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.

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.

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.

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.

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.

Efficient Deep Network Architectures for Fast Chest X-Ray Tuberculosis Screening and Visualization.

Automated diagnosis of tuberculosis (TB) from chest X-Rays (CXR) has been tackled with either hand-crafted algorithms or machine learning approaches such as support vector machines (SVMs) and convolutional neural networks (CNNs). Most deep neural network applied to the task of tuberculosis diagnosis have been adapted from natural image classification. These models have a large number of parameters as well as high hardware requirements, which makes them prone to overfitting and harder to deploy in mobile settings. We propose a simple convolutional neural network optimized for the problem which is faster and more efficient than previous models but preserves their accuracy. Moreover, the visualization capabilities of CNNs have not been fully investigated. We test saliency maps and grad-CAMs as tuberculosis visualization methods, and discuss them from a radiological perspective.

Dynamic In Vivo Chest X-ray Dark-Field Imaging in Mice.

X-ray grating interferometry is a powerful emerging tool in biomedical imaging, providing access to three complementary image modalities. In addition to the conventional attenuation modality, interferometry provides a phase modality, which visualizes soft tissue structures, and a dark-field modality, which relates to the number and size of sub-resolution scattering objects. A particularly strong dark-field signal originates from the alveoli or air sacs in the lung. Dark-field lung radiographs in animal models have already shown increased sensitivity in diagnosing lung diseases, such as lung cancer or emphysema, compared to conventional X-ray chest radiography. However, to date, X-ray dark-field lung imaging has either averaged information over several breaths or has been captured during a breath hold. In this paper, we demonstrate the first time-resolved dark-field imaging of a breath cycle in a mechanically ventilated mouse, in vivo, which was obtained using a grating interferometer. We achieved a time resolution of 0.1 s, visualizing the changes in the dark-field, phase, and attenuation images during inhalation and exhalation. These measurements show that the dark-field signal depends on the air volume and, hence, the alveolar dimensions of the lung. Conducting this type of scan with animal disease models would help to locate the optimum breath point for single-image diagnostic dark-field imaging and could indicate if the changes in the dark-field signal during breath provide a diagnostically useful complementary measure.

Fabrication of gadolinium particle-based absorption gratings for neutron grating interferometry.

The imaging performance of a neutron-based Talbot-Lau interferometer depends to a great extent on the absorption characteristics of the source and analyzer gratings. Due to its high neutron attenuation, gadolinium (Gd) is the preferred material for grating fabrication, but suffers from difficulties with deposition time, stability, uniformity, and selectivity into high aspect ratio structures. Here we present a simple alternative method of Gd deposition into grating structures based on metallic particle suspension casting and subsequent doctor-blading. Surface analysis by confocal and electron scanning microscopy shows that a nearly clear, particle free silicon interface of the grating structure over a large area could be reached. Additionally, characterization by neutron radiography confirms a high effective Gd height and homogeneity over the whole grating area. In particular, grating trenches well below 10 µm width could be successfully filled with Gd and deliver excellent absorbing performance down to the sub-2 Å wavelength range. The findings confirm that we obtained an effective binary absorption profile for the fabricated gratings which is of great benefit for grating-based neutron imaging.

[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.

Design of Acquisition Schemes and Setup Geometry for Anisotropic X-ray Dark-Field Tomography (AXDT).

Anisotropic X-ray Dark-field Tomography (AXDT) is a new imaging technique for reconstructing the three-dimensional scattering profile within a sample using the dark-field signal measured in an X-ray grating interferometry setup. As in any tomographic measurement, the acquisition geometry plays a key role in the accurate reconstruction of the scattering information. More- over, the anisotropic nature of the dark-field signal poses additional challenges for designing the acquisition protocols. In this work, we present an efficient approach to measure scattering orientations spread over the unit sphere and prove its efficacy using the knowledge from conventional tomography. In addition, we conclude (using analytical and experimental results) that placing the gratings such that the grating bars make an angle of 45 degrees with respect to the vertical direction is the optimal setup configuration for AXDT.

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.

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.

Basis material decomposition in spectral CT using a semi-empirical, polychromatic adaption of the Beer-Lambert model.

Following the development of energy-sensitive photon-counting detectors using high-Z sensor materials, application of spectral x-ray imaging methods to clinical practice comes into reach. However, these detectors require extensive calibration efforts in order to perform spectral imaging tasks like basis material decomposition. In this paper, we report a novel approach to basis material decomposition that utilizes a semi-empirical estimator for the number of photons registered in distinct energy bins in the presence of beam-hardening effects which can be termed as a polychromatic Beer-Lambert model. A maximum-likelihood estimator is applied to the model in order to obtain estimates of the underlying sample composition. Using a Monte-Carlo simulation of a typical clinical CT acquisition, the performance of the proposed estimator was evaluated. The estimator is shown to be unbiased and efficient according to the Cramér-Rao lower bound. In particular, the estimator is capable of operating with a minimum number of calibration measurements. Good results were obtained after calibration using less than 10 samples of known composition in a two-material attenuation basis. This opens up the possibility for fast re-calibration in the clinical routine which is considered an advantage of the proposed method over other implementations reported in the literature.

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.

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.

Helical X-ray phase-contrast computed tomography without phase stepping.

X-ray phase-contrast computed tomography (PCCT) using grating interferometry provides enhanced soft-tissue contrast. The possibility to use standard polychromatic laboratory sources enables an implementation into a clinical setting. Thus, PCCT has gained significant attention in recent years. However, phase-contrast CT scans still require significantly increased measurement times in comparison to conventional attenuation-based CT imaging. This is mainly due to a time-consuming stepping of a grating, which is necessary for an accurate retrieval of the phase information. In this paper, we demonstrate a novel scan technique, which directly allows the determination of the phase signal without a phase-stepping procedure. The presented work is based on moiré fringe scanning, which allows fast data acquisition in radiographic applications such as mammography or in-line product analysis. Here, we demonstrate its extension to tomography enabling a continuous helical sample rotation as routinely performed in clinical CT systems. Compared to standard phase-stepping techniques, the proposed helical fringe-scanning procedure enables faster measurements, an extended field of view and relaxes the stability requirements of the system, since the gratings remain stationary. Finally, our approach exceeds previously introduced methods by not relying on spatial interpolation to acquire the phase-contrast signal.

Bilateral filtering using the full noise covariance matrix applied to x-ray phase-contrast computed tomography.

The purpose of this work is to develop an image-based de-noising algorithm that exploits complementary information and noise statistics from multi-modal images, as they emerge in x-ray tomography techniques, for instance grating-based phase-contrast CT and spectral CT. Among the noise reduction methods, image-based de-noising is one popular approach and the so-called bilateral filter is a well known algorithm for edge-preserving filtering. We developed a generalization of the bilateral filter for the case where the imaging system provides two or more perfectly aligned images. The proposed generalization is statistically motivated and takes the full second order noise statistics of these images into account. In particular, it includes a noise correlation between the images and spatial noise correlation within the same image. The novel generalized three-dimensional bilateral filter is applied to the attenuation and phase images created with filtered backprojection reconstructions from grating-based phase-contrast tomography. In comparison to established bilateral filters, we obtain improved noise reduction and at the same time a better preservation of edges in the images on the examples of a simulated soft-tissue phantom, a human cerebellum and a human artery sample. The applied full noise covariance is determined via cross-correlation of the image noise. The filter results yield an improved feature recovery based on enhanced noise suppression and edge preservation as shown here on the example of attenuation and phase images captured with grating-based phase-contrast computed tomography. This is supported by quantitative image analysis. Without being bound to phase-contrast imaging, this generalized filter is applicable to any kind of noise-afflicted image data with or without noise correlation. Therefore, it can be utilized in various imaging applications and fields.

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.

Grating-based X-ray Dark-field Computed Tomography of Living Mice.

Changes in x-ray attenuating tissue caused by lung disorders like emphysema or fibrosis are subtle and thus only resolved by high-resolution computed tomography (CT). The structural reorganization, however, is of strong influence for lung function. Dark-field CT (DFCT), based on small-angle scattering of x-rays, reveals such structural changes even at resolutions coarser than the pulmonary network and thus provides access to their anatomical distribution. In this proof-of-concept study we present x-ray in vivo DFCTs of lungs of a healthy, an emphysematous and a fibrotic mouse. The tomographies show excellent depiction of the distribution of structural - and thus indirectly functional - changes in lung parenchyma, on single-modality slices in dark field as well as on multimodal fusion images. Therefore, we anticipate numerous applications of DFCT in diagnostic lung imaging. We introduce a scatter-based Hounsfield Unit (sHU) scale to facilitate comparability of scans. In this newly defined sHU scale, the pathophysiological changes by emphysema and fibrosis cause a shift towards lower numbers, compared to healthy lung tissue.