A generalized reconstruction framework for unconventional PET systems.

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.

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.

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.

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.

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.

Small-animal positron emission tomography as a tool for neuropharmacology

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.

High spatial resolution Positron Emission Tomography (PET) imaging provides functional data about a patient's body and provides us with a range of new possibilities, including medicine development, new diagnostic methods, and others. The use of Depth of Interaction (DOI) detectors is one effective technique for the improvement of whole-body PET imaging, as is evident in the fact that most small animal PET images are taken using a DOI system. In this study, we developed a prototype whole-body DOI- equipped PET system and evaluated its performance. This scanner's DOI detectors consist of dual-layer (front and rear) 9 x 10 array of GSO/GSO crystals, a light guide and two rectangular double-anode photo multiplier tubes (PMTs). The DOI layers are discriminated according to decay time differences, which are controlled by Ce concentrations. The DOI detectors are arranged in a circular detector ring, with a diameter of 664 mm. In order to avoid parallax errors, coincidental events, including rear layer detection, were addressed to the nearest neighbor LOR front-layer coincidence pair. To evaluate the spatial resolution of this PET system at various radial positions, 22Na point sources at 1, 10, 20, and 25 cm offset from the center were reconstructed, both with and without DOI information. Results showed that spatial resolution degradation at 25 cm improved from 195 % to 154 % as a result of using DOI data. During a visual evaluation using a Derenzo phantom, image reconstruction using DOI data clarified the image and corrected hot rod shapes. The results presented here show that DOI detectors were useful in creating an effective whole-body PET system.

The effect of the THM growth rate on the CdTe crystalline quality and the detector performance was intensively investigated. The maximum growth rate for the single crystal growth was found to be approximately 15 mm/day which was 3 times greater than the conventional one. By optimizing other growth conditions, 90% of every ingot volume has become a single crystal. Te inclusions in the CdTe single crystal grown at various growth rates were also investigated by IR transmission microscopy. There was no correlation between the behavior of Te inclusions and the growth rate. The detector performance was also independent of the growth rate. Taking advantage of the large volume CdTe single crystals, about 700 000 Schottky detectors with 4 mm × 7.5 mm × 1 mm were fabricated for the research and development of the new positron emission tomography (PET) system using CdTe detectors. The average FWHM for the 662 keV line from <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">137</sup> Cs and its standard deviation were 2.24% and 0.48%, respectively. This uniformity was essential for the development of the new PET system.

Positron Emission Tomography (PET) is a unique tool for the study of metabolism and biochemical mechanisms in human being. However clinical applications require that PET systems combine high resolution and low statistical fluctuations in order to provide an accurate quantitation of the radionuclide distribution in selected organs of the human body. Recently the Time of Flight (TOF) information has been shown to improve image quality (1,2,3,4) and is now used in different PET systems. Nevertheless the objectives of PET will only be reached when all physical aspects of positron emission and annihilation radiation detection are correctly taken into account.

We introduce a re-configurable system design for positron emission tomography (PET) for purpose of maximizing the cost effectiveness of PET. In this new design concept, a PET system employs a small number of compact, flat-panel (cFP) PET detectors (which we believe will be made available in near future by us or others) to assume various scanner geometries so that the performance properties desired in various imaging applications can be met by a single PET system. For purpose of demonstration, we consider the design of a re-configurable small-animal system consisting of four cFP detectors that are approximately 8×8 cm2 in size and made of 10mm thick LSO. We consider four geometries for the scanner and conduct Monte-Carlo simulations to study their sensitivity, scatter fractions, random fractions, and noise-equivalent count rates. Our results indicate that, in terms of sensitivity and imaging field-of-view (FOV) the re-configurable system that we consider are very promising for small-animal imaging.

The physical performances of two current state-of-the-art scanners dedicated to functional imaging of the brain, one a single-photon emission tomography (SPET) scanner and the other a positron emission tomography (PET) scanner, have been compared under identical conditions. The aim of the study was to compare the capabilities of the devices under conditions resembling the routine clinical environment, as well as to consider other issues such as radiation burden for some common investigations. Both systems have slightly less than 11-cm axial fields of view. The PET system can be operated in a septa-less (3D) mode as well as conventionally with septa (2D). The spatial resolution of both devices was less than 8 mm in all dimensions in scattering media. On average, the PET scanner's resolution was approximately 10%-15% better than the SPET system. Energy resolution on the SPET system was superior due the scintillator used [NaI(Tl)]. Sensitivity in air with a line source on the PET system was found to be approximately 150 times greater in 3D and approximately 25 times greater in 2D than with the SPET system. A normal subject was studied on each system in an attempt to obtain the highest quality data possible for a subjective comparison. It is clear that, while PET retains the advantages of more desirable radiopharmaceuticals and higher sensitivity, the quality obtainable from SPET devices has improved markedly. SPET may prove as useful for many clinical investigations.

In positron emission tomography (PET) applications, coincidence timing resolution is crucial for rejecting random events, while the extremely high timing resolution can be used for time-of-flight (TOF) reconstruction. The timing resolution of PET system is determined by many factors, including the scintillator crystal, the photomultiplier (PMT) and the data acquisition system. Many efforts have been focused on these three aspects to improve the timing resolution. However, the different average arrival times of events (referred to below as timing shift) in different positions of the detector are not thoroughly studied yet. In this work, the timing shift in different positions are measured, their influence on the timing resolution of an real world PET system is investigated, and a calibration method for improving the timing resolution with timing shifts is proposed. The primary results show that the differences among timing shifts in the actual PET system worsen the timing resolution, and our method can calibrate the timing shift and improve the timing resolution.

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.