Cross-calibration of the Siemens mMR:easily acquired accurate PET phantom measurements, long-term stability and reproducibility

BACKGROUND: We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom. LONG-TERM STABILITY: The mMR calibration stability was evaluated over a 3-year period where 54 cross-calibrations were acquired, showing that the mMR on average underestimated the concentration by 16 %, consistently due to the use of MR-based μ-maps. The mMR produced the narrowest calibration ratio range with the lowest standard deviation, implying it is the most stable of the six systems in the study over a 3-year period. MMR ACCURACY WITH PREDEFINED μ-MAPS: With the latest mMR software version, VB20P, it is possible to utilize predefined phantom μ-maps. We evaluated both the system-integrated, predefined μ-map of the long mMR water phantom and our own user-defined CT-based μ-map of the mCT water phantom, which is used for cross-calibration. For seven scans, which were reconstructed with correctly segmented μ-maps, the mMR produced cross-calibration ratios of 1.00–1.02, well within the acceptance range [0.95–1.05], showing high accuracy. CONCLUSIONS: The mMR is the most stable PET system in this study, and the mean underestimation is no longer an issue with the easily accessible μ-map, which resulted in correct cross-calibration ratios in all seven tests. We will share the user-defined μ-map of the mCT phantom and the protocol with interested mMR users

Associations between duck harvest, hunting wing ratios and measures of reproductive output in Northern Europe

Ducks are important game species, hunted in several countries throughout their annual cycle. We investigated whether the size of the annual duck harvest in Finland and Denmark reflected annual reproductive output in three common quarry duck species. Finland represents an important breeding area and Denmark important staging/wintering grounds for common teal (Anas crecca), Eurasian wigeon (Mareca penelope) and common goldeneye (Bucephala clangula). We assessed whether (i) annual duck harvest in these two countries correlated with variation in Finnish reproductive output or adult population size during 1990-2016 and (ii) variation in reproductive output of Finnish ducks was reflected in the juvenile ratios of birds harvested in Finland (2005-2007, 2014-2016) or Denmark (1990-2016). We hypothesised that variation in Finnish reproductive output would positively affect the size and juvenile ratio of the harvest, and that this effect would be stronger closer to the breeding grounds. Our data showed that the annual harvest of goldeneye in Finland was positively correlated with reproductive output, a desirable basis for applying sustainable management to this species. Teal and wigeon have much longer, more complex flyways, and their harvest did not mirror the annual production of young, although the wigeon harvest in Denmark increased with increasing juvenile ratio there. For these populations, we need to better define population units if we are to be able to assess harvest sustainability. We urgently need to monitor duck breeding success and harvest at larger spatial scales to support a comprehensive analysis of how well the harvest reflects reproductive output.Peer reviewe

Improved PET imaging of uPAR expression using new (64)Cu-labeled cross-bridged peptide ligands:comparative in vitro and in vivo studies

The correlation between uPAR expression, cancer cell invasion and metastases is now well-established and has prompted the development of a number of uPAR PET imaging agents, which could potentially identify cancer patients with invasive and metastatic lesions. In the present study, we synthesized and characterized two new cross-bridged (64)Cu-labeled peptide conjugates for PET imaging of uPAR and performed a head-to-head comparison with the corresponding and more conventionally used DOTA conjugate. Based on in-source laser-induced reduction of chelated Cu(II) to Cu(I), we now demonstrate the following ranking with respect to the chemical inertness of their complexed Cu ions: DOTA-AE105 << CB-TE2A-AE105 < CB-TE2A-PA-AE105, which is correlated to their corresponding demetallation rate. No penalty in the uPAR receptor binding affinity of the targeting peptide was encountered by conjugation to either of the macrobicyclic chelators (IC(50) ~ 5-10 nM) and high yields and radiochemical purities (>95%) were achieved in all cases by incubation at 95ºC. In vivo, they display identical tumor uptake after 1h, but differ significantly after 22 hrs, where the DOTA-AE105 uptake remains surprisingly high. Importantly, the more stable of the new uPAR PET tracers, (64)Cu-CB-TE2A-PA-AE105, exhibits a significantly reduced liver uptake compared to (64)Cu-DOTA-AE105 as well as (64)Cu-CB-TE2A-AE105, (p<0.0001), emphasizing that our new in vitro stability measurements by mass spectrometry predicts in vivo stability in mice. Specificity of the best performing ligand, (64)Cu-CB-TE2A-PA-AE105 was finally confirmed in vivo using a non-binding (64)Cu-labeled peptide as control ((64)Cu-CB-TE2A-PA-AE105(mut)). This control PET-tracer revealed significantly reduced tumor uptake (p<0.0001), but identical hepatic uptake compared to its active counterpart ((64)Cu-CB-TE2A-PA-AE105) after 1h. In conclusion, our new approach using in-source laser-induced reduction of Cu(II)-chelated PET-ligands provides useful information, which are predictive for the tracer stability in vivo in mice. Furthermore, the increased stability of our new macrobicyclic (64)Cu-CB-TE2A-PA-AE105 PET ligand is paralleled by an excellent imaging contrast during non-invasive PET scanning of uPAR expression in preclinical mouse cancer models. The translational promises displayed by this PET-tracer for future clinical cancer patient management remains, however, to be investigated

Integrated Optimization of Transit Networks with Schedule- and Frequency-Based Services Subject to the Bounded Stochastic User Equilibrium

In many European metropolitan areas, the urban transit system is a mixture of schedule- and frequency-based services. This study proposes an integrated transit frequency and schedule design problem (ITFSDP), where frequencies and schedules are simultaneously determined, and develops a biobjective model for the ITFSDP to minimize operation costs and total passenger-perceived generalized travel cost. Meanwhile, the passengers' route choice behavior is described by the bounded stochastic user equilibrium (BSUE). The in-vehicle congestion effect is represented using a set of constraints that differ in terms of the sitting and standing costs as sitting and standing passengers perceive crowding differently. This set of constraints captures the realistic behavioral feature that having occupied a seat, users remain seated at subsequent stops in the same vehicle. The problem is formulated as a mixed integer nonlinear programming problem, which is subsequently linearized to a mixed integer linear programming problem and solved using a branch and bound algorithm. A column generation and reduction phase is embedded in the solution algorithm to obtain the bounded choice set according to the BSUE constraints. Experiments are conducted to illustrate the model's properties and the performance of the solution method. In particular, we demonstrate a Braess-like paradoxical phenomenon in the context of transit scheduling and highlight that well-synchronized transit services can deteriorate the network performance in terms of the total passengers' generalized travel cost when considering passenger congestion costs because of crowding

Angiogenesis PET Tracer Uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs

Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p &lt; 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p &lt; 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated