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Background: Long-axial field-of-view (LAFOV) Positron Emission Tomography (PET) scanners provide high sensitivity, but throughput is limited because of time-consuming patient positioning. To enhance throughput, a novel Walk-Through PET (WT-PET) scanner has been developed, allowing patients to stand upright, supported by an adjustable headrest and hand supports. This study evaluates the degree of motion in the WT-PET system and compares it with the standard PET-CT., Methods: Three studies were conducted with healthy volunteers to estimate motion. The first two studies assessed motion in the WT-PET's Design I (Study 1) and Design II (Study 2), while the third study compared motion on a standard PET-CT scanner bed (Study 3). Infrared markers placed on the head, shoulders, chest, and abdomen were tracked and processed using image-processing techniques involving thresholding and connected component analysis. Videos were recorded for normal breathing and breath-holding conditions, and 2D centroids were transformed into 3D coordinates using depth information., Results: The results shows a significant reduction in motion during breath-holding, especially for the abdomen. Mean motion distances decreased from 2.63 mm to 2.18 mm in Study 1 and from 2.42 mm to 1.67 mm in Study 2. Statistical analysis revealed notable differences in motion between the WT-PET and mCT scanners. The Shapiro-Wilk test indicated non-normal motion distributions in the head, right shoulder, and abdomen for both systems, leading to the use of the Wilcoxon signed-rank test for all markers. Significant differences were found in the right shoulder (p = 0.0266), left shoulder (p = 0.0004) and chest (p < 0.0001) but no significant differences were observed in the head (p = 0.1327) and abdomen (p = 0.8404)., Conclusion: This study provides a comprehensive analysis of patient motion in a WT-PET scanner with respect to the standard PET. The findings highlight a significant increase in shoulder and chest motion, while the head and abdomen regions showed more stability., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no Conflict of interest., (© 2024. The Author(s).)

Background: This study investigates the integration of Artificial Intelligence (AI) in compensating the lack of time-of-flight (TOF) of the GE Omni Legend PET/CT, which utilizes BGO scintillation crystals., Methods: The current study evaluates the image quality of the GE Omni Legend PET/CT using a NEMA IQ phantom. It investigates the impact on imaging performance of various deep learning precision levels (low, medium, high) across different data acquisition durations. Quantitative analysis was performed using metrics such as contrast recovery coefficient (CRC), background variability (BV), and contrast to noise Ratio (CNR). Additionally, patient images reconstructed with various deep learning precision levels are presented to illustrate the impact on image quality., Results: The deep learning approach significantly reduced background variability, particularly for the smallest region of interest. We observed improvements in background variability of 11.8 % , 17.2 % , and 14.3 % for low, medium, and high precision deep learning, respectively. The results also indicate a significant improvement in larger spheres when considering both background variability and contrast recovery coefficient. The high precision deep learning approach proved advantageous for short scans and exhibited potential in improving detectability of small lesions. The exemplary patient study shows that the noise was suppressed for all deep learning cases, but low precision deep learning also reduced the lesion contrast (about -30 % ), while high precision deep learning increased the contrast (about 10 % )., Conclusion: This study conducted a thorough evaluation of deep learning algorithms in the GE Omni Legend PET/CT scanner, demonstrating that these methods enhance image quality, with notable improvements in CRC and CNR, thereby optimizing lesion detectability and offering opportunities to reduce image acquisition time., (© 2024. The Author(s).)

Background: This study evaluates the lesion contrast in a cost-effective long axial field of view (FOV) PET scanner, called the walk-through PET (WT-PET). The scanner consists of two flat detector panels covering the entire torso and head, scanning patients in an upright position for increased throughput. High-resolution, depth-of-interaction capable, monolithic detector technology is used to provide good spatial resolution and enable detection of smaller lesions., Methods: Monte Carlo GATE simulations are used in conjunction with XCAT anthropomorphic phantoms to evaluate lesion contrast in lung, liver and breast for various lesion diameters (10, 7 and 5 mm), activity concentration ratios (8:1, 4:1 and 2:1) and patient BMIs (18-37). Images were reconstructed iteratively with listmode maximum likelihood expectation maximization, and contrast recovery coefficients (CRCs) were obtained for the reconstructed lesions., Results: Results shows notable variations in contrast recovery coefficients (CRC) across different lesion sizes and organ locations within the XCAT phantoms. Specifically, our findings reveal that 10 mm lesions consistently exhibit higher CRC compared to 7 mm and 5 mm lesions, with increases of approximately 54% and 330%, respectively, across all investigated organs. Moreover, high contrast recovery is observed in most liver lesions regardless of diameter or activity ratio (average CRC = 42%), as well as in the 10 mm lesions in the lung. Notably, for the 10 mm lesions, the liver demonstrates 42% and 62% higher CRC compared to the lung and breast, respectively. This trend remains consistent across lesion sizes, with the liver consistently exhibiting higher CRC values compared to the lung and breast: 7 mm lesions show an increase of 96% and 41%, while 5 mm lesions exhibit approximately 294% and 302% higher CRC compared to the lung and breast, respectively., Conclusion: A comparison with a conventional pixelated LSO long axial FOV PET shows similar performance, achieved at a reduced cost for the WT-PET due to a reduction in required number of detectors., (© 2024. The Author(s).)

Purpose: Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10 MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images., Procedures: For 36 mice, a 15-min [ 18 F]FDG (8.15 ± 1.34 MBq) PET scan was acquired at 40 min post-injection on the Molecubes β-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75 min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs., Results: The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1 MBq or sub-1 min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([ 18 F]PSMA, [ 18 F]FAPI, and [ 68  Ga]FAPI)., Conclusion: Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Although a new generation of tomographs with a longer axial field-of-view called total-body PET have been developed, they are not widely utilized due to their high cost compared to conventional scanners. The newly designed walk-through total-body PET scanner is introduced as a high-throughput and cost-efficient alternative to total-body PET scanners, by making use of a flat panel geometry and lower cost, depth-of-interaction capable, monolithic BGO detectors. The main aim of the presented study is to evaluate through Monte Carlo simulation the system characteristics of the walk-through total-body PET scanner by comparing it with a Quadra-like total-body PET of similar attributes to the Siemens Biograph Vision Quadra., Methods: The walk-through total-body PET is comprised of two flat detector panels, spaced 50 cm apart. Each panel, 70 [Formula: see text] 106 cm[Formula: see text] in size, consists of 280 BGO-based monolithic detectors. The Quadra-like TB-PET has been simulated based on the characteristics of the Biograph Vision Quadra, one of the most common total-body PET scanners with 106 cm of axial field-of-view, which is constructed with pixelated LSO scintillation crystals. The spatial resolution, sensitivity, count rate performance, scatter fractions, and image quality of both scanners are simulated in the GATE simulation toolkit for comparison., Results: Due to the DOI-capable detectors used in the walk-through total-body PET, the values of the spatial resolution of this scanner were all below 2 mm along directions parallel to the panels, and reached a maximum of 3.36 mm in the direction perpendicular to the panels. This resolution is a large improvement compared to the values of the Quadra-like TB-PET. The walk-through total-body PET uses its maximum sensitivity (154 cps/kBq) for data acquisition and image reconstruction., Conclusion: Based on the combination of very good spatial resolution and high sensitivity of the walk-through total-body PET, along with a 2.2 times lower scintillation crystal volume and 1.8 times lower SiPM surface, this scanner can be a very cost-efficient alternative for total-body PET scanners in cases where concomitant CT is not required., (© 2023. The Author(s).)

Purpose: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems., Methods: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET., Results: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV., Conclusions: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators., (© 2023. The Author(s).)

Background: In preclinical settings, micro-computed tomography (CT) provides a powerful tool to acquire high resolution anatomical images of rodents and offers the advantage to in vivo non-invasively assess disease progression and therapy efficacy. Much higher resolutions are needed to achieve scale-equivalent discriminatory capabilities in rodents as those in humans. High resolution imaging however comes at the expense of increased scan times and higher doses. Specifically, with preclinical longitudinal imaging, there are concerns that dose accumulation may affect experimental outcomes of animal models., Purpose: Dose reduction efforts under the ALARA (as low as reasonably achievable) principles are thus a key point of attention. However, low dose CT acquisitions inherently induce higher noise levels which deteriorate image quality and negatively impact diagnostic performance. Many denoising techniques already exist, and deep learning (DL) has become increasingly popular for image denoising, but research has mostly focused on clinical CT with limited studies conducted on preclinical CT imaging. We investigate the potential of convolutional neural networks (CNN) for restoring high quality micro-CT images from low dose (noisy) images. The novelty of the CNN denoising frameworks presented in this work consists of utilizing image pairs with realistic CT noise present in the input as well as the target image used for the model training; a noisier image acquired with a low dose protocol is matched to a less noisy image acquired with a higher dose scan of the same mouse., Methods: Low and high dose ex vivo micro-CT scans of 38 mice were acquired. Two CNN models, based on a 2D and 3D four-layer U-Net, were trained with mean absolute error (30 training, 4 validation and 4 test sets). To assess denoising performance, ex vivo mice and phantom data were used. Both CNN approaches were compared to existing methods, like spatial filtering (Gaussian, Median, Wiener) and iterative total variation image reconstruction algorithm. Image quality metrics were derived from the phantom images. A first observer study (n = 23) was set-up to rank overall quality of differently denoised images. A second observer study (n = 18) estimated the dose reduction factor of the investigated 2D CNN method., Results: Visual and quantitative results show that both CNN algorithms exhibit superior performance in terms of noise suppression, structural preservation and contrast enhancement over comparator methods. The quality scoring by 23 medical imaging experts also indicates that the investigated 2D CNN approach is consistently evaluated as the best performing denoising method. Results from the second observer study and quantitative measurements suggest that CNN-based denoising could offer a 2-4× dose reduction, with an estimated dose reduction factor of about 3.2 for the considered 2D network., Conclusions: Our results demonstrate the potential of DL in micro-CT for higher quality imaging at low dose acquisition settings. In the context of preclinical research, this offers promising future prospects for managing the cumulative severity effects of radiation in longitudinal studies., (© 2023 American Association of Physicists in Medicine.)

Background: In light of the milestones achieved in PET design so far, further sensitivity improvements aim to optimise factors such as the dose, throughput, and detection of small lesions. While several longer axial field-of-view (aFOV) PET systems based on pixelated detectors have been installed, continuous monolithic scintillation detectors recently gained increased attention due to their depth of interaction capability and superior intrinsic resolution. As a result, the aim of this work is to present and evaluate the performance of two long aFOV, monolithic LYSO-based PET scanner designs., Methods: Geant4 Application for Tomographic Emission (GATE) v9.1 was used to perform the simulations. Scanner designs A and B have an aFOV of 36.2 cm (7 rings) and 72.6 cm (14 rings), respectively, with 40 detector modules per ring each and a bore diameter of 70 cm. Each module is a 50 × 50 × 16 mm 3 monolithic LYSO crystal. Sensitivity, noise equivalent count rate (NECR), scatter fraction, spatial resolution, and image quality tests were performed based on NEMA NU-2018 standards., Results: The sensitivity of design A was calculated to be 29.2 kcps/MBq at the centre and 27 kcps/MBq at 10 cm radial offset; similarly, the sensitivity of design B was found to be 106.8 kcps/MBq and 98.3 kcps/MBq at 10 cm radial offset. NECR peaks were reached at activity concentrations beyond the range of activities used for clinical studies. In terms of spatial resolution, the values for the point sources were below 2 mm for the radial, tangential, and axial full width half maximum. The contrast recovery coefficient ranged from 53% for design B and 4:1 contrast ratio to 90% for design A and 8:1 ratio, with a reasonably low background variability., Conclusions: Longer aFOV PET designs using monolithic LYSO have superior spatial resolution compared to current pixelated total-body PET (TB-PET) scanners. These systems combine high sensitivity with improved contrast recovery., (© 2023. The Author(s).)

Purpose: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative., Methods: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows., Conclusions: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective. Time-of-flight positron emission tomography based on bismuth germanate (BGO) detectors is made possible due to fast emission of Cerenkov light. Only around 17 Cerenkov photons are produced per 511 keV photoelectric event, making high photon collection efficiency crucial for obtaining good time-of-flight capabilities. In this study, we investigate how different lateral and back surface finishes affect the photon collection efficiency and Cerenkov based timing performance in monolithic BGO. Approach. The study is performed using GATE for gamma and optical photon modeling, with surface reflections of photons simulated by the LUT Davis model. We compare for different detector configurations (regarding size and surface finishes) the photon collection efficiency, detection delays of the first few optical photons and coincidence time resolution estimations obtained by modeling the SiPM signals and performing leading edge discrimination. An additional comparison is made to LYSO scintillators and pixelated detectors. Main results. Although Cerenkov photon emission is directional, many high incidence angle Cerenkov photons are emitted due to electron scattering in the crystal. Substituting a polished back (photodetector side) surface for a rough surface increases the collection efficiency of these high angle of incidence photons. Results show that for a monolithic 50 × 50 × 12 mm 3 BGO detector with reflective side surfaces, this leads to an overall increase in photon collection efficiency of 34%. Cerenkov photon collection efficiency is also improved, resulting in a reduction of the photon detection delays (and the variation therein) of the first few optical photons. This leads to a better coincidence time resolution, primarily achieved by a shortening of the tails in the time-of-flight kernel, with an 18% reduction in full width at tenth maximum. Significance. This study shows the importance of the photon collection efficiency for timing performance in Cerenkov based monolithic detectors, and how it can be improved with different surface finishes., (© 2023 Institute of Physics and Engineering in Medicine.)

This article presents the protocol on Quality Controls in PET/CT and PET/MRI published online in May 2022 by the European Federation of Organisations for Medical Physics (EFOMP), which was developed by the Working group for PET/CT and PET/MRI Quality Control (QC) protocol. The main objective of this protocol was to comprehensively provide simple and practical procedures that may be integrated into clinical practice to identify changes in the PET/CT/MRI system's performance and avoid short- and long-term quality deterioration. The protocol describes the quality control procedures on radionuclide calibrators, weighing scales, PET, CT and MRI systems using selected and measurable parameters that are directly linked to clinical images quality. It helps to detect problems before they can impact clinical studies in terms of safety, image quality, quantification accuracy and patient radiation dose. CT and MRI QCs are described only in the context of their use for PET (attenuation correction and anatomical localization) imaging. Detailed step-by-step instructions have been provided, limiting any misinterpretations or interpersonal variations as much as possible. This paper presents the main characteristics of the protocol illustrated together with a brief summary of the content of each chapter. A regular QC based on the proposed protocol would guarantee that PET/CT and PET/MRI systems operate under optimal conditions, resulting in the best performance for routine clinical tasks., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: An EFOMP Working Group (WG) was created in 2020 to establish recommendations for PET/CT/MRI Quality Control (QC). The WG's intention was to create a document containing a set of measurements suitable for routine practice. In order to map the current situation in PET facilities, the WG prepared a survey addressed to European Medical Physics Experts (MPE)., Methods: The survey was conducted using an electronic questionnaire with 10 sections, for a total of 43 multiple choice or open questions. Data regarding general information, model of installed scanners, contract of maintenance and phantoms available were collected. The focal part of the questionnaire concerned the QC protocol adopted and accreditation programs., Results: 123 answers from 24 countries were collected. 90.2% of the respondents are affiliated as staff MPEs; 45% have non-digital TOF PET/CT scanners with a contract of maintenance (97.6%). In 98.4% and 86.8% of responding centres a sealed source for daily QC and the NEMA Image Quality Phantom were present. 94.3% of respondents perform daily QC according to manufacturer recommendations, while NEMA Tests are not performed routinely (51.2%). 56.1% of the respondents have scanners accredited by a national or international organization. 56% of the centres perform annual CT tests, while more than 90% do not perform any MRI QCs., Conclusions: The results of the survey show that there is a lack of harmonization in the PET QC procedures across Europe. The information obtained will guide the WG in proposing a guideline containing a set of measurements suitable for the clinical routine., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Objective. We investigate the use of 3D convolutional neural networks for gamma arrival time estimation in monolithic scintillation detectors. Approach. The required data is obtained by Monte Carlo simulation in GATE v8.2, based on a 50 × 50 × 16 mm 3 monolithic LYSO crystal coupled to an 8 × 8 readout array of silicon photomultipliers (SiPMs). The electronic signals are simulated as a sum of bi-exponentional functions centered around the scintillation photon detection times. We include various effects of statistical fluctuations present in non-ideal SiPMs, such as dark counts and limited photon detection efficiency. The data was simulated for two distinct overvoltages of the SensL J-Series 60 035 SiPMs, in order to test the effects of different SiPM parameters. The neural network uses the array of detector waveforms, digitized at 10 GS s -1 , to predict the time at which the gamma arrived at the crystal. Main results. Best results were achieved for an overvoltage of +6 V, at which point the SiPM reaches its optimal photon detection efficiency, resulting in a coincidence time resolution (CTR) of 141 ps full width at half maximum (FWHM). It is a 26% improvement compared to a simple averaging of the first few SiPM timestamps obtained by leading edge discrimination, which in comparison produced a CTR of 177 ps FWHM. In addition, better detector uniformity was achieved, although some degradation near the corners did remain. Significance. These improvements in time resolution can lead to higher signal-to-noise ratios in time-of-flight positron emission tomography, ultimately resulting in better diagnostic capabilities., (© 2022 Institute of Physics and Engineering in Medicine.)

Background: In recent years, there has been a rapid proliferation in micro-computed tomography (micro-CT) systems becoming more available for routine preclinical research, with applications in many areas, including bone, lung, cancer, and cardiac imaging. Micro-CT provides the means to non-invasively acquire detailed anatomical information, but high-resolution imaging comes at the cost of longer scan times and higher doses, which is not desirable given the potential risks related to x-ray radiation. To achieve dose reduction and higher throughputs without compromising image quality, fewer projections can be acquired. This is where iterative reconstruction methods can have the potential to reduce noise since these algorithms can better handle sparse projection data, compared to filtered backprojection PURPOSE: We evaluate the performance characteristics of a compact benchtop micro-CT scanner that provides iterative reconstruction capabilities with GPU-based acceleration. We thereby investigate the potential benefit of iterative reconstruction for dose reduction., Methods: Based on a series of phantom experiments, the benchtop micro-CT system was characterized in terms of image uniformity, noise, low contrast detectability, linearity, and spatial resolution. Whole-body images of a plasticized ex vivo mouse phantom were also acquired. Different acquisition protocols (general-purpose versus high-resolution, including low dose scans) and different reconstruction strategies (analytic versus iterative algorithms: FDK, ISRA, ISRA-TV) were compared., Results: Signal uniformity was maintained across the radial and axial field-of-view (no cupping effect) with an average difference in Hounsfield units (HU) between peripheral and central regions below 50. For low contrast detectability, regions with at least ∆HU of 40 to surrounding material could be discriminated (for rods of 2.5 mm diameter). A high linear correlation (R 2  = 0.997) was found between measured CT values and iodine concentrations (0-40 mg/ml). Modulation transfer function (MTF) calculations on a wire phantom evaluated a resolution of 10.2 lp/mm at 10% MTF that was consistent with the 8.3% MTF measured on the 50 µm bars (10 lp/mm) of a bar-pattern phantom. Noteworthy changes in signal-to-noise and contrast-to-noise values were found for different acquisition and reconstruction protocols. Our results further showed the potential of iterative reconstruction to deliver images with less noise and artefacts., Conclusions: In summary, the micro-CT system that was evaluated in the present work was shown to provide a good combination of performance characteristics between image uniformity, low contrast detectability, and resolution in short scan times. With the iterative reconstruction capabilities of this micro-CT system in mind (ISRA and ISRA-TV), the adoption of such algorithms by GPU-based acceleration enables the integration of noise reduction methods which here demonstrated potential for high-quality imaging at reduced doses., (© 2022 American Association of Physicists in Medicine.)

The vast majority of PET detectors in the field today are based on pixelated scintillators. Yet, the resolution of this type of detector is limited by the pixel size. To overcome this limitation, one can use monolithic detectors. However, this detector architecture demands specific and high-speed detector readout of the photodetector array. A commonly used approach is to integrate the current pulses generated by every pixel but such circuitry quickly becomes bulky, power consuming and expensive. The objective of this work is to investigate a novel readout and event positioning scheme for monolithic PET detectors, based on time-over-threshold (ToT). In this case, we measure the time that the pulse is above a certain threshold through a comparator. The pulse widths are used for event positioning using a mean nearest neighbour approach (mNN ToT ). For energy determination one integrating multiplexed channel is foreseen. We evaluate the positioning accuracy and uniformity of such a ToT detector by means of Monte Carlo simulations. The impact of the threshold value is investigated and the results are compared to a detector using mean nearest neighbour with pulse-integration (mNN int ), which has already proven to allow sub-mm resolution. We show minimal degradation in spatial resolution and bias performance compared to mNN int . The highest threshold results in the worst resolution performance but degradation remains below 0.1 mm. Bias is largely constant over different thresholds for mNN ToT and close to identical to mNN int . Furthermore we show that ToT performs well in terms of detector uniformity and that scattered photons can be positioned inside the crystal with high accuracy. We conclude from this work that ToT is a valuable alternative to pulse-integration for monolithic PET detectors. This novel approach has an impact on PET detector development since it has the advantage of lower power consumption, compactness and inherent amplitude-to-time conversion., (© 2021 Institute of Physics and Engineering in Medicine.)

The use of deep learning in medical imaging has increased rapidly over the past few years, finding applications throughout the entire radiology pipeline, from improved scanner performance to automatic disease detection and diagnosis. These advancements have resulted in a wide variety of deep learning approaches being developed, solving unique challenges for various imaging modalities. This paper provides a review on these developments from a technical point of view, categorizing the different methodologies and summarizing their implementation. We provide an introduction to the design of neural networks and their training procedure, after which we take an extended look at their uses in medical imaging. We cover the different sections of the radiology pipeline, highlighting some influential works and discussing the merits and limitations of deep learning approaches compared to other traditional methods. As such, this review is intended to provide a broad yet concise overview for the interested reader, facilitating adoption and interdisciplinary research of deep learning in the field of medical imaging., (© 2021. The Author(s).)

The system spatial resolution of whole-body positron emission tomography (PET) is limited to around 2 mm due to positron physics and the large diameter of the bore. To stay below this 'physics'-limit a scintillation detector with an intrinsic spatial resolution of around 1.3 mm is needed. Currently used detector technology consists of arrays of 2.6-5 mm segmented scintillator pixels which are the dominant factor contributing to the system resolution. Pixelated detectors using smaller pixels exist but face major drawbacks in sensitivity, timing, energy resolution and cost. Monolithic continuous detectors, where the spatial resolution is determined by the shape of the light distribution on the photodetector array, are a promising alternative. Without having the drawbacks of pixelated detectors, monolithic ones can also provide depth-of-interaction (DOI) information. In this work we present a monolithic detector design aiming to serve high-resolution clinical PET systems while maintaining high sensitivity. A 50 × 50 × 16 mm 3 Lutetium-Yttrium oxyorthosilicate scintillation crystal with silicon photomultiplier (SiPM) backside readout is calibrated in singles mode by a collimated beam obtaining a reference dataset for the event positioning. A mean nearest neighbour (MNN) algorithm and an artificial neural network for positioning are compared. The targeted intrinsic detector resolution of 1.3 mm needed to reach a 2 mm resolution on system level was accomplished with both algorithms. The neural network achieved a mean spatial resolution of 1.14 mm FWHM for the whole detector and 1.02 mm in the centre (30 × 30 mm 2 ). The MNN algorithm performed slightly worse with 1.17 mm for the whole detector and 1.13 mm in the centre. The intrinsic DOI information will also result in uniform system spatial resolution over the full field of view., (© 2021 Institute of Physics and Engineering in Medicine.)

Due to its high sensitivity and specificity for tumor detection, positron emission tomography (PET) has become a standard and widely used molecular imaging technique. Given the popularity of PET, both clinically and preclinically, its use has been extended to study plants. However, only a limited number of research groups worldwide report PET-based studies, while we believe that this technique has much more potential and could contribute extensively to plant science. The limited application of PET may be related to the complexity of putting together methodological developments from multiple disciplines, such as radio-pharmacology, physics, mathematics and engineering, which may form an obstacle for some research groups. By means of this manuscript, we want to encourage researchers to study plants using PET. The main goal is to provide a clear description on how to design and execute PET scans, process the resulting data and fully explore its potential by quantification via compartmental modeling. The different steps that need to be taken will be discussed as well as the related challenges. Hereby, the main focus will be on, although not limited to, tracing 11 CO 2 to study plant carbon dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mincke, Courtyn, Vanhove, Vandenberghe and Steppe.)

Built on top of the Geant4 toolkit, GATE is collaboratively developed for more than 15 years to design Monte Carlo simulations of nuclear-based imaging systems. It is, in particular, used by researchers and industrials to design, optimize, understand and create innovative emission tomography systems. In this paper, we reviewed the recent developments that have been proposed to simulate modern detectors and provide a comprehensive report on imaging systems that have been simulated and evaluated in GATE. Additionally, some methodological developments that are not specific for imaging but that can improve detector modeling and provide computation time gains, such as Variance Reduction Techniques and Artificial Intelligence integration, are described and discussed., (Creative Commons Attribution license.)

To detect gamma rays with good spatial, timing and energy resolution while maintaining high sensitivity we need accurate and efficient algorithms to estimate the first gamma interaction position from the measured light distribution. Furthermore, monolithic detectors are investigated as an alternative to pixelated detectors due to increased sensitivity, resolution and intrinsic DOI encoding. Monolithic detectors, however, are challenging because of complicated calibration setups and edge effects. In this work, we evaluate the use of neural networks to estimate the 3D first (Compton or photoelectric) interaction position. Using optical simulation data of a 50 × 50 × 16 mm 3 LYSO crystal, performance is evaluated as a function of network complexity (two to five hidden layers with 64 to 1024 neurons) and amount of training data (1000-8000 training events per calibration position). We identify and address the potential pitfall of overfitting on the training grid through evaluation on intermediate positions that are not in the training set. Additionally, the performance of neural networks is directly compared with nearest neighbour positioning. Optimal performance was achieved with a network containing three hidden layers of 256 neurons trained on 1000 events/position. For more complex networks, the performance degrades at intermediate positions and overfitting starts to occur. A median 3D positioning error of 0.77 mm and a 2D FWHM of 0.46 mm is obtained. This is a 17% improvement in terms of FWHM compared to the nearest neighbour algorithm. Evaluation only on events that are not Compton scattered results in a 3D positioning error of 0.40 mm and 2D FWHM of 0.42 mm. This reveals that Compton scatter results in a considerable increase of 93% in positioning error. This study demonstrates that very good spatial resolutions can be achieved with neural networks, superior to nearest neighbour positioning. However, potential overfitting on the training grid should be carefully evaluated., (© 2021 Institute of Physics and Engineering in Medicine.)

Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with x-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting cancer in complete remission. Moreover, there is an increasing demand for reducing the radioactive doses injected to the patients without impairing image quality. There are three ways to improve PET scanner sensitivity: improving detector efficiency, increasing geometrical acceptance of the imaging device and pushing the timing performance of the detectors. Currently, some pre-localization of the electron-positron annihilation along a line-of-response (LOR) given by the detection of a pair of annihilation photons is provided by the detection of the time difference between the two photons, also known as the time-of-flight (TOF) difference of the photons, whose accuracy is given by the coincidence time resolution (CTR). A CTR of about 10 picoseconds FWHM will ultimately allow to obtain a direct 3D volume representation of the activity distribution of a positron emitting radiopharmaceutical, at the millimetre level, thus introducing a quantum leap in PET imaging and quantification and fostering more frequent use of 11 C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.

Rationale: Positive surgical margins for invasive breast cancer (BC) treated with breast-conserving surgery (BCS) are defined as ink on tumor. The rate of positive margins is approximately 20%, since a time- and cost-effective method for margin assessment is lacking. In this study, we investigated margin status by intra-operative imaging using high-resolution 18 F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) and X-ray computed tomography (CT). Methods: Twenty patients were enrolled and received 4   MBq/kg of FDG prior to surgery. Intra-operative imaging of the specimens was performed by the MOLECUBES β-CUBE (PET) and X-CUBE (CT). Margin status was assessed by three surgeons and compared with an algorithm. The sensitivity and specificity were calculated by using histopathological assessment as a gold standard. Results: A region with high FDG uptake was visualized in all specimens. Automated analysis showed a sensitivity of 90%, a specificity of 60%, and an area under the curve (AUC) of 0.86 after ROC analysis. Margin assessment by the surgeons resulted in a mean sensitivity and specificity of 79% and 72%, respectively. Conclusions: This proof-of-concept study demonstrates that high-resolution FDG-PET/CT can facilitate intra-operative margin assessment during BCS. This technique achieves good sensitivity and specificity and may therefore reduce re-operation rates in the future.

NEMA characterization of PET systems is generally based on 18 F because it is the most relevant radioisotope for the clinical use of PET. 18 F has a half-life of 109.7 min and decays into stable 18 O via β+ emission with a probability of over 96% and a maximum positron energy of 0.633 MeV. Other commercially available PET radioisotopes, such as 82 Rb and 68 Ga have more complex decay schemes with a variety of prompt gammas, which can directly fall into the energy window and induce false coincidence detections by the PET scanner., Methods: Aim of this work was three-fold: (A) Develop a GATE model of the GE Signa PET/MR to perform realistic and relevant Monte Carlo simulations (B) Validate this model with published sensitivity and Noise Equivalent Count Rate (NECR) data for 18 F and 68 Ga (C) Use the validated GATE-model to predict the system performance for other PET isotopes including 11 C, 15 O, 13 N, 82 Rb, and 68 Ga and to evaluate the effect of a 3T magnetic field on the positron range., Results: Simulated sensitivity and NECR tests performed with the GATE-model for different radioisotopes were in line with literature values. Simulated sensitivities for 18 F and 68 Ga were 21.2 and 19.0/kBq, respectively, for the center position and 21.1 and 19.0 cps/kBq, respectively, for the 10 cm off-center position compared to the corresponding measured values of 21.8 and 20.0 cps/kBq for the center position and 21.1 and 19.6 cps/kBq for the 10 cm off-center position. In terms of NECR, the simulated peak NECR was 216.8 kcps at 17.40 kBq/ml for 18 F and 207.1 kcps at 20.10 kBq/ml for 68 Ga compared to the measured peak NECR of 216.8 kcps at 18.60 kBq/ml and 205.6 kcps at 20.40 kBq/ml for 18 F and 68 Ga, respectively. For 11 C, 13 N, and 15 O, results confirmed a peak NECR similar to 18 F with the effective activity concentration scaled by the inverse of the positron fraction. For 82 Rb, and 68 Ga, the peak NECR was lower than for 18 F while the corresponding activity concentrations were higher. For the higher energy positron emitters, the positron range was confirmed to be tissue-dependent with a reduction of the positron range by a factor of 3 to 4 in the plane perpendicular to the magnetic field and an increased positron range along the direction of the magnetic field., Conclusion: Monte-Carlo simulations were used to predict sensitivity and NECR performance of GE Signa PET/MR for 18 F, 15 O, 13 N, 11 C, 82 Rb, and 68 Ga radioisotopes and were in line with literature data. Simulations confirmed that sensitivity and NECR were influenced by the particular decay scheme of each isotope. As expected, the positron range decreased in the direction perpendicular to the 3T magnetic field. However, this will be only partially improving the resolution properties of a clinical PET/MR system due to the limiting spatial resolution of the PET detector., (Copyright © 2020 Caribé, Vandenberghe, Diogo, Pérez-Benito, Efthimiou, Thyssen, D’Asseler and Koole.)

Respired CO2 in woody tissues can build up in the xylem and dissolve in the sap solution to be transported through the plant. From the sap, a fraction of the CO2 can either be radially diffuse to the atmosphere or be assimilated in chloroplasts present in woody tissues. These processes occur simultaneously in stems and branches, making it difficult to study their specific dynamics. Therefore, an 11C-enriched aqueous solution was administered to young branches of Populus tremula L., which were subsequently imaged by positron emission tomography (PET). This approach allows in vivo visualization of the internal movement of CO2 inside branches at high spatial and temporal resolution, and enables direct measurement of the transport speed of xylem-transported CO2 (vCO2). Through compartmental modeling of the dynamic data obtained from the PET images, we (i) quantified vCO2 and (ii) proposed a new method to assess the fate of xylem-transported 11CO2 within the branches. It was found that a fraction of 0.49 min-1 of CO2 present in the xylem was transported upwards. A fraction of 0.38 min-1 diffused radially from the sap to the surrounding parenchyma and apoplastic spaces (CO2,PA) to be assimilated by woody tissue photosynthesis. Another 0.12 min-1 of the xylem-transported CO2 diffused to the atmosphere via efflux. The remaining CO2 (i.e., 0.01 min-1) was stored as CO2,PA, representing the build-up within parenchyma and apoplastic spaces to be assimilated or directed to the atmosphere. Here, we demonstrate the outstanding potential of 11CO2-based plant-PET in combination with compartmental modeling to advance our understanding of internal CO2 movement and the respiratory physiology within woody tissues., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Preclinical PET/CT is a well-established noninvasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially nonexistent. This study (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multicenter data, optimized for routine scanning in the preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and the United States were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols, followed by developing standardized protocols. PET, CT, and absorbed dose biases were assessed. Results: Site default CT protocols were the following: greatest extracted Hounsfield units (HU) were 133 HU for water and -967 HU for air; significant differences in all tissue equivalent material (TEM) groups were measured. The average CT absorbed doses for mouse and rat were 72 mGy and 40 mGy, respectively. Standardized CT protocol were the following: greatest extracted HU were -77 HU for water and -990 HU for air; TEM precision improved with a reduction in variability for each tissue group. The average CT absorbed dose for mouse and rat decreased to 37 mGy and 24 mGy, respectively. Site default PET protocols were the following: uniformity was substandard in one scanner, recovery coefficients (RCs) were either over- or underestimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocols were the following: scanner with substandard uniformity improved by 36%, RC variability decreased by 13% points, and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative biases in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

The intrinsic spatial resolution of clinical positron emission tomography (PET) detectors is ~3-4 mm. A further improvement of the resolution using pixelated detectors will not only result in a prohibitive cost, but is also inevitably accompanied by a strong degradation of important performance parameters like timing, energy resolution and sensitivity. Therefore, it is likely that future generation high resolution PET detectors will be based on continuous monolithic scintillation detectors. Monolithic detectors have attractive properties to reach superior 3D spatial resolution while outperforming pixelated detectors in timing, energy resolution and sensitivity. In this work, optical simulations including an advanced surface reflection model, allow us to investigate the influence of three parameters on the spatial resolution: silicon photomultiplier (SiPM) pixel size, photon detection efficiency (PDE) and the number of channels used to read out the SiPM array. A lutetium-yttrium oxyorthosilicate (LYSO) crystal with dimensions 50  ×  50  ×  16 mm 3 coupled to an SiPM array is calibrated and a nearest neighbor (NN) algorithm is used to position events. Findings show that the tested parameters affect the spatial resolution resulting in 0.40-0.66 mm full width at half maximum (FWHM). Best resolution could be obtained with smaller SiPM pixels, higher PDE, and an individual channel readout. However, it was shown that combining channels by adding their signals can significantly reduce the amount of readout channels while having small or no significant impact on the resolution. The mean depth of interaction (DOI) estimation error is 1.6 mm. This study demonstrates the ultimate spatial resolution that can be obtained with this detector without being constrained by practical limitations of experimental setups. In the future these optical simulations may be used as a more precise and fast method to obtain calibration data for real monolithic detectors.

Phloem transport is of great importance in trees to distribute assimilated carbon across the entire tree. Nevertheless, knowledge of phloem is incomplete, because of the complexity of measuring its transport and characteristics. Only few studies have addressed how phloem transport might alter under climatic changes, with most data originating from theoretical studies. We measured phloem characteristics in leaves of young Populus tremula L. trees grown during 5 months under ambient (TA, 404 ppm ± 5) and elevated (TE, 659 ppm ± 3) atmospheric CO2 concentration ([CO2]) using a combination of positron emission tomography (PET) and compartmental modelling. Short-term phloem dynamics were measured in vivo and non-invasively using the short-lived isotope of carbon, 11C (half-life 20.4 min). Trees were scanned in well-watered and dry conditions to assess changes in phloem characteristics induced by drought. Reliability of the PET-derived results was verified with reported observations in the literature. Phloem speed was highest in well-watered TE trees and strongly reduced by 81% under drought, whereas phloem speed reduced by 61% in TA trees at the same level of drought. These findings led us to speculate that phloem transport in TE trees might be more vulnerable to drought. We discuss how a higher phloem vulnerability to drought in a changing climate could impact tree hydraulic functioning. Taken together our results suggest that trees grown for 5 months under elevated [CO2] seem to be less well-acclimated to face projected hotter droughts in a changing climate., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Peptide receptor radionuclide therapy with 177 Lu-DOTATATE has become a standard treatment modality in neuroendocrine tumours (NETs). No consensus has yet been reached however regarding the absorbed dose threshold for lesion response, the absorbed dose limit to organs-at-risk, and the optimal fractionation and activity to be administered. This is partly due to a lack of uniform and comparable dosimetry protocols. The present article details the development of an organ-at-risk dosimetry procedure, which could be implemented and used routinely in a clinical context., Methods: Forty-seven patients with NETs underwent 177 Lu-DOTATATE therapy. Three SPECT/CT images were acquired at 4, 24 and 144-192 h post-injection. Three blood samples were obtained together with the SPECT/CT acquisitions and 2 additional samples were obtained around 30 min and 1 h post-injection. A bi-exponential fit was used to compute the source organ time-integrated activity coefficients. Coefficients were introduced into OLINDA/EXM software to compute organ-at-risk absorbed doses. Median values for all patients were computed for absorbed dose coefficient D/A 0 and for late effective half-life T 1/2eff for kidneys, spleen and red marrow., Results: Dosimetry resulted in a median[interquartile range] of 0.78[0.35], 1.07[0.58] and 0.028[0.010] Gy/GBq for D/A 0 and of 55[9], 71[9] and 52[18] h for T 1/2eff for kidneys, spleen and red marrow respectively., Conclusions: A dosimetry procedure for organs-at-risk in 177 Lu-DOTATATE therapy based on serial SPECT/CT images and blood samples can be implemented routinely in a clinical context with limited patient burden. The results obtained were in accordance with those of other centres., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

The performances of an intra-operative optical imaging system for Cerenkov luminescence imaging of resected tumor specimens were evaluated with phantom studies. The spatial resolution, the linearity of the measured signal with the activity concentration and the minimum detectable activity concentration were considered. A high linearity was observed over a broad range of activity concentration (R 2 ⩾0.99 down to ∼40 kBq/ml of 18 F-FDG). For 18 F-FDG activity distributions 2 mm deep in biological tissue, the measured detection limit was 8 kBq/ml and a spatial resolution of 2.5 mm was obtained. The detection limit of the imaging system is comparable with clinical activity concentrations in tumor specimens, and the spatial resolution is compatible with clinical requirements., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background: In order to obtain a reliable 177 Lu-DOTATATE therapy dosimetry, it is crucial to acquire accurate and precise activity measurements with the radionuclide calibrator, the SPECT/CT camera, and the NaI(Tl) well counter. The aim of this study was to determine, in a clinical context, the accuracy and the precision of their activity quantification over a range of activities and time. Ninety-three 177 Lu sources from the manufacturer were measured in the radionuclide calibrator over 2.5 years to evaluate its calibration accuracy and precision compared to the manufacturer's value. A NEMA 2012/IEC 2008 phantom was filled with a 177 Lu activity concentration sphere-to-background ratio of five. It was acquired with the SPECT/CT camera to determine the reconstruction parameters offering the best compromise between partial volume effect and signal-to-noise ratio. The calibration factor was computed accordingly. The calibration quality was monitored over 2.5 years with 33 phantom acquisitions with activities ranging from 7040 to 0.6 MBq. Home-made sources were used to calibrate the well counter. Its reliability was evaluated with activities ranging from 150 to 0.2 kBq measured 34 times over 2.5 years., Results: For the radionuclide calibrator, median [interquartile range] for the error on activity measurement was -0.99 [1.31] %. The optimal SPECT reconstruction parameters were obtained with 16 iterations, 16 subsets and a 12-mm Gaussian post-filter. The calibration factor was 9.87 cps/MBq with an error of -1.05 [2.12] %. The well counter was calibrated with 31.5 cps/kBq, and the error was evaluated to -12.89 [16.55] %., Conclusions: The accuracy and the precision of activity quantification using dedicated quality control were found to be sufficient for use in dosimetry implemented in clinical routine. The proposed methodology could be implemented in other centres to obtain reproducible 177 Lu-based treatment dosimetry.

The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32  ×  32 mm 2 monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier arrays. The six considered designs differ in axial lengths (27.2 cm, 54.4 cm and 102 cm) and crystal thicknesses (22 mm and 11 mm). The simulations are based on measured detector response data. We study two possible detector arrangements: 22 mm-thick crystals with dual-sided readout and 11 mm-thick crystals with back-sided readout. The six designs are simulated by means of the GEANT4 application for tomographic emission software, using the measured spatial, energy and time response of the monolithic scintillator detectors as input. The performance of the six designs is compared on the basis of four studies: (1) spatial resolution; (2) NEMA NU2-2012 sensitivity and scatter fraction (SF) tests; (3) non-prewhitening signal-to-noise ratio observer study; and (4) receiver operating characteristics analysis. Based on the results, two designs are identified as cost-effective solutions for fast and efficient imaging of children: one with 54.4 cm axial field-of-view (FOV) and 22 mm-thick crystals, and another one with 102 cm axial FOV and 11 cm-thick crystals. The first one has a higher center point sensitivity than the second one, but requires dual-sided readout. The second design has the advantage of allowing a whole-body scan in a single bed position acquisition. Both designs have the potential to provide an excellent spatial resolution (∼2 mm) and an ultra-high sensitivity (>100 cps [Formula: see text]).

Targeted radionuclide therapy (TRT) is a promising technique for cancer therapy. However, in order to deliver the required dose to the tumor, minimize potential toxicity in normal organs, as well as monitor therapeutic effects, it is important to assess the individualized internal dosimetry based on patient-specific data. Advanced imaging techniques, especially radionuclide imaging, can be used to determine the spatial distribution of administered tracers for calculating the organ-absorbed dose. While planar scintigraphy is still the mainstream imaging method, SPECT, PET and bremsstrahlung imaging have promising properties to improve accuracy in quantification. This article reviews the basic principles of TRT and discusses the latest development in radionuclide imaging techniques for different theranostic agents, with emphasis on their potential to improve personalized TRT dosimetry., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LE pow and (ii) LE conn respectively). By comparing LE pow and LE conn , we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LE pow  = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LE pow  ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LE conn  = 0 mm and 94% for LE conn  ≤ 10 mm. FC provided a significant added value to ESI alone ( p  < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.

Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity analysis estimated the SOZ consistently closer to the simulated EZ/RZ than localization based on maximal power. Performance, however, decreased when 128 electrodes or less were used, especially in the realistic data. The results show the added value of functional connectivity analysis for SOZ localization, when the EEG is obtained with a high-density setup. Next to this, the method can potentially be used as objective tool in clinical settings.

We investigated the influence of different skull modeling approaches on EEG source imaging (ESI), using data of six patients with refractory temporal lobe epilepsy who later underwent successful epilepsy surgery. Four realistic head models with different skull compartments, based on finite difference methods, were constructed for each patient: (i) Three models had skulls with compact and spongy bone compartments as well as air-filled cavities, segmented from either computed tomography (CT), magnetic resonance imaging (MRI) or a CT-template and (ii) one model included a MRI-based skull with a single compact bone compartment. In all patients we performed ESI of single and averaged spikes marked in the clinical 27-channel EEG by the epileptologist. To analyze at which time point the dipole estimations were closer to the resected zone, ESI was performed at two time instants: the half-rising phase and peak of the spike. The estimated sources for each model were validated against the resected area, as indicated by the postoperative MRI. Our results showed that single spike analysis was highly influenced by the signal-to-noise ratio (SNR), yielding estimations with smaller distances to the resected volume at the peak of the spike. Although averaging reduced the SNR effects, it did not always result in dipole estimations lying closer to the resection. The proposed skull modeling approaches did not lead to significant differences in the localization of the irritative zone from clinical EEG data with low spatial sampling density. Furthermore, we showed that a simple skull model (MRI-based) resulted in similar accuracy in dipole estimation compared to more complex head models (based on CT- or CT-template). Therefore, all the considered head models can be used in the presurgical evaluation of patients with temporal lobe epilepsy to localize the irritative zone from low-density clinical EEG recordings.

The mouse model is widely used in a vast range of biomedical and preclinical studies. Thanks to the ability to detect and quantify biological processes at the molecular level in vivo, PET has become a well-established tool in these investigations. However, the need to visualize and quantify radiopharmaceuticals in anatomic structures of millimetre or less requires good spatial resolution and sensitivity from small-animal PET imaging systems.In previous work we have presented a proof-of-concept of a dedicated high-resolution small-animal PET scanner based on thin monolithic scintillator crystals and Digital Photon Counter photosensor. The combination of thin monolithic crystals and MLE positioning algorithm resulted in an excellent spatial resolution of 0.7 mm uniform in the entire field of view (FOV). However, the limitation of the scanner was its low sensitivity due to small thickness of the lutetium-yttrium oxyorthosilicate (LYSO) crystals (2 mm).Here we present an improved detector design for a small-animal PET system that simultaneously achieves higher sensitivity and sustains a sub-millimetre spatial resolution. The proposed detector consists of a 5 mm thick monolithic LYSO crystal optically coupled to a Digital Photon Counter. Mean nearest neighbour (MNN) positioning combined with depth of interaction (DOI) decoding was employed to achieve sub-millimetre spatial resolution. To evaluate detector performance the intrinsic spatial resolution, energy resolution and coincidence resolving time (CRT) were measured. The average intrinsic spatial resolution of the detector was 0.60 mm full-width-at-half-maximum (FWHM). A DOI resolution of 1.66 mm was achieved. The energy resolution was 23% FWHM at 511 keV and CRT of 529 ps were measured. The improved detector design overcomes the sensitivity limitation of the previous design by increasing the nominal sensitivity of the detector block and retains an excellent intrinsic spatial resolution.

Electrical source imaging of interictal spikes observed in EEG recordings of patients with refractory epilepsy provides useful information to localize the epileptogenic focus during the presurgical evaluation. However, the selection of the time points or time epochs of the spikes in order to estimate the origin of the activity remains a challenge. In this study, we consider a Bayesian EEG source imaging technique for distributed sources, i.e. the multiple volumetric sparse priors (MSVP) approach. The approach allows to estimate the time courses of the intensity of the sources corresponding with a specific time epoch of the spike. Based on presurgical averaged interictal spikes in six patients who were successfully treated with surgery, we estimated the time courses of the source intensities for three different time epochs: (i) an epoch starting 50 ms before the spike peak and ending at 50% of the spike peak during the rising phase of the spike, (ii) an epoch starting 50 ms before the spike peak and ending at the spike peak and (iii) an epoch containing the full spike time period starting 50 ms before the spike peak and ending 230 ms after the spike peak. To identify the primary source of the spike activity, the source with the maximum energy from 50 ms before the spike peak till 50% of the spike peak was subsequently selected for each of the time windows. For comparison, the activity at the spike peaks and at 50% of the peaks was localized using the LORETA inversion technique and an ECD approach. Both patient-specific spherical forward models and patient-specific 5-layered finite difference models were considered to evaluate the influence of the forward model. Based on the resected zones in each of the patients, extracted from post-operative MR images, we compared the distances to the resection border of the estimated activity. Using the spherical models, the distances to the resection border for the MSVP approach and each of the different time epochs were in the same range as the LORETA and ECD techniques. We found distances smaller than 23 mm, with robust results for all the patients. For the finite difference models, we found that the distances to the resection border for the MSVP inversions of the full spike time epochs were generally smaller compared to the MSVP inversions of the time epochs before the spike peak. The results also suggest that the inversions using the finite difference models resulted in slightly smaller distances to the resection border compared to the spherical models. The results we obtained are promising because the MSVP approach allows to study the network of the estimated source-intensities and allows to characterize the spatial extent of the underlying sources.

Small-animal imaging has become an important technique for the development of new radiotracers, drugs and therapies. Many laboratories have now a combination of different small-animal imaging systems, which are being used by biologists, pharmacists, medical doctors and physicists. The aim of this paper is to give an overview of the important factors in the design of a small animal, nuclear medicine and imaging experiment. Different experts summarize one specific aspect important for a good design of a small-animal experiment.

Parallel-hole SPECT collimators have traditionally been manufactured by stacking sheets of lead foil or by casting. These techniques significantly restrict our options in terms of collimator geometry. However, recent developments in metal additive manufacturing are making novel collimator designs possible, giving rise to new opportunities in SPECT imaging. In this paper we propose an innovative type of collimator for stationary SPECT, using parallel-holes whose collimation direction depends on their axial position. Its main advantage compared to current stationary SPECT systems (which are based on pinholes) is that, using only axial bed translations, we can achieve complete angular sampling of an increased portion of the transaxial area of the collimator bore. This allows the system to be much more compact than current stationary SPECT systems that image objects of the same size. We describe three possible designs, for full-body, brain and small-animal imaging, respectively, and test their feasibility using simulations. The system modeling method is validated against realistic Monte Carlo simulations, and then used in the evaluation of the systems' performances and reconstructions. The simulations show that the system is able to reconstruct objects occupying the predicted field of view ([Formula: see text] of the transaxial area of the bore) without sampling artifacts. In particular, we perform reconstructions from noisy projection data obtained for an activity and scanning time similar to standard protocols for the three applications, and the resulting images indicate the possibility of using the proposed systems in practice.

Purpose: Brain single photon emission computed tomography (SPECT) imaging is an important clinical tool, with unique tracers for studying neurological diseases. Nowadays, most commercial SPECT systems are combined with x-ray computed tomography (CT) in so-called SPECT/CT systems to obtain an anatomical background for the functional information. However, while CT images have a high spatial resolution, they have a low soft-tissue contrast, which is an important disadvantage for brain imaging. Magnetic resonance imaging (MRI), on the other hand, has a very high soft-tissue contrast and does not involve extra ionizing radiation. Therefore, the authors designed a brain SPECT insert that can operate inside a clinical MRI., Methods: The authors designed and simulated a compact stationary multipinhole SPECT insert based on digital silicon photomultiplier detector modules, which have shown to be MR-compatible and have an excellent intrinsic resolution (0.5 mm) when combined with a monolithic 2 mm thick LYSO crystal. First, the authors optimized the different parameters of the SPECT system to maximize sensitivity for a given target resolution of 7.2 mm in the center of the field-of-view, given the spatial constraints of the MR system. Second, the authors performed noiseless simulations of two multipinhole configurations to evaluate sampling and reconstructed resolution. Finally, the authors performed Monte Carlo simulations and compared the SPECT insert with a clinical system with ultrahigh-resolution (UHR) fan beam collimators, based on contrast-to-noise ratio and a visual comparison of a Hoffman phantom with a 9 mm cold lesion., Results: The optimization resulted in a stationary multipinhole system with a collimator radius of 150.2 mm and a detector radius of 172.67 mm, which corresponds to four rings of 34 diSPM detector modules. This allows the authors to include eight rings of 24 pinholes, which results in a system volume sensitivity of 395 cps/MBq. Noiseless simulations show sufficient axial sampling (in a Defrise phantom) and a reconstructed resolution of 5.0 mm (in a cold-rod phantom). The authors compared the 24-pinhole setup with a 34-pinhole system (with the same detector radius but a collimator radius of 156.63 mm) and found that 34 pinholes result in better uniformity but a worse reconstruction of the cold-rod phantom. The authors also compared the 24-pinhole system with a clinical triple-head UHR fan beam system based on contrast-to-noise ratio and found that the 24-pinhole setup performs better for the 6 mm hot and the 16 mm cold lesions and worse for the 8 and 10 mm hot lesions. Finally, the authors reconstructed noisy projection data of a Hoffman phantom with a 9 mm cold lesion and found that the lesion was slightly better visible on the multipinhole image compared to the fan beam image., Conclusions: The authors have optimized a stationary multipinhole SPECT insert for MRI and showed the feasibility of doing brain SPECT imaging inside a MRI with an image quality similar to the best clinical SPECT systems available.

The accurate determination of the local impulse response and the covariance in voxels from penalized maximum likelihood reconstructed images requires performing reconstructions from many noise realizations of the projection data. As this is usually a very time-consuming process, efficient analytical approximations based on the Fisher information matrix (FIM) have been extensively used in PET and SPECT to estimate these quantities. For 3D imaging, however, additional approximations need to be made to the FIM in order to speed up the calculations. The most common approach is to use the local shift-invariant (LSI) approximation of the FIM, but this assumes specific conditions which are not always necessarily valid. In this paper we take a single-pinhole SPECT system and compare the accuracy of the LSI approximation against two other methods that have been more recently put forward: the non-uniform object-space pixelation (NUOP) and the subsampled FIM. These methods do not assume such restrictive conditions while still increasing the speed of the calculations considerably. Our results indicate that in pinhole SPECT the NUOP and subsampled FIM approaches could be more reliable than the LSI approximation, especially when a high accuracy is required.