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Abstract Background Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. Methods For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens’ Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. Results With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ( $$\sim$$ ∼ 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. Conclusion Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Abstract Purpose In living organisms, the positron-electron annihilation (occurring during the PET imaging) proceeds in about 30% via creation of a metastable ortho-positronium atom. In the tissue, due to the pick-off and conversion processes, over 98% of ortho-positronia annihilate into two 511 keV photons. In this article, we assess the feasibility for reconstruction of the mean ortho-positronium lifetime image based on annihilations into two photons. The main objectives of this work include the (i) estimation of the sensitivity of the total-body PET scanners for the ortho-positronium mean lifetime imaging using 2γ annihilations and (ii) estimation of the spatial and time resolution of the ortho-positronium image as a function of the coincidence resolving time (CRT) of the scanner. Methods Simulations are conducted assuming that radiopharmaceutical is labeled with 44 S c isotope emitting one positron and one prompt gamma. The image is reconstructed on the basis of triple coincidence events. The ortho-positronium lifetime spectrum is determined for each voxel of the image. Calculations were performed for cases of total-body detectors build of (i) LYSO scintillators as used in the EXPLORER PET and (ii) plastic scintillators as anticipated for the cost-effective total-body J-PET scanner. To assess the spatial and time resolution, the four cases were considered assuming that CRT is equal to 500 ps, 140 ps, 50 ps, and 10 ps. Results The estimated total-body PET sensitivity for the registration and selection of image forming triple coincidences (2γ+γ prompt) is larger by a factor of 13.5 (for LYSO PET) and by factor of 5.2 (for plastic PET) with respect to the sensitivity for the standard 2γ imaging by LYSO PET scanners with AFOV = 20 cm. The spatial resolution of the ortho-positronium image is comparable with the resolution achievable when using TOF-FBP algorithms already for CRT = 50 ps. For the 20-min scan, the resolution better than 20 ps is expected for the mean ortho-positronium lifetime image determination. Conclusions Ortho-positronium mean lifetime imaging based on the annihilations into two photons and prompt gamma is shown to be feasible with the advent of the high sensitivity total-body PET systems and time resolution of the order of tens of picoseconds.

Abstract Purpose Q.Clear is a block sequential regularized expectation maximization (BSREM) penalized-likelihood reconstruction algorithm for PET. It tries to improve image quality by controlling noise amplification during image reconstruction. In this study, the noise properties of this BSREM were compared to the ordered-subset expectation maximization (OSEM) algorithm for both phantom and patient data acquired on a state-of-the-art PET/CT. Methods The NEMA IQ phantom and a whole-body patient study were acquired on a GE DMI 3-rings system in list mode and different datasets with varying noise levels were generated. Phantom data was evaluated using four different contrast ratios. These were reconstructed using BSREM with different β-factors of 300–3000 and with a clinical setting used for OSEM including point spread function (PSF) and time-of-flight (TOF) information. Contrast recovery (CR), background noise levels (coefficient of variation, COV), and contrast-to-noise ratio (CNR) were used to determine the performance in the phantom data. Findings based on the phantom data were compared with clinical data. For the patient study, the SUV ratio, metabolic active tumor volumes (MATVs), and the signal-to-noise ratio (SNR) were evaluated using the liver as the background region. Results Based on the phantom data for the same count statistics, BSREM resulted in higher CR and CNR and lower COV than OSEM. The CR of OSEM matches to the CR of BSREM with β = 750 at high count statistics for 8:1. A similar trend was observed for the ratios 6:1 and 4:1. A dependence on sphere size, counting statistics, and contrast ratio was confirmed by the CNR of the ratio 2:1. BSREM with β = 750 for 2.5 and 1.0 min acquisition has comparable COV to the 10 and 5.0 min acquisitions using OSEM. This resulted in a noise reduction by a factor of 2–4 when using BSREM instead of OSEM. For the patient data, a similar trend was observed, and SNR was reduced by at least a factor of 2 while preserving contrast. Conclusion The BSREM reconstruction algorithm allowed a noise reduction without a loss of contrast by a factor of 2–4 compared to OSEM reconstructions for all data evaluated. This reduction can be used to lower the injected dose or shorten the acquisition time.

Abstract Background Fully integrated PET/MR systems are being used frequently in clinical research and routine. National Electrical Manufacturers Association (NEMA) characterization of these systems is generally done with 18F which is clinically the most relevant PET isotope. However, other PET isotopes, such as 68Ga and 90Y, are gaining clinical importance as they are of specific interest for oncological applications and for follow-up of 90Y-based radionuclide therapy. These isotopes have a complex decay scheme with a variety of prompt gammas in coincidence. 68Ga and 90Y have higher positron energy and, because of the larger positron range, there may be interference with the magnetic field of the MR compared to 18F. Therefore, it is relevant to determine the performance of PET/MR for these clinically relevant and commercially available isotopes. Methods NEMA NU 2–2007 performance measurements were performed for characterizing the spatial resolution, sensitivity, image quality, and the accuracy of attenuation and scatter corrections for 18F, 68Ga, and 90Y. Scatter fraction and noise equivalent count rate (NECR) tests were performed using 18F and 68Ga. All phantom data were acquired on the GE Signa integrated PET/MR system, installed in UZ Leuven, Belgium. Results 18F, 68Ga, and 90Y NEMA performance tests resulted in substantially different system characteristics. In comparison with 18F, the spatial resolution is about 1 mm larger in the axial direction for 68Ga and no significative effect was found for 90Y. The impact of this lower resolution is also visible in the recovery coefficients of the smallest spheres of 68Ga in image quality measurements, where clearly lower values are obtained. For 90Y, the low number of counts leads to a large variability in the image quality measurements. The primary factor for the sensitivity change is the scale factor related to the positron emission fraction. There is also an impact on the peak NECR, which is lower for 68Ga than for 18F and appears at higher activities. Conclusions The system performance of GE Signa integrated PET/MR was substantially different, in terms of NEMA spatial resolution, image quality, and NECR for 68Ga and 90Y compared to 18F. But these differences are compensated by the PET/MR scanner technologies and reconstructions methods.

Copulas have already proven their flexibility in rainfall modelling. Yet, their use is generally restricted to the description of bivariate dependence. Recently, vine copulas have been introduced, allowing multi-dimensional dependence structures to be described on the basis of a stage by stage mixing of 2-dimensional copulas. This paper explores the use of such vine copulas in order to incorporate all relevant dependences between the storm variables of interest. On the basis of such fitted vine copulas, an external storm structure is modelled. An internal storm structure is superimposed based on Huff curves, such that a continuous time series of rainfall is generated. The performance of the rainfall model is evaluated through a statistical comparison between an ensemble of synthetical rainfall series and the observed rainfall series and through the comparison of the annual maxima.

Of all natural disasters, the economic and environmental consequences of droughts are among the highest because of their longevity and widespread spatial extent. Because of their extreme behaviour, studying droughts generally requires long time series of historical climate data. Rainfall is a very important variable for calculating drought statistics, for quantifying historical droughts or for assessing the impact on other hydrological (e.g. water stage in rivers) or agricultural (e.g. irrigation requirements) variables. Unfortunately, time series of historical observations are often too short for such assessments. To circumvent this, one may rely on the synthetic rainfall time series from stochastic point process rainfall models, such as Bartlett–Lewis models. The present study investigates whether drought statistics are preserved when simulating rainfall with Bartlett–Lewis models. Therefore, a 105 yr 10 min rainfall time series obtained at Uccle, Belgium is used as a test case. First, drought events were identified on the basis of the Effective Drought Index (EDI), and each event was characterized by two variables, i.e. drought duration (D) and drought severity (S). As both parameters are interdependent, a multivariate distribution function, which makes use of a copula, was fitted. Based on the copula, four types of drought return periods are calculated for observed as well as simulated droughts and are used to evaluate the ability of the rainfall models to simulate drought events with the appropriate characteristics. Overall, all Bartlett–Lewis model types studied fail to preserve extreme drought statistics, which is attributed to the model structure and to the model stationarity caused by maintaining the same parameter set during the whole simulation period.

Most of the hydrological and hydraulic studies refer to the notion of a return period to quantify design variables. When dealing with multiple design variables, the well-known univariate statistical analysis is no longer satisfactory, and several issues challenge the practitioner. How should one incorporate the dependence between variables? How should a multivariate return period be defined and applied in order to yield a proper design event? In this study an overview of the state of the art for estimating multivariate design events is given and the different approaches are compared. The construction of multivariate distribution functions is done through the use of copulas, given their practicality in multivariate frequency analyses and their ability to model numerous types of dependence structures in a flexible way. A synthetic case study is used to generate a large data set of simulated discharges that is used for illustrating the effect of different modelling choices on the design events. Based on different uni- and multivariate approaches, the design hydrograph characteristics of a 3-D phenomenon composed of annual maximum peak discharge, its volume, and duration are derived. These approaches are based on regression analysis, bivariate conditional distributions, bivariate joint distributions and Kendall distribution functions, highlighting theoretical and practical issues of multivariate frequency analysis. Also an ensemble-based approach is presented. For a given design return period, the approach chosen clearly affects the calculated design event, and much attention should be given to the choice of the approach used as this depends on the real-world problem at hand.

The calibration of stochastic point process rainfall models, such as of the Bartlett-Lewis type, suffers from the presence of multiple local minima which local search algorithms usually fail to avoid. To meet this shortcoming, four relatively new global optimization methods are presented and tested for their ability to calibrate the Modified Bartlett-Lewis Model. The list of tested methods consists of: the Downhill Simplex Method, Simplex-Simulated Annealing, Particle Swarm Optimization and Shuffled Complex Evolution. The parameters of these algorithms are first optimized to ensure optimal performance, after which they are used for calibration of the Modified Bartlett-Lewis model. Furthermore, this paper addresses the choice of weights in the objective function. Three alternative weighing methods are compared to determine whether or not simulation results (obtained after calibration with the best optimization method) are influenced by the choice of weights.

Fine-scale rainfall data is important for many hydrological applications. However, often the only data available is at a coarse scale. To bridge this gap in resolution, stochastic disaggregation methods can be used. Such methods generally assume that the distribution of the field is stationary, i.e. the distribution for the entire (fine-scale) field is the same as the distribution of a smaller region within the field. This assumption is generally incorrect and we provide a proof of concept of a method to estimate the distribution of a smaller region. In this method, a copula is used to construct a bivariate distribution describing the relation between the scales. This distribution is then used to estimate the distribution of the fine-scale rainfall within a single coarse-scale pixel, by conditioning on the coarse-scale rainfall depth.

The use of design storms can be very useful in many hydrological and hydraulic practices. In this study, the concept of a copula-based secondary return period in combination with the concept of mass curves is used to generate point-scale design storms. The analysis is based on storms selected from the 105 year rainfall time series with a 10 min resolution, measured at Uccle, Belgium. In first instance, bivariate copulas and secondary return periods are explained, together with a focus on which couple of storm variables is of highest interest for the analysis and a discussion of how the results might be affected by the goodness-of-fit of the copula. Subsequently, the fitted copula is used to sample storms with a predefined secondary return period for which characteristic variables such as storm duration and total storm depth can be derived. In order to construct design storms with a realistic storm structure, mass curves of 1st, 2nd, 3rd and 4th quartile storms are developed. An analysis shows that the assumption of independence between the secondary return period and the internal storm structure could be made. Based on the mass curves, a technique is developed to randomly generate an intrastorm structure. The coupling of both techniques eventually results in a methodology for stochastic design storm generation. Finally, its practical usefulness for design studies is illustrated based on the generation of a set of statistically identical design storm and rainfall-runoff modelling.

In this paper, a method for analysis and modeling of coplanartransmission interconnect lines that are placed on top ofsilicon-silicon oxide substrates is presented. The potential functionis expressed by series expansions in terms of solutions of the Laplaceequation for each homogeneous region of layered structure. Theexpansion coefficients of different series are related to each otherand to potentials applied to the conductors via boundary conditions. Inthe plane of conductors, boundary conditions are satisfied at Nddiscrete points with Nd being equal to the number of terms in theseries expansions. The resulting system of inhomogeneous linearequations is solved by matrix inversion. No iterations are required. Adiscussion of the calculated line admittance parameters as functions ofwidth of conductors, thickness of the layers, and frequency is given.The interconnect capacitance and conductance per unit length resultsare given and compared with those obtained using full wave solutions,and good agreement have been obtained in all the cases treated.

Today, new single photon emission computed tomography (SPECT) reconstruction techniques rely on accurate Monte Carlo (MC) simulations to optimize reconstructed images. However, existing MC scintillation camera models which usually include an accurate description of the collimator and crystal, lack correct implementation of the gamma camera's back compartments. In the case of dual isotope simultaneous acquisition (DISA), where backscattered photons from the highest energy isotope are detected in the imaging energy window of the second isotope, this approximation may induce simulation errors. Here, we investigate the influence of backscatter compartment modelling on the simulation accuracy of high-energy isotopes. Three models of a scintillation camera were simulated: a simple model (SM), composed only of a collimator and a NaI(Tl) crystal; an intermediate model (IM), adding a simplified description of the backscatter compartments to the previous model and a complete model (CM), accurately simulating the materials and geometries of the camera. The camera models were evaluated with point sources (67Ga, 99mTc, 111In, 123I, 131I and 18F) in air without a collimator, in air with a collimator and in water with a collimator. In the latter case, sensitivities and point-spread functions (PSFs) simulated in the photopeak window with the IM and CM are close to the measured values (error below 10.5%). In the backscatter energy window, however, the IM and CM overestimate the FWHM of the detected PSF by 52% and 23%, respectively, while the SM underestimates it by 34%. The backscatter peak fluence is also overestimated by 20% and 10% with the IM and CM, respectively, whereas it is underestimated by 60% with the SM. The results show that an accurate description of the backscatter compartments is required for SPECT simulations of high-energy isotopes (above 300 keV) when the backscatter energy window is of interest. [ABSTRACT FROM AUTHOR]

A PACS (Picture Archiving and Communication System) is a system that is able to store, exchange, display and manipulate images and associated diagnoses from any modality within a hospital in a timely and cost-effective way. Several developments, such as the DICOM standard, fast and convenient networking, and new storage solutions for large amounts of data, make the setup of such a PACS system possible. As the information acquired with various imaging modalities is then available and often complementary, it is desirable for the clinician to have a point-by-point spatial co-registration of images from different modalities in order to enable a synergistic use of the multimodality imaging of a patient for increased diagnostic accuracy. Various types of algorithms are available for the matching of medical images from the same or from different modalities. Co-registration algorithms based on voxel properties consist of a similarity or dissimilarity measure and an iterative or non-iterative method minimizing the dissimilarity or maximizing the similarity between the two images by a transformation of one image relative to the other. [ABSTRACT FROM AUTHOR]

Particle therapy is a highly conformal radiotherapy technique which reduces the dose deposited to the surrounding normal tissues. In order to fully exploit its advantages, treatment monitoring is necessary to minimize uncertainties related to the dose delivery. Up to now, the only clinically feasible technique for the monitoring of therapeutic irradiation with particle beams is Positron Emission Tomography (PET). In this work we have compared a Resistive Plate Chamber (RPC)-based PET scanner with a scintillation-crystal-based PET scanner for this application. In general, the main advantages of the RPC-PET system are its excellent timing resolution, low cost, and the possibility of building large area systems. We simulated a partial-ring scanner based on an RPC prototype under construction within the Fondazione per Adroterapia Oncologica (TERA). For comparison with the crystal-based PET scanner we have chosen the geometry of a commercially available PET scanner, the Philips Gemini TF. The coincidence time resolution used in the simulations takes into account the current achievable values as well as expected improvements of both technologies. Several scenarios (including patient data) have been simulated to evaluate the performance of different scanners. Initial results have shown that the low sensitivity of the RPC hampers its application to hadron-beam monitoring, which has an intrinsically low positron yield compared to diagnostic PET. In addition, for in-beam PET there is a further data loss due to the partial ring configuration. In order to improve the performance of the RPC-based scanner, an improved version of the RPC detector (modifying the thickness of the gas and glass layers), providing a larger sensitivity, has been simulated and compared with an axially extended version of the crystal-based device. The improved version of the RPC shows better performance than the prototype, but the extended version of the crystal-based PET outperforms all other options. [ABSTRACT FROM AUTHOR]

The majority of current whole-body PET scanners are based on pixelated scintillator arrays with a transverse pixel size of 4 mm. However, recent studies have shown that decreasing the pixel size to 2 mm can significantly improve image spatial resolution. In this study, the performance of Digital Photon Counter (DPC) from Philips Digital Photon Counting (PDPC) was evaluated to determine their potential for high-resolution whole-body time of flight (TOF) PET scanners. Two detector configurations were evaluated. First, the DPC3200-44-22 DPC array was coupled to a LYSO block of 15  ×  15 2  ×  2 × 22 mm3 pixels through a 1 mm thick light guide. Due to light sharing among the dies neighbour logic of the DPC was used. In a second setup the same DPC was coupled directly to a scalable 4  ×  4 LYSO matrix of 1.9  ×  1.9  ×  22 mm3 crystals with a dedicated reflector arrangement allowing for controlled light sharing patterns inside the matrix. With the first approach an average energy resolution of 14.5% and an average CRT of 376 ps were achieved. For the second configuration an average energy resolution of 11% and an average CRT of 295 ps were achieved. Our studies show that the DPC is a suitable photosensor for a high-resolution TOF-PET detector. The dedicated reflector arrangement allows one to achieve better performances than the light guide approach. The count loss, caused by dark counts, is overcome by fitting the matrix size to the size of DPC single die. [ABSTRACT FROM AUTHOR]

In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance.

Citric acid is the most important organic acid produced in tonnage and is extensively used in food and pharmaceutical industries. It is produced mainly by submerged fermentation using Aspergillus niger or Candida sp. from different sources of carbohydrates, such as molasses and starch based media. However, other fermentation techniques, e.g. solid state fermentation and surface fermentation, and alternative sources of carbon such as agro-industrial residues have been intensively studied showing great perspective to its production. This paper reviews recent developments on citric acid production by presenting a brief summary of the subject, describing micro-organisms, production techniques, and substrates, etc.O ácido cítrico é o ácido mais produzido em termos de tonagem e é extensivamente utilizado pelas indústrias alimentícia e farmacêutica. É produzido principalmente por fermentação submersa utilizando o fungo Aspergillus niger e leveduras do gênero Candida sp. à partir de diferentes fontes de carbono, como a glicose e meios à base de amido. No entanto, outras técnicas de fermentação, e.g. fermentação no estado sólido e em superfície, e fontes alternativas de carbono tem sido intensamente estudadas mostrando grande perspectivas para o processo. O presente trabalho apresenta um resumo dos últimos avanços sobre a produção do ácido cítrico, descrevendo de maneira sucinta os trabalhos mais recentes, descrevendo microrganismos, técnicas de produção e substratos empregados, etc.

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).)

Neutrophil cationic proteins (NCPs) are a group of granule antimicrobial and inflammatory proteins released by activated neutrophils. These proteins primarily function via their positively charged structure, which facilitates interactions with bacterial membranes and the formation of immunogenic DNA complexes, thereby contributing to the initiation of wound repair in injured skin. After analyzing the structural properties of secreted neutrophil granule proteins, we identified OLFM4 as the only negatively charged molecule that interferes with NCP oligomerization. Through this interference, OLFM4 can inhibit neutrophil-mediated bacterial killing and DNA complex-dependent activation of Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDCs) and neutrophils. While addition of exogenous OLFM4 blocks these processes, OLFM4 inhibition enhances neutrophil-dependent bacterial killing and DNA complex formation, ultimately leading to accelerated closure of skin wounds., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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: Ad26.RSV.preF-RSV preF protein showed 80·0% vaccine efficacy against respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in older adults during one RSV season. No RSV vaccines have shown three-season efficacy. We aimed to evaluate efficacy of Ad26.RSV.preF-RSV preF protein over three RSV seasons., Methods: CYPRESS was a randomised, double-blind, placebo-controlled, phase 2b study done at 40 US clinical research centres wherein adults aged 65 years or older were centrally randomly assigned 1:1 by computer algorithm to receive Ad26.RSV.preF-RSV preF protein or placebo (one intramuscular injection) on day 1. Investigators, participants, site personnel, and the sponsor were masked to vaccine allocation, except for individuals involved in preparation of study vaccinations. The primary endpoint (first occurrence of RSV-mediated LRTD meeting one of three case definitions) was previously reported. Here, the predefined exploratory endpoint of vaccine efficacy against RSV-positive LRTD was assessed in the per-protocol efficacy set (all participants randomly assigned and vaccinated without protocol deviations affecting efficacy) through season 1 and from day 365 until the end of season 3. Humoral and cellular immunogenicity was assessed in a subset of randomly assigned and vaccinated participants. The secondary endpoint of safety through the first RSV season was previously reported; follow-up for selected safety outcomes (fatal adverse events, adverse events leading to study discontinuation, serious adverse events, and vaccine-related serious adverse events) until study completion is reported here in all randomly assigned and vaccinated participants. This trial is registered with ClinicalTrials.gov, NCT03982199 and is complete., Findings: Of 6672 adults screened, 5782 participants (2891 each receiving vaccine or placebo) were enrolled and vaccinated between Aug 5 and Nov 13, 2019. The season 2 per-protocol efficacy set included 2124 vaccine recipients and 2126 placebo recipients (season 3: 864 and 881; across three seasons: 2795 and 2803, respectively). Vaccine efficacy against RSV LRTD was 76·1% (95% CI 26·9-94·2) over seasons 2 and 3 and 78·7% (57·3-90·4) across three seasons. For those in the immunogenicity subset (vaccine n=97; placebo n=98), immune responses remained above baseline for at least 1 year. Serious adverse events occurred in 47 (2·1%) and 12 (1·3%) vaccine recipients and 45 (2·1%) and 10 (1·1%) placebo recipients during seasons 2 and 3, respectively. No treatment-related serious or fatal adverse events were reported., Interpretation: Ad26.RSV.preF-RSV preF protein maintained high efficacy against RSV LRTD in older adults across three RSV seasons., Funding: Janssen Vaccines & Prevention., Competing Interests: Declaration of interests ARF has received institutional research grants from Janssen, Merck Sharp & Dohme, Pfizer, BioFire Diagnostics, Vaccine Company, Moderna, and CyanVac; consulting fees from Arrowhead Pharmaceuticals, GSK, and ADMA Biologics; payment or honoraria for lectures, presentations, or speakers bureaus from Sanofi Pasteur; and personal fees for serving on a data safety monitoring board from Novavax and for attending meetings or travel from GSK, Moderna, and Sanofi Pasteur. SV is an employee of Janssen Infectious Diseases. EKHC is an employee of Janssen Global Services, a subsidiary of Johnson & Johnson, and holds stock in Johnson & Johnson. TH, ARB, and CAC are former employees of Janssen Vaccines & Prevention. MD and EH are former employees of Janssen Vaccines & Prevention and hold stock in Johnson & Johnson. BC is a former employee of, and has patents pending with, Janssen Vaccines & Prevention and holds stock in Johnson & Johnson., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

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).)

Autoinflammation is a sterile inflammatory process resulting from increased neutrophil infiltration and overexpression of IL-1 cytokines. The factors that trigger these events are, however, poorly understood. By investigating pustular forms of psoriasis, we show that human neutrophils constitutively express IL-26 and abundantly release it from granular stores upon activation. In pustular psoriasis, neutrophil-derived IL-26 drives the pathogenic autoinflammation process by inducing the expression of IL-1 cytokines and chemokines that further recruit neutrophils. This occurs via activation of IL-26R in keratinocytes and via the formation of complexes between IL-26 and microbiota DNA, which trigger TLR9 activation of neutrophils. Thus our findings identify neutrophils as an important source of IL-26 and point to IL-26 as the key link between neutrophils and a self-sustaining autoinflammation loop in pustular psoriasis., (© 2024 Baldo et al.)

Anaphylactic reactions at the time of chimeric antigen receptor T (CAR-T) cell infusion are adverse events that have not been reported in pivotal clinical trials or in real-world series. We report the case of patient with severe anaphylaxis with cardiac arrest after tisagenlecleucel injection for Diffuse Large B cell Lymphoma, who recovered after resuscitation and intensive care treatment; we also conducted a Food and Drug Administration Adverse Event Reporting System database analysis and found several cases of severe anaphlyaxis after CAR-T cell injection. Although not reported in pivotal CAR-T cell studies, anaphylaxis can occur after CAR-T cell injection, highlighting the need to include anaphylaxis as a possible side effect in future studies., Competing Interests: Yves Chalandon: advisory board from MSD; BMS, Novartis, Roche, Jazz, Gilead, Amgen, Incyte, Astra Zeneca, and Servier. Travel expenses to scientific meetings supported by MSD, Roche Gilead Amgen Incyte Abbvie, Janssen, Astra‐Zeneca, Jazz, and Sanofi. Federico Simonetta: institutional consulting fees from BMS/Celgene, Incyte, and Kite/Gilead; speaker fees from Kite/Gilead, Incyte; travel support from Kite/Gilead, Novartis, AstraZeneca, Neovii, and Janssen; research funding from Kite/Gilead, Novartis, and BMS/Celgene., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

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.)

Although CO2 field-flooding was first used during cardiac surgery more than 60 years ago, its efficacy is still disputed. The invisible nature of the gas and the difficulty in determining the "safe" quantity to protect the patient are two of the main obstacles to overcome for its validation. Moreover, CO2 concentration in the chest cavity is highly sensitive to procedural aspects, such suction and hand movements. Based on our review of the existing literature, we identified four major factors that influence the intra-cavity CO2 concentration during open-heart surgery: type of delivery device (diffuser), delivery CO2 flow rate, diffuser position around the wound cavity, and its orientation inside the cavity. In this initial study, only steady state conditions were considered to establish a basic understanding on the effect of the four above-mentioned factors. Transient factors, such as suction or hand movements, will be reported separately., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Puthettu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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).)

Background: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity., Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3)., Results: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively)., Conclusions: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.)., (Copyright © 2023 Massachusetts Medical Society.)

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: External cardiac assist devices are based on a promising and simple concept for treating heart failure, but they are surprisingly difficult to design. Thus, a structured approach combining experiments with computer-based optimization is essential. The latter provides the motivation for the work presented in this paper., Methods: We present a computational modeling framework for realistic representation of the heart's tissue structure, electrophysiology and actuation. The passive heart tissue is described by a nonlinear anisotropic material law, considering fiber and sheetlet directions. For muscle contraction, an orthotropic active-strain model is employed, initiated by a periodically propagating electrical potential. The model allows for boundary conditions at the epicardium accounting for external assist devices, and it is coupled to a circulation network providing appropriate pressure boundary conditions inside the ventricles., Results: Simulated results from an unsupported healthy and a pathological heart model are presented and reproduce accurate deformations compared to phenomenological measurements. Moreover, cardiac output and ventricular pressure signals are in good agreement too. By investigating the impact of applying an exemplary external actuation to the pathological heart model, it shows that cardiac patches can restore a healthy blood flow., Conclusion: We demonstrate that the devised computational modeling framework is capable of predicting characteristic trends (e.g. apex shortening, wall thickening and apex twisting) of a healthy heart, and that it can be used to study pathological hearts and external activation thereof., (© 2022. The Author(s).)

Lung cancer is the most prevalent cancer worldwide. Despite advances in surgery and immune-chemotherapy, the therapeutic outcome remains poor. In recent years, the anticancer properties of natural compounds, along with their low toxic side effects, have attracted the interest of researchers. Resveratrol (RSV) and many of its derivatives received particular attention for their beneficial bioactivity. Here we studied the activity of RSV and of its analogue 4,4'-dihydroxystilbene (DHS) in C57BL/6J mice bearing cancers resulting from Lung Lewis Carcinoma (LLC) cell implantation, considering tumour mass weight, angiogenesis, cell proliferation and death, autophagy, as well as characterization of their immune microenvironment, including infiltrating cancer-associated fibroblasts (CAFs). C57BL/6J mice started treatment with RSV or DHS, solubilised in drinking water, one week before LLC implantation, and continued for 21 days, at the end of which they were sacrificed, and the tumour masses collected. Histology was performed according to standard procedures; angiogenesis, cell proliferation and death, autophagy, infiltrating-immune cells, macrophages and fibroblasts were assessed by immunodetection assays. Both stilbenic compounds were able to contrast the tumour growth by increasing apoptosis and autophagy in LLC tumour masses. Additionally, they contrasted the tumour-permissive microenvironment by limiting the infiltration of tumour-associated immune-cells and, more importantly, by counteracting CAF maturation. Therefore, both stilbenes could be employed to synergise with conventional oncotherapies to limit the contribution of stromal cells in tumour growth.

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.)

Background: There is no established technique for managing large thrombus burden (LTB) in patients with acute coronary syndrome (ACS)., Aims: The aim of this study was to assess the safety and efficacy of the NeVa (Vesalio) mechanical thrombectomy device (MTD) in ACS patients with LTB., Methods: Consecutive patients with ACS and LTB were treated with the NeVa MTD as the primary vessel recanalisation and thrombus removal modality, followed by conventional intervention. We further developed a bench model and applied to a subset of patients, a vacuum-assisted aspiration technique, exploiting 6 Fr-compatible conventional guiding catheter extensions, as an adjudicative manoeuvre to the use of stent-based MTD. A core laboratory reviewed the angiographic images for procedural complications, Thrombolysis In Myocardial Infarction (TIMI) flow, myocardial blush grade (MBG) and TIMI thrombus grade (TTG)., Results: Between November 2019 and March 2021, 61 patients underwent thrombectomy with the NeVa device. Non-flow limiting and reversible coronary spasm occurred in 14 (23%) patients. One patient (#10) suffered from side branch embolisation, which was successfully treated with the NeVa, triggering the development of a vacuum-assisted aspiration technique in a bench model, which was then applied to the subsequent 51 patients. No other device-related complications occurred. After NeVa use, TIMI flow <3 decreased from 68.3% at baseline to 10.3% (p<0.001), MBG <2 from 65% to 27.6% (p<0.001), TTG ≥3 from 96.7% to 43.2% (p<0.001), respectively., Conclusions: In patients with LTB, the NeVa MTD was safe and associated with high rates of vessel recanalisation and thrombus removal. The concomitant use of vacuum-assisted aspiration has potential to improve the effectiveness and safety of the technique.

Objective: Space limitations during minimally invasive cardiac surgery impede consistent use of CO 2 field-flooding. We compared different gas delivery methods, flow rates and the effect of patient inclination., Methods: A gastight model of MICS surgery with internal organs and right thoracotomy wound was created from a mannequin and equipped with a CO 2 concentration sensor in the left ventricle. Maximum achievable CO 2 concentration was compared for gas delivery via three commercial CO 2 diffusors (CarbonMini, Temed, Andocor) and also via a trocar with side port. Gas flow rates of 1, 3, 5 and 8 L per minute were tested. The model was placed either in supine position or with 20° oblique tilt. A simplified transparent model was also created and placed in an optical test bench to evaluate the gas cloud motions via real-time visualization., Results: The trocar consistently achieved higher CO 2 concentrations inside the left ventricle. At 1 l/min, approximately 2.5 min were needed to fill the supine model to its maximum CO 2 concentration, which was limited to a range of 48-82% in the left ventricle. At higher flow rates, filling time and concentration were significantly improved. In a tilted model, all devices and all flow rates generated on average 99% CO 2 in the ventricle. Imaging revealed constant gas exchange via the main incision, with CO 2 outflow via bottom and air inflow via the top of the incision., Conclusions: CO 2 field flooding in minimally invasive cardiac surgery is highly effective if the patient is tilted. Else a flow rate of 5 l/min is recommended to achieve the same protection., (© 2022. The Author(s).)

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.)

Air emboli are reported to enter the cardiovascular system during cardiac surgery despite air-bubble filters in the arterial line of the cardiopulmonary bypass (CPB). A potential association with stroke, covert cerebral insults and cognitive decline after cardiac surgery has been hypothesized. Although most of the previous studies failed to prove it, this hypothesis cannot be rejected because the situation in the operating room (OR) is multifactorial and complex. Therefore, rigorous and standardized protocols are needed to investigate sources, patterns, as well as effective quantity and volume of air embolism.  We hereby present our protocol in detail for systematic data collection as a standard quality control measure at our center, where air bubbles in the cardiopulmonary bypass circuit are measured by a commercial bubble counter. We also show a preview of the type of information that can be obtained for future analysis. The eventual aim is to determine a potential association between air emboli and adverse postoperative outcomes, as well as to identify major sources of air bubbles generation and in the long run to find effective prevention strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Puthettu et al.)

Carbon dioxide (CO 2 ) field-flooding during cardiac surgery is a prevention technique to avoid blood-air contact and subsequent embolization. Although it was first used more than 60 years ago, there is still some perplexity around its efficacy, mainly because the gas is invisible and air embolization is difficult to quantify. An accurate assessment of field-flooding can, therefore, best be performed in models where various methods can be tried in a controlled environment and evaluated with industrial-grade sensors. Multiple options are available for anatomically correct models that reproduce a sternotomy situation, but models for minimally invasive cardiac surgery are expensive and normally meant for training of surgical techniques where only the top side of the model is important. We created a low-cost and "home-made" gastight mini-thoracotomy model with internal organs and left atrial incision to investigate CO 2 insufflation in a simulated minimally invasive mitral valve surgery. The model was validated with CO 2 field-flooding tests with a commercial diffuser, while three sensors continuously registered the local concentration of CO 2 gas., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Puthettu et al.)

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.)