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Ultra-high-speed synchrotron-based hard X-ray (i.e. above 10 keV) imaging is gaining a growing interest in a number of scientific domains for tracking non-repeatable dynamic phenomena at spatio-temporal microscales. This work describes an optimized indirect X-ray imaging microscope designed to achieve high performance at micrometre pixel size and megahertz acquisition speed. The entire detector optical arrangement has an improved sensitivity within the near-ultraviolet (NUV) part of the emitted spectrum (i.e. 310–430 nm wavelength). When combined with a single-crystal fast-decay scintillator, such as LYSO:Ce (Lu2−xYxSiO5:Ce), it exploits the potential of the NUV light-emitting scintillators. The indirect arrangement of the detector makes it suitable for high-dose applications that require high-energy illumination. This allows for synchrotron single-bunch hard X-ray imaging to be performed with improved true spatial resolution, as herein exemplified through pulsed wire explosion and superheated near-nozzle gasoline injection experiments at a pixel size of 3.2 µm, acquisition rates up to 1.4 MHz and effective exposure time down to 60 ps.

Abstract Background Patient-specific aiming devices (PSAD) may improve precision and accuracy of glenoid component positioning in total shoulder arthroplasty, especially in degenerative glenoids. The aim of this study was to compare precision and accuracy of guide wire positioning into different glenoid models using a PSAD versus a standard guide. Methods Three experienced shoulder surgeons inserted 2.5 mm K-wires into polyurethane cast glenoid models of type Walch A, B and C (in total 180 models). Every surgeon placed guide wires into 10 glenoids of each type with a standard guide by DePuy Synthes in group (I) and with a PSAD in group (II). Deviation from planned version, inclination and entry point was measured, as well as investigation of a possible learning curve. Results Maximal deviation in version in B- and C-glenoids in (I) was 20.3° versus 4.8° in (II) (p

Abstract Background With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy. Methods Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTRasym) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry. Results During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models. Conclusion Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition.

Abstract Background Response assessment of targeted cancer therapies is becoming increasingly challenging, as it is not adequately assessable with conventional morphological and volumetric analyses of tumor lesions. The tumor microenvironment is particularly constituted by tumor vasculature which is altered by various targeted therapies. The aim of this study was to noninvasively assess changes in tumor perfusion and vessel permeability after targeted therapy in murine models of breast cancer with divergent degrees of malignancy. Methods Low malignant 67NR or highly malignant 4T1 tumor-bearing mice were treated with either the multi-kinase inhibitor sorafenib or immune checkpoint inhibitors (ICI, combination of anti-PD1 and anti-CTLA4). Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with i.v. injection of albumin-binding gadofosveset was conducted on a 9.4 T small animal MRI. Ex vivo validation of MRI results was achieved by transmission electron microscopy, immunohistochemistry and laser ablation-inductively coupled plasma-mass spectrometry. Results Therapy-induced changes in tumor vasculature differed between low and highly malignant tumors. Sorafenib treatment led to decreased tumor perfusion and endothelial permeability in low malignant 67NR tumors. In contrast, highly malignant 4T1 tumors demonstrated characteristics of a transient window of vascular normalization with an increase in tumor perfusion and permeability early after therapy initiation, followed by decreased perfusion and permeability parameters. In the low malignant 67NR model, ICI treatment also mediated vessel-stabilizing effects with decreased tumor perfusion and permeability, while ICI-treated 4T1 tumors exhibited increasing tumor perfusion with excessive vascular leakage. Conclusion DCE-MRI enables noninvasive assessment of early changes in tumor vasculature after targeted therapies, revealing different response patterns between tumors with divergent degrees of malignancy. DCE-derived tumor perfusion and permeability parameters may serve as vascular biomarkers that allow for repetitive examination of response to antiangiogenic treatment or immunotherapy.

Introduction: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). Materials and methods: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. Results and discussions: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Typical standards in aerospace applications require the ultrasonic testing (UT) of bar and wire stock with a highly reliable detection of small defects over a wide depth range in the material. Characteristic reference reflectors are flat bottom holes (FBH) with diameters smaller than 1 mm. Typically, such inspections are done with immersion tanks using a set of probes optimized for each depth. However, for industrial applications there are disadvantages such as slow scan speed, the time-consuming inlet and outlet process, complicated mechanics and significant costs of the specialized probes. This contribution demonstrates an in-line phased array inspection system with integrated multi-zone inspection, which is based on the Krautkrämer ROWA™ Ux machine. After a short description of the setup special focus is given on the implemented testing concept which is optimized with respect to a multi-zone inspection and includes a dedicated automated adjustment of the system. Furthermore, the powerful electronics allows a flexible setting of focus point, aperture size and filtering. This significantly reduces the need for special probes and by means of digital depth focusing (DDF) also the number of test shots. At the end, the flaw detectability in different depths is illustrated and achievable test speeds are presented. Moreover, external boundary conditions are discussed.

Background: Fracture classifications of the distal clavicle are based on ligamentous integrity. The influence of osseous microarchitecture on fracture occurrence, morphology, and the lesion’s stability has not yet been investigated. We aimed to characterize osseous microarchitecture according to common fracture classification systems based on ligamentous integrity and investigated the possible effects of age, gender, and osteoporosis in distal clavicle fractures. Methods: N = 20 human cadaveric distal clavicles were scanned using XtremeCT with an isometric voxel size of 82 μm. In the sagittal plane, each data set was evaluated in 11 sections of approximately 7 mm thickness. Three topographic regions were defined: the bone lateral to the trapezoid (LTR), intertubercular (ITR), and medial to the conoid (MCR) ligament. Cortical bone mineral density (BMD) [mgHA/cm3] and cortical porosity (1- (BV/TV) [%]) were determined and evaluated relative to age and gender. Results: Along the mediolateral axis, there was an >20-fold increase in median cortical porosity (P ≤ .001). There were significant differences in cortical porosity between LTR and ITR (P ≤ .001) but not between ITR and MCR (P = .09). In ITR, cortical porosity was significantly greater in >60-year-old compared to younger donors (P = .01). For BMD, there was an >2-fold decrease toward the distal apex (P ≤ .001). BMD was significantly greater in ITR compared to LTR (P ≤ .001) and in MCR compared to ITR (P = .02). In ITR and MCR, clavicles of >60-year-old donors had significantly lower BMD values compared to younger donors (P 60-year-olds (P > .6). Conclusion: The distal clavicle features a characteristic bony microarchitecture. The present study revealed a significant difference in bone quality of lateral, intertubercular, and medial zones of the distal clavicle and could specify target areas and strategies for surgical treatment of unstable fractures. Age, gender, and osteoporosis have a limited effect on bone quality and fracture genesis. In contrast, ligamentous quality is supposed to exert a substantial influence on fracture characteristics, especially in ITR. Fracture morphology of the distal clavicle is determined by a bony-ligamentous conjunction, which remains to be characterized.

Abstract Hierarchical guidance is developed for three-dimensional (3D) nanoscale X-ray imaging, enabling identification, refinement, and tracking of regions of interest (ROIs) within specimens considerably exceeding the field of view. This opens up new possibilities for in situ investigations. Experimentally, the approach takes advantage of rapid multiscale measurements based on magnified projection microscopy featuring continuous zoom capabilities. Immediate and continuous feedback on the subsequent experimental progress is enabled by suitable on-the-fly data processing. For this, by theoretical justification and experimental validation, so-called quasi-particle phase-retrieval is generalised to conical-beam conditions, being key for sufficiently fast computation without significant loss of imaging quality and resolution compared to common approaches for holographic microscopy. Exploiting 3D laminography, particularly suited for imaging of ROIs in laterally extended plate-like samples, the potential of hierarchical guidance is demonstrated by the in situ investigation of damage nucleation inside alloy sheets under engineering-relevant boundary conditions, providing novel insight into the nanoscale morphological development of void and particle clusters under mechanical load. Combined with digital volume correlation, we study deformation kinematics with unprecedented spatial resolution. Correlation of mesoscale (i.e. strain fields) and nanoscale (i.e. particle cracking) evolution opens new routes for the understanding of damage nucleation within sheet materials with application-relevant dimensions.

Composite materials are increasingly used to help in reducing the carbon footprint of transportation and upscaling renewable energy infrastructure that provides clean energy for future cities. However, the inherent susceptibility of carbon fibre reinforced polymers to impact damage results in knock-down in design and is linked to the micro-mechanistic response of the material to damage. In situ experimental and high-resolution imaging techniques using X-ray computed tomography (X-ray CT) have been used to gain a mechanistic understanding of the key factors controlling crack path — and hence macro-scale toughness within a composite. Multiscale Synchrotron Radiation Computed Tomography (SRCT) and lab-based micro-focus X-ray CT are used to investigate different material systems toughness response from standard Double Cantilever Beam tests. The crack transition to the weaker ply region of the composite is identified as a controlling factor across a scale of mm’s, and ‘trigger’ regions are reported on and investigated. The ‘trigger’ regions were identified as gaps in the ply adjacent to the interlayer. This work feeds directly into delamination growth predictions, a better understanding of material response, and enabling informed manufacture and design, allowing for reduced material usage, longer life and more sustainable vehicles and infrastructure.

The electrochemical reduction of CO2 is pivotal for the chemical industry to reach climate neutrality. Here, the authors utilize high-resolution neutron imaging to unravel electrode flooding and salt precipitation, both major hurdles to steady operation of CO2 electrolyzers.

Water management plays a key role in ensuring optimum polymer electrolyte fuel cell (PEFC) performance, and flow field design can influence the ability of a cell to balance maintaining hydration, whilst avoiding flooding and cell failure. This work deepens the understanding of water evolution in different PEFC flow channel designs, namely single serpentine (SS), double serpentine (DS) and parallel, using our novel high-speed neutron computed tomography method. We developed our previously-reported method by introducing continuous cell rotation, enabling 18 s per tomogram during 1 h holds at 300, 400 and 500 mA cm ^−2 . The volume of water evolved in the cathode, membrane electrode assembly and anode was quantified, and key mechanisms for water droplet formation in the different flow channel designs were elucidated. The parallel flow field design had the poorest water management, with 47% of the cathode flow channel becoming filled after 1 h at 400 mA cm ^−2 . This significant flooding blocked reactant sites and contributed to unstable cell performance and, ultimately, cell failure at higher current densities. The SS cell displayed the best water management, with only 11% of the cathode channel filled with water after 1 h at 500 mA cm ^−2 , compared with 28% of the DS cathode channel. 3D visualisation and analysis of droplet behaviour elucidated how water ‘slugs’ in the SS were removed in the gas stream, whereas three of the four parallel cathode flow channels became entirely filled with water plugs, blocking gas flow and exacerbating cell flooding. The new insights gained here are expected to extend to novel flow field designs and image-based models, with the use of operando neutron CT demonstrated as a powerful technique for both visualising and quantifying water management in operating PEFCs, as well as deepening the knowledge of droplet behaviour in different flow field types.