Clinical PET scanners have long been explored for preclinical imaging, but limited spatial resolution and sensitivity have restricted their use for preclinical studies. The recent availability of total-body (TB) PET/CT scanners with extended axial fields of view (FOVs) has largely overcome sensitivity limitations, enabling potential new opportunities for small-animal imaging. This study evaluated the feasibility and performance of the Biograph Vision Quadra TB-PET/CT for rodent imaging compared to the dedicated small-animal PET scanner Inveon DPET. Recovery coefficients (RC), image noise, and optimum image reconstruction parameters were assessed using the preclinical NEMA NU 4–2008 image quality phantom and a sub-cohort of three anesthetized mice as a proof-of-concept demonstrating the feasibility of the setup. In vivo quantification accuracy was evaluated by scanning nine frozen mice simultaneously in three different arrangements with the Quadra compared with individual scans at the Inveon. To ensure comparability, all mice were snap-frozen after 1 h uptake of [1⁸F]FDG, scanned sequentially and individually at the Inveon (90 min p.i.), and subsequently scanned at the Quadra with decay-corrected acquisition times. SUVmean and SUVmax values were determined for liver, muscle and brain regions on both systems. To evaluate potential position-dependent effects within the extended axial FOV, a single frozen mouse was scanned at multiple positions. Phantom rods ≥ 2 mm could be resolved with the Quadra, showing a comparable RC for larger structures, e.g. for the 5 mm rod of 1.17 compared to 1.09 (Inveon) when using point-spread-function modeling, whilst having lower noise of 5.1

The high sensitivity and axial coverage of large axial field of view (LAFOV) PET scanners have an unmet potential for total-body PET research. Despite these technological advances, inherent challenges to PET scans such as patient motion persist. To provide simulation-derived ground truth information, we developed a digital replica of the Biograph Vision Quadra LAFOV PET/CT scanner closely mimicking real event processing and image reconstruction. The framework uses a GATE model in combination with vendor-specific software prototypes for event processing and image reconstruction (e7 tools, Siemens Healthineers). The framework was validated against experimental measurements following the NEMA NU-2 2018 standard. In addition, patient-like simulations were performed with the XCAT phantom, including respiratory motion and modeled lesions of 5, 10, 20 mm size, to assess the impact of motion artefacts on PET images using a motion-free reference. The simulation framework demonstrated high accuracy in replicating scanner performance in terms of image quality, contrast recovery (37 mm sphere: 86.5

The aim of this guideline is to provide recommendations for the implementation of an effective and efficient quality control (QC) programme for SPECT and PET systems in a preclinical imaging lab. These recommendations aim to strengthen the translational power of preclinical imaging results obtained using preclinical SPECT and PET. As for clinical imaging, reliability, reproducibility, and repeatability are essential when groups of animals are used in a longitudinal imaging experiment. The larger the variability of the imaging endpoint, the more animals are needed to be able to observe statistically significant differences between groups. Therefore, preclinical imaging requires quality control procedures to maintain reliability, reproducibility, and repeatability of imaging procedures, and to ensure the accuracy and precision of SPECT and PET quantification. While the Physics Committee of the European Association of Nuclear Medicine (EANM) has already published excellent procedure guidelines for Routine Quality Control Recommendations for Nuclear Medicine Instrumentation that also includes procedures for small animal PET systems, and important steps have already been made concerning preclinical quality control aspects, this new guideline provides a review and update of these previous guidelines such that guidelines are also adapted to new technological developments.

Purpose Preclinical imaging, with translational potential, lacks a standardized method for defining volumes of interest (VOIs), impacting data reproducibility. The aim of this study was to determine the interobserver variability of VOI sizes and standard uptake values (SUVmean and SUVmax) of different organs using the same [18F]FDG-PET and PET/CT datasets analyzed by multiple observers. In addition, the effect of a standardized analysis approach was evaluated.Procedures In total, 12 observers (4 beginners and 8 experts) analyzed identical preclinical [18F]FDG-PET-only and PET/CT datasets according to their local default image analysis protocols for multiple organs. Furthermore, a standardized protocol was defined, including detailed information on the respective VOI size and position for multiple organs, and all observers reanalyzed the PET/CT datasets following this protocol.Results Without standardization, significant differences in the SUVmean and SUVmax were found among the observers. Coregistering CT images with PET images improved the comparability to a limited extent. The introduction of a standardized protocol that details the VOI size and position for multiple organs reduced interobserver variability and enhanced comparability.Conclusions The protocol offered clear guidelines and was particularly beneficial for beginners, resulting in improved comparability of SUVmean and SUVmax values for various organs. The study suggested that incorporating an additional VOI template could further enhance the comparability of the findings in preclinical imaging analyses.

Correlated Multimodal Imaging (CMI) gathers information about the same specimen with two or more modalities that–combined–create a composite and complementary view of the sample (including insights into structure, function, dynamics and molecular composition). CMI allows one to reach beyond what is possible with a single modality and describe biomedical processes within their overall spatio-temporal context and gain a mechanistic understanding of cells, tissues, and organisms in health and disease by untangling their molecular mechanisms within their native environment. The field of CMI has grown substantially over the last decade and previously unanswerable biological questions have been solved by applying novel CMI workflows. To disseminate these workflows and comprehensively share the scattered knowledge present within the CMI community, an initiative was started to bring together imaging, image analysis, and biomedical scientists and work towards an open community that promotes and disseminates the field of CMI. This community project was funded for the last 4 years by an EU COST Action called COMULIS (COrrelated MUltimodal imaging in the LIfe Sciences). In this review we share some of the showcases and lessons learnt from the action. We also briefly look ahead at how we anticipate building on this initial initiative.

Several genetic pathogenic variants increase the risk of Parkinson’s disease (PD) with pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene being among the most common. A joint pattern analysis based on multi-set canonical correlation analysis (MCCA) was utilized to extract PD and LRRK2 pathogenic variant-specific spatial patterns in relation to healthy controls (HCs) from multi-tracer Positron Emission Tomography (PET) data. Spatial patterns were extracted for individual subject cohorts, as well as for pooled subject cohorts, to explore whether complementary spatial patterns of dopaminergic denervation are different in the asymptomatic and symptomatic stages of PD. The MCCA results are also compared to the traditional univariate analysis, which serves as a reference.We identified PD-induced spatial distribution alterations common to DAT and VMAT2 in both asymptomatic LRRK2 pathogenic variant carriers and PD subjects. The inclusion of HCs in the analysis demonstrated that the dominant common PD-induced pattern is related to an overall dopaminergic terminal density denervation, followed by asymmetry and rostro-caudal gradient with deficits in the less affected side still being the best marker of disease progression.The analysis was able to capture a trend towards PD-related patterns in the LRRK2 pathogenic variant carrier cohort with increasing age in line with the known increased risk of this patient cohort to develop PD as they age. The advantage of this method thus resides in its ability to identify not only regional differences in tracer binding between groups, but also common disease-related alterations in the spatial distribution patterns of tracer binding, thus potentially capturing more complex aspects of disease induced alterations.

The sensitivity of a PET system highly depends on the axial acceptance angle or maximum ring difference (MRD), which can be particularly high for total-body scanners due to their larger axial field of views (aFOVs). This study aims to evaluate the impact on image quality (IQ) and noise performance when MRD85 (18°), the current standard for clinical use, is increased to MRD322 (52°) for the Biograph Vision Quadra (Siemens Healthineers). METHODS:Studies with a cylindrical phantom covering the 106 cm aFOV and an IEC phantom filled with 18F, 68Ga and 89Zr were performed for acquisition times from 60 to 1800 s and activity concentrations from 0.4 to 3 kBq/ml to assess uniformity, contrast recovery coefficients (CRCs) and to characterize noise by coefficient of variation (CV). Spatial resolution was compared for both MRDs by sampling a quadrant of the FOV with a point source. Further IQ, CV, liver SUVmean and SUVmax were compared for a cohort of 5 patients scanned with [18F]FDG (3 MBq/kg, 1 h p.i.) from 30 to 300 s. RESULTS:CV was improved by a factor of up to 1.49 and is highest for short acquisition times, peaks at the center field of view and mitigates parabolic in axial direction with no difference to MRD85 beyond the central 80 cm. No substantial differences between the two evaluated MRDs in regards to uniformity, SUVmean or CRC for the different isotopes were observed. A degradation of the average spatial resolution of 0.9 ± 0.2 mm in the central 40 cm FOV was determined with MRD322. Depending on the acquisition time MRD322 resulted in a decrease of SUVmax between 23.8% (30 s) and 9.0% (300 s). CONCLUSION:Patient and phantom studies revealed that scan time could be lowered by approximately a factor of two with MRD322 while maintaining similar noise performance. The moderate degradation in spatial resolution for MRD322 is worth to exploit the full potential of the Quadra by either shorten scan times or leverage noise performance in particular for low count scenarios such as ultra-late imaging or dynamic studies with high temporal resolution.

Monte Carlo simulation studies potentially support understanding and characterizing new total-body PET/CT scanners such as the Biograph Vision Quadra (Siemens Healthineers), which enable a broad field of novel applications. This work aims to develop and validate two simulation workflows using the Geant4 Application for Emission Tomography (GATE). Workflow 1 is designed to model the response of the Biograph Vision Quadra as closely as possible by using a custom readout and digitizer modeling tool with an integrated coincidence sorter. Further, the same image reconstruction is performed as for real scan data with the e7 tools (Siemens Healthineers). Workflow 2 is developed for increased flexibility based on open-source software and the Customizable and Advanced Software for Tomographic Reconstruction (CASToR) code for image reconstruction. Phantom simulation studies were performed to validate the workflows against measurement data. Using the normalization matrix of the real scanner with an adapted calibration factor, Workflow 1 demonstrated an excellent quantification accuracy with differences of less than 1% for three different phantoms. Image quality analysis using an IEC phantom simulation with 60 s scan time showed good agreements of contrast recovery coefficients and lung residual error with experimental data. The anthropomorphic XCAT phantom was used for patient-like simulations. The successful NEMA-NU validation of the simulation workflows will enable the investigation of scenarios which practically cannot be tested on patients. Further, the generation of training and validation data sets including simulation ground truth data for machine learning algorithms will be enabled.

Ziel/Aim The new generation of total body PET scanners enables a broad field of innovative applications, such as low dose, late or simultaneous multi-organ imaging. The ground truth information and easy repeatability of simulations are highly suitable to address the need for the establishment of scan protocols or validation of corrections in this field with limited experience. The purpose of this study was to develop and validate a Monte Carlo simulation framework of the Biograph Vision Quadra.

Background Total-body PET scanners with axial field of views (FOVs) longer than 1 m enable new applications to study multiple organs (e.g., the brain-gut-axis) simultaneously. As the spatial resolution and the associated partial volume effect (PVE) can vary significantly along the FOV, detailed knowledge of the contrast recovery coefficients (CRCs) is a prerequisite for image analysis and interpretation of quantitative results. The aim of this study was to determine the CRCs, as well as voxel noise, for multiple isotopes throughout the 1.06 m axial FOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). Materials and Methods Cylindrical phantoms equipped with three different sphere sizes (inner diameters 7.86 mm, 28 and 37 mm) were utilized for the PVE evaluation. The 7.86 mm sphere was filled with F-18 (8:1 and 4:1), Ga-68 (8:1) and Zr-89 (8:1). The 28 mm and 37 mm spheres were filled with F-18 (8:1). Background concentration in the respective phantoms was of ~ 3 kBq/ml. The phantoms were measured at multiple positions in the FOV (axial: 0, 10, 20, 30, 40 and 50 cm, transaxial: 0, 10, 20 cm). The data were reconstructed with the standard clinical protocol, including PSF correction and TOF information with up to 10 iterations for maximum ring differences (MRDs) of 85 and 322; CRCs, as well as voxel noise levels, were determined for each position. Results F-18 CRCs (SBR 8:1 and 4:1) of the 7.86 mm sphere decreased up to 18% from the center FOV (cFOV) toward the transaxial edge and increased up to 17% toward the axial edge. Noise levels were below 15% for the default clinical reconstruction parameters. The larger spheres exhibited a similar pattern. Zr-89 revealed ~ 10% lower CRCs than F-18 but larger noise (9.1% (F-18), 19.1% (Zr-89); iteration 4, cFOV) for the default reconstruction. Zr-89 noise levels in the cFOV significantly decreased (~ 28%) when reconstructing the data with MRD322 compared with MRD85 along with a slight decrease in CRC values. Ga-68 exhibited the lowest CRCs for the three isotopes and noise characteristics comparable to those of F-18. Conclusions Distinct differences in the PVE within the FOV were detected for clinically relevant isotopes F-18, Ga-68 and Zr-89, as well as for different sphere sizes. Depending on the positions inside the FOV, the sphere-to-background ratios, count statistics and isotope used, this can result in an up to 50% difference between CRCs. Hence, these changes in PVE can significantly affect the quantitative analysis of patient data. MRD322 resulted in slightly lower CRC values, especially in the center FOV, whereas the voxel noise significantly decreased compared with MRD85.

Objective. Three different breast positron emission tomography (PET) insert geometries are proposed for integration into an existing magnetic resonance imaging (MRI) breast coil (Breast Biopsy Coil, NORAS MRI products) to be used inside a whole-body PET/MRI scanner (Biograph mMR, Siemens Healthineers) to enhance the sensitivity and spatial resolution of imaging inside the breast. Approach. Monte Carlo simulations were performed to predict and compare the performance characteristics of the three geometries in terms of the sensitivity, spatial resolution, scatter fraction, and noise equivalent count rate (NECR). In addition, the background single count rate due to organ uptake in a clinical scan scenario was predicted using a realistic anthropomorphic phantom. Main results. In the center of the field of view (cFOV), absolute sensitivities of 3.1%, 2.7%, and 2.2% were found for Geometry A (detectors arranged in two cylinders), Geometry B (detectors arranged in two partial cylinders), and Geometry C (detectors arranged in two half cylinders combined with two plates), respectively. The full width at half maximum spatial resolution was determined to be 1.7 mm (Geometry A), 1.8 mm (Geometry B) and 2.0 mm (Geometry C) at 5 mm from the cFOV. Designs with multiple scintillation-crystal layers capable of determining the depth of interaction (DOI) strongly improved the spatial resolution at larger distances from the transaxial cFOV. The system scatter fractions were 33.1% (Geometries A and B) and 32.3% (Geometry C). The peak NECRs occurred at source activities of 300 MBq (Geometry A), 310 MBq (Geometry B) and 340 MBq (Geometry C). The background single-event count rates were 17.1 × 106 cps (Geometry A), 15.3 × 106 cps (Geometry B) and 14.8 × 106 cps (Geometry C). Geometry A in the three-layer DOI variant exhibited the best PET performance characteristics but could be challenging to manufacture. Geometry C had the lowest impact on the spatial resolution and the lowest sensitivity among the investigated geometries. Significance. Geometry B in the two-layer DOI variant represented an effective compromise between the PET performance and manufacturing difficulty and was found to be a promising candidate for the future breast PET insert.

Ziel/Aim We aim to gain a better understanding of how to optimize application-specific protocols and analyses for the Biograph Vision Quadra (Siemens Healthineers, Erlangen, Germany) by performing comprehensive phantom measurements, postprocessing and simulations.

Aim Recently, total-body PET/CT systems with an extended axial field-of-view (aFOV) became commercially available which allow acquiring physiologic information of multiple organs simultaneously. However, the nominal aFOV may clinically not be used effectively due to the inherently reduced sensitivity at the distal ends of the aFOV. The aim of this study was to assess the extent of the useful aFOV of the Biograph Vision Quadra PET/CT system. Methods A NEMA image quality (IQ) phantom mimicking a standard [ 18 F]FDG examination was used. Image contrast and noise were assessed across the 106 cm aFOV of the Biograph Vision Quadra PET/CT system (Siemens Healthineers). Phantom acquisitions were performed at different axial positions. PET data were rebinned to simulate different acquisition times for a standard injected activity and reconstructed using different filter settings to evaluate the noise and images along the axial direction. Results Image noise and contrast were stable within the central 80 cm of the aFOV. Outside this central area, image contrast variability as well as image noise increased. This degradation of IQ was in particular evident for short acquisition times of less than 30 s. At 10 min acquisition time and in the absence of post-reconstruction filtering, the useful aFOV was 100 cm. For a 2 min acquisition time, a useful aFOV with image noise below 15% was only achievable using Gaussian filtering with axial extents of between 83 and 103 cm when going from 2 to 6 mm full-width-half-maximum, respectively. Conclusion Image noise increases substantially towards the ends of the aFOV. However, good IQ in compliance with generally accepted benchmarks is achievable for an aFOV of > 90 cm. When accepting higher image noise or using dedicated protocol settings such as stronger filtering a useful aFOV of around 1 m can be achieved for a 2 min acquisition time.

An avalanche photodiode (APD)-based small animal positron emission tomography (PET)-insert was fully evaluated for its PET performance, as well as potential influences on magnetic resonance imaging (MRI) performance. This PET-insert has an extended axial field of view (FOV) compared with the previous design to increase system sensitivity, as well as an updated cooling and temperature regulation to enable stable and reproducible PET acquisitions. The PET performance was evaluated according to the National Electrical Manufacturers Association NU4-2008 protocol. The energy and timing resolution's full width at half maximum were 16.1% and 4.7 ns, respectively. The reconstructed radial spatial resolution of the PET-insert was 1.8 mm full width at half maximum at the center FOV using filtered back projection for reconstruction and sensitivity was 3.68%. The peak noise equivalent count rates were 70 kcps for a rat-like and 350 kcps for a mouse-like phantom, respectively. Image quality phantom values and contrast recovery were comparable to state-of-the art PET-inserts and standalone systems. Regarding MR compatibility, changes in the mean signal-to-noise ratio for turbo spin echo and echo-planar imaging sequences were below 8.6%, for gradient echo sequences below 1%. Degradation of the mean homogeneity was below 2.3% for all tested sequences. The influence of the PET-insert on theB0maps was negligible and no influence on functional MRI sequences was detected. A mouse and rat imaging study demonstrated the feasibility ofin vivosimultaneous PET/MRI.