Description: Research on neotectonics and related seismicity has hitherto been mostly focused on active plate boundaries that are characterized by generally high levels of earthquake activity. Current seismic hazard estimates for intraplate domains are mainly based on probabilistic analyses of historical and instrumental earthquake catalogues. The accuracy of such hazard estimates is limited by the fact that available catalogues are restricted to a few hundred years, which, on geological time scales, is insignificant and not suitable for the assessment of tectonic processes controlling the observed earthquake activity. More reliable hazard prediction requires access to high quality data sets covering a geologically significant time span in order to obtain a better understanding of processes controlling on-going intraplate deformation. The Alpine Orogen and the intraplate sedimentary basins and rifts in its northern foreland are associated with a much higher level of neotectonic activity than hitherto assumed. Seismicity and stress indicator data, combined with geodetic and geomorphologic observations, demonstrate that deformation of the Northern Alpine foreland is still on-going and will continue in the future. This has major implications for the assessment of natural hazards and the environmental degradation potential of this densely populated area. We examine relationships between deeper lithospheric processes, neotectonics and surface processes in the northern Alpine Foreland, and their implications for tectonically induced topography. For the Environmental Tectonics Project (ENTEC), the Upper and Lower Rhine Graben (URG and LRG) and the Vienna Basin (VB) were selected as natural laboratories. The Vienna Basin developed during the middle Miocene as a sinistral pull-apart structure on top of the East Alpine nappe stack, whereas the Upper and Lower Rhine grabens are typical intracontinental rifts. The Upper Rhine Graben opened during its Late Eocene and Oligocene initial rifting phase by nearly orthogonal crustal extension, whereas its Neogene evolution was controlled by oblique extension. Seismic tomography suggests that during extension the mantle-lithosphere was partially decoupled from the upper crust at the level of the lower crust. However, whole lithospheric folding controlled the mid-Miocene to Pliocene uplift of the Vosges–Black Forest Arch, whereas thermal thinning of the mantle–lithosphere above a mantle plume contributed substantially to the past and present uplift of the Rhenish Massif. By contrast, oblique crustal extension, controlling the late Oligocene initial subsidence stage of the Lower Rhine Graben, gave way to orthogonal extension at the transition to the Neogene. The ENTEC Project integrated geological, geophysical, geomorphologic, geodetic and seismological data and developed dynamic models to quantify the societal impact of neotectonics in areas hosting major urban and industrial activity concentrations. The response of Europe's intraplate lithosphere to Late Neogene compressional stresses depends largely on its thermo-mechanical structure, which, in turn, controls vertical motions, topography evolution and related surface processes.

Description: Physical analogue experiments are used to investigate the effect of plate and intra-lithospheric coupling on the efficiency of continental lithosphere subduction and the style of collision. Key parameters investigated in this study are: the degree of plate coupling, regulated by the viscosity ratio of the decoupling zone and the surrounding crust and/or mantle lithosphere; and the depth of decoupling. The experimental results show that subduction of the slab is deepest in cases with strong decoupling at the plate interface and at the level of the lower crust of the downgoing plate, with upper-plate deformation restricted to the area close to the plate contact. In these cases, the strongly asymmetric orogenic wedge is widest, consists of a series of imbricated upper-crustal slices derived from the lower plate, and lacks a retro-wedge. In contrast, a reduced strength contrast across the plate interface, at the depth of either the lithospheric mantle or the ductile crust, leads to a combination of subduction and thickening of the mantle lithosphere in both the upper and the lower plates. The degree of plate coupling determines the efficiency of subduction of continental lithosphere under conditions of collision of neutrally buoyant lithospheres, whereas the vertical position of decoupling horizons within the subducting plate controls the amount of subducted lower crust. Transfer of strain to the upper plate depends critically on (1) the degree of plate coupling, with stronger coupling leading to more deformation, and (2) the presence of decoupling horizons within the upper plate, which act as strain guides to propagate deformation into the upper plate. The experimental results explain the geometry and the sequence of deformation in subduction dominated orogens, such as the Carpathians or the Dinarides, and provide a mechanical basis for the transfer of strain to the upper plate.

Description: TOPO-EUROPE addresses the 4-D topographic evolution of the orogens and intra-plate regions of Europe through a multidisciplinary approach linking geology, geophysics, geodesy and geotechnology. TOPO-EUROPE integrates monitoring, imaging, reconstruction and modelling of the interplay between processes controlling continental topography and related natural hazards. Until now, research on neotectonics and related topography development of orogens and intra-plate regions has received little attention. TOPO-EUROPE initiates a number of novel studies on the quantification of rates of vertical motions, related tectonically controlled river evolution and land subsidence in carefully selected natural laboratories in Europe. From orogen through platform to continental margin, these natural laboratories include the Alps/Carpathians–Pannonian Basin System, the West and Central European Platform, the Apennines–Aegean–Anatolian region, the Iberian Peninsula, the Scandinavian Continental Margin, the East-European Platform, and the Caucasus–Levant area. TOPO-EUROPE integrates European research facilities and know-how essential to advance the understanding of the role of topography in Environmental Earth System Dynamics. The principal objective of the network is twofold. Namely, to integrate national research programs into a common European network and, furthermore, to integrate activities among TOPO-EUROPE institutes and participants. Key objectives are to provide an interdisciplinary forum to share knowledge and information in the field of the neotectonic and topographic evolution of Europe, to promote and encourage multidisciplinary research on a truly European scale, to increase mobility of scientists and to train young scientists. This paper provides an overview of the state-of-the-art of continental topography research, and of the challenges to TOPO-EUROPE researchers in the targeted natural laboratories

Description: The combined α-, -, and x-ray emitter 213 Bi (half-life, 46 min) is promising for radionuclide therapy. SPECT imaging of 213 Bi is challenging, because most emitted photons have a much higher energy (440 keV) than common in SPECT. We assessed 213 Bi imaging capabilities of the Versatile Emission Computed Tomograph (VECTor) dedicated to (simultaneous) preclinical imaging of both SPECT and PET isotopes over a wide photon energy range of 25–600 keV. Methods: VECTor was equipped with a dedicated clustered pinhole collimator. Both the 79 keV x-rays and the 440 keV -rays emitted by 213 Bi could be imaged. Phantom experiments were performed to determine the maximum resolution, contrast-to-noise ratio, and activity recovery coefficient for different energy window settings. Additionally, imaging of [ 213 Bi-DOTA,Tyr 3 ]octreotate and 213 Bi-diethylene triamine pentaacetic acid (DTPA) in mouse models was performed. Results: Using 440 keV -rays instead of 79 keV x-rays in image reconstruction strongly improved the resolution (0.75 mm) and contrast-to-noise characteristics. Results obtained with a single 440 keV energy window setting were close to those with a combined 79 keV/440 keV window. We found a reliable activity recovery coefficient down to 0.240 MBq/mL with 30-min imaging time. In a tumor-bearing mouse injected with 3 MBq of [ 213 Bi-DOTA,Tyr 3 ]octreotate, tumor uptake could be visualized with a 1-h postmortem scan. Imaging a nontumor mouse at 5-min frames after injection of 7.4 MBq of 213 Bi-DTPA showed renal uptake and urinary clearance, visualizing the renal excretion pathway from cortex to ureter. Quantification of the uptake data allowed kinetic modeling and estimation of the absorbed dose to the kidneys. Conclusion: It is feasible to image 213 Bi down to a 0.75-mm resolution using a SPECT system equipped with a dedicated collimator.

Description: SPECT with submegabecquerel amounts of tracer or subsecond time resolution would enable a wide range of new imaging protocols such as screening tracers with initially low yield or labeling efficiency, imaging low receptor densities, or even performing SPECT outside regular radiation laboratories. To this end we developed dedicated ultra-high-sensitivity pinhole SPECT. Methods: A cylindric collimator with 54 focused 2.0-mm-diameter conical pinholes was manufactured and mounted in a stationary small-animal SPECT system. The system matrix for image reconstruction was calculated via a hybrid method based on both 99m Tc point source measurements and ray-tracing analytic modeling. SPECT images were reconstructed using pixel-based ordered-subsets expectation maximization. Performance was evaluated with phantoms and low-dose bone, dynamic kidney, and cardiac mouse scans. Results: The peak sensitivity reached 1.3% (13,080 cps/MBq). The reconstructed spatial resolution (rod visibility in a micro-Jaszczak phantom) was 0.85 mm. Even with only a quarter megabecquerel of activity, 30-min bone SPECT scans provided surprisingly high levels of detail. Dynamic dual-isotope kidney and 99m Tc-sestamibi cardiac scans were acquired with a time-frame resolution down to 1 s. Conclusion: The high sensitivity achieved increases the range of mouse SPECT applications by enabling in vivo imaging with less than a megabecquerel of tracer activity or down to 1-s frame dynamics.

Description: Longitudinal imaging of intratumoral distributions of antibodies in vivo in mouse cancer models is of great importance for developing cancer therapies. In this study, multipinhole SPECT with sub–half-millimeter resolution was tested for exploring intratumoral distributions of radiolabeled antibodies directed toward the epidermal growth factor receptor (EGFr) and compared with full 3-dimensional target expression assessed by immunohistochemistry. Methods: 111 In-labeled zalutumumab, a human monoclonal human EGFr-targeting antibody, was administered at a nonsaturating dose to 3 mice with xenografted A431 tumors exhibiting high EGFr expression. Total-body and focused in vivo tumor SPECT was performed at 0 and 48 h after injection and compared both visually and quantitatively with full 3-dimensional immunohistochemical staining for EGFr target expression. Results: SPECT at 48 h after injection showed that activity was predominantly concentrated in the tumor (10.5% ± 1.3% of the total-body activity; average concentration, 30.1% ± 4.6% of the injected dose per cubic centimeter). 111 In-labeled EGFr-targeting antibodies were distributed heterogeneously throughout the tumor. Some hot spots were observed near the tumor rim. Immunohistochemistry indicated that the antibody distributions obtained by SPECT were morphologically similar to those obtained for ex vivo EGFr target expression. Regions showing low SPECT activity were necrotic or virtually negative for EGFr target expression. A good correlation ( r = 0.86, P 〈 0.0001) was found between the percentage of regions showing low activity on SPECT and the percentage of necrotic tissue on immunohistochemistry. Conclusion: Multipinhole SPECT enables high-resolution visualization and quantification of the heterogeneity of 111 In-zalutumumab concentrations in vivo.

Description: PET imaging of rodents is increasingly used in preclinical research, but its utility is limited by spatial resolution and signal-to-noise ratio of the images. A recently developed preclinical PET system uses a clustered-pinhole collimator, enabling high-resolution, simultaneous imaging of PET and SPECT tracers. Pinhole collimation strongly departs from traditional electronic collimation achieved via coincidence detection in PET. We investigated the potential of such a design by direct comparison to a traditional PET scanner. Methods: Two small-animal PET scanners, 1 with electronic collimation and 1 with physical collimation using clustered pinholes, were used to acquire data from Jaszczak (hot rod) and uniform phantoms. Mouse brain imaging using 18 F-FDG PET was performed on each system and compared with quantitative ex vivo autoradiography as a gold standard. Bone imaging using 18 F-NaF allowed comparison of imaging in the mouse body. Images were visually and quantitatively compared using measures of contrast and noise. Results: Pinhole PET resolved the smallest rods (diameter, 0.85 mm) in the Jaszczak phantom, whereas the coincidence system resolved 1.1-mm-diameter rods. Contrast-to-noise ratios were better for pinhole PET when imaging small rods (〈1.1 mm) for a wide range of activity levels, but this reversed for larger rods. Image uniformity on the coincidence system (〈3%) was superior to that on the pinhole system (5%). The high 18 F-FDG uptake in the striatum of the mouse brain was fully resolved using the pinhole system, with contrast to nearby regions equaling that from autoradiography; a lower contrast was found using the coincidence PET system. For short-duration images (low-count), the coincidence system was superior. Conclusion: In the cases for which small regions need to be resolved in scans with reasonably high activity or reasonably long scan times, a first-generation clustered-pinhole system can provide image quality in terms of resolution, contrast, and the contrast-to-noise ratio superior to a traditional PET system.

Description: Small-animal SPECT systems with stationary detectors and focusing multiple pinholes can achieve excellent resolution–sensitivity trade-offs. These systems are able to perform fast total-body scans by shifting the animal bed through the collimator using an automated xyz stage. However, so far, a large number of highly overlapping central fields of view have been used, at the cost of overhead time needed for animal repositioning and long image reconstruction times due to high numbers of projection views. Methods: To improve temporal resolution and reduce image reconstruction time for such scans, we have developed and tested spiral trajectories (STs) of the animal bed requiring fewer steps. In addition, we tested multiplane trajectories (MPTs) of the animal bed, which is the standard acquisition method of the U-SPECT-II system that is used in this study. Neither MPTs nor STs require rotation of the animal. Computer simulations and physical phantom experiments were performed for a wide range of numbers of bed positions. Furthermore, we tested STs in vivo for fast dynamic mouse scans. Results: We found that STs require less than half the number of bed positions of MPTs to achieve sufficient sampling. The reduced number of bed positions made it possible to perform a dynamic total-body bone scan and a dynamic hepatobiliary scan with time resolutions of 60 s and 15 s, respectively. Conclusion: STs open up new possibilities for high throughput and fast dynamic radio-molecular imaging.

Description: Today, PET and SPECT tracers cannot be imaged simultaneously at high resolutions but require 2 separate imaging systems. This paper introduces a Versatile Emission Computed Tomography system (VECTor) for radionuclides that enables simultaneous submillimeter imaging of single-photon and positron-emitting radiolabeled molecules. Methods: -photons produced both by electron–positron annihilation and by single-photon emitters are projected onto the same detectors by means of a novel cylindric high-energy collimator containing 162 narrow pinholes that are grouped in clusters. This collimator is placed in an existing SPECT system (U-SPECT-II) with 3 large-field-of-view -detectors. From the acquired projections, PET and SPECT images are obtained using statistical image reconstruction that corrects for energy-dependent system blurring. Results: For PET tracers, the tomographic resolution obtained with a Jaszczak hot rod phantom was less than 0.8 mm, and 0.5-mm resolution images of SPECT tracers were acquired simultaneously. SPECT images were barely degraded by the simultaneous presence of a PET tracer, even when the activity concentration of the PET tracer exceeded that of the SPECT tracer by up to a factor of 2.5. Furthermore, we simultaneously acquired fully registered 3- and 4-dimensional multiple functional images from living mice that, in the past, could be obtained only sequentially. Conclusion: High-resolution complementary information about tissue function contained in SPECT and PET tracer distributions can now be obtained simultaneously using a fully integrated imaging device. These combined unique capabilities pave the way for new perspectives in imaging the biologic systems of rodents.

Description: Central and Northern Asia is a key natural laboratory for the study of active intra-continental deformation in response to the ongoing far-field collision of India and Eurasia. The induced tectonic processes strongly depend on the thermo-mechanical and compositional (density and thickness) structure of the lithosphere. In particularly, density anomalies within the crust and upper mantle are important factors that control Earth deformations at shallow and deep levels. Moreover, the inherited heterogeneity is responsible also for the local and regional stress field. The main aim of this collaborative research project is to construct new high-resolution 3-D models of the compositional, thermal and rheological structure of the lithosphere of the study area. These models will be constructed by combining and jointly analysing satellite gravity data with terrestrial data (seismic velocity distributions, seismic tomography, GPS derived surface deformations, heat flow measurements and terrestrial gravity). These models will be the basis for subsequent 3-D numerical modelling of the intra-plate stress and strain fields in Central and Northern Asia. Here we present a new crustal model including Moho and seismic velocity distribution for Central and Northern Asia. This model is primarily based on seismic data. Where data coverage is insufficient additional data such as topography and outline of the main tectonic provinces is used to obtain homogeneous models. The new crustal model will be used for the construction of the gravity, thermal, compositional and rheological models of the lithosphere. In the next phase of the project, the new model, combined with a thermal model of the crust and upper mantle, will be used to assess the 3D rheological strength (in)homogeneity of the lithosphere. Probing possible rheological strength variations is essential for a successful quantitative assessment of the present-day intra-plate deformation of the study area.