Synchrotron x ray induced axonal transections in the brain of rats assessed by high-field diffusion tensor imaging tractography

Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.

In-situ X-ray micro-diffraction studies of heterogeneous interfaces between cementitious materials and geological formations

In the present study the challenge of analyzing complex micro X-ray diffraction (microXRD) patterns from cement–clay interfaces has been addressed. In order to extract the maximum information concerning both the spatial distribution and the crystal structure type associated with each of the many diffracting grains in heterogeneous, polycrystalline samples, an approach has been developed in which microXRD was applied to thin sections which were rotated in the X-ray beam. The data analysis, performed on microXRD patterns collected from a filled vein of a cement–clay interface from the natural analogue in Maqarin (Jordan), and a sample from a two-year-old altered interface between cement and argillaceous rock, demonstrate the potential of this method.

Quantitative 3D strain analysis in analogue experiments: Integration of X-ray computed tomography and digital volume correlation techniques

The combination of scaled analogue experiments, material mechanics, X-ray computed tomography (XRCT) and Digital Volume Correlation techniques (DVC) is a powerful new tool not only to examine the 3 dimensional structure and kinematic evolution of complex deformation structures in scaled analogue experiments, but also to fully quantify their spatial strain distribution and complete strain history. Digital image correlation (DIC) is an important advance in quantitative physical modelling and helps to understand non-linear deformation processes. Optical non-intrusive (DIC) techniques enable the quantification of localised and distributed deformation in analogue experiments based either on images taken through transparent sidewalls (2D DIC) or on surface views (3D DIC). X-ray computed tomography (XRCT) analysis permits the non-destructive visualisation of the internal structure and kinematic evolution of scaled analogue experiments simulating tectonic evolution of complex geological structures. The combination of XRCT sectional image data of analogue experiments with 2D DIC only allows quantification of 2D displacement and strain components in section direction. This completely omits the potential of CT experiments for full 3D strain analysis of complex, non-cylindrical deformation structures. In this study, we apply digital volume correlation (DVC) techniques on XRCT scan data of “solid” analogue experiments to fully quantify the internal displacement and strain in 3 dimensions over time. Our first results indicate that the application of DVC techniques on XRCT volume data can successfully be used to quantify the 3D spatial and temporal strain patterns inside analogue experiments. We demonstrate the potential of combining DVC techniques and XRCT volume imaging for 3D strain analysis of a contractional experiment simulating the development of a non-cylindrical pop-up structure. Furthermore, we discuss various options for optimisation of granular materials, pattern generation, and data acquisition for increased resolution and accuracy of the strain results. Three-dimensional strain analysis of analogue models is of particular interest for geological and seismic interpretations of complex, non-cylindrical geological structures. The volume strain data enable the analysis of the large-scale and small-scale strain history of geological structures.

The Galactic Cosmic Ray Intensity over the Past 106–109 Years as Recorded by Cosmogenic Nuclides in Meteorites and Terrestrial Samples

Concentrations of stable and radioactive nuclides produced by cosmic ray particles in meteorites allow us to track the long term average of the primary flux of galactic cosmic rays (GCR). During the past ∼10 Ma, the average GCR flux remained constant over timescales of hundreds of thousands to millions of years, and, if corrected for known variations in solar modulation, also during the past several years to hundreds of years. Because the cosmic ray concentrations in meteorites represent integral signals, it is difficult to assess the limits of uncertainty of this statement, but they are larger than the often quoted analytical and model uncertainties of some 30%. Time series of concentrations of the radionuclide 10Be in terrestrial samples strengthen the conclusions drawn from meteorite studies, indicating that the GCR intensity on a ∼0.5 million year scale has remained constant within some ±10% during the past ∼10 million years. The very long-lived radioactive nuclide 40K allows to assess the GCR flux over about the past one billion years. The flux over the past few million years has been the same as the longer-term average in the past 0.5–1 billion years within a factor of ∼1.5. However, newer data do not confirm a long-held belief that the flux in the past few million years has been higher by some 30–50% than the very long term average. Neither does our analysis confirm a hypothesis that the iron meteorite data indicate a ∼150 million year periodicity in the cosmic ray flux, possibly related to variations in the long-term terrestrial climate.

Hohlraum Target for Overcoming Refractive Losses in Plasma X-ray Lasers

Refractive losses in laser-produced plasmas used as gain media are caused by electron density gradients, and limit the energy transport range. The pump pulse is thus deflected from the high-gain region and the short wavelength laser signal also steers away, causing loss of collimation. A Hohlraum used as a target makes the plasma homogeneous and can mitigate refractive losses by means of wave-guiding. A computational study combining a hydrodynamics code and an atomic physics code is presented, which includes a ray-tracing modeling based on the eikonal theory of the trajectory equation. This study presents gain calculations based on population inversion produced by free-electron collisions exciting bound electrons into metastable levels in the 3d94d1(J = 0) → 3d94p1(J = 1) transition of Ni-like Sn. Further, the Hohlraum suggests a dramatic enhancement of the conversion efficiency of collisionally excited x-ray lasing for Ni-like Sn.

High-density large-scale field emitter arrays for x-ray free electron laser cathodes

High brightness electron sources are of great importance for the operation of the hard X-ray free electron lasers. Field emission cathodes based on the double-gate metallic field emitter arrays (FEAs) can potentially offer higher brightness than the currently used ones. We report on the successful application of electron beam lithography for fabrication of the large-scale single-gate as well as double-gate FEAs. We demonstrate operational high-density single-gate FEAs with sub-micron pitch and total number of tips up to 106 as well as large-scale double-gate FEAs with large collimation gate apertures. The details of design, fabrication procedure and successful measurements of the emission current from the single- and double-gate cathodes are presented.

Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study

OBJECTIVE To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. METHODS ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. RESULTS Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). CONCLUSIONS Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER NCT00810199.

X-ray image calibration and its application to clinical orthopedics.

X-ray imaging is one of the most commonly used medical imaging modality. Albeit X-ray radiographs provide important clinical information for diagnosis, planning and post-operative follow-up, the challenging interpretation due to its 2D projection characteristics and the unknown magnification factor constrain the full benefit of X-ray imaging. In order to overcome these drawbacks, we proposed here an easy-to-use X-ray calibration object and developed an optimization method to robustly find correspondences between the 3D fiducials of the calibration object and their 2D projections. In this work we present all the details of this outlined concept. Moreover, we demonstrate the potential of using such a method to precisely extract information from calibrated X-ray radiographs for two different orthopedic applications: post-operative acetabular cup implant orientation measurement and 3D vertebral body displacement measurement during preoperative traction tests. In the first application, we have achieved a clinically acceptable accuracy of below 1° for both anteversion and inclination angles, where in the second application an average displacement of 8.06±3.71 mm was measured. The results of both applications indicate the importance of using X-ray calibration in the clinical routine.

Combining Monte Carlo methods with coherent wave optics for the simulation of phase-sensitive X-ray imaging

Phase-sensitive X-ray imaging shows a high sensitivity towards electron density variations, making it well suited for imaging of soft tissue matter. However, there are still open questions about the details of the image formation process. Here, a framework for numerical simulations of phase-sensitive X-ray imaging is presented, which takes both particle- and wave-like properties of X-rays into consideration. A split approach is presented where we combine a Monte Carlo method (MC) based sample part with a wave optics simulation based propagation part, leading to a framework that takes both particle- and wave-like properties into account. The framework can be adapted to different phase-sensitive imaging methods and has been validated through comparisons with experiments for grating interferometry and propagation-based imaging. The validation of the framework shows that the combination of wave optics and MC has been successfully implemented and yields good agreement between measurements and simulations. This demonstrates that the physical processes relevant for developing a deeper understanding of scattering in the context of phase-sensitive imaging are modelled in a sufficiently accurate manner. The framework can be used for the simulation of phase-sensitive X-ray imaging, for instance for the simulation of grating interferometry or propagation-based imaging.