Abstract Background Breast cancer causes the largest number of cancer-related deaths among women worldwide. With the aim of improving Positron Emission Tomography (PET) technology for accurate breast cancer diagnosis and staging, we propose a system design based on monolithic crystals with inherent Depth of Interaction (DOI) capabilities and an innovative edgeless detector ring. This approach eliminates the physical gaps between PET detectors, improving the system detection efficiency while potentially enhancing the image quality since edge effects are reduced. We have developed a dedicated breast PET system prototype (DeepBreast) to show the feasibility of this design. The system is composed of 14 curved LYSO monolithic scintillators of 12.5 mm thickness glued side-by-side with a high-refractive index compound. The useful transaxial and axial Field of View (FOV) of the system are 160 mm and 50 mm, respectively. A Neural Network technique was used for the x- and y- photon impact position estimation. The impact DOI and energy values were determined using the Voronoi calibration methodology. An initial experimental evaluation of the DeepBreast system has been performed inspired by the NEMA protocols for whole-body and small-animals PET scanners. Results A nearly flat spatial resolution as a function of radial position was obtained, which indicates the DOI capability of the system to mitigate parallax errors. An average spatial resolution of 1.9 ± 0.1 mm, 1.9 ± 0.1 mm and 1.7 ± 0.1 mm FWHM was achieved at the center of the axial FOV for the radial, tangential, and axial directions, respectively. A maximum sensitivity value of 2% was measured at the center of the FOV. The noise equivalent count rate peak reached 15 kcps at 13.4 MBq. Moreover, percent contrast values of 27.9%, 28.8%, 56.8%, 72.5%, 87.2% and 84.2% were achieved for 4.5 mm, 6 mm, 9 mm, 12 mm, 15 mm and 20 mm cylinders of a larger dedicated IQ phantom, respectively. Conclusions The initial experimental results demonstrate the feasibility of the DeepBreast as an innovative PET scanner for breast cancer imaging.

To develop chitosan based efficient gene carriers, highly purified chitosan oligosaccharides (COSs) were chemically modified with deoxycholic acid (DOCA). Owing to the amphiphilic characters, the DOCA-conjugated COSs (COSDs) formed self-aggregated nanoparticles in aqueous milieu. The physicochemical characterization revealed that the particle size of the nanoparticles was in the range of 200∼240 nm and the critical aggregation concentration (cacs) was 0.012∼0.046 g/L, depending on the degree of substitution (DS). As efficient gene carriers, the COSD nanoparticles showed superior gene condensation and protection of condensed gene from endonuclease attack than unmodified COSs. Furthermore, COSDs showed great potential for gene carrier with the high level of gene transfection efficiencies, even in the presence of serum. Considered with the negligible cytotoxic effects, DOCA-modified chitosan oligosaccharides can be considered as potential candidates for efficient non-viral gene carriers.

Conventional Positron Emission Tomography (PET) scanners are usually built of multiple detectors arranged in a cylindrical geometry with both transaxial and axial gaps between them. These gaps decrease the system sensitivity and degrade the spatial resolution towards the edges of the detector blocks.To mitigate these constrains, we have designed and constructed a PET system based on 14 curved monolithic LYSO crystals. The crystals were glued together using a high refractive index material (n=1.7), and coupled to arrays of 12×12 SiPMs located in custom flexible Printed Circuit Boards (PCBs). This approach eliminates the gaps in the transaxial axis and allows the light transmission between adjacent crystals.This contribution summarizes the design and the assembling process of the proposed system which is intended for breast imaging studies.

Conventional Positron Emission Tomography (PET) and Single Photon Emission Tomography (SPECT) scanners are usually built using multiple detectors placed in a cylindrical geometry leading to both transaxial and axial gaps between detectors. These undesired gaps decrease system’s sensitivity and degrade spatial resolution towards the edges of the detector. To reduce gaps, we propose to construct a dedicated-breast PET made out of 14 curved LYSO crystals glued together using a high refractive coupling media (n=1.7). The aims of the current work are: i) to reduce edge effects when using glued crystals, and ii) to show the feasibility of the proposed edge-less PET system.We have glued the lateral sides of two cuboid LYSO crystals (n=1.81) of 33.0×25.4×10.0 mm 3 using Meltmount (n=1.7)and acquired data moving a 22 Na pencil beam (~450 µm slit) along the x- and y-axes. Results were compared with the standard case in which the lateral sides are black painted and keep an air gap (0.4 mm) in between the two blocks. The photon interaction coordinates were estimated using a Neural Network (NN) and, the detector performance was evaluated using the mean average error (MAE) parameter. Additionally, we show the design details of a system based on 14 LYSO curved crystals coupled to 12×12 SiPM arrays mounted on a custom flexible board containing also the readout electronics. We have experimentally acquired data and we also simulated (GATE/Geant4 platform) a back-to-back source at the center of the Field of View (cFOV). Data was reconstructed using MLEM with 4 iterations and a voxel size of 0.5 mm.Results show that gluing scintillation crystals with a high refractive index compound and using NN for impact position determination reduces edge effects, achieving spatial resolution of 0.7 mm from the simulated back-to-back source at the cFOV.

An open geometry dedicated PET scanner that allows patient motion is proposed. This PET configuration poses several challenges to image reconstruction, such as angular limitation, the presence of motion in the acquisition and the sensitivity correction problem. To correct the motion artifacts, a frame-based motion correction in three phases that uses an external tracking system is proposed. An experimental study of a moving source with different speeds has been carried out to study the influence of the speed on the degradation of the image corrected by our algorithm. The method can divide the acquired data from the scanner in frames, considering the size of the object of study. This approach allows working with low statistical information without losing image quality. The frames are later registered using spatio-temporal registration developed in a multi-level way. To validate these results, three performance tests are applied showing excellent values of similarity (in the range of 90-95%) with the ground-truth (static) image, and high signal-noise ratios (around 60 decibels). It also finds a small degradation of the image (0.01 error) when the speed of the source motion is higher than the spatial precision of the tracking system.

Many efforts have been devoted over the years to enhance the capabilities of PET detectors and to develop novel and efficient scanner concepts. Indeed, following several technological advances, the standards in the performance of these detectors have now been greatly expanded. However, in several cases compromises have to be made. In this work, we present our approach to develop an ultra-high spatial and timing resolution PET system, making use of the Compton-PET concept for mouse brain imaging. In particular, we will describe the detector elements of the scatter layer of such PET configuration. For this purpose, scintillators with just 3 mm thickness are tested when coupled to SiPM arrays of 3 mm × 3 mm. The aim, is to explore the optimal detector configuration for sub-100 ps resolution scanners. We make use of detectors based on crystal arrays of 0.95 mm × 0.95 mm pixel (12×12 elements) of the type LYSO(Ca) coupled to SiPMs arrays with 3 mm × 3 mm active area. As it will be discussed, we have been able to reach a detector timing resolution of 100 ps FWHM in some cases, while we were also capable to resolve all crystal pixels of 0.95 mm size.

Molecular imaging systems, such as positron emission tomography (PET), use detectors providing energy and a 3-D interaction position of a gamma ray within a scintillation block. Monolithic crystals are becoming an alternative to crystal arrays in PET. However, calibration processes are required to correct for nonuniformities, mainly produced by the truncation of the scintillation light distribution at the edges. We propose a calibration method based on the Voronoi diagrams. We have used $50 \times 50 \times 15$ mm(3) LYSO blocks coupled to a $12\times 12$ SiPMs array. We have first studied two different interpolation algorithms: 1) weighted average method (WAM) and 2) natural neighbor (NN). We have compared them with an existing calibration based on 1-D monomials. Here, the crystal was laterally black painted and a retroreflector (RR) layer added to the entrance face. The NN exhibited the best results in terms of XY impact position, depth of Interaction, and energy, allowing us to calibrate the whole scintillation volume. Later, the NN interpolation has been tested against different crystal surface treatments, allowing always to correct edge effects. Best energy resolutions were observed when using the reflective layers (12%-14%). However, better linearity was observed with the treatments using black paint. In particular, we obtained the best overall performance when lateral black paint is combined with the RR.

In recent years high efforts have been devoted to enhance spatial and temporal resolutions of PET detectors. However, accurately combining these two main features is, in most of the cases, challenging. Typically, a compromise has to be made between the number of readout channels, scintillator type and size, and photosensors arrangement if aiming for a good system performance, while keeping a moderate cost. In this work, we have studied several detector configurations for PET based on a set of 8x8 Silicon Photomultiplier (SiPMs) of 3x3 mm(2) active area, and LYSO crystal arrays with different pixel sizes. An exhaustive evaluation in terms of spatial, energy and timing resolution was made for all detector configurations. In some cases, when using pixel sizes different than SiPM active area, a significant amount of scintillation light may spread among several SiPMs. Therefore, we made use of a calibration method considering the different SiPM timing contributions. Best Detector Time Resolution (DTR) of 156 ps FWHM was measured when using 3x3 mm(2) crystal pixels directly coupled to the 3x3 mm(2) SiPMs. However, when using 1.5 mm crystal pixels with the same photosensor array, although we could clearly resolve all crystal pixels, an average DTR of 250 ps FWHM was achieved. We also shed light in this work on the timing dependency of the crystal pixel and photosensor alignment.

Abstract 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.

Monolithic scintillators are more frequently used in PET instrumentation due to their advantages in terms of accurate position estimation of the impinging gamma rays both planar and depth of interaction, their increased efficiency, and expected timing capabilities. Such timing performance has been studied when those blocks are coupled to digital photosensors showing an excellent timing resolution. In this work we study the timing behaviour of detectors composed by monolithic crystals and analog SiPMs read out by an ASIC. The scintillation light spreads across the crystal towards the photosensors, resulting in a high number of SiPMs and ASIC channels fired. This has been studied in relation with the Coincidence Timing Resolution (CTR). We have used LYSO monolithic blocks with dimensions of 50 x 50 x 15 mm(3) coupled to SiPM arrays (8 x 8 elements with 6 x 6 mm(2) area) which compose detectors suitable for clinical applications. While a CTR as good as 186 ps FWHM was achieved for a pair of 3 x 3 x 5 mm(3) LYSO crystals, when using the monolithic block and the SiPM arrays, a raw CTR over 1 ns was observed. An optimal timestamp assignment was studied as well as compensation methods for the time-skew and time-walk errors. This work describes all steps followed to improve the CTR. Eventually, an average detector time resolution of 497 ps FWHM was measured for the whole thick monolithic block. This improves to 380 ps FWHM for a central volume of interest near the photosensors. The timing dependency with the photon depth of interaction and planar position are also included.

Two of the limitation factors of current PET scanners are their low sensitivity and lack of high image contrast. In order to improve these parameters, Compton interactions, which are usually discarded or unavoidably averaged, must be distinguished and included in the image reconstruction process. To achieve this, one of our proposals is a multi-layer detector approach employing thin scintillation layers with photodetectors coupled to all four lateral sides of the crystal. In the work presented here, a characterization of detectors based on LYSO and CeBr 3 crystals with lateral sides readout has been performed. Both crystals have an active volume of 51×51×3 mm 3 , resulting in a very high aspect ratio of 17. The CeBr 3 crystal also includes a 5 mm thick quartz glass frame due to encapsulation constraints. The obtained results show an energy resolution of 12.1% and 9.1% FWHM for the LYSO and CeBr 3 detectors, respectively. Pilot spatial resolutions ranging from 2.7 mm up to 4.3 mm for the LYSO crystal and from 4.1 mm up to 11.2 mm for the CeBr 3 crystal were observed. These results suggest that the quartz glass frame surrounding the CeBr 3 crystal significantly affects the light distribution of the optical photons reaching the photodetectors, worsening the performance of this kind of encapsulated detector.

Motion correction algorithms are necessary in PET studies where the patient cannot remain totally static. Otherwise, artifacts appear in the final reconstructed image, degrading the spatial resolution or even misplacing the radiation distribution source. In this work we propose a new enhanced motion correction algorithm (EMAF) based on the multiple acquisition frames (MAF). This methodology can be applied to two PET system geometries (a ring and a multi-panel system). Using simulated data, the comparison of static and motion corrected profiles shows minimum differences keeping more than 99% of the events after the process, with a minimal inter-frame error (the maximum range of loss counts is around 0.6%). To measure the quality of the correction method, two error metrics as peak signal to noise ratio (PSNR) and intensity matching precision (IMP) are proposed. A Mini-Derenzo in a ring PET system reveals a remarkable improvement both for these two metrics (44.5 dB and 98.7%) when compared to the uncorrected images (41.1 dB and 56%, respectively). An equivalent analysis for a point-like source also shows a sizeable enhancement both in contrast and resolution (64 dB and 98% versus 62.5 dB and 17.9%, PSNR and IMP correspondingly). The proposed algorithm minimizes the image artifacts and its simplicity, independency of PET configuration system and rapid reconstruction and registration times, makes it a useful tool in preclinical PET studies.

Gamma cameras are of great interest due to their high potential in the field of Nuclear Medicine Imaging. They allow for an early diagnosis of reduced size tumors, and also for a wide variety of preclinical studies with the aim of designing more effective treatments against cancer. In this work we propose a significantly improved multi-pinhole collimator gamma camera and perform a first Monte Carlo analysis of its characteristics. Maintaining the configuration of a multi-pinhole collimator with a high degree of overlapping (thus with a high sensitivity), we add a new element, an active septa , that besides acting as a collimator, is able to measure the impact coordinates of the incident photon. This way one is able to unambiguously identify through which pinhole any gamma ray passes before being detected. The result is a high sensitivity and resolution multi-pinhole gamma camera with an arbitrarily large field of view. As a consequence, the final reconstructed image does not suffer from the undesired artifacts or truncation associated to the multiplexing phenomenon. In this study we focus on the development of a system able to visualize in 3D tumors, nodes and metastasis in real time in the operating room with very low dose. We also briefly analyse and propose a novel design for a Single Photon Emission Computed Tomography system.

PET scanners are based both on crystal arrays or monolithic crystals. There exist systems for clinical and preclinical applications that are making use of the single continuous crystal technology. It has been debated about the challenges involving the calibration of these crystals, in contrast to crystal arrays where the accuracy in the pixel localization is enough to provide XY impact position. In monolithic blocks, the crystal treatment and type of readout significantly affects the position decoding. The calibration method also affects the linearity and accuracy of the detector. In this work we describe a method for the calibration of monolithic crystals using arrays of known collimated radioactive sources and the so-called Voronoi diagrams. This method allows one for the calibration of the entire crystal volume. Besides a positioning bias, that strongly depends on the crystal thickness and treatment, the method can calibrate well all impacts. The proposed method has shown a very good linearity and the capability to resolve impacts at any crystal position. Obviously, due to the scintillation light truncation a poorer performance is observed at the edges. We have made use of this method also to calibrate the energy dependence on the impact position. In monolithic crystals, especially when some absorbent material is used, there is observed a scintillation light collection dependence with the impact position. This dependence weakens at the laterals and corners.

The aim of this work is to show the potential capabilities of monolithic crystals coupled to large SiPM arrays, to be considered as detector blocks for PET scanners enabling Time Of Flight (TOF) capabilities. Monolithic blocks allow one to decode the 3D photon impact position. This approach, along with TOF information, can be of high interest in clinical Positron emission tomography (PET) applications where a typical ring configuration is used. In this manuscript, we evaluate an ASIC- based readout for digitizing all signals coming from analog photosensors. Validation results with one-to-one coupling resulted in a Coincidence Time Resolution (CTR) of 202 ps FWHM. Providing timing resolution when using detectors based on monolithic crystals is however challenging. The wide distribution of scintillation light on the photosensors causes a poor SNR, which makes the system sensible to false triggering and to time walk errors. In this direction, we present a calibration method, designed to correct all recorded timestamps and also to compensate variations in time-paths among all channels. Thereafter, a CTR improvement nearing 45 observed for all measurements. Moreover, we show a novel approach that describes the use of averaging methods to assign a single timestamp to each gamma impact. This approach results in a further improvement of the CTR in the range of 100 ps FWHM, reaching a time resolution of 585 ps FWHM when using a large 50x50x10 mm3 LYSO scintillator coupled to an 8x8 SiPM (6x6 mm2) array. These pilot studies show detector capabilities regarding TOF information when using monolithic scintillators.

In this manuscript, detector blocks for Positron-Emission-Tomography (PET) are being evaluated for their integration in a TOF-PET system. In this contribution, detector concepts based on analog SiPM photosensors have been tested along with different types of scintillation materials. Firstly, pixelated crystals have been evaluated showing accurate results in terms of spatial, energy and timing resolution. Then, monolithic blocks were coupled to large SiPM photosensors arrays to determine their capabilities to resolve the gamma impacts in terms of position and timing. The read-out and the digitation of all signals were performed by a commercially available Application-Specific-Integrated-Circuit (ASIC) named TOFPET2. The obtained results as well as some methodologies that imrove the timing performance of the monolithic blocks, are being described in this paper.

Hybrid molecular and anatomical imaging devices, especially when simultaneously working, have shown to provide advantages over sequential acquisitions. In particular, we present in this preliminary study, the working performance of a brain positron emission tomography (PET) insert, within a 3T magnetic resonance imaging (MRI) system. To our knowledge, this is the largest PET system based on monolithic LYSO blocks. It consists of 60 scintillator blocks of $50\ \text{mm} \times 50\ \text{mm} \times 20\ \text{mm}$ arranged in 3 rings of 20 detector modules each. An effective field of view (FOV) of 240 mm in diameter and 154 mm axially is defined. The crystals included a retroreflector layer at the entrance face, and are coupled to custom arrays of $12 \times 12$ silicon photomultipliers (SiPM), $3\ \text{mm} \times 3\ \text{mm}$ each. Frontend electronics provide ${X}$ and ${Y}$ projections of the scintillation light by sampling each row and column of the SiPM arrays. The insert is thermally stabilized by using temperature-controlled air to about 27 °C. The PET insert has been installed at the Klinikum rechts der Isar (Munich) and tested within the whole-body Siemens biograph mMR, a 3T MRI combined with a PET scanner. A system sensitivity of almost 7% for an energy window of 350–650 keV was measured using a small size source at the center of the FOV (CFOV). Current system evaluation showed a spatial resolution at the CFOV of 1.7 mm using iterative algorithms, being below 2 mm within a centered diameter of 120 mm. Rods of a small Derenzo phantom of 2.5 mm were clearly resolved, independently of all tested MRI sequences including echo-planar imaging, ultrashort time echo, MPrage, and T2-flair or arterial spin labeling. The PET insert did not show any count rate degradation also under those sequences for a variety of MR imaging acquisitions.

In this review, we will cover both clinical and technical aspects of the advantages and disadvantages of organ specific (dedicated) molecular imaging (MI) systems, namely positron emission tomography (PET) and single photon emission computed tomography, including gamma cameras. This review will start with the introduction to the organ-dedicated MI systems. Thereafter, we will describe the differen...

In this contribution, large SiPM arrays (8 x 8 elements of 6 x 6 mm(2) each) are processed with an ASIC-based readout and coupled to a monolithic LYSO crystal to explore their potential use for TOF-PET applications. The aim of this work is to study the integration of this technology in the development of clinical PET systems reaching sub-300 ps coincidence resolving time (CRT). The SiPM and readout electronics have been evaluated first, using a small size 1.6 mm (6 mm height) crystal array (32 x 32 elements). All pixels were well resolved and they exhibited an energy resolution of about 20% (using Time-over-Threshold methods) for the 511 keV photons. Several parameters have been scanned to achieve the optimum readout system performance, obtaining a CRT as good as 330 +/- 5 ps FWHM. When using a black-painted monolithic block, the spatial resolution was measured to be on average 2.6 +/- 0.5 mm, without correcting for the source size. Energy resolution appears to be slightly above 20%. CRT measurements with the monolithic crystal detector were also carried out. Preliminary results as well as calibration methods specifically designed to improve timing performance, are being analyzed in the present manuscript. (C) 2017 Elsevier B.V. All rights reserved.

In gamma ray imaging, a scintillation crystal is typically used to convert the gamma radiation into visible light. Photosensors are used to transform this light into measurable signals. Several types of photosensors are currently in use depending on the application, most known are Position Sensitive Photomultiplier Tubes (PSPMT) or arrays of Silicon Photomultipliers (SiPMs). There have been investigations towards reducing the number of output signals from those photosensors in order to decrease system costs and complexity without impacting system performance. We propose here two different reduction schemes without degradation of the detector performance, keeping a good spatial, energy and timing resolution, specially well suited for monolithic scintillation crystals based detectors. We have carried out comparative results that will be shown.