3D sub-pixel correlation length imaging.

Quantitative 2D neutron dark-field-imaging with neutron grating interferometry has been used to characterize structures in the size range below the imaging resolution. We present the first 3D quantitative neutron dark-field imaging experiment. We characterize sub-pixel structure sizes below the imaging resolution in tomography by quantitatively analyzing the change in dark-field contrast with varying neutron wavelength. This proof of principle experiment uses a dedicated reference sample with four different solutions of microspheres, each with a different diameter. The result is a 3D tomogram featuring a real space scattering function in each voxel. The presented experiment is expected to mark the path for future material science research through the individual quantification of small-angle scattering structures in each voxel of a volume of a bulk inhomogeneous sample material.

Visualizing the heterogeneous breakdown of a fractal microstructure during compaction by neutron dark-field imaging.

Structural properties of cohesive powders are dominated by their microstructural composition. Powders with a fractal microstructure show particularly interesting properties during compaction where a microstructural transition and a fractal breakdown happen before compaction and force transport. The study of this phenomenon has been challenging due to its long-range effect and the subsequent necessity to characterize these microstructural changes on a macroscopic scale. For the detailed investigation of the complex nature of powder compaction for various densification states along with the heterogeneous breakdown of the fractal microstructure we applied neutron dark-field imaging in combination with a variety of supporting techniques with various spatial resolutions, field-of-views and information depths. We used scanning electron microscopy to image the surface microstructure in a small field-of-view and X-ray tomography to image density variations in 3D with lower spatial resolution. Non-local spin-echo small-angle neutron scattering results are used to evaluate fitting models later used as input parameters for the neutron dark-field imaging data analysis. Finally, neutron dark-field imaging results in combination with supporting measurements using scanning electron microscopy, X-ray tomography and spin-echo small angle scattering allowed us to comprehensively study the heterogeneous transition from a fractal to a homogeneous microstructure of a cohesive powder in a quantitative manner.

Chasing quantitative biases in neutron imaging with scintillator-camera detectors: a practical method with black body grids.

We propose a method for improving the quantification of neutron imaging measurements with scintillator-camera based detectors by correcting for systematic biases introduced by scattered neutrons and other sources such as light reflections in the detector system. This method is fully experimental, using reference measurements with a grid of small black bodies (BB) to measure the bias contributions directly. Using two test samples, one made of lead alloy and having a moderate (20%) neutron transmission and one made of stainless-steel and having a very low (1%) transmission, we evaluated the improvement brought by this method in reducing both the average quantification bias and the uncertainty around this average bias after tomographic reconstruction. The results show that a reduction of the quantification bias of up to one order of magnitude can be obtained. For moderately transparent samples, little sensitivity is observed to the parameters used for the correction. For the more challenging sample with very low transmission, a correct placement of the BB grid is of utmost importance for a successful correction.

On the needle clogging of staked-in-needle pre-filled syringes: Mechanism of liquid entering the needle and solidification process.

Staked-in-needle prefilled syringes (SIN-PFS) are widely used for the parenteral administration of drug product solutions. During stability studies, clogging of the injection needle was observed in syringes filled with concentrated antibody solution. A prerequisite for this phenomenon is that liquid has entered the needle. In this study, we characterized the mechanism causing the entry and movement of liquid in the needle using neutron imaging without manipulating the container closure integrity of the syringe. The gas pressure difference between inside and outside of the syringe was identified as the major cause of liquid movement. The influence of external factors, such as temperature fluctuation and physical pressure on the stopper, were tested and were confirmed to have a relevant impact on the processes of liquid entering and moving inside the injection needle. In a second step, the solidification process of the liquid segments inside the needle via solvent evaporation was further investigated, and the process was found to be dependent on storage time, environmental climate and interaction between the drug product solution and the needle surface. The presence of air/liquid segments was identified as a further factor for the stochastic behavior of needle clogging. For the first time, this fundamental mechanism behind the needle clogging issue was investigated in depth and the results will help to reduce the defect rate for clogged SIN-PFS products.

A Monte Carlo approach for scattering correction towards quantitative neutron imaging of polycrystals.

The development of neutron imaging from a qualitative inspection tool towards a quantitative technique in materials science has increased the requirements for accuracy significantly. Quantifying the thickness or the density of polycrystalline samples with high accuracy using neutron imaging has two main problems: (i) the scattering from the sample creates artefacts on the image and (ii) there is a lack of specific reference attenuation coefficients. This work presents experimental and simulation results to explain and approach these problems. Firstly, a series of neutron radiography and tomography experiments of iron, copper and vanadium are performed and serve as a reference. These materials were selected because they attenuate neutrons mainly through coherent (Fe and Cu) and incoherent (V) scattering. Secondly, an ad hoc Monte Carlo model was developed, based on beamline, sample and detector parameters, in order to simulate experiments, understand the physics involved and interpret the experimental data. The model, developed in the McStas framework, uses a priori information about the sample geometry and crystalline structure, as well as beamline settings, such as spectrum, geometry and detector type. The validity of the simulations is then verified with experimental results for the two problems that motivated this work: (i) the scattering distribution in transmission imaging and (ii) the calculated attenuation coefficients.

Clogging in staked-in needle pre-filled syringes (SIN-PFS): Influence of water vapor transmission through the needle shield.

Staked-in needle pre-fillable syringes (SIN-PFS) are a convenient delivery system widely established in the growing pharmaceutical market. Under specific storage conditions, the needle of PFS containing high concentration drug product (DP) solution is prone to clogging, which prevents administration of the liquid. The purpose of this study is to clarify the clogging phenomenon of SIN-PFS and to elucidate the role of water vapor transmission via the needle shield. The presence of liquid within needles is a prerequisite condition for clogging and was investigated non-invasively by neutron imaging (NI) to confirm that liquid can migrate into the needle under certain processing conditions. The water vapor transmission rate (WVTR) of different needle shields was measured and the impact of temperature and relative humidity (rH) on the WVTR was investigated on sheets with the same composition as used in commercial needle shields. Our study clearly showed that the partial vapor pressure difference (ΔPP) across the needle shield is the dominant driving factor for water vapor transmission. A linear correlation between ΔPP and WVTR was found and a model to predict the water vapor transmission for PFS under specific storage conditions was developed. The impact of the WVTR on needle clogging was confirmed by clogging tests performed on SIN-PFS stored under different conditions. Thereby, we clearly show that high water loss induced by higher WVTR can be correlated to an increased occurrence of needle clogging. In conclusion, the WVTR of the needle shield plays a key role in needle clogging and the established WVTR model can be employed to assess the clogging risk for product development.

Statistical uncertainty in the dark-field and transmission signal of grating interferometry.

We present a framework to estimate the fundamental statistical uncertainty of grating interferometer experiments based on a Monte-Carlo method. Using the framework, we are able to determine the uncertainty of individual measurements as well as suggesting experimental protocols that minimise the statistical uncertainty for given overall exposure times. The method presented here is valid for both X-rays and neutrons and can be generalised for any modulation measurement.

The influence of laser scribing on magnetic domain formation in grain oriented electrical steel visualized by directional neutron dark-field imaging.

The performance and degree of efficiency of transformers are directly determined by the bulk magnetic properties of grain oriented electrical steel laminations. The core losses can be improved by post manufacturing methods, so-called domain refinement techniques. All these methods induce mechanical or thermal stress that refines the domain structure. The most commonly used technique is laser scribing due to the no-contact nature and the ease of integration in existing production systems. Here we show how directional neutron dark-field imaging allows visualizing the impact of laser scribing on the bulk and supplementary domain structure. In particular, we investigate the domain formation during magnetization of samples depending on laser treatment parameters such as laser energy and line distances. The directional dark-field imaging findings were quantitatively interpreted in the context with global magnetic hysteresis measurements. Especially we exploit the orientation sensitivity in the dark-field images to distinguish between different domain structures alignment and their relation to the laser scribing process.

Solvent and solute ingress into hydrogels resolved by a combination of imaging techniques.

Using simultaneous neutron, fluorescence, and optical brightfield transmission imaging, the diffusion of solvent, fluorescent dyes, and macromolecules into a crosslinked polyacrylamide hydrogel was investigated. This novel combination of different imaging techniques enables us to distinguish the movements of the solvent and fluorescent molecules. Additionally, the swelling or deswelling of the hydrogels can be monitored. From the sequence of images, dye and solvent concentrations were extracted spatially and temporally resolved. Diffusion equations and different boundary conditions, represented by different models, were used to quantitatively analyze the temporal evolution of these concentration profiles and to determine the diffusion coefficients of solvent and solutes. Solute size and network properties were varied and their effect was investigated. Increasing the crosslinking ratio or partially drying the hydrogel was found to hinder solute diffusion due to the reduced pore size. By contrast, solvent diffusion seemed to be slightly faster if the hydrogel was only partially swollen and hence solvent uptake enhanced.

Real-Time Neutron Imaging to Detect Origin of Blocking in Drug Injection Devices.

Nondestructive testing is a common method for root cause investigations of malfunction of mechanical devices, for example, medical devices for drug dose delivery. Radiography is a method that has the advantage that it is possible to see through the sample. In this work we are using neutron radiography to observe drug distribution in drug injection devices during the injection process and as post-injection examination. Using neutrons it is possible to show small amounts of liquid in capillaries, and foam bubbles are shown with great contrast compared to metal and glass. The investigation has two parts optimized for high spatial and high temporal resolution, respectively. Using high spatial resolution it is possible to resolve the thin films of drug product in foam and even to detect the drug residues in the injection needle. Switching to high temporal resolution we demonstrate that it is possible to follow the injection process. Spatio-temporal data sets of the injection process were acquired using remotely triggered injection devices and a camera allowing sub-second frame rates.The motion analysis required the application of an edge-preserving spatio-temporal denoising filter to improve the signal-to-noise ratio. After filtering it is possible to detect relevant edges and extract motion curves from the spatio-temporal data. LAY ABSTRACT: Neutron imaging is a nondestructive method based on radiography using neutrons and is suitable for detecting small amounts of aqueous liquids even in metallic casing/sheath/tubing. This property has here been used to visualize the distribution of a drug product in a syringe needle of a drug injection device. In the static case the method clearly showed the difference between needles that were empty, full, or contained a mix of gas and liquid. A second investigation was aimed to visualize the dynamic behavior of an auto-injector device. In this experiment the imaging method was capable of following the injection phase of the device. By analyzing the acquired images in time and space it is possible to measure the injection velocity curves of the piston and drug, respectively.

Visualizing the morphology of vortex lattice domains in a bulk type-II superconductor.

Alike materials in the solid state, the phase diagram of type-II superconductors exhibit crystalline, amorphous, liquid and spatially inhomogeneous phases. The multitude of different phases of vortex matter has thence proven to act as almost ideal model system for the study of both the underlying properties of superconductivity but also of general phenomena such as domain nucleation and morphology. Here we show how neutron grating interferometry yields detailed information on the vortex lattice and its domain structure in the intermediate mixed state of a type-II niobium superconductor. In particular, we identify the nucleation regions, how the intermediate mixed state expands, and where it finally evolves into the Shubnikov phase. Moreover, we complement the results obtained from neutron grating interferometry by small-angle neutron scattering that confirm the spatially resolved morphology found in the intermediate mixed state, and very small-angle neutron scattering that confirm the domain structure of the vortex lattice.

Neutron, fluorescence, and optical imaging: An in situ combination of complementary techniques.

An apparatus which enables the simultaneous combination of three complementary imaging techniques, optical imaging, fluorescence imaging, and neutron radiography, is presented. While each individual technique can provide information on certain aspects of the sample and their time evolution, a combination of the three techniques in one setup provides a more complete and consistent data set. The setup can be used in transmission and reflection modes and thus with optically transparent as well as opaque samples. Its capabilities are illustrated with two examples. A polymer hydrogel represents a transparent sample and the diffusion of fluorescent particles into and through this polymer matrix is followed. In reflection mode, the absorption of solvent by a nile red-functionalized mesoporous silica powder and the corresponding change in fluorescent signal are studied.

Quantification of the sensitivity range in neutron dark-field imaging.

In neutron grating interferometry, the dark-field image visualizes the scattering properties of samples in the small-angle and ultra-small-angle scattering range. These angles correspond to correlation lengths from several hundred nanometers up to several tens of micrometers. In this article, we present an experimental study that demonstrates the potential of quantitative neutron dark-field imaging. The dark-field signal for scattering from different particle sizes and concentrations of mono-dispersive polystyrene particles in aqueous solution is compared to theoretical predictions and the good agreement between measurements and calculations underlines the quantitative nature of the measured values and reliability of the technique with neutrons.

Three-dimensional imaging of magnetic domains.

Magnetic domains have been the subject of much scientific investigation since their theoretical existence was first postulated by P.-E. Weiss over a century ago. Up to now, the three-dimensional (3D) domain structure of bulk magnets has never been observed owing to the lack of appropriate experimental methods. Domain analysis in bulk matter thus remains one of the most challenging tasks in research on magnetic materials. All current domain observation methods are limited to studying surface domains or thin magnetic films. As the properties of magnetic materials are strongly affected by their domain structure, the development of a technique capable of investigating the shape, size and distribution of individual domains in three dimensions is of great importance. Here, we show that the novel technique of Talbot-Lau neutron tomography with inverted geometry enables direct imaging of the 3D network of magnetic domains within the bulk of FeSi crystals.

Neutron dark-field tomography.

We report how a grating interferometer yields neutron dark-field scatter images for tomographic investigations. The image contrast is based on ultrasmall-angle scattering. It provides otherwise inaccessible spatially resolved information about the distribution of micrometer and submicrometer sized structural formations. Three complementary sets of tomographic data corresponding to attenuation, differential phase, and small-angle scattering can be obtained from one measurement. The method is compatible with conventional imaging and provides significantly higher efficiency than existing techniques.

Neutron decoherence imaging for visualizing bulk magnetic domain structures.

Here we introduce a novel neutron imaging method, which is based on the effect that the spatial coherence of the neutron wave front can be changed through small-angle scattering of neutrons at magnetic domain walls in the specimen. We show that the technique can be used to visualize internal bulk magnetic domain structures that are difficult to access by other techniques. The method is transferable to a wide variety of specimens, extendable to three dimensions, and well suited for investigating materials under the influence of external parameters, as, e.g., external magnetic field, temperature, or pressure.

Design, fabrication, and characterization of diffraction gratings for neutron phase contrast imaging.

We have developed a neutron phase contrast imaging method based on a grating interferometer setup. The principal constituents are two absorption gratings made of gadolinium and a phase modulating grating made of silicon. The design parameters of the setup, such as periodicity, structure heights of the gratings, and the distances between the gratings, are calculated. The fabrication of each grating is described in detail. The produced diffraction gratings were finally characterized within the setup, by locally evaluating the produced contrast (visibility) in each detector pixel, resulting in a visibility map over the whole grating size. An averaged value of 23% is achieved.

Hard-X-ray dark-field imaging using a grating interferometer.

Imaging with visible light today uses numerous contrast mechanisms, including bright- and dark-field contrast, phase-contrast schemes and confocal and fluorescence-based methods. X-ray imaging, on the other hand, has only recently seen the development of an analogous variety of contrast modalities. Although X-ray phase-contrast imaging could successfully be implemented at a relatively early stage with several techniques, dark-field imaging, or more generally scattering-based imaging, with hard X-rays and good signal-to-noise ratio, in practice still remains a challenging task even at highly brilliant synchrotron sources. In this letter, we report a new approach on the basis of a grating interferometer that can efficiently yield dark-field scatter images of high quality, even with conventional X-ray tube sources. Because the image contrast is formed through the mechanism of small-angle scattering, it provides complementary and otherwise inaccessible structural information about the specimen at the micrometre and submicrometre length scale. Our approach is fully compatible with conventional transmission radiography and a recently developed hard-X-ray phase-contrast imaging scheme. Applications to X-ray medical imaging, industrial non-destructive testing and security screening are discussed.

Highly absorbing gadolinium test device to characterize the performance of neutron imaging detector systems.

We report on the fabrication and application of a novel neutron imaging test device made of gadolinium. It is designed for a real time evaluation of the spatial resolution, resolution direction, and distortions of a neutron imaging detector system. Measurements of the spatial resolution of (6)LiF doped ZnS scintillator screens with different thicknesses and of imaging plates were performed. The obtained results are in good agreement with comparison measurements using the standard knife edge detection method.

Grating interferometer based scanning setup for hard X-ray phase contrast imaging.

In x-ray radiography, particularly for technical and industrial applications, a scanning setup is very often favorable when compared to a direct two-dimensional image acquisition. Here, we report on an efficient scanning method for grating based x-ray phase contrast imaging with tube based sources. It uses multiple line detectors for staggered acquisition of the individual phase-stepping images. We find that the total exposure time does not exceed the time needed in an equivalent scanning setup for absorption radiography. Therefore, we conclude that it should be possible to implement the method into a scanning system without affecting the scanning speed or significant increase in cost but with the advantage of providing both the phase contrast and the absorption information at once.