Phase contrast micro-CT with adjustable in-slice spatial resolution at constant magnification.

To report on a micro computed tomography (micro-CT) system capable of x-ray phase contrast imaging and of increasing spatial resolution at constant magnification.The micro-CT system implements the edge illumination (EI) method, which relies on two absorbing masks with periodically spaced transmitting apertures in the beam path; these split the beam into an array of beamlets and provide sensitivity to the beamlets' directionality, i.e.

X-ray phase-contrast microtomography of soft tissues using a compact laboratory system with two-directional sensitivity.

X-ray microtomography is a nondestructive, three-dimensional inspection technique applied across a vast range of fields and disciplines, ranging from research to industrial, encompassing engineering, biology, and medical research. Phase-contrast imaging extends the domain of application of x-ray microtomography to classes of samples that exhibit weak attenuation, thus appearing with poor contrast in standard x-ray imaging. Notable examples are low-atomic-number materials, like carbon-fiber composites, soft matter, and biological soft tissues.

Technical note: Cartilage imaging with sub-cellular resolution using a laboratory-based phase-contrast x-ray microscope.

Background: Microscopic imaging of cartilage is a key tool for the study and development of treatments for osteoarthritis. When cellular and sub-cellular resolution is required, histology remains the gold standard approach, albeit limited by the lack of volumetric information as well as by processing artifacts. Cartilage imaging with the sub-cellular resolution has only been demonstrated in the synchrotron environment.

Femtosecond multimodal imaging with a laser-driven X-ray source.

Laser-plasma accelerators are compact linear accelerators based on the interaction of high-power lasers with plasma to form accelerating structures up to 1000 times smaller than standard radiofrequency cavities, and they come with an embedded X-ray source, namely betatron source, with unique properties: small source size and femtosecond pulse duration. A still unexplored possibility to exploit the betatron source comes from combining it with imaging methods able to encode multiple information like transmission and phase into a single-shot acquisition approach. In this work, we combine edge illumination-beam tracking (EI-BT) with a betatron X-ray source and present the demonstration of multimodal imaging (transmission, refraction, and scattering) with a compact light source down to the femtosecond timescale.

Utility of knife-edge position tracking in cycloidal computed tomography.

Cycloidal computed tomography provides high-resolution images within relatively short scan times by combining beam modulation with dedicated under-sampling. However, implementing the technique relies on accurate knowledge of the sample's motion, particularly in the case of continuous scans, which is often unavailable due to hardware or software limitations. We have developed an easy-to-implement position tracking technique using a sharp edge, which can provide reliable information about the trajectory of the sample and thus improve the reconstruction process.

Volumetric High-Resolution X-Ray Phase-Contrast Virtual Histology of Breast Specimens With a Compact Laboratory System.

The assessment of margin involvement is a fundamental task in breast conserving surgery to prevent recurrences and reoperations. It is usually performed through histology, which makes the process time consuming and can prevent the complete volumetric analysis of large specimens. X-ray phase contrast tomography combines high resolution, sufficient penetration depth and high soft tissue contrast, and can therefore provide a potential solution to this problem.

Optimization of multipoint phase retrieval in edge illumination X-ray imaging: A theoretical and experimental analysis.

Purpose: In this work, an analytical model describing the noise in the retrieved three contrast channels, transmission, refraction, and ultra small-angle scattering, obtained with edge illumination X-ray phase-based imaging system is presented and compared to experimental data.

Methods: In EI, images acquired at different displacements of the presample mask (i.e.

Detection of involved margins in breast specimens with X-ray phase-contrast computed tomography.

Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively.

Fast, non-iterative algorithm for quantitative integration of X-ray differential phase-contrast images.

X-ray phase contrast imaging is gaining importance as an imaging tool. However, it is common for X-ray phase detection techniques to be sensitive to the derivatives of the phase. Therefore, the integration of differential phase images is a fundamental step both to access quantitative pixel content and for further analysis such as segmentation.

A compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast.

A significant number of patients receiving breast-conserving surgery (BCS) for invasive carcinoma and ductal carcinoma in situ (DCIS) may need reoperation following tumor-positive margins from final histopathology tests. All current intraoperative margin assessment modalities have specific limitations. As a first step towards the development of a compact system for intraoperative specimen imaging based on edge illumination x-ray phase contrast, we prove that the system's dimensions can be reduced without affecting imaging performance.

A Gaussian extension for Diffraction Enhanced Imaging.

Unlike conventional x-ray attenuation one of the advantages of phase contrast x-ray imaging is its capability of extracting useful physical properties of the sample. In particular the possibility to obtain information from small angle scattering about unresolvable structures with sub-pixel resolution sensitivity has drawn attention for both medical and material science applications. We report on a novel algorithm for the analyzer based x-ray phase contrast imaging modality, which allows the robust separation of absorption, refraction and scattering effects from three measured x-ray images.

Large field of view, fast and low dose multimodal phase-contrast imaging at high x-ray energy.

X-ray phase contrast imaging (XPCI) is an innovative imaging technique which extends the contrast capabilities of 'conventional' absorption based x-ray systems. However, so far all XPCI implementations have suffered from one or more of the following limitations: low x-ray energies, small field of view (FOV) and long acquisition times. Those limitations relegated XPCI to a 'research-only' technique with an uncertain future in terms of large scale, high impact applications.

Morphoproteomic Characterization of Lung Squamous Cell Carcinoma Fragmentation, a Histological Marker of Increased Tumor Invasiveness.

Accurate stratification of tumors is imperative for adequate cancer management. In addition to staging, morphologic subtyping allows stratification of patients into additional prognostic groups. In this study, we used an image-based computational method on pan-cytokeratin IHC stainings to quantify tumor fragmentation (TF), a measure of tumor invasiveness of lung squamous cell carcinoma (LSCC).

Asymmetric masks for laboratory-based X-ray phase-contrast imaging with edge illumination.

We report on an asymmetric mask concept that enables X-ray phase-contrast imaging without requiring any movement in the system during data acquisition. The method is compatible with laboratory equipment, namely a commercial detector and a rotating anode tube. The only motion required is that of the object under investigation which is scanned through the imaging system.

Amyloid-β plaque deposition measured using propagation-based X-ray phase contrast CT imaging.

Amyloid beta accumulation into insoluble plaques (Aβp) is known to play a significant role in the pathological process in Alzheimer's disease (AD). The presence of Aβp is also one of the neuropathological hallmarks for the disease. AD final diagnosis is generally acknowledged after the evaluation of Aβp deposition in the brain.

A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies.

Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to develop technologies for continuous antibody delivery applicable to disease prevention.

Ascending Aortic Aneurysm in Angiotensin II-Infused Mice: Formation, Progression, and the Role of Focal Dissections.

Objective: To understand the anatomy and physiology of ascending aortic aneurysms in angiotensin II-infused ApoE(-/-) mice.

Approach And Results: We combined an extensive in vivo imaging protocol (high-frequency ultrasound and contrast-enhanced microcomputed tomography at baseline and after 3, 10, 18, and 28 days of angiotensin II infusion) with synchrotron-based ultrahigh resolution ex vivo imaging (phase contrast X-ray tomographic microscopy) in n=47 angiotensin II-infused mice and 6 controls. Aortic regurgitation increased significantly over time, as did the luminal volume of the ascending aorta.

Early post-metamorphic, Carboniferous blastoid reveals the evolution and development of the digestive system in echinoderms.

Inferring the development of the earliest echinoderms is critical to uncovering the evolutionary assembly of the phylum-level body plan but has long proven problematic because early ontogenetic stages are rarely preserved as fossils. Here, we use synchrotron tomography to describe a new early post-metamorphic blastoid echinoderm from the Carboniferous (approx. 323 Ma) of China.

Chronic Rho-kinase inhibition improves left ventricular contractile dysfunction in early type-1 diabetes by increasing myosin cross-bridge extension.

Background: Impaired actin-myosin cross-bridge (CB) dynamics correlate with impaired left ventricular (LV) function in early diabetic cardiomyopathy (DCM). Elevated expression and activity of Rho kinase (ROCK) contributes to the development of DCM. ROCK targets several sarcomeric proteins including myosin light chain 2, myosin binding protein-C (MyBP-C), troponin I (TnI) and troponin T that all have important roles in regulating CB dynamics and contractility of the myocardium.

Ex vivo differential phase contrast and magnetic resonance imaging for characterization of human carotid atherosclerotic plaques.

Non-invasive detection of specific atherosclerotic plaque components related to vulnerability is of high clinical relevance to prevent cerebrovascular events. The feasibility of magnetic resonance imaging (MRI) for characterization of plaque components was already demonstrated. We aimed to evaluate the potential of ex vivo differential phase contrast X-ray tomography (DPC) to accurately characterize human carotid plaque components in comparison to high field multicontrast MRI and histopathology.

Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering.

Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue.

Functional and Electrical Integration of Induced Pluripotent Stem Cell-Derived Cardiomyocytes in a Myocardial Infarction Rat Heart.

In vitro expanded beating cardiac myocytes derived from induced pluripotent stem cells (iPSC-CMs) are a promising source of therapy for cardiac regeneration. Meanwhile, the cell sheet method has been shown to potentially maximize survival, functionality, and integration of the transplanted cells into the heart. It is thus hypothesized that transplanted iPSC-CMs in a cell sheet manner may contribute to functional recovery via direct mechanical effects on the myocardial infarction (MI) heart.

Self-assembled gold coating enhances X-ray imaging of alginate microcapsules.

Therapeutic biomolecules produced from cells encapsulated within alginate microcapsules (MCs) offer a potential treatment for a number of diseases. However the fate of such MCs once implanted into the body is difficult to establish. Labelling the MCs with medical imaging contrast agents may aid their detection and give researchers the ability to track them over time thus aiding the development of such cellular therapies.

Dissecting abdominal aortic aneurysm in Ang II-infused mice: suprarenal branch ruptures and apparent luminal dilatation.

Aims: In this work, we provide novel insight into the morphology of dissecting abdominal aortic aneurysms in angiotensin II-infused mice. We demonstrate why they exhibit a large variation in shape and, unlike their human counterparts, are located suprarenally rather than infrarenally.

Methods And Results: We combined synchrotron-based, ultra-high resolution ex vivo imaging (phase contrast X-Ray tomographic microscopy) with in vivo imaging (high-frequency ultrasound and contrast-enhanced micro-CT) and image-guided histology.