Unraveling Pre-filled Syringe Needle Clogging: Exploring a Fresh Outlook Through Innovative Techniques.

OBJECTIVE: This study aimed to investigate the movement of liquid in the needle region of staked-in-needle pre-filled syringes using neutron imaging and synchrotron X-ray tomography. The objective was to gain insights into the dynamics of liquid presence and understand the factors contributing to needle clogging. METHODS: Staked-in-needle pre-filled syringes were examined using neutron radiography and synchrotron X-ray phase-contrast computed tomography. Neutron radiography provided a 2D visualization of liquid presence in the needle, while synchrotron X-ray tomography offered high-resolution 3D imaging to study detailed morphological features of the liquid. RESULTS: Neutron radiography revealed liquid presence in the needle region for as-received samples and after temperature and pressure cycling. Pressure cycling had a more pronounced effect on liquid formation. Synchrotron X-ray tomography confirmed the presence of liquid and revealed various morphologies, including droplets of different sizes, liquid segments blocking sections of the needle, and a thin layer covering the needle wall. Liquid presence was also observed between the steel needle and the glass barrel. CONCLUSIONS: The combination of neutron imaging and synchrotron X-ray tomography provided valuable insights into the dynamics of liquid movement in staked-in-needle pre-filled syringes. Temperature and pressure cycling were found to contribute to additional liquid formation, with pressure changes playing a significant role. The detailed morphological analysis enhanced the understanding of microstructural arrangements within the needle. This research contributes to addressing the issue of needle clogging and can guide the development of strategies to improve pre-filled syringe performance.

Multi-resolution X-ray phase-contrast and dark-field tomography of human cerebellum with near-field speckles.

In this study, we use synchrotron-based multi-modal X-ray tomography to examine human cerebellar tissue in three dimensions at two levels of spatial resolution (2.3 µm and 11.9 µm). We show that speckle-based imaging (SBI) produces results that are comparable to propagation-based imaging (PBI), a well-established phase-sensitive imaging method. The different SBI signals provide complementary information, which improves tissue differentiation. In particular, the dark-field signal aids in distinguishing tissues with similar average electron density but different microstructural variations. The setup's high resolution and the imaging technique's excellent phase sensitivity enabled the identification of different cellular layers and additionally, different cell types within these layers. We also correlated this high-resolution phase-contrast information with measured dark-field signal levels. These findings demonstrate the viability of SBI and the potential benefit of the dark-field modality for virtual histology of brain tissue.

Unraveling the role of TGFß signaling in thoracic aortic aneurysm and dissection using Fbn1 mutant mouse models.

Although abnormal TGFß signaling is observed in several heritable forms of thoracic aortic aneurysms and dissections including Marfan syndrome, its precise role in aortic disease progression is still disputed. Using a mouse genetic approach and quantitative isobaric labeling proteomics, we sought to elucidate the role of TGFß signaling in three Fbn1 mutant mouse models representing a range of aortic disease from microdissection (without aneurysm) to aneurysm (without rupture) to aneurysm and rupture. Results indicated that reduced TGFß signaling and increased mast cell proteases were associated with microdissection. In contrast, increased abundance of extracellular matrix proteins, which could be reporters for positive TGFß signaling, were associated with aneurysm. Marked reductions in collagens and fibrillins, and increased TGFß signaling, were associated with aortic rupture. Our data indicate that TGFß signaling performs context-dependent roles in the pathogenesis of thoracic aortic disease.

Fluid-Structure Interaction Modeling of the Aortic Hemodynamics in Adult Zebrafish: A Pilot Study Based on Synchrotron X-Ray Tomography.

OBJECTIVE: The zebrafish is increasingly used as a small animal model for cardiovascular disease, including vascular disorders. Nevertheless, a comprehensive biomechanical understanding of the zebrafish cardiovascular circulation is still lacking and possibilities for phenotyping the zebrafish heart and vasculature at adult - no longer optically transparent - stages are limited. To improve these aspects, we developed imaging-based 3D models of the cardiovascular system of wild-type adult zebrafish. METHODS: In vivo high-frequency echocardiography and ex vivo synchrotron X-ray tomography were combined to build fluid-structure interaction finite element models of the fluid dynamics and biomechanics inside the ventral aorta. RESULTS: We successfully generated a reference model of the circulation in adult zebrafish. The dorsal side of the most proximal branching region was found as the location of highest first principal wall stress and was also a location of low wall shear stress. Reynolds number and oscillatory shear were very low compared to mice and humans. SIGNIFICANCE: The presented wild-type results provide a first extensive biomechanical reference for adult zebrafish. This framework can be used for advanced cardiovascular phenotyping of adult genetically engineered zebrafish models of cardiovascular disease, showing disruptions of the normal mechano-biology and homeostasis. By providing reference values for key biomechanical stimuli (including wall shear stress and first principal stress) in wild-type animals, and a pipeline for image-based animal-specific computational biomechanical models, this study contributes to a more comprehensive understanding of the role of altered biomechanics and hemodynamics in heritable cardiovascular pathologies.

Brittle fracture studied by ultra-high-speed synchrotron X-ray diffraction imaging.

In situ investigations of cracks propagating at up to 2.5 km s-1 along an (001) plane of a silicon single crystal are reported, using X-ray diffraction megahertz imaging with intense and time-structured synchrotron radiation. The studied system is based on the Smart Cut process, where a buried layer in a material (typically Si) is weakened by microcracks and then used to drive a macroscopic crack (10-1 m) in a plane parallel to the surface with minimal deviation (10-9 m). A direct confirmation that the shape of the crack front is not affected by the distribution of the microcracks is provided. Instantaneous crack velocities over the centimetre-wide field of view were measured and showed an effect of local heating by the X-ray beam. The post-crack movements of the separated wafer parts could also be observed and explained using pneumatics and elasticity. A comprehensive view of controlled fracture propagation in a crystalline material is provided, paving the way for the in situ measurement of ultra-fast strain field propagation.

Corrigendum: X-ray Phase Contrast Tomography Serves Preclinical Investigation of Neurodegenerative Diseases.

[This corrects the article DOI: 10.3389/fnins.2020.584161.].

X-ray Phase Contrast Tomography Serves Preclinical Investigation of Neurodegenerative Diseases.

We report a qualitative study on central nervous system (CNS) damage that demonstrates the ability of X-ray phase contrast tomography (XPCT) to confirm data obtained with standard 2D methodology and permits the description of additional features that are not detected with 2D or other 3D techniques. In contrast to magnetic resonance or computed tomography, XPCT makes possible the high-resolution 3D imaging of soft tissues classically considered "invisible" to X-rays without the use of additional contrast agents, or without the need for intense processing of the tissue required by 2D techniques. Most importantly for studies of CNS diseases, XPCT enables a concomitant multi-scale 3D biomedical imaging of neuronal and vascular networks ranging from cells through to the CNS as a whole. In the last years, we have used XPCT to investigate neurodegenerative diseases, such as Alzheimer's disease (AD) and multiple sclerosis (MS), to shed light on brain damage and extend the observations obtained with standard techniques. Here, we show the cutting-edge ability of XPCT to highlight in 3D, concomitantly, vascular occlusions and damages, close associations between plaques and damaged vessels, as well as dramatic changes induced at neuropathological level by treatment in AD mice. We corroborate data on the well-known blood-brain barrier dysfunction in the animal model of MS, experimental autoimmune encephalomyelitis, and further show its extent throughout the CNS axis and at the level of the single vessel/capillary.

Author Correction: Supervised deep learning for real-time quality monitoring of laser welding with X-ray radiographic guidance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Auditory chain reaction: Effects of sound pressure and particle motion on auditory structures in fishes.

Despite the diversity in fish auditory structures, it remains elusive how otolith morphology and swim bladder-inner ear (= otophysic) connections affect otolith motion and inner ear stimulation. A recent study visualized sound-induced otolith motion; but tank acoustics revealed a complex mixture of sound pressure and particle motion. To separate sound pressure and sound-induced particle motion, we constructed a transparent standing wave tube-like tank equipped with an inertial shaker at each end while using X-ray phase contrast imaging. Driving the shakers in phase resulted in maximised sound pressure at the tank centre, whereas particle motion was maximised when shakers were driven out of phase (180°). We studied the effects of two types of otophysic connections-i.e. the Weberian apparatus (Carassius auratus) and anterior swim bladder extensions contacting the inner ears (Etroplus canarensis)-on otolith motion when fish were subjected to a 200 Hz stimulus. Saccular otolith motion was more pronounced when the swim bladder walls oscillated under the maximised sound pressure condition. The otolith motion patterns mainly matched the orientation patterns of ciliary bundles on the sensory epithelia. Our setup enabled the characterization of the interplay between the auditory structures and provided first experimental evidence of how different types of otophysic connections affect otolith motion.

Supervised deep learning for real-time quality monitoring of laser welding with X-ray radiographic guidance.

Laser welding is a key technology for many industrial applications. However, its online quality monitoring is an open issue due to the highly complex nature of the process. This work aims at enriching existing approaches in this field. We propose a method for real-time detection of process instabilities that can lead to defects. Hard X-ray radiography is used for the ground truth observations of the sub-surface events that are critical for the quality. A deep artificial neural network is applied to reveal the unique signatures of those events in wavelet spectrograms from the laser back-reflection and acoustic emission signals. The autonomous classification of the revealed signatures is tested on real-life data, while the real-time performance is reached by means of parallel computing. The confidence of the quality classification ranges between 71% and 99%, with a temporal resolution down to 2 ms and a computation time per classification task as low as 2 ms. This approach is a new paradigm in the digitization of industrial processes and can be exploited to provide feedbacks in a closed-loop quality control system.

Time and Mechanism of Nanoparticle Functionalization by Macromolecular Ligands during Pulsed Laser Ablation in Liquids.

Laser ablation of gold in liquids with nanosecond laser pulses in aqueous solutions of inorganic electrolytes and macromolecular ligands for gold nanoparticle size quenching is probed inside the laser-induced cavitation bubble by in situ X-ray multicontrast imaging with a Hartmann mask (XHI). It is found that (i) the in situ size quenching power of sodium chloride (NaCl) in comparison to the ablation in pure water can be observed by the scattering contrast from XHI already inside the cavitation bubble, while (ii) for polyvinylpyrrolidone (PVP) as a macromolecular model ligand an in situ size quenching cannot be observed. Complementary ex situ characterization confirms the overall size quenching ability of both additive types NaCl and PVP. The macromolecular ligand as well as its monomer N-vinylpyrrolidone (NVP) are mainly effective for growth quenching of larger nanoparticles on later time scales, leading to the conclusion of an alternative interaction mechanism with ablated nanoparticles compared to the electrolyte NaCl, probably outside of the cavitation bubble, in the surrounding liquid phase. While monomer and polymer have similar effects on the particle properties, with the polymer being slightly more efficient, only the polymer is effective against hydrodynamic aggregation.

Ultra-high-speed indirect x-ray imaging system with versatile spatiotemporal sampling capabilities.

A new generation of cameras has made ultra-high-speed x-ray imaging at synchrotron light sources a reality, revealing never-before-seen details of sub-surface transient phenomena. We introduce a versatile indirect imaging system capable of capturing-for the first time-hundreds of sequential x-ray pulses in 16-bunch mode at the European Synchrotron Radiation Facility, recording at 5.68 Mfps over dozens of microseconds, with an effective exposure of 100 ps. The versatile multiplex camera construction of the system allows for various arrangements, including different scintillator configurations, and simultaneous imaging with different resolutions and regions of interest. Image results from a gas gun impact experiment, in which an additive manufactured aluminum lattice was dynamically compressed, is presented as a demonstration of the system's capabilities.

Towards a practical implementation of X-ray ghost imaging with synchrotron light.

An experimental procedure for transmission X-ray ghost imaging using synchrotron light is presented. Hard X-rays from an undulator were divided by a beamsplitter to produce two copies of a speckled incident beam. Both beams were simultaneously measured on an indirect pixellated detector and the intensity correlation between the two copies was used to retrieve the ghost image of samples placed in one of the two beams, without measuring the samples directly. Aiming at future practical uses of X-ray ghost imaging, the authors discuss details regarding data acquisition, image reconstruction strategies and measure the point-spread function of the ghost-imaging system. This approach may become relevant for applications of ghost imaging with X-ray sources such as undulators in storage rings, free-electron lasers and lower-coherence laboratory facilities.

In-situ visualization of sound-induced otolith motion using hard X-ray phase contrast imaging.

Regarding the basics of ear structure-function relationships in fish, the actual motion of the solid otolith relative to the underlying sensory epithelium has rarely been investigated. Otolith motion has been characterized based on a few experimental studies and on approaches using mathematical modeling, which have yielded partially conflicting results. Those studies either predicted a simple back-and-forth motion of the otolith or a shape-dependent, more complex motion. Our study was designed to develop and test a new set-up to generate experimental data on fish otolith motion in-situ. Investigating the basic parameters of otolith motion requires an approach with high spatial and temporal resolution. We therefore used hard X-ray phase contrast imaging (XPCI). We compared two anatomically well-studied cichlid species, Steatocranus tinanti and Etroplus maculatus, which, among other features, differ in the 3D shape of their otoliths. In a water-filled tank, we presented a pure tone of 200 Hz to 1) isolated otoliths embedded in agarose serving as a simple model or 2) to a fish (otoliths in-situ). Our new set-up successfully visualized the motion of otoliths in-situ and therefore paves the way for future studies evaluating the principles of otolith motion.

MHz frame rate hard X-ray phase-contrast imaging using synchrotron radiation.

Third generation synchrotron light sources offer high photon flux, partial spatial coherence, and ~10-10 s pulse widths. These enable hard X-ray phase-contrast imaging (XPCI) with single-bunch temporal resolutions. In this work, we exploited the MHz repetition rates of synchrotron X-ray pulses combined with indirect X-ray detection to demonstrate the potential of XPCI with millions of frames per second multiple-frame recording. This allows for the visualization of aperiodic or stochastic transient processes which are impossible to be realized using single-shot or stroboscopic XPCI. We present observations of various phenomena, such as crack tip propagation in glass, shock wave propagation in water and explosion during electric arc ignition, which evolve in the order of km/s (µm/ns).

Fluence Threshold Behaviour on Ablation and Bubble Formation in Pulsed Laser Ablation in Liquids.

The ablation yield and bubble-formation process during nanosecond pulsed-laser ablation of silver in water are analysed by stroboscopic videography, time-resolved X-ray radiography and in situ UV/Vis spectroscopy. This process is studied as function of lens-target distance and laser fluence. Both the ablation yield and the bubble-cavitation process exhibit threshold behaviour as a function of fluence, which is linked to the efficiency of coupling of energy at the water/target interface. Although ablation happens below this threshold, quantitative material emission is linked to bubble formation. Above the threshold, both bubble size and ablation show linear behaviour.

Hard X-ray phase-contrast tomography of non-homogeneous specimens: grating interferometry versus propagation-based imaging.

X-ray phase-contrast imaging is an effective approach to drastically increase the contrast and sensitivity of microtomographic techniques. Numerous approaches to depict the real part of the complex-valued refractive index of a specimen are nowadays available. A comparative study using experimental data from grating-based interferometry and propagation-based phase contrast combined with single-distance phase retrieval applied to a non-homogeneous sample is presented (acquired at beamline ID19-ESRF). It is shown that grating-based interferometry can handle density gradients in a superior manner. The study underlines the complementarity of the two techniques for practical applications.