and shared among all others, and (ii) TEST2, where the calibration map is slightly modified for each module as a function of their detector uniformity map. The experimental data from a dedicated prostate PET system was used to compare the standard calibration procedure with both the proposed methods. A greater similarity was exhibited between the TEST2 methodology and the Normal procedure; obtaining spatial resolution variances within 0.1 mm error bars and count rate deviations as small as 0.2%. Moreover, the negligible reconstructed image differences (13% deviation at most in the contrast-to-noise ratio) and almost identical contrast values were reported. Therefore, this proposed method allows us to calibrate the PET systems based on the monolithic crystals reducing the calibration time by approximately 80% compared with the Normal procedure.

Study of optical reflectors for a 100ps coincidence time resolution TOF-PET detector design.

Positron Emission Tomography (PET) reconstructed image signal-to-noise ratio (SNR) can be improved by including the 511 keV photon pair coincidence time-of-flight (TOF) information. The degree of SNR improvement from this TOF capability depends on the coincidence time resolution (CTR) of the PET system, which is essentially the variation in photon arrival time differences over all coincident photon pairs detected for a point positron source placed at the system center. The CTR is determined by several factors including the intrinsic properties of the scintillation crystals and photodetectors, crystal-to-photodetector coupling configurations, reflective materials, and the electronic readout configuration scheme. The goal of the present work is to build a novel TOF-PET system with 100 picoseconds (ps) CTR, which provides an additional factor of 1.5-2.0 improvement in reconstructed image SNR compared to state-of-the-art TOF-PET systems which achieve 225-400 ps CTR. A critical parameter to understand is the optical reflector's influence on scintillation light collection and transit time variations to the photodetector. To study the effects of the reflector covering the scintillation crystal element on CTR, we have tested the performance of four different reflector materials: Enhanced Specular Reflector (ESR) -coupled with air or optical grease to the scintillator; Teflon tape; BaSO4paint alone or mixed with epoxy; and TiO2paint. For the experimental set-up, we made use of 3 × 3 × 10 mm3fast-LGSO:Ce scintillation crystal elements coupled to an array of silicon photomultipliers (SiPMs) using a novel 'side-readout' configuration that has proven to have lower variations in scintillation light collection efficiency and transit time to the photodetector.Results: show CTR values of 102.0 ± 0.8, 100.2 ± 1.2, 97.3 ± 1.8 and 95.0 ± 1.0 ps full-width-half-maximum (FWHM) with non-calibrated energy resolutions of 10.2 ± 1.8, 9.9 ± 1.2, 7.9 ± 1.2, and 8.6 ± 1.7% FWHM for the Teflon, ESR (without grease), BaSO4(without epoxy) and TiO2paint treatments, respectively.

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.

Scalable electronic readout design for a 100 ps coincidence time resolution TOF-PET system.

We have developed a scalable detector readout design for a 100 ps coincidence time resolution (CTR) time of flight (TOF) positron emission tomography (PET) detector technology. The basic scintillation detectors studied in this paper are based on 2 × 4 arrays of 3 × 3 × 10 mm3'fast-LGSO:Ce' scintillation crystals side-coupled to 6 × 4 arrays of 3 × 3 mm2silicon photomultipliers (SiPMs). We employed a novel mixed-signal front-end electronic configuration and a low timing jitter Field Programming Gate Array-based time to digital converter for data acquisition. Using a22Na point source, >10 000 coincidence events were experimentally acquired for several SiPM bias voltages, leading edge time-pickoff thresholds, and timing channels. CTR of 102.03 ± 1.9 ps full-width-at-half-maximum (FWHM) was achieved using single 3 × 3 × 10 mm3'fast-LGSO' crystal elements, wrapped in Teflon tape and side coupled to a linear array of 3 SiPMs. In addition, the measured average CTR was 113.4 ± 0.7 ps for the side-coupled 2 × 4 crystal array. The readout architecture presented in this work is designed to be scalable to large area module detectors with a goal to create the first TOF-PET system with 100 ps FWHM CTR.

Pilot performance of a dedicated prostate PET suitable for diagnosis and biopsy guidance.

BACKGROUND: Prostate cancer (PCa) represents one of the most common types of cancers facing the male population. Nowadays, to confirm PCa, systematic or multiparametric MRI-targeted transrectal or transperineal biopsies of the prostate are required. However, due to the lack of an accurate imaging technique capable to precisely locate cancerous cells in the prostate, ultrasound biopsies sample random parts of the prostate and, therefore, it is possible to miss regions where those cancerous cells are present. In spite of the improvement with multiparametric MRI, the low reproducibility of its reading undermines the specificity of the method. Recent development of prostate-specific radiotracers has grown the interest on using positron emission tomography (PET) scanners for this purpose, but technological improvements are still required (current scanners have resolutions in the range of 4-5 mm). RESULTS: The main goal of this work is to improve state-of-the-art PCa imaging and diagnosis. We have focused our efforts on the design of a novel prostate-dedicated PET scanner, named ProsPET. This system has small scanner dimensions defined by a ring of just 41 cm inner diameter. In this work, we report the design, implementation, and evaluation (both through simulations and real data) of the ProsPET scanner. We have been able to achieve < 2 mm resolution in reconstructed images and high sensitivity. In addition, we have included a comparison with the Philips Gemini-TF scanner, which is used for routine imaging of PCa patients. The ProsPET exhibits better contrast, especially for rod sizes as small as 4.5 mm in diameter. Finally, we also show the first reconstructed image of a PCa patient acquired with the ProsPET. CONCLUSIONS: We have designed and built a prostate specific PET system, with a small footprint and improved spatial resolution when compared to conventional whole-body PET scanners. The gamma ray impact within each detector block includes accurate DOI determination, correcting for the parallax error. The potential role of combined organ-dedicated prostate-specific membrane antigen (PSMA) PET and ultrasound devices, as a prebiopsy diagnostic tool, could be used to guide sampling of the most aggressive sites in the prostate.

Calibration Methodology of an Edgeless PET System Prototype.

Instrumentation research in small animal Positron Emission Tomography (PET) imaging is driven by improving timing, spatial resolution and sensitivity. Conventional PET scanners are built of multiple detectors placed in a cylindrical geometry with gaps between them in both the transaxial and axial planes. These gaps decrease sensitivity and degrade spatial resolution towards the edges of the system field of view (FOV). To mitigate these problems, we have designed and validated an edgeless pre-clinical PET system based on a single LYSO annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2 each. The scintillation light is read out using the row and columns of Silicon Photomultipliers (SiPMs) mounted in magnetic-field compatible PCBs. The objective of this work is to provide a calibration method for this system. The particular design of the annulus produces some undesirable effects in the light distributions (LD) at the module joints, which needs to be addressed. Nevertheless, after calibration, the system allows one to properly retrieve both, the energy and 3D photon impact positions.

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube.

There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.