Multi-Isotope Multi-Pinhole SPECT Bildgebung in kleinen Labortieren: Experimentelle Messungen und Monte Carlo Simulationen

Single photon emission computed tomography (SPECT) in small laboratory animals has become an integral part of translational medicine. It enables non-invasive validation of drug targeting, safety and efficacy in living organisms, which is progressively gaining importance in pharmaceutical industry. The increasing demand for efficiency in pharmaceutical research could be addressed by novel multitracer study designs. Multi-isotope multi-pinhole sampling allows validation of multiple tracers in a single experiment and consolidation of consecutive research trials. Due to physical and technical limitations, however, image quality and quantification can be substantially reduced. Advanced corrective procedures are required to establish multi-isotope multi-pinhole SPECT as a reliable and quantitative imaging technique for widespread use. For this purpose, the present work aimed to investigate the technical capabilities and physical limitations of multi-isotope multi-pinhole SPECT imaging in small laboratory animals. Based on experimental measurements and Monte Carlo simulations, specific error sources have been identified and procedures for quantitative image correction have been developed. A Monte Carlo simulation model of a state-of-the art SPECT/CT system has been established to provide a generalized framework for in-silico optimization of imaging hardware, acquisition protocols and reconstruction algorithms. The findings of this work can be used to improve image quality and quantification of SPECT in-vivo data for multi-isotope applications. They guide through the laborious process of multi-isotope protocol optimization and support the 3R welfare initiative that aims to replace, reduce and refine animal experimentation.Die Einzelphotonen-Emissionscomputertomographie (SPECT) in kleinen Labortieren hat sich als wichtiger Bestandteil der translationalen Medizin etabliert. Sie ermöglicht die nicht-invasive Validierung der Zielgenauigkeit, Wirksamkeit und Sicherheit von Wirkstoffen in lebenden Organismen und gewinnt zunehmend an Bedeutung in der pharmazeutischen Industrie. Die Forderung nach mehr Effizienz in der pharmazeutischen Forschung könnte durch neuartige Multitracer-Studien adressiert werden. Die Multi-Isotopen Akquisition mit Multi-Pinhole Kollimatoren ermöglicht die Validierung mehrerer Tracer in einem einzelnen Experiment und die Konsolidierung konsekutiver Bildgebungsstudien. Aufgrund physikalischer und technischer Limitationen ist die Bildqualität und Quantifizierbarkeit bei diesem Verfahren jedoch häufig reduziert. Um die Multi-Isotopen SPECT als zuverlässige und quantitative Bildgebungsmethode für den breiten Einsatz zu etablieren sind komplexe Korrekturverfahren erforderlich. Ziel der vorliegenden Arbeit war daher, die technischen Möglichkeiten und physikalischen Limitationen der Multi-Isotopen SPECT-Bildgebung in kleinen Labortieren systematisch zu untersuchen. Mithilfe von experimentellen Messungen und Monte Carlo Simulationen wurden spezifische Fehlerquellen identifiziert und Verfahren zur quantitativen Bildkorrektur entwickelt. Zudem wurde das Monte-Carlo Modell eines neuartigen SPECT/CT-Systems etabliert, um eine Plattform für die in-silico Optimierung von Bildgebungshardware, Aufnahmeprotokollen und Rekonstruktionsalgorithmen zu schaffen. Die Ergebnisse dieser Arbeit können die Bildqualität und Quantifizierbarkeit von SPECT in-vivo Daten für Multi-Isotopen Anwendungen verbessern. Sie führen beispielhaft durch den Prozess der Multi-Isotopen Protokolloptimierung und unterstützen die 3R-Initiative mit dem Ziel, experimentelle Tierversuche zu vermeiden (Replace), zu vermindern (Reduce) und zu verbessern (Refine)

Expression of SV2 in the developing chick cerebellum: comparison with Calbindin and AMPA glutamate receptors 2/3

The well-organized cerebellum is an ideal model to investigate the developmental appearance and localization of pre- and postsynaptic structures. One of the synaptic proteins abundant in the central nervous system and localized in presynaptic vesicle membranes is the synaptic vesicle protein 2 (SV2). SV2 was shown to be involved in priming and modulating synaptic vesicles and having an effect in epileptic diseases. So far there are no data available describing the developmental localization of this protein in the cerebellum. We followed the expression pattern of SV2 and compared it with the expression of the neuronal calcium-binding protein Calbindin and the AMPA glutamate receptor subunits 2/3 (GluR 2/3), both shown to be early expressed in the developing chick cerebellum predominantly in Purkinje cells. We detected the expression of SV2 in presynaptic terminals (mainly from climbing and mossy fibers) as soon as they are formed at embryonic day 16 in the inner molecular layer. Purkinje cells express Calbindin and GluR 2/3 in the soma and postsynaptically in the primary dendrites at this stage. With ongoing development, the pattern of SV2 expression follows the development of Purkinje cell dendrites in the molecular layer, suggesting a synaptic refinement of labeled climbing and later parallel fibers

Reconstructed spatial resolution and contrast recovery with Bayesian penalized likelihood reconstruction (Q.Clear) for FDG-PET compared to time-of-flight (TOF) with point spread function (PSF)

BACKGROUND: Bayesian penalized likelihood reconstruction for PET (e.g., GE Q.Clear) aims at improving convergence of lesion activity while ensuring sufficient signal-to-noise ratio (SNR). This study evaluated reconstructed spatial resolution, maximum/peak contrast recovery (CRmax/CRpeak) and SNR of Q.Clear compared to time-of-flight (TOF) OSEM with and without point spread function (PSF) modeling. METHODS: The NEMA IEC Body phantom was scanned five times (3 min scan duration, 30 min between scans, background, 1.5-3.9 kBq/ml F18) with a GE Discovery MI PET/CT (3-ring detector) with spheres filled with 8-, 4-, or 2-fold the background activity concentration (SBR 8:1, 4:1, 2:1). Reconstruction included Q.Clear (beta, 150/300/450), "PSF+TOF4/16" (iterations, 4; subsets, 16; in-plane filter, 2.0 mm), "OSEM+TOF4/16" (identical parameters), "PSF+TOF2/17" (2 it, 17 ss, 2.0 mm filter), "OSEM+TOF2/17" (identical), "PSF+TOF4/8" (4 it, 8 ss, 6.4 mm), and "OSEM+TOF2/8" (2 it, 8 ss, 6.4 mm). Spatial resolution was derived from 3D sphere activity profiles. RC as (sphere activity concentration [AC]/true AC). SNR as (background mean AC/background AC standard deviation). RESULTS: Spatial resolution of Q.Clear150 was significantly better than all conventional algorithms at SBR 8:1 and 4:1 (Wilcoxon, each p < 0.05). At SBR 4:1 and 2:1, the spatial resolution of Q.Clear300/450 was similar or inferior to PSF+TOF4/16 and OSEM+TOF4/16. Small sphere CRpeak generally underestimated true AC, and it was similar for Q.Clear150/300/450 as with PSF+TOF4/16 or PSF+TOF2/17 (i.e., relative differences < 10%). Q.Clear provided similar or higher CRpeak as OSEM+TOF4/16 and OSEM+TOF2/17 resulting in a consistently better tradeoff between CRpeak and SNR with Q.Clear. Compared to PSF+TOF4/8/OSEM+TOF2/8, Q.Clear150/300/450 showed lower SNR but higher CRpeak. CONCLUSIONS: Q.Clear consistently improved reconstructed spatial resolution at high and medium SBR compared to PSF+TOF and OSEM+TOF, but only with beta = 150. However, this is at the cost of inferior SNR with Q.Clear150 compared to Q.Clear300/450 and PSF+TOF4/16/PSF+TOF2/17 while CRpeak for the small spheres did not improve considerably. This suggests that Q.Clear300/450 may be advantageous for the 3-ring detector configuration because the tradeoff between CR and SNR with Q.Clear300/450 was superior to PSF+TOF4/16, OSEM+TOF4/16, and OSEM+TOF2/17. However, it requires validation by systematic evaluation in patients at different activity and acquisition protocols

Bundling Digital Journalism: Exploring the Potential of Subscription-Based Product Bundles

This study explores the potential of cross-publisher bundled offers as a strategy for increasing subscription sales in digital journalism. While innovative forms of bundling are an integral part of media distribution in music (e.g., Spotify) and film (e.g., Netflix), their adoption in digital journalism has been limited, despite research showing that bundled access to products can increase consumers’ willingness to pay, especially in younger target groups. Against this background, we conduct a choice-based conjoint analysis using data from a representative survey of the German online population (n = 1,542). Results show that bundling digital journalism has the potential to raise publisher revenues and subscription sales in digital markets. In particular, they highlight that a comprehensive, cross-publisher bundled offer, available at a fixed monthly rate, has the potential to stimulate digital journalism sales among different consumer groups in a relatively balanced way, including those who are typically more reluctant towards journalism. These findings align with the principles of information goods economics, which posit that maximising the size of digital content bundles often tends to be the most profitable distribution strategy. However, it is crucial to examine these findings in the context of the potential negative effects associated with this emerging business model in digital journalism, such as the cannibalisation of print subscriptions, diminished brand identification, and a possible imbalanced distribution of revenues

OREOS: Oriented Recognition of 3D Point Clouds in Outdoor Scenarios

We introduce a novel method for oriented place recognition with 3D LiDAR scans. A Convolutional Neural Network is trained to extract compact descriptors from single 3D LiDAR scans. These can be used both to retrieve near-by place candidates from a map, and to estimate the yaw discrepancy needed for bootstrapping local registration methods. We employ a triplet loss function for training and use a hard-negative mining strategy to further increase the performance of our descriptor extractor. In an evaluation on the NCLT and KITTI datasets, we demonstrate that our method outperforms related state-of-the-art approaches based on both data-driven and handcrafted data representation in challenging long-term outdoor conditions

Exchange-enhanced Ultrastrong Magnon-Magnon Coupling in a Compensated Ferrimagnet

The ultrastrong coupling of (quasi-)particles has gained considerable attention due to its application potential and richness of the underlying physics. Coupling phenomena arising due to electromagnetic interactions are well explored. In magnetically ordered systems, the quantum-mechanical exchange-interaction should furthermore enable a fundamentally different coupling mechanism. Here, we report the observation of ultrastrong intralayer exchange-enhanced magnon-magnon coupling in a compensated ferrimagnet. We experimentally study the spin dynamics in a gadolinium iron garnet single crystal using broadband ferromagnetic resonance. Close to the ferrimagnetic compensation temperature, we observe ultrastrong coupling of clockwise and anticlockwise magnon modes. The magnon-magnon coupling strength reaches more than 30% of the mode frequency and can be tuned by varying the direction of the external magnetic field. We theoretically explain the observed phenomenon in terms of an exchange-enhanced mode-coupling mediated by a weak cubic anisotropy