Sensorimotor and body perception assessments of nonspecific chronic low back pain: a cross-sectional study.

BACKGROUND: Low back pain (LBP) is one of the most common musculoskeletal disorders, causing significant personal and social burden. Current research is focused on the processes of the central nervous system (particularly the sensorimotor system) and body perception, with a view to developing new and more efficient ways to treat chronic low back pain (CLBP). Several clinical tests have been suggested that might have the ability to detect alterations in the sensorimotor system. These include back-photo assessment (BPA), two-point discrimination (TPD), and the movement control tests (MCT). The aim of this study was to determine whether the simple clinical tests of BPA, TPD or MCT are able to discriminate between nonspecific CLBP subjects with altered body perception and healthy controls. METHODS: A cross-sectional study was conducted. At one point in time, 30 subjects with CLBP and 30 healthy controls were investigated through using BPA, TPD and MCT on the lower back. Correlations among the main covariates and odds ratios for group differences were calculated. RESULTS: MCT showed an odds ratio for the presence of CLBP of 1.92, with a statistically significant p-value (0.049) and 95%CI. The TPD and BPA tests were unable to determine significant differences between the groups. CONCLUSIONS: Of the three tests investigated, MCT was found to be the only suitable assessment to discriminate between nonspecific CLBP subjects and healthy controls. The MCT can be recommended as a simple clinical tool to detect alterations in the sensorimotor system of nonspecific CLBP subjects. This could facilitate the development of tailored management strategies for this challenging LBP subgroup. However, further research is necessary to elucidate the potential of all the tests to detect alterations in the sensorimotor system of CLBP subjects. TRIAL REGISTRATION: No trial registration was needed as the study contains no intervention. The study was approved by the Swiss Ethics Commission of Northwest and Central Switzerland (EKNZ) reference number 2015-243.

The microstructure and micromechanics of the tendon-bone insertion.

The exceptional mechanical properties of the load-bearing connection of tendon to bone rely on an intricate interplay of its biomolecular composition, microstructure and micromechanics. Here we identify that the Achilles tendon-bone insertion is characterized by an interface region of ∼500 µm with a distinct fibre organization and biomolecular composition. Within this region, we identify a heterogeneous mechanical response by micromechanical testing coupled with multiscale confocal microscopy. This leads to localized strains that can be larger than the remotely applied strain. The subset of fibres that sustain the majority of loading in the interface area changes with the angle of force application. Proteomic analysis detects enrichment of 22 proteins in the interfacial region that are predominantly involved in cartilage and skeletal development as well as proteoglycan metabolism. The presented mechanisms mark a guideline for further biomimetic strategies to rationally design hard-soft interfaces.

[X­ray Phase Contrast : Principles, potential and advances in clinical translation]. / Röntgen-Phasenkontrast : Grundlagen, Potenzial und Fortschritte in der klinischen Translation.

More than 100 years ago Max von Laue in Munich discovered that X­rays can be interpreted not only as X­ray quanta in a particle picture, but also show a wave character. This property has been used for a long time in basic research (e.g. in crystallography for determining the structure of proteins), but so far has had no application in medical imaging. In the last 10 years, however, very impressive technological progress could be made in preclinical research, which also makes the utilization of the wave character of X­ray light possible for medical imaging. These novel radiography procedures, so-called phase-contrast and dark-field imaging, have a great potential for a pronounced improvement in X­ray imaging and therefore, also the diagnosis of important diseases. This article describes the basic principles of these novel procedures, summarizes the preclinical research results already achieved exemplified by various organs and shows the potential for future clinical utilization in radiography and computed tomography.

Application of sensitive, high-resolution imaging at a commercial lab-based X-ray micro-CT system using propagation-based phase retrieval.

Several dedicated commercial lab-based micro-computed tomography (µCT) systems exist, which provide high-resolution images of samples, with the capability to also deliver in-line phase contrast. X-ray phase contrast is particularly beneficial when visualizing very small features and weakly absorbing samples. The raw measured projections will include both phase and absorption effects. Extending our previous work that addressed the optimization of experimental conditions at the commercial ZEISS Xradia 500 Versa system, single-distance phase-contrast imaging is demonstrated on complex biological and material samples. From data captured at this system, we demonstrate extraction of the phase signal or the correction of the mixed image for the phase shift, and show how this procedure increases the contrast and removes artefacts. These high-quality images, measured without the use of a synchrotron X-ray source, demonstrate that highly sensitive, micrometre-resolution imaging of 3D volumes is widely accessible using commercially advanced laboratory devices.

Two-shot X-ray dark-field imaging.

In this article, we report on a novel acquisition scheme for time- and dose-saving retrieval of dark-field data in grating-based phase-contrast imaging. In comparison to currently available techniques, the proposed approach only requires two phase steps. More importantly, our method is capable of accurately retrieving the dark-field signal where conventional approaches fail, for instance in the case of very low photon statistics. Finally, we successfully extend two-shot dark-field imaging to tomographic investigations, by implementing an iterative reconstruction with appropriate weights. Our results indicate an important progression towards the clinical feasibility of dark-field tomography.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

UNLABELLED: Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. INTRODUCTION: Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. METHODS: To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. RESULTS: +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. CONCLUSIONS: Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Anisotropic X-Ray Dark-Field Tomography: A Continuous Model and its Discretization.

The x-ray dark-field signal measured in grating interferometers is anisotropic, depending on both the beam direction and the grating orientation with respect to the sample. We present a novel general closed-form, continuous forward model of the anisotropic dark-field signal. Furthermore, we derive a discretization using spherical harmonics, leading to a large-scale linear inverse problem. We present first experimental results of a wooden sample, demonstrating marked advantages over previous results, in particular, the resolution of multiple scattering directions in one volume element.

Increasing the field of view in grating based X-ray phase contrast imaging using stitched gratings.

Grating based X-ray differential phase contrast imaging (DPCI) allows for high contrast imaging of materials with similar absorption characteristics. In the last years' publications, small animals or parts of the human body like breast, hand, joints or blood vessels have been studied. Larger objects could not be investigated due to the restricted field of view limited by the available grating area. In this paper, we report on a new stitching method to increase the grating area significantly: individual gratings are merged on a carrier substrate. Whereas the grating fabrication process is based on the LIGA technology (X-ray lithography and electroplating) different cutting and joining methods have been evaluated. First imaging results using a 2×2 stitched analyzer grating in a Talbot-Lau interferometer have been generated using a conventional polychromatic X-ray source. The image quality and analysis confirm the high potential of the stitching method to increase the field of view considerably.

Trimodal low-dose X-ray tomography.

X-ray grating interferometry is a coherent imaging technique that bears tremendous potential for three-dimensional tomographic imaging of soft biological tissue and other specimens whose details exhibit very weak absorption contrast. It is intrinsically trimodal, delivering phase contrast, absorption contrast, and scattering ("dark-field") contrast. Recently reported acquisition strategies for grating-interferometric phase tomography constitute a major improvement of dose efficiency and speed. In particular, some of these techniques eliminate the need for scanning of one of the gratings ("phase stepping"). This advantage, however, comes at the cost of other limitations. These can be a loss in spatial resolution, or the inability to fully separate the three imaging modalities. In the present paper we report a data acquisition and processing method that optimizes dose efficiency but does not share the main limitations of other recently reported methods. Although our method still relies on phase stepping, it effectively uses only down to a single detector frame per projection angle and yields images corresponding to all three contrast modalities. In particular, this means that dark-field imaging remains accessible. The method is also compliant with data acquisition over an angular range of only 180° and with a continuous rotation of the specimen.

Energy-resolved visibility analysis of grating interferometers operated at polychromatic X-ray sources.

Grating interferometry has been successfully adapted at standard X-ray tubes and is a promising candidate for a broad use of phase-contrast imaging in medical diagnostics or industrial testing. The achievable image quality using this technique is mainly dependent on the interferometer performance with the interferometric visibility as crucial parameter. The presented study deals with experimental investigations of the spectral dependence of the visibility in order to understand the interaction between the single contributing energies. Especially for the choice which type of setup has to be preferred using a polychromatic source, this knowledge is highly relevant. Our results affirm previous findings from theoretical investigations but also show that measurements of the spectral contributions to the visibility are necessary to fully characterize and optimize a grating interferometer and cannot be replaced by only relying on simulated data up to now.

Speckle-based x-ray phase-contrast and dark-field imaging with a laboratory source.

We report on the observation and application of near-field speckles with a laboratory x-ray source. The detection of speckles is possible thanks to the enhanced brilliance properties of the used liquid-metal-jet source, and opens the way to a range of new applications in laboratory-based coherent x-ray imaging. Here, we use the speckle pattern for multimodal imaging of demonstrator objects. Moreover, we introduce algorithms for phase and dark-field imaging using speckle tracking, and we show that they yield superior results with respect to existing methods.

Three-dimensional imaging of whole mouse models: comparing nondestructive X-ray phase-contrast micro-CT with cryotome-based planar epi-illumination imaging.

In this study, we compare two evolving techniques for obtaining high-resolution 3D anatomical data of a mouse specimen. On the one hand, we investigate cryotome-based planar epi-illumination imaging (cryo-imaging). On the other hand, we examine X-ray phase-contrast micro-computed tomography (micro-CT) using synchrotron radiation. Cryo-imaging is a technique in which an electron multiplying charge coupled camera takes images of a cryo-frozen specimen during the sectioning process. Subsequent image alignment and virtual stacking result in volumetric data. X-ray phase-contrast imaging is based on the minute refraction of X-rays inside the specimen and features higher soft-tissue contrast than conventional, attenuation-based micro-CT. To explore the potential of both techniques for studying whole mouse disease models, one mouse specimen was imaged using both techniques. Obtained data are compared visually and quantitatively, specifically with regard to the visibility of fine anatomical details. Internal structure of the mouse specimen is visible in great detail with both techniques and the study shows in particular that soft-tissue contrast is strongly enhanced in the X-ray phase images compared to the attenuation-based images. This identifies phase-contrast micro-CT as a powerful tool for the study of small animal disease models.

Unwrapping differential x-ray phase-contrast images through phase estimation from multiple energy data.

We present a spectral phase unwrapping approach for grating-based differential phase-contrast data where the unwrapped interferometer phase shift is estimated from energy discriminated measurements using maximum likelihood principles. We demonstrate the method on tomographic data sets of a test specimen taken at different x-ray energies using synchrotron radiation. The proposed unwrapping technique was demonstrated to successfully correct the data set for phase wrapping.

Spectral photon counting for panoramic dental imaging.

Panoramic x-ray imaging is a versatile, low-dose imaging tool, which is routinely used for dental applications. In this work, we explore a further improvement of the concept by introducing recently developed spectral photon-counting detector technology into a conventional panoramic imaging unit. In addition we adapt spectral material decomposition algorithms to panoramic imaging needs. Finally, we provide first experimental results, demonstrating decomposition of an anthropomorphic head phantom into soft tissue and dentin basis material panoramic images, while keeping the noise level acceptable using regularization approaches. The obtained results reveal a potential benefit of spectral photon-counting technology also for dental imaging applications.

Assessment of the Factors Influencing the Recording Performance of Circumneural Electrodes.

The quality of recorded peripheral nerve signals is decisive for their application in therapies. The electroneurogram can be recorded via implantable circumeural electrodes that are wrapped around the peripheral nerve. The shape and amplitude of the signal recorded by the electrode are influenced by the design and contact configuration of the electrode. In this paper, the impact of the number of contacts, contact size and electrical insulation to the outside is investigated to predict the single fiber action potential based on the measured impedance data.

X-ray dark-field imaging modeling.

Dark-field images are formed from x-ray small-angle scattering signals. The small-angle scattering signals are particularly sensitive to structural variation and density fluctuation on a length scale of several tens to hundreds of nanometers, offering a unique contrast mechanism to reveal subtle structural features of an object. In this study, based on the principle of energy conservation, we develop a physical model to describe the relationship between x-ray small-angle scattering coefficients of an object and dark-field intensity images. This model can be used to reconstruct volumetric x-ray small-angle scattering images of an object using classical tomographic algorithms. We also establish a relationship between the small-angle scattering intensity and the visibility function measured with x-ray grating imaging. The numerical simulations and phantom experiments have demonstrated the accuracy and practicability of the proposed model.

Multi-Scale Investigation of Human Renal Tissue in Three Dimensions.

Histopathology as a diagnostic mainstay for tissue evaluation is strictly a 2D technology. Combining and supplementing this technology with 3D imaging has been proposed as one future avenue towards refining comprehensive tissue analysis. To this end, we have developed a laboratory-based X-ray method allowing for the investigation of tissue samples in three dimensions with isotropic volume information. To assess the potential of our method for micro-morphology evaluation, we selected several kidney regions from three patients with cystic kidney disease, obstructive nephropathy and diabetic glomerulopathy. Tissue specimens were processed using our in-house-developed X-ray eosin stain and investigated with a commercial microCT and our in-house-built NanoCT. The microCT system provided overview scans with voxel sizes of [Formula: see text] and the NanoCT was employed for higher resolutions including voxel sizes from [Formula: see text] to 210 nm. We present a methodology allowing for a precise micro-morphologic investigation in three dimensions which is compatible with conventional histology. Advantages of our methodology are its versatility with respect to multi-scale investigations, being laboratory-based, allowing for non-destructive imaging and providing isotropic volume information. We believe, that after future developmental work this method might contribute to advanced multi-modal tissue diagnostics.

Molecular X-ray computed tomography of myelin in a rat brain.

In this work we demonstrate the feasibility of applying small-angle X-ray scattering computed tomography (SAXS-CT) for non-invasive molecular imaging of myelin sheaths in a rat brain. Our results show that the approach yields information on several quantities, including the relative myelin concentration, its periodicity, the total thickness of the myelin sheaths, and the relative concentration of cytoskeletal neurofilaments. For example the periodicity of the myelin sheaths varied in the range from 17.0 to 18.2 nm around an average of 17.6 (±0.3) nm. We believe that imaging, i.e., spatially resolved measuring these quantities could provide general means for understanding the relation to a number of neurodegenerative diseases.

One-dimensional small-angle X-ray scattering tomography of dip-coated polyamide 6 monofilaments.

A synchrotron study is presented in which the concept of one-dimensional tomographic reconstruction of small-angle X-ray scattering patterns is applied to investigate polyamide 6 monofilaments, dip-coated with alumina particles. The filaments are scanned with a focused synchrotron beam and the resulting scattering patterns are recorded with a PILATUS 2M detector. The reconstructed sequence of SAXS images reflects the local nanostructure variation along the filament radius. In particular, the influence of coating process parameters on the polyamide 6 is investigated.

Revealing the Microscopic Structure of Human Renal Cell Carcinoma in Three Dimensions.

For fully characterizing renal cell carcinoma (RCC), information about the 3D tissue microstructure is essential. Histopathology, which represents the current diagnostic gold standard, is destructive and only provides 2D information. 3D X-ray histology endeavors to overcome these limitations by generating 3D data. In a laboratory environment, most techniques struggle with limited resolution and the weak X-ray attenuation contrast of soft tissue. We recently developed a laboratory-based method combining nanoscopic X-ray CT with a cytoplasm-specific X-ray stain. Here, we present the application of this method to human RCC biopsies. The NanoCT slices enable pathological characterization of crucial structures by reproducing tissue morphology with a similar detail level as corresponding histological light microscopy images. Beyond that, our data offer deeper insights into the 3D configuration of the tumor. By demonstrating the compatibility of the X-ray stain with standard pathological stains, we highlight the feasibility of integrating staining based NanoCT into the pathological routine.