Search

The DIAD beamline for Dual Imaging and Diffraction at Diamond Light Source has opted to use an industrial robot to position its Dectris Pilatus 2M CdTe diffraction detector. This setup was chosen to enable flexible positioning of the detector in a quarter-sphere around the sample position whilst reliably holding the large weight of 139 kg of detector, detector mount and cabling in a stable position. Metrology measurements showed that the detector can be positioned with a linear repeatability of

The human brain is one of the most fascinating and important structures in nature. So far, his-tology has been the gold standard for imaging anatomical features on the sub-cellular level. Us-ing standard optical microscopy spatial resolution is restricted to a fraction of a micron. Recip-rocal-space techniques, including small-angle X-ray scattering (SAXS), with an inverse relation-ship between a nanostructure's size and scattering angle, have been used to study animal and human tissues. The myelin sheaths responsible for insulating axons, for example, exhibit a pe-riodicity between 15 and 18 nm. To localize their abundance and orientation, we have performed SAXS measurements with a micrometer-sized beam along a slice of the human brain and related them to the histology of myelin-stained tissue. The experimental results elucidate that, compared to histology, micrometer resolved SAXS provides information about the orientation of myelin, and consequently, axons, in addition to myelin abundance. The acquired data show color-coded orientation maps of the nanostructures, thereby providing a detailed insight into a relevant part of the human brain's nano-anatomy.

Atherosclerosis gives rise to blood vessel occlusion associated with blood flow alteration and substantial increase of average wall shear stress. This modification was proved acting as a purely physical trigger for targeted vasodilator release from a particular type of liposomes composed of 1,3-diaminophospholipids (Pad-PC-Pad). The flow-induced structural changes of these faceted liposomes, however, are completely unknown. Therefore, spatially resolved small-angle X-ray scattering was combined with microfluidics to uniquely study the purely physical mechanisms, which give rise to the highly efficient drug release from mechanoresponsive liposomes of nanometer size. The microfluidic device, designed to mimic a stenotic blood vessel, consisted of a 1-mm-wide channel with a constriction, 125 ​μm in diameter. Here, the changes of the average bilayer thickness and the mean size of the mechanoresponsive liposomes have been locally detected under flow conditions. Overall shape and bilayer thickness do change already near the constriction inlet, but the alteration is dominant near the outlet. At a flow rate of 0.2 ​μL/s, the liposome's bilayer thickness increased by 30% compared to the situation well before the constriction and under static condition. The detected bilayer thickness increase of the faceted liposomes is in line with the mechanically induced loss of interdigitation between the phospholipid amide chains. These results imply that rather the gradient force than the wall shear stress provokes structural changes of Pad-PC-Pad liposomes and the related drug release at stenoses. The approach, i.e. the combination of microfluidics and spatially resolved small-angle X-ray scattering, paves the way to design highly efficient and specific systems for the targeted drug delivery at constrictions with predefined morphology.

Abstract There have been great efforts on the nanoscale 3D probing of brain tissues to image subcellular morphologies. However, limitations in terms of tissue coverage, anisotropic resolution, stain dependence, and complex sample preparation all hinder achieving a better understanding of the human brain functioning in the subcellular context. Herein, X‐ray nanoholotomography is introduced as an emerging synchrotron radiation‐based technology for large‐scale, label‐free, direct imaging with isotropic voxel sizes down to 25 nm, exhibiting a spatial resolution down to 88 nm. The procedure is nondestructive as it does not require physical slicing. Hence, it allows subsequent imaging by complementary techniques, including histology. The feasibility of this 3D imaging approach is demonstrated on human cerebellum and neocortex specimens derived from paraffin‐embedded tissue blocks. The obtained results are compared to hematoxylin and eosin stained histological sections and showcase the ability for rapid hierarchical neuroimaging and automatic rebuilding of the neuronal architecture at the level of a single cell nucleolus. The findings indicate that nanoholotomography can complement microscopy not only by large isotropic volumetric data but also by morphological details on the sub‐100 nm level, addressing many of the present challenges in brain tissue characterization and probably becoming an important tool in nanoanatomy.

Micro computed tomography has been combined with dedicated data analysis for the in vitro quantification of sub-surface enamel lesion mineralization. Two artificial white spot lesions, generated on a human molar crown in vitro, were examined. One lesion was treated with a self-assembling peptide intended to trigger nucleation of hydroxyapatite crystals. We non-destructively determined the local X-ray attenuation within the specimens before and after treatment. The three-dimensional data was rigidly registered. Three interpolation methods, i.e., nearest neighbor, tri-linear, and tri-cubic interpolation were evaluated. The mineralization of the affected regions was quantified via joint histogram analysis, i.e., a voxel-by-voxel comparison of the tomography data before and after mineralization. After ten days incubation, the mean mineralization coefficient reached 35.5% for the peptide-treated specimen compared to 11.5% for the control. This pilot study does not give any evidence for the efficacy of peptide treatment nor allows estimating the necessary number of specimens to achieve significance, but shows a sound methodological approach on the basis of the joint histogram analysis.

Radiography has long been the standard approach to characterize carious lesions. Spatially resolved X-ray diffraction, specifically small-angle X-ray scattering (SAXS), has recently been applied to caries research. The aims of this combined SAXS and micro computed tomography (µCT) study were to locally characterize and compare the micro- and nanostructures of one natural carious lesion and of one artificially induced enamel lesion; and demonstrate the feasibility of an automated approach to combined SAXS and µCT data in segmenting affected and unaffected enamel. Enamel, demineralized by natural or artificial caries, exhibits a significantly reduced X-ray attenuation compared to sound enamel and gives rise to a drastically increased small-angle scattering signal associated with the presence of nanometer-size pores. In addition, X-ray scattering allows the assessment of the overall orientation and the degree of anisotropy of the nanostructures present. Subsequent to the characterization with µCT, specimens were analyzed using synchrotron radiation-based SAXS in transmission raster mode. The bivariate histogram plot of the projected data combined the local scattering signal intensity with the related X-ray attenuation from µCT measurements. These histograms permitted the segmentation of anatomical features, including the lesions, with micrometer precision. The natural and artificial lesions showed comparable features, but they also exhibited size and shape differences. The clear identification of the affected regions and the characterization of their nanostructure allow the artificially induced lesions to be verified against selected natural carious lesions, offering the potential to optimize artificial demineralization protocols. Analysis of joint SAXS and µCT histograms objectively segmented sound and affected enamel.

Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15) and osteoarthritic (n = 22) lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.