Investigating a re-configurable PET system design

The idea of a very sensitive positron emission tomography (PET) system covering a large portion of the body of a patient already dates back to the early 1990s. In the period 2000–2010, only some prototypes with long axial field of view (FOV) have been built, which never resulted in systems used for clinical research. One of the reasons was the limitations in the available detector technology, which did not yet have sufficient energy resolution, timing resolution or countrate capabilities for fully exploiting the benefits of a long axial FOV design. PET was also not yet as widespread as it is today: the growth in oncology, which has become the major application of PET, appeared only after the introduction of PET-CT (early 2000).The detector technology used in most clinical PET systems today has a combination of good energy and timing resolution with higher countrate capabilities and has now been used since more than a decade to build time-of-flight (TOF) PET systems with fully 3D acquisitions. Based on this technology, one can construct total body PET systems and the remaining challenges (data handling, fast image reconstruction, detector cooling) are mostly related to engineering. The direct benefits of long axial FOV systems are mostly related to the higher sensitivity. For single organ imaging, the gain is close to the point source sensitivity which increases linearly with the axial length until it is limited by solid angle and attenuation of the body. The gains for single organ (compared to a fully 3D PET 20-cm axial FOV) are limited to a factor 3–4. But for long objects (like body scans), it increases quadratically with scanner length and factors of 10–40 × higher sensitivity are predicted for the long axial FOV scanner. This application of PET has seen a major increase (mostly in oncology) during the last 2 decades and is now the main type of study in a PET centre. As the technology is available and the full body concept also seems to match with existing applications, the old concept of a total body PET scanner is seeing a clear revival. Several research groups are working on this concept and after showing the potential via extensive simulations; construction of these systems has started about 2 years ago. In the first phase, two PET systems with long axial FOV suitable for large animal imaging were constructed to explore the potential in more experimental settings. Recently, the first completed total body PET systems for human use, a 70-cm-long system, called PennPET Explorer, and a 2-m-long system, called uExplorer, have become reality and first clinical studies have been shown. These results illustrate the large potential of this concept with regard to low-dose imaging, faster scanning, whole-body dynamic imaging and follow-up of tracers over longer periods. This large range of possible technical improvements seems to have the potential to change the current clinical routine and to expand the number of clinical applications of molecular imaging. The J-PET prototype is a prototype system with a long axial FOV built from axially arranged plastic scintillator strips.This paper gives an overview of the recent technical developments with regard to PET scanners with a long axial FOV covering at least the majority of the body (so called total body PET systems). After explaining the benefits and challenges of total body PET systems, the different total body PET system designs proposed for large animal and clinical imaging are described in detail. The axial length is one of the major factors determining the total cost of the system, but there are also other options in detector technology, design and processing for reducing the cost these systems. The limitations and advantages of different designs for research and clinical use are discussed taking into account potential applications and the increased cost of these systems.

Quantitative estimation of the radionuclide activity concentration in positron emission tomography (PET) requires precise modeling of PET physics. The authors are focused on designing unconventional PET geometries for specific applications. This work reports the creation of a generalized reconstruction framework, capable of reconstructing tomographic PET data for systems that use right cuboidal detector elements positioned at arbitrary geometry using a regular Cartesian grid of image voxels. The authors report on a variety of design choices and optimization for the creation of the generalized framework. The image reconstruction algorithm is maximum likelihood-expectation-maximization. System geometry can be specified using a simple script. Given the geometry, a symmetry seeking algorithm finds existing symmetry in the geometry with respect to the image grid to improve the memory usage/speed. Normalization is approached from a geometry independent perspective. The system matrix is computed using the Siddon's algorithm and subcrystal approach. The program is parallelized through open multiprocessing and message passing interface libraries. A wide variety of systems can be modeled using the framework. This is made possible by modeling the underlying physics and data correction, while generalizing the geometry dependent features. Application of the framework for three novel PET systems, each designed for a specific application, is presented to demonstrate the robustness of the framework in modeling PET systems of unconventional geometry. Three PET systems of unconventional geometry are studied. (1) Virtual-pinhole half-ring insert integrated into Biograph-40: although the insert device improves image quality over conventional whole-body scanner, the image quality varies depending on the position of the insert and the object. (2) Virtual-pinhole flat-panel insert integrated into Biograph-40: preliminary results from an investigation into a modular flat-panel insert are presented. (3) Plant PET system: a reconfigurable PET system for imaging plants, with resolution of greater than 3.3 mm, is shown. Using the automated symmetry seeking algorithm, the authors achieved a compression ratio of the storage and memory requirement by a factor of approximately 50 for the half-ring and flat-panel systems. For plant PET system, the compression ratio is approximately five. The ratio depends on the level of symmetry that exists in different geometries. This work brings the field closer to arbitrary geometry reconstruction. A generalized reconstruction framework can be used to validate multiple hypotheses and the effort required to investigate each system is reduced. Memory usage/speed can be improved with certain optimizations.

Positron Emission Tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction when imaging rodents. The purpose of this study is first to design and fabricate a dedicated cone-shaped phantom which can be used for measurement of object size dependent SF and noise equivalent count (NEC) rates and second, to evaluate those parameters for two small animal PET scanners, namely the X-PET™ and LabPET™-8 as function of radial offset, object size and lower energy threshold. Both scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and noise equivalent count rate (NECR). The dedicated phantom was designed and fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 150 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9°.The relative difference between simulated and experimental results for the LabPET™-8 scanner varied between 0.66% and 10% except for few results where it was below 16%. Depending on the radial offset from the axial centre for a central field of view (3–6 cm diameter), the SF for the cone-shaped phantom varied from 26.3 to 18.2% (X-PET™); 34.4 to 26.9% (LabPET™-8), 18.6 to 13.1% (X-PET™); 19.1 to 17.0% (LabPET™-8); 10.1 to 7.6% (X-PET™) and 9.1 to 7.3% (LabPET™-8) for lower energy thresholds of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, lower energy threshold (LET) decreases and object size increases. The SF values are higher for the LabPET™-8 compared to the X-PET™. The NECR increases as the radial offset increases and object size decreases. Maximum NECR was obtained at a LET of 350 keV for LabPET™-8 whereas 250 keV for X-PET™. High correlation coefficients (R2) for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical (EVC) phantom for the three considered axial fields-of-view. A single cone-shaped phantom enables the assessment of effects of three factors, namely radial offset, energy threshold and object size on small animal PET imaging characteristics like SF and NECR. Hence, a cone-shaped phantom may be more suited for evaluation of object size-dependent SF and NECR instead of using various discrete phantoms of different size.

Comparing positron emission tomography (PET) systems which have different features is not straightforward. To address this, we propose to image the same object with all considered PET systems using a fixed scan time, and reconstruct from each scan an image at the same predefined spatial resolution. With such resolution matched reconstructions, the images should be identical except for their noise. Therefore, the PET system that produces the image with the lowest variance has the best performance. An analytical model is described to compute this variance, assuming that the PET system is (approximately) cylindrical, the imaged object is a uniform cylinder centered in the field of view, and the variance is only computed at the center of the reconstructed image. The model takes into account the solid angle covered by the detectors, the detector stopping power, the time-of-flight (TOF) resolution, the scatter fraction and the spatial resolution of the system, the attenuation and diameter of the cylinder and the desired spatial resolution of the reconstructed image. The inverse of this variance can be considered as the effective sensitivity of the system. This effective sensitivity can be calibrated based on the NEMA line source sensitivity. As a performance metric for scanning long objects, the minimum sensitivity achieved over the object is computed, with an optimal number of bed positions and optimal overlap between them. The influence of the spatial and TOF resolution on the effective sensitivity is verified with simulations.

For small animal positron emission tomography (PET) research using high radioactivity, such as dynamic studies, the resulting high random coincidence rate of the system degrades image quality. The random coincidence rate is increased not only by the gamma photons from inside the axial-field-of-view (axial-FOV) of the PET system but also by those from outside the axial-FOV. For brain imaging in small animal studies, significant interference is observed from gamma photons emitted from the body. Single gamma photons from the body enter the axial-FOV and increase the random and scatter coincidences. Shielding against the gamma photons from outside the axial-FOV would improve the image quality. For this purpose, we developed a body shield for a small animal PET system, the microPET Primate 4-ring system, and evaluated its performance. The body shield is made of 9-mm-thick lead and it surrounds most of a rat’s body. We evaluated the effectiveness of the body shield using a head phantom and a body phantom with a radioactivity concentration ratio of 1:2 and a maximum total activity of approximately 250 MBq. The random coincidence rate was dramatically decreased to ~1/10, and the noise equivalent count rate (NECR) was increased ~6 times with an activity of 7 MBq in the head phantom. The true count rate was increased to ~35% due to the decrease in system deadtime. The average scatter fraction was decreased to 1/2.5 with the body shield. Count rate measurements of rat were also conducted with an injection activity of approximately 25 MBq of [C-11]N,N-dimethyl-2-(2-amino-4-cyanophenylthio) benzylamine ([C-11]DASB) and approximately 70 and 310 MBq of 2-deoxy-2-(F-18)fluoro-D-glucose ([F-18]FDG). Using the body shield, [F-18]FDG images of rats were improved by increasing the amount of radioactivity injected. The body shield designed for small animal PET systems is a promising tool for improving image quality and quantitation accuracy in small animal molecular imaging research.

Positron emission tomography (PET) is one of the most promising techniques for hadron therapy monitoring. This method uses imaging of the annihilation photons resulting from positron emitting isotopes produced during patient irradiation in hadron therapy. In order to maximize the sensitivity, in-beam PET is the preferred option, which requires a partial ring configuration. The usage of partial ring PET systems causes image artefacts and low quality images due to incomplete data. The inclusion of Time-of-flight (TO F) information into the reconstruction algorithm provides better image quality for PET systems. Therefore, a PET system with very good time and spatial resolution is necessary for hadron therapy monitoring. The Resistive-Plate-Chambers (RPCs), providing very good time and spatial resolution might be used for the quality control of hadron therapy. However, they have lower sensitivity than crystal-based systems. The objective of this study is the comparison of the performance of two TOF-PET systems, a RPC-based PET system currently under investigation by the TERA group and a commercially available crystal-based PET system, with respect to their feasibility of being applied to monitor cancer treatment with ion- and proton-beams. Various Monte-Carlo simulations were performed using GATE to evaluate the performance of both systems following NEMA protocols. Furthermore, a set of sources emulating the annihilation photons from β+-emitters produced after proton pencil beam irradiation on a PMMA target were obtained. These sources were employed to study the capability to reproduce the proton beam path and the distal edge position. Finally, we calculated the activity distribution produced by carbon ions on the basis of one field of a real treatment plan. The results obtained indicate that a RPC-based system has five times lower sensitivity, similar spatial resolution and about two times higher scatter fraction compared to the crystal-based system. The low sensitivity obtained by the RPC-based system is not sufficient to determine range deviations.

Small-animal positron emission tomography as a tool for neuropharmacology

The adoption of solid-state photodetectors for positron emission tomography (PET) system design and the interest in 3D interaction information from PET detectors has lead to an increasing number of readout channels in PET systems. To handle these additional readout channels, PET readout electronics should be simplified to reduce the power consumption, cost, and size of the electronics for a single channel. Pulse-width modulation (PWM), where detector pulses are converted to digital pulses with width proportional to the detected photon energy, promises to simplify PET readout by converting the signals to digital form at the beginning of the processing chain, and allowing a single time-to-digital converter to perform the data acquisition for many channels rather than routing many analogue channels and digitizing in the back end. Integrator based PWM systems, also known as charge-to-time converters (QTCs), are especially compact, reducing the front-end electronics to an op-amp integrator with a resistor discharge, and a comparator. QTCs, however, have a long dead-time during which dark count noise is integrated, reducing the output signal-to-noise ratio. This work presents a QTC based PWM circuit with a gated integrator that shows performance improvements over existing QTC based PWM. By opening and closing an analogue switch on the input of the integrator, the circuit can be controlled to integrate only the portions of the signal with a high signal-to-noise ratio. It also allows for multiplexing different detectors into the same PWM circuit while avoiding uncorrelated noise propagation between photodetector channels. Four gated integrator PWM circuits were built to readout the spatial channels of two position sensitive solid-state photomultiplier (PS-SSPM). Results show a 4 × 4 array 0.9 mm × 0.9 mm × 15 mm of LYSO crystals being identified on the 5 mm × 5 mm PS-SSPM at room temperature with no degradation for twofold multiplexing. In principle, much larger multiplexing ratios are possible, limited only by count rate issues.

The aim of the CaLIPSO project (French acronym for Liquid Ionization Calorimeter, Scintillation Position Organometallic) is to develop the proof of concept for a new gamma detector for Positron Emission Tomography (PET) scanner for small animals and human brain imaging. The objective is to achieve a spatial resolution about 1 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> without losing efficiency with respect to current PET systems. Moreover, excellent time resolution, important for coincidence selection, is also targeted. Such performances are possible thanks to the concept of double detection of the signal created by photoelectron from the photon conversion in trimethyl bismuth, a innovative liquid filling a PET cell. The ongoing work is focused on prototypes developments for light and ionization detection systems. In this conference record we discuss the results of the simulation for the optical prototype and its comparison to the data obtained during the detector tests. We also present the performances of the PET scanner simulated with GATE and a comparison with a high resolution PET system.

Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm(2) cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.

During particle therapy irradiation, positron emitters with half-lives ranging from 2 to 20 min are generated from nuclear processes. The half-lives are such that it is possible either to detect the positron signal in the treatment room using an in-beam positron emission tomography (PET) system, right after the irradiation, or to quickly transfer the patient to a close PET/CT scanner. Since the activity distribution is spatially correlated with the dose, it is possible to use PET imaging as an indirect method to assure the quality of the dose delivery. In this work, we present a new dedicated PET system able to operate in-beam. The PET apparatus consists in two 10 cm × 10 cm detector heads. Each detector is composed of four scintillating matrices of 23 × 23 LYSO crystals. The crystal size is 1.9 mm × 1.9 mm × 16 mm. Each scintillation matrix is read out independently with a modularized acquisition system. The distance between the two opposing detector heads was set to 20 cm. The system has very low dead time per detector area and a 3 ns coincidence window, which is capable to sustain high single count rates and to keep the random counts relatively low. This allows a new full-beam monitoring modality that includes data acquisition also while the beam is on. The PET system was tested during the irradiation at the CATANA (INFN, Catania, Italy) cyclotron-based proton therapy facility. Four acquisitions with different doses and dose rates were analysed. In all cases the random to total coincidences ratio was equal or less than 25%. For each measurement we estimated the accuracy and precision of the activity range on a set of voxel lines within an irradiated PMMA phantom. Results show that the inclusion of data acquired during the irradiation, referred to as beam-on data, improves both the precision and accuracy of the range measurement with respect to data acquired only after irradiation. Beam-on data alone are enough to give precisions better than 1 mm when at least 5 Gy are delivered.

The purpose of this study was to do a feasibility study on a microstrip transmission line (MS) RF coil for a positron emission tomography (PET) insert in a 7 Tesla human MRI system. The proposed MS coil integrated the RF shield of the PET detector as the ground conductor of the coil. We called the integrated module "MS PET coil." A single-channel MS PET coil was developed with an integrated RF-shielded PET detector module. For comparison, we also studied a conventional MS coil with a single-layer ground conductor. A lutetium fine silicate (LFS) scintillation crystal block (14 × 14 × 4-layer) with a silicon photomultiplier (Hamamatsu Photonics K.K., Shizuoka, Japan) and a front-end readout circuit board were mounted inside the shield cage of the MS PET coil. The MS PET coil was studied with and without PET detectors. All three coil configurations were studied with a homogeneous phantom in a 7T MRI system (Siemens Healthineers, Erlangen, Germany). PET data measurements were conducted using a Cesium-137 radiation point source. The MR images were similar for the MS coil and the empty MS PET coil, as well as for the cases of MS PET coil with and without PET measurements. Compared to the empty MS PET coil (without PET detector and cable RF shield), decreases in SNR, increases in image noise and RF power, and a slight decrease in resonance frequency were seen for the case of the MS PET coil with the detector and cable shield. Differences in the PET energy histograms or in the crystal identification maps with and without MRI measurements were negligible. Both the MRI and PET performances of the MS PET coil showed responses that matched the MS coil responses. The performance variations of MRI data with and without PET measurement and PET data with and without MR imaging were negligible.

Newer high-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability to preserve diagnostic image quality with low count density, while maintaining a high raw photon detection sensitivity that would allow for a reduction in injected dose or rapid data acquisition. To assess this, we performed quantitative and visual assessments of the PET images acquired using a highly sensitive (23.3cps/kBq) large field of view (25-cm axial) silicon photomultiplier (SiPM)-based TOF PET (400-ps timing resolution) integrated with 3T-MRI in comparison to PET images acquired on non-TOF PET/x-ray computed tomography (CT) systems. Whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT was acquired for 15 patients followed by whole body PET/magnetic resonance imaging (MRI) with an average injected dose of 325±84MBq. The PET list mode data from PET/MRI were reconstructed using full datasets (4min/bed) and reduced datasets (2, 1, 0.5, and 0.25min/bed). Qualitative assessment between PET/CT and PET/MR images were made. A Likert-type scale between 1 and 5, 1 for non-diagnostic, 3 equivalent to PET/CT, and 5 superior quality, was used. Maximum and mean standardized uptake values (SUVmax and SUVmean) of normal tissues and lesions detected were measured and compared. Mean visual assessment scores were 3.54±0.32, 3.62±0.38, and 3.69±0.35 for the brain and 3.05±0.49, 3.71±0.45, and 4.14±0.44 for the whole-body maximum intensity projections (MIPs) for 1, 2, and 4min/bed PET/MR images, respectively. The SUVmean values for normal tissues were lower and statistically significant for images acquired at 4, 2, 1, 0.5, and 0.25min/bed on the PET/MR, with values of -18±28% (p < 0.001), - 16±29% (p = 0.001), - 16±31% (p = 0.002), - 14±35% (p < 0.001), and - 13±34% (p = 0.002), respectively. SUVmax and SUVpeak values of all lesions were higher and statistically significant (p < 0.05) for 4, 2, 1, 0.50, and 0.25min/bed PET/MR datasets. High-sensitivity TOF PET showed comparable but still better visual image quality even at a much reduced activity in comparison to lower-sensitivity non-TOF PET. Our data translates to a seven times reduction in either injection dose for the same time or total scan time for the same injected dose. This "ultra-sensitivity" PET system provides a path to clinically acceptable extremely low-dose FDG PET studies (e.g., sub 1mCi injection or sub-mSv effective dose) or PET studies as short as 1min/bed (e.g., 6min of total scan time) to cover whole body without compromising diagnostic performance.

Recent years have witnessed an increased use of in vivo imaging techniques in both medicine and biomedical research. Positron Emission Tomography (PET) is a functional in vivo imaging technique relying on the metabolism of molecules which are injected into the blood stream and have a high chemical affinity to a specific biological substrate. These substances are labelled with positron emitters resulting in gamma rays which can be recorded outside the body using coincidence detection. Radiation can be detected using a variety of solutions, in terms of transducers and system geometries, and combined to produce images using suitable image reconstruction algorithms. The applications of PET imaging (e.g. cancer, brain function, cardiac function and gene expression) are currently benefiting from technological developments leading to the proposal of new PET systems. These are more sensitive, dedicated to imaging specific organs or research animals and are becoming multimodal. These advances are fostering new uses of PET, for example in biology labs to study the onset, progression and therapy of disease or to image the female breast. New materials and equipment are also, being developed allowing combining PET with other imaging techniques, such as MRI. The purpose of this review is to illustrate the most important inventions patented in PET since 2006 in areas concerning data acquisition and processing for human and research use of PET. Finally the manuscript will present the authors views about forthcoming developments in PET. Keywords: PET, PET developments, multimodality imaging, time of flight PET, dedicated PET systems, Positron Emission Tomography, in vivo imaging techniques, chemical affinity, Time-of-Flight PET, MRI, radiopharmaceuticals, PET-CT systems, sequential acquisitions, simultaneous acquisitions, scintillation light, split-magnet solution

Positron emission tomography (PET) images suffer from a noticeable amount of statistical noise. In order to reduce the noise, a post smoothing process is usually adopted in the conventional PET systems. However, its performance is limited because the process is mostly based on a Gaussian random noise which is quite distinct from the noise of PET images. It has been reported that noise variance of each voxel is proportional to the square of the mean value in a PET image reconstructed by expectation-maximization (EM). In addition, we also observe that the variance varies with the spatial sensitivity distribution in a PET system. Based on those properties, we determine a unique formula representing a relationship between the mean and variance for a given PET system. Meanwhile, a block matching 3D (or 4D) algorithm is known as the state of the art in Gaussian noise reduction. To effectively apply it for noise reduction of PET images, we first perform a noise characteristic conversion from the PET image noise to Gaussian random noise using a pre-determined relationship. We then apply a block matching 4D (BM4D) algorithm and reconvert the result. Using the Monte Carlo simulation, we demonstrate that proposed algorithm can effectively reduce the noise in the whole image region while minimizing the image resolution degradation.