Alzheimer's disease (AD) remains one of the foremost public health challenges of our time. Recently, attention has turned to the gut-brain axis, a complex network of communication between the gastrointestinal tract and the brain, as a potential player in the pathogenesis of AD. Here we exploited x-ray Phase Contrast Tomography to provide an in-depth analysis of the link between the gut condition and AD, exploring gut anatomy and structure in murine models. We conducted a comprehensive analysis by comparing the outcomes in various mouse models of cognitive impairment, including AD, frail mice, and frontotemporal dementia affected mice. We discovered an association between substantial changes in the gut structure and the presence of amyloid-beta (Aβ) in the brain. We found that the most important gut alterations are related to Aβ occurrence in the brain. In particular, we investigated the gut morphology, the distribution of enteric micro-processes and neurons in the ileum.
X-ray phase-contrast tomography (XPCT) offers a highly sensitive 3D imaging approach to investigate different disease-relevant networks from the single cell to the whole organ. We present here a concomitant study of the evolution of tissue damage and inflammation in potential target organs of the disease in the murine model of multiple sclerosis. XPCT identifies and monitors structural and cellular alterations throughout the central nervous system, but also in the gut and eye, of mice induced to develop multiple sclerosis-like disease and sacrificed at pre-symptomatic and symptomatic time points. This approach rests on a multiscale analysis to detect early appearance of imaging indicators potentially acting as biomarkers predictive of the disease. The longitudinal data permit an original evaluation of the sequential evolution of multi-organ damage in the mouse model, shedding light on the role of the gut-brain axis in the disease initiation and progression, of relevance for the human case.
The human olfactory bulb (OB), an important part of the brain responsible for the sense of smell, is a complex structure composed of multiple layers and cell types. Studying the OB morphological structure is essential for understanding the decline in olfactory function related to aging, neurodegenerative disorders, and other pathologies. Traditional microscopy methods in which slices are stained with solutions to contrast individual elements of the morphological structure are destructive. Non-destructive high-resolution technique is the X-ray phase-contrast tomography. However, manual segmentation of the reconstructed images are time-consuming due to large amount of data and prone to errors. U-Net-based model to optimize the segmentation of OB morphological structures, focusing specifically on glomeruli, in tomographic images of the human OB is proposed. The strategy to address overfitting and enhance the model's accuracy is described. This method addresses the challenges posed by complex limited data containing abundant details, similar grayscale levels between soft tissues, and blurry image details. Additionally, it successfully overcomes the limitations of a small dataset containing images with extremely dense point clouds, preventing the models from overfitting.
To date there have been only indirect indications of the presence of bound sodium accumulation in muscle and skin tissues. Despite their osmotic inactivity, such sodium deposits can effect on mechanical properties of the heart muscle impairing its elasticity and leading to serious heart dysfunctions. In this work an accurate study of the chemical composition of the heart muscle tissue at the cellular level was carried out using the methods of X-ray absorption and fluorescence microscopy. The experiments were carried out on a TwinMic X-ray scanning microscope [3] at ELETTRA synchrotron (Italy) with a resolution of about 1 μm. Comparison of the obtained maps of intra- and extracellular sodium distribution in heart tissues of different laboratory animals has resulted in the first experimental confirmation of the hypotheses about the existence of deposited sodium states in the intercellular space. The paper demonstrates an example of the state-of-the-art medical applications of high spectral brilliance X-ray sources.
Despite significant progress in computer vision, pattern recognition, and image analysis, artifacts in imaging still hampers the progress in many scientific fields relying on the results of image analysis. We here present an advanced image-based artifacts suppression algorithm for high-resolution tomography. The algorithm is based on guided filtering of a reconstructed image mapped from the Cartesian to the polar coordinates space. This postprocessing method efficiently reduces both ring- and radial streak artifacts in a reconstructed image. Radial streak artifacts can appear in tomography with an off-center rotation of a large object over 360 degrees used to increase the reconstruction field of view. We successfully applied the developed algorithm for improving x-ray phase-contrast images of human post-mortem pineal gland and olfactory bulbs.
The method of Computed Tomography (CT) has progressed throughout the past decade with advances in CT apparatus and program parts that have resulted in an increasing number of CT applications. Today innovative CT Xray detectors have high spatial resolution till a tenth or hundredth of a micron. However, itsfield of view is significantly limited. The object being scanned with a high resolution does not always completely enter in (covered by) the field of view of the detector. The collected projections data may be incomplete. The use of incomplete data in classical reconstruction methods leads to image quality loss. This paper provides a new advanced reconstruction method that demonstrates image quality improvements compared with classical methods when incomplete data collected. The method uses the hypothesis about the consistency of object description in sinogram space and reconstruction space. Input data for the algorithm proposed are incomplete data, and the output data are the reconstructed image and the confidence values for all pixels of the image (reconstruction reliability). A detailed description of the algorithm is presented. Its quality characteristics are based on Shepp-Logan phantom studies.
The paper presents a novel method for suppression of the orthotropic stripe artifacts typical for sensitive optical detector arrays. The algorithm is based on the guided filtering technique where the guidance image is constructed from the input frame in a way that removes artifacts from local contrast structures while disregarding the low-frequency distortions. The artifact suppression procedure was applied to the images of human faces taken with the IR -- THz camera in the diagnosis of psycho-emotional states. In this case, the presence of orthotropic artifacts prevents digital image stabilization. We also demonstrated that adaptation of the alg
Computer vision for biomedical imaging applications is fast developing and at once demanding field of computer science. In particular, computer vision technique provides excellent results for detection and segmentation problems in tomographic imaging. X-ray phase contrast Tomography (XPCT) is a noninvasive 3D imaging technique with high sensitivity for soft tissues. Despite a considerable progress in XPCT data acquisition and data processing methods, the problem in degradation of image quality due to artifacts remains a widespread and often critical issue for computer vision applications. One of the main problems originates from a sample alteration during a long tomographic scan. We proposed and tested Simultaneous Iterative Reconstruction algorithm with Total Variation regularization to reduce the number of projections in high resolution XPCT scans of ex-vivo mouse spinal cord. We have shown that the proposed algorithm allows tenfold reducing the number of projections and, therefore, the exposure time, with conservation of the important morphological information in 3D image with quality acceptable for computer graphics and computer vision applications. Our research paves a way for more effective implementation of advanced computer technologies in phase contrast tomographic research.
Theranostics is an innovative research field that aims to develop high target specificity cancer treatments by administering small metal-based nanoparticles (NPs). This new generation of compounds exhibits diagnostic and therapeutic properties due to the high atomic number of their metal component. In the framework of a combined research program on low dose X-ray imaging and theranostic NPs, X-ray Phase Contrast Tomography (XPCT) was performed at ESRF using a 3 μm pixel optical system on two samples: a mouse brain bearing melanoma metastases injected with gadolinium NPs and, a mouse liver injected with gold NPs. XPCT is a non-destructive technique suitable to achieve the 3D reconstruction of a specimen and, widely used at micro-scale to detect abnormalities of the vessels, which are associated to the tumor growth or to the development of neurodegenerative diseases. Moreover, XPCT represents a promising and complementary tool to study the biodistribution of theranostic NPs in biological materials, thanks to the strong contrast with respect to soft tissues that metal-based NPs provide in radiological images. This work is relied on an original imaging approach based on the evaluation of the contrast differences between the images acquired below and above K-edge energies, as a proof of the certain localization of NPs. We will present different methods aiming to enhance the localization of NPs and a 3D map of their distribution in large volume of tissues.
We present in this paper the basic principle of novel X-ray optics composed of confocal nested reflecting mirrors that allows
more photons from a source of X-ray radiation to be accepted compared with a single mirror and that can be fabricated using
relatively cheap microfabrication tools. In order to optimize relevant parameters of the proposed system, we developed a ray-
tracing code for nested surfaces. The choice of parameters of the mirror system (length, position, eccentricity, etc.) is carried
out starting from theoretical considerations, which have been recently developed and, through simple equations, give optimal
parameters of X-ray mirrors providing a maximal acceptance angle of the system.
The idea of an X-ray waveguide has its origin in 1974 from a paper of Spiller and Segmuller1, but only then years ago2-5
it has been demonstrated that a submicrometer X-ray beam could be produced by the waveguides. From the first
experiments up to now the efficiency has been improved by three orders of magnitude6, and a nanometer beam confined
in two directions has been also produced7. Recently, as it will be shown in this paper, the possibility to use waveguides
with laboratory sources has been also demonstrated. The unique characteristics of the beam produced by the waveguides
(nanometer beam size, high degree of coherence, well defined beam profile, etc.) make it appealing for several
applications in microimaging, microdiffraction, etc. In this work the principles of X-ray waveguides together with the
view of the present activity and applications of this optics will be presented.
The analysis of the roughness of B4C films of different thickness as well as W/B4C multilayer mirrors of different periods is performed basing on AFM and x-ray scattering (XRS) measurements. It is demonstrated that the linear model of a film growth is able to describe the whole set of experimental data including films at initial island stage of growth, if suppose the relaxation processes of a film surface to depend on the film thickness. New approach to the inverse problem of x-ray reflectometry consisting in inferring the dielectric constant profile from the reflectivity data is shortly discussed.
The potentialities of the x-ray scattering methods (XRS) for quantitative testing of supersmooth surfaces, thin films, and multilayer structures are discussed. The results of the surface roughness study with the use of XRS technique in hard and sort x-ray spectral regions are compared with independent measurements of the roughness by atomic force microscopy (AFM). It is demonstrated that the results obtained by XRS and AFM are in a very good agreement in spite of different physical principles and underlying the methods. XRS technique is applied for the roughness study of thin films which are used in applications for x-ray and UV optics. The XRS method is demonstrated to enable quantitative evaluation of PSD functions of both the film interfaces and the correlation between the substrate and film roughnesses. X-ray investigations of the correlation of the roughnesses of short-period multilayer structures are discussed as well. The use of the whispering gallery effect is demonstrated to extend the XRS method to control of the concave surface roughness.
We propose to extend x-ray scattering method to the investigation of concave surface roughness. Our approach is based on the use of the whispering gallery effect, which consists in that an x-ray beam falling tangentially on to a concave surface slides along a surface due to successive total external reflections. During its propagation the beam gradually broadens because the scattering transfers some part of radiation to the range of larger glancing angles. Fitting of a simulated angular distribution of outgoing beam to a measure done enables the determination of statistical parameters of concave surface roughness. Possible experimental schemes are analyzed by using ray-tracing technique, radiation scattering by surface roughness being modeled by the Monte Carlo method. Results of experiments in x-ray spectral region are discussed. Carbon-coated cylindrical surfaces with the radius of curvature of 6 cm and the arc angle of 45 and 60 degrees are studied with soft x-rays. The measured angular distributions of outgoing radiation are shown to agree quantitatively with the theoretical calculations when the scattering of x-rays by the surface roughness are taken into account. The rms roughness and the correlation length of the studied surface are found to be about 1.2 nm and 0.3 micrometers , respectively. The possibility of the study of concave surface roughness with the use of hard x-rays is also discussed.
A new approach is proposed for the design of wide band-pass multilayer optical elements for the hard x-ray spectral region. The method, based on the combination of analytical and numerical methods, solves the inverse problem consisting of inferring the composition profile of a depth-graded multilayer coating. First, assuming the multilayer d-spacing profile to be a monotone function of the depth and the d- spacing gradient to be large enough, we derived the differential equation that describes the change of period necessary to guarantee a given spectral reflectivity profile. Then, a computer code using an algorithm of steepest descent was used to refine numerically the multilayer period profile, each layer thickness being treated as an independent variable. When using the solution to the differential equation as a starting point of the direct problem, a many-fold decrease of computer time could be obtained. At each step, the spectral dependence of reflectivity was accurately computed using a standard matrix method. Simulations of the particular case of constant reflectivity and maximum integrated reflectivity over a wide spectral range are presented. The best choice of material pairs for comprising a depth-graded multilayer structure is discussed from the viewpoint of maximum achievable reflectivity and least number of bi-layers. Features of depth-graded multilayer mirrors, which are distinctive from conventional periodic mirrors, are examined.
Recent progress in the manufacturing of X-ray multilayers has opened up new possibilities in the field of hard x-ray optics allowing to produce wide bandpass optical elements through the design of depth-graded multilayer coatings. However, the inverse problem consisting of inferring the composition profile of the multilayer has only been addressed in a semi- empirical way, which encouraged us to develop a new (theoretical) approach. Our method is composed of three steps. First, we use an approximate analytical expression to describe the x-ray reflectivity spectral dependence of any arbitrary graded-multilayer structure. Such an approximation is obtained by assuming the multilayer d-spacing profile to be a monotone function of the depth. The d-spacing gradient is also assumed to be large enough, so that the reflection condition for each given energy is fulfilled in a depth zone that is small compared to the thickness of the multilayer stack. On this basis we could derive the differential equation that describes the change of period necessary to guarantee a given spectral reflectivity profile. Then, a computer code, written for solving the inverse problem, lead us to the desired multilayer period profile. Finally, the effective spectral dependence of reflectivity was accurately computed using a standard matrix method. Simulations of the particular case of constant reflectivity over a wide spectral range are presented. Possible applications of wide bandpass multilayers in synchrotron and astrophysics hard x-ray optics are discussed.
Basic properties of whispering gallery mirrors in soft X-ray region are considered. The following applications of whispering gallery optics are discussed: increasing of utilization efficiency of point source radiation, deflection of synchrotron radiation beam to vertical plane and its transportation to another horizontal level, resonators for soft X-ray lasers and the use of whispering gallery effect for investigation of roughness of concave surfaces.
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