Paclitaxel alters the microvascular network in the central and peripheral nervous system of rats with chemotherapy-induced painful peripheral neuropathy.

Background And Aims: Chemotherapy-induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose-limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN.

X-ray multiscale 3D neuroimaging to quantify cellular aging and neurodegeneration postmortem in a model of Alzheimer's disease.

Purpose: Modern neuroimaging lacks the tools necessary for whole-brain, anatomically dense neuronal damage screening. An ideal approach would include unbiased histopathologic identification of aging and neurodegenerative disease.

Methods: We report the postmortem application of multiscale X-ray phase-contrast computed tomography (X-PCI-CT) for the label-free and dissection-free organ-level to intracellular-level 3D visualization of distinct single neurons and glia.

X-Ray Phase Contrast 3D Virtual Histology: Evaluation of Lung Alterations After Microbeam Irradiation.

Purpose: This study provides the first experimental application of multiscale 3-dimensional (3D) x-ray phase contrast imaging computed tomography (XPCI-CT) virtual histology for the inspection and quantitative assessment of the late-stage effects of radio-induced lesions on lungs in a small animal model.

Methods And Materials: Healthy male Fischer rats were irradiated with x-ray standard broad beams and microbeam radiation therapy, a high-dose rate (14 kGy/s), FLASH spatially fractionated x-ray therapy to avoid beamlet smearing owing to cardiosynchronous movements of the organs during the irradiation. After organ dissection, ex vivo XPCI-CT was applied to all the samples and the results were quantitatively analyzed and correlated to histologic data.

A Multi-Scale and Multi-Technique Approach for the Characterization of the Effects of Spatially Fractionated X-ray Radiation Therapies in a Preclinical Model.

The purpose of this study is to use a multi-technique approach to detect the effects of spatially fractionated X-ray Microbeam (MRT) and Minibeam Radiation Therapy (MB) and to compare them to seamless Broad Beam (BB) irradiation. Healthy- and Glioblastoma (GBM)-bearing male Fischer rats were irradiated in-vivo on the right brain hemisphere with MRT, MB and BB delivering three different doses for each irradiation geometry. Brains were analyzed post mortem by multi-scale X-ray Phase Contrast Imaging-Computed Tomography (XPCI-CT), histology, immunohistochemistry, X-ray Fluorescence (XRF), Small- and Wide-Angle X-ray Scattering (SAXS/WAXS).

Multiscale X-ray phase contrast imaging of human cartilage for investigating osteoarthritis formation.

Background: The evolution of cartilage degeneration is still not fully understood, partly due to its thinness, low radio-opacity and therefore lack of adequately resolving imaging techniques. X-ray phase-contrast imaging (X-PCI) offers increased sensitivity with respect to standard radiography and CT allowing an enhanced visibility of adjoining, low density structures with an almost histological image resolution. This study examined the feasibility of X-PCI for high-resolution (sub-) micrometer analysis of different stages in tissue degeneration of human cartilage samples and compare it to histology and transmission electron microscopy.

Mammary tumors in Sprague Dawley rats induced by N-ethyl-N-nitrosourea for evaluating terahertz imaging of breast cancer.

The objective of this study is to quantitatively evaluate terahertz (THz) imaging for differentiating cancerous from non-cancerous tissues in mammary tumors developed in response to injection of N-ethyl-N-nitrosourea (ENU) in Sprague Dawley rats. While previous studies have investigated the biology of mammary tumors of this model, the current work is the first study to employ an imaging modality to visualize these tumors. A pulsed THz imaging system is utilized to experimentally collect the time-domain reflection signals from each pixel of the rat's excised tumor.

Deletion of the Imprinted Gene Increases Placental Passive Permeability in the Mouse.

Genomic imprinting, an epigenetic phenomenon that causes the expression of a small set of genes in a parent-of-origin-specific manner, is thought to have co-evolved with placentation. Many imprinted genes are expressed in the placenta, where they play diverse roles related to development and nutrient supply function. However, only a small number of imprinted genes have been functionally tested for a role in nutrient transfer capacity in relation to the structural characteristics of the exchange labyrinthine zone.

Convolutional neuronal networks combined with X-ray phase-contrast imaging for a fast and observer-independent discrimination of cartilage and liver diseases stages.

We applied transfer learning using Convolutional Neuronal Networks to high resolution X-ray phase contrast computed tomography datasets and tested the potential of the systems to accurately classify Computed Tomography images of different stages of two diseases, i.e. osteoarthritis and liver fibrosis.

High-Spatial-Resolution Three-dimensional Imaging of Human Spinal Cord and Column Anatomy with Postmortem X-ray Phase-Contrast Micro-CT.

Background Modern high-spatial-resolution radiologic methods enable increasingly detailed volumetric postmortem investigations of human neuroanatomy for diagnostic, research, and educational purposes. Purpose To evaluate the viability of postmortem x-ray phase-contrast micro-CT to provide tissue-conserving, high-spatial-resolution, three-dimensional neuroimaging of the human spinal cord and column by comparing quality of x-ray phase-contrast micro-CT images of nondissected Thiel-embalmed human spines with images of extracted formalin-fixed human spinal cords. Specific focus was placed on assessing the detection of micrometric spinal cord soft-tissue structure and vasculature.

Multiscale pink-beam microCT imaging at the ESRF-ID17 biomedical beamline.

Recent trends in hard X-ray micro-computed tomography (microCT) aim at increasing both spatial and temporal resolutions. These challenges require intense photon beams. Filtered synchrotron radiation beams, also referred to as `pink beams', which are emitted by wigglers or bending magnets, meet this need, owing to their broad energy range.

Establishing sample-preparation protocols for X-ray phase-contrast CT of rodent spinal cords: Aldehyde fixations and osmium impregnation.

Background: Dense and unbiased cellular-resolution representations of extended volumetric central nervous system soft-tissue anatomy are difficult to obtain, even in experimental post-mortem settings. Interestingly, X-ray phase-contrast computed tomography (X-PCI-CT), an emerging soft-tissue-sensitive volumetric imaging technique, can provide multiscale organ- to cellular-level morphological visualizations of neuroanatomical structure.

New Method: Here, we tested different nervous-tissue fixation procedures, conventionally used for transmission electron microscopy, to better establish X-PCI-CT-specific sample-preparation protocols.

Camk2n1 Is a Negative Regulator of Blood Pressure, Left Ventricular Mass, Insulin Sensitivity, and Promotes Adiposity.

Metabolic syndrome is a cause of coronary artery disease and type 2 diabetes mellitus. Camk2n1 resides in genomic loci for blood pressure, left ventricle mass, and type 2 diabetes mellitus, and in the spontaneously hypertensive rat model of metabolic syndrome, Camk2n1 expression is cis-regulated in left ventricle and fat and positively correlates with adiposity. Therefore, we knocked out Camk2n1 in spontaneously hypertensive rat to investigate its role in metabolic syndrome.

Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography.

Purpose: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection.

Quantitative Assessment of Degenerative Cartilage and Subchondral Bony Lesions in a Preserved Cadaveric Knee: Propagation-Based Phase-Contrast CT Versus Conventional MRI and CT.

Objective: The aim of this study was to quantitatively assess hyaline cartilage and subchondral bone conditions in a fully preserved cadaveric human knee joint using high-resolution x-ray propagation-based phase-contrast imaging (PBI) CT and to compare the performance of the new technique with conventional CT and MRI.

Materials And Methods: A cadaveric human knee was examined using an x-ray beam of 60 keV, a detector with a 90-mm FOV, and a pixel size of 46 × 46 μm. PBI CT images were reconstructed with both the filtered back projection algorithm and the equally sloped tomography method.

Deep transfer learning for characterizing chondrocyte patterns in phase contrast X-Ray computed tomography images of the human patellar cartilage.

Phase contrast X-ray computed tomography (PCI-CT) has been demonstrated to be effective for visualization of the human cartilage matrix at micrometer resolution, thereby capturing osteoarthritis induced changes to chondrocyte organization. This study aims to systematically assess the efficacy of deep transfer learning methods for classifying between healthy and diseased tissue patterns. We extracted features from two different convolutional neural network architectures, CaffeNet and Inception-v3 for characterizing such patterns.

Synchrotron-generated microbeams induce hippocampal transections in rats.

Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats.

Characterization of a sCMOS-based high-resolution imaging system.

The detection system is a key part of any imaging station. Here the performance of the novel sCMOS-based detection system installed at the ID17 biomedical beamline of the European Synchrotron Radiation Facility and dedicated to high-resolution computed-tomography imaging is analysed. The system consists of an X-ray-visible-light converter, a visible-light optics and a PCO.

Complement Factor B Is a Determinant of Both Metabolic and Cardiovascular Features of Metabolic Syndrome.

CFB (complement factor B) is elevated in adipose tissue and serum from patients with type 2 diabetes mellitus and cardiovascular disease, but the causal relationship to disease pathogenesis is unclear. Cfb is also elevated in adipose tissue and serum of the spontaneously hypertensive rat, a well-characterized model of metabolic syndrome. To establish the role of CFB in metabolic syndrome, we knocked out the gene in the spontaneously hypertensive rat.

X-Ray Phase Contrast Tomography Reveals Early Vascular Alterations and Neuronal Loss in a Multiple Sclerosis Model.

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks.

Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat.

We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions.

A method for high-energy, low-dose mammography using edge illumination x-ray phase-contrast imaging.

Since the breast is one of the most radiosensitive organs, mammography is arguably the area where lowering radiation dose is of the uttermost importance. Phase-based x-ray imaging methods can provide opportunities in this sense, since they do not require x-rays to be stopped in tissue for image contrast to be generated. Therefore, x-ray energy can be considerably increased compared to those usually exploited by conventional mammography.

A single-image retrieval method for edge illumination X-ray phase-contrast imaging: Application and noise analysis.

Purpose: Edge illumination (EI) X-ray phase-contrast imaging (XPCI) has been under development at University College London in recent years, and has shown great potential for both laboratory and synchrotron applications. In this work, we propose a new acquisition and processing scheme. Contrary to existing retrieval methods for EI, which require as input two images acquired in different setup configurations, the proposed approach can retrieve an approximate map of the X-ray phase from a single image, thus significantly simplifying the acquisition procedure and reducing data collection times.

Hard X-ray index of refraction tomography of a whole rabbit knee joint: A feasibility study.

We report results of the computed tomography reconstruction of the index of refraction in a whole rabbit knee joint examined at the photon energy of 51keV. Refraction based images make it possible to delineate the bone, cartilage, and soft tissues without adjusting the contrast window width and level. Density variations, which are related to tissue composition and are not visible in absorption X-ray images, are detected in the obtained refraction based images.

The effects of differences in pspA alleles and capsular types on the resistance of Streptococcus pneumoniae to killing by apolactoferrin.

Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S.