Imaging Breast Microcalcifications Using Dark-Field Signal in Propagation-Based Phase-Contrast Tomography

Breast microcalcifications are an important primary radiological indicator of breast cancer. However, microcalcification classification and diagnosis may be still challenging for radiologists due to limitations of the standard 2D mammography technique, including spatial and contrast resolution. In this study, we propose an approach to improve the detection of microcalcifications in propagation-based phase-contrast X-ray computed tomography of breast tissues. Five fresh mastectomies containing microcalcifications were scanned at different X-ray energies and radiation doses using synchrotron radiation. Both bright-field (i.e. conventional phase-retrieved images) and dark-field images were extracted from the same data sets using different image processing methods. A quantitative analysis was performed in terms of visibility and contrast-to-noise ratio of microcalcifications. The results show that while the signal-to-noise and the contrast-to-noise ratios are lower, the visibility of the microcalcifications is more than two times higher in the dark-field images compared to the bright-field images. Dark-field images have also provided more accurate information about the size and shape of the microcalcifications

Elemental Contrast X-ray Tomography Using Ross Filter Pairs with a Polychromatic Laboratory Source

The majority of current laboratory based X-ray sources are polychromatic and are not tuneable. This lack of monochromaticity limits the range of applications for these sources and in particular it reduces the elemental specificity of laboratory based X-ray imaging experiments. Here we present a solution to this problem based on the use of Ross filter pairs. Although such Ross filter arrangements have been applied in proof-of-principle spectroscopy experiments, to date there have been no reports of this approach used for full-field X-ray imaging. Here we report on the experimental demonstration of Ross filter pairs being used for quasi-monochromatic, full-field imaging. This arrangement has several important benefits for laboratory based X-ray imaging including, as we demonstrate, elemental contrast enhancement. The method is demonstrated both for two-dimensional radiography and for three-dimensional X-ray tomography

A rationale for the influence of grain size on failure of magnesium alloy AZ31: An in situ X-ray microtomography study

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An intronic mutation in Chd7 creates a cryptic splice site, causing aberrant splicing in a mouse model of CHARGE syndrome

Alternate splicing is a critical regulator of gene expression in eukaryotes, however genetic mutations can cause erroneous splicing and disease. Most recorded splicing disorders are caused by mutations of splice donor/acceptor sites, however intronic mutations can affect splicing. Clinical exome analyses largely ignore intronic sequence, limiting the detection of mutations to within coding regions. We describe 'Trooper', a novel mouse model of CHARGE syndrome harbouring a pathogenic point mutation in Chd7. The mutation is 18 nucleotides upstream of exon 10 and creates a cryptic acceptor site, causing exon skipping and partial intron retention. This mutation, though detectable in exome sequence, was initially dismissed by computational filtering due to its intronic location. The Trooper strain exhibited many of the previously described CHARGE-like anomalies of CHD7 deficient mouse lines; including hearing impairment, vestibular hypoplasia and growth retardation. However, more common features such as facial asymmetry and circling were rarely observed. Recognition of these characteristic features prompted manual reexamination of Chd7 sequence and subsequent validation of the intronic mutation, highlighting the importance of phenotyping alongside exome analyses. The Trooper mouse serves as a valuable model of atypical CHARGE syndrome and reveals a molecular mechanism that may underpin milder clinical presentation of the syndrome

Anti-apoptotic gene Bcl2 is required for stapes development and hearing

In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2⁻/⁻ mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2⁻/⁻ mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2⁻/⁻Bim⁻/⁻ mice and partially rescued in Bcl2⁻/⁻Bim⁺/⁻ mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2⁻/⁻ defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development

X-ray Phase-Contrast Computed Tomography for Soft Tissue Imaging at the Imaging and Medical Beamline (IMBL) of the Australian Synchrotron

The Imaging and Medical Beamline (IMBL) is a superconducting multipole wiggler-based beamline at the 3 GeV Australian Synchrotron operated by the Australian Nuclear Science and Technology Organisation (ANSTO). The beamline delivers hard X-rays in the 25–120 keV energy range and offers the potential for a range of biomedical X-ray applications, including radiotherapy and medical imaging experiments. One of the imaging modalities available at IMBL is propagation-based X-ray phase-contrast computed tomography (PCT). PCT produces superior results when imaging low-density materials such as soft tissue (e.g., breast mastectomies) and has the potential to be developed into a valuable medical imaging tool. We anticipate that PCT will be utilized for medical breast imaging in the near future with the advantage that it could provide better contrast than conventional X-ray absorption imaging. The unique properties of synchrotron X-ray sources such as high coherence, energy tunability, and high brightness are particularly well-suited for generating PCT data using very short exposure times on the order of less than 1 min. The coherence of synchrotron radiation allows for phase-contrast imaging with superior sensitivity to small differences in soft-tissue density. Here we also compare the results of PCT using two different detectors, as these unique source characteristics need to be complemented with a highly efficient detector. Moreover, the application of phase retrieval for PCT image reconstruction enables the use of noisier images, potentially significantly reducing the total dose received by patients during acquisition. This work is part of ongoing research into innovative tomographic methods aimed at the introduction of 3D X-ray medical imaging at the IMBL to improve the detection and diagnosis of breast cancer. Major progress in this area at the IMBL includes the characterization of a large number of mastectomy samples, both normal and cancerous, which have been scanned at clinically acceptable radiation dose levels and evaluated by expert radiologists with respect to both image quality and cancer diagnosis

Iron-specific Signal Separation from within Heavy Metal Stained Biological Samples Using X-Ray Microtomography with Polychromatic Source and Energy-Integrating Detectors

Biological samples are frequently stained with heavy metals in preparation for examining the macro, micro and ultra-structure using X-ray microtomography and electron microscopy. A single X-ray microtomography scan reveals detailed 3D structure based on staining density, yet it lacks both material composition and functional information. Using a commercially available polychromatic X-ray source, energy integrating detectors and a two-scan configuration labelled by their energy- "High" and "Low", we demonstrate how a specific element, here shown with iron, can be detected from a mixture with other heavy metals. With proper selection of scan configuration, achieving strong overlap of source characteristic emission lines and iron K-edge absorption, iron absorption was enhanced enabling K-edge imaging. Specifically, iron images were obtained by scatter plot material analysis, after selecting specific regions within scatter plots generated from the "High" and "Low" scans. Using this method, we identified iron rich regions associated with an iron staining reaction that marks the nodes of Ranvier along nerve axons within mouse spinal roots, also stained with osmium metal commonly used for electron microscopy

Comparison of propagation-based phase-contrast CT and absorption-based CT for breast imaging using synchrotron radiation

Propagation-based phase-contrast CT (PB-CT) is a novel imaging technique that visualises variations in both X-ray attenuation and refraction. This study aimed to compare the clinical image quality of breast PB-CT using synchrotron radiation with conventional absorption-based CT (AB-CT), at the same radiation dose. Seven breast mastectomy specimens were scanned and evaluated by a group of 14 radiologists and medical imaging experts who assessed the images based on seven radiological image quality criteria. Visual grading characteristics (VGC) were used to analyse the results and the area under the VGC curve was obtained to measure the differences between the two techniques. For six image quality criteria (overall quality, perceptible contrast, lesion sharpness, normal tissue interfaces, calcification visibility and image noise), PB-CT images were superior to AB-CT images of the same dose (AUCVGC: 0.704 to 0.914, P≤.05). For the seventh criteria (artefacts), PB-CT images were also rated better than AB-CT images (AUCVGC: 0.647) but the difference was not significant. The results of this study provide a solid basis for future experimental and clinical protocols of breast PB-CT

Effect of x-ray energy on the radiological image quality in propagation-based phase-contrast computed tomography of the breast

Purpose: Breast cancer is the most common cancer in women in developing and developed countries and is responsible for 15% of women’s cancer deaths worldwide. Conventional absorption-based breast imaging techniques lack sufficient contrast for comprehensive diagnosis. Propagation-based phase-contrast computed tomography (PB-CT) is a developing technique that exploits a more contrast-sensitive property of x-rays: x-ray refraction. X-ray absorption, refraction, and contrast-to-noise in the corresponding images depend on the x-ray energy used, for the same/fixed radiation dose. The aim of this paper is to explore the relationship between xray energy and radiological image quality in PB-CT imaging. Approach: Thirty-nine mastectomy samples were scanned at the imaging and medical beamline at the Australian Synchrotron. Samples were scanned at various x-ray energies of 26, 28, 30, 32, 34, and 60 keV using a Hamamatsu Flat Panel detector at the same object-to-detector distance of 6 m and mean glandular dose of 4 mGy. A total of 132 image sets were produced for analysis. Seven observers rated PB-CT images against absorption-based CT (AB-CT) images of the same samples on a five-point scale. A visual grading characteristics (VGC) study was used to determine the difference in image quality. Results: PB-CT images produced at 28, 30, 32, and 34 keV x-ray energies demonstrated statistically significant higher image quality than reference AB-CT images. The optimum x-ray energy, 30 keV, displayed the largest area under the curve ðAUCVGCÞ of 0.754 (p ¼ 0.009). This was followed by 32 keV (AUCVGC ¼ 0.731, p ≤ 0.001), 34 keV (AUCVGC ¼ 0.723, p ≤ 0.001), and 28 keV (AUCVGC ¼ 0.654, p ¼ 0.015). Conclusions: An optimum energy range (around 30 keV) in the PB-CT technique allows for higher image quality at a dose comparable to conventional mammographic techniques. This results in improved radiological image quality compared with conventional techniques, which may ultimately lead to higher diagnostic efficacy and a reduction in breast cancer mortalities