Experimentelle Phasenkontrastbildgebung der Brust

Hintergrund: Während die konventionelle Röntgenbildgebung lediglich die Absorption (Schwächung) der Strahlung in Materie misst, erfasst die Phasenkontrastbildgebung zusätzlich simultan die Phasenverschiebung, die die elektromagnetischen Wellen beim Durchtritt durch Materie erfahren sowie die Kleinwinkelstreuung (entspricht dem sogenannten Dunkelfeldbild) im durchstrahlten Gewebe. Eine dreidimensionale Rekonstruktion analog zur konventionellen Computertomographie ist möglich. Ziel des Habilitationsprojektes war es, das Potential der Phasenkontrastbildgebung zur Anwendung in der Mammadiagnostik im Hinblick auf die Verbesserung des Weichgewebekontrasts und der verbesserten Tumordetektion (Teilgebiet 1: Phasenkontrast-Mammographie) sowie auf die maximale Auflösung von Weichgewebestrukturen mit der Möglichkeit der dreidimensionalen Rekonstruktion in Korrelation mit der Histologie mittels Phasenkontrast-Computertomographie (Teilgebiet 2: Phasenkontrast-Computertomographie) zu erforschen. Material und Methoden: Die Untersuchungen fanden ex-vivo an Brustabladaten und -exzidaten statt. Die akquirierten Bilder wurden mit der klinischen Bildgebung (Mammographie, Mamma-Sonographie, Mamma-MRT) und der Histologie als Goldstandard verglichen. Im Teilprojekt Phasenkontrast-Mammographie wurde die Darstellbarkeit von multifokalen Mikrokalk-besetzten Tumorherden untersucht und ein Fourier Fusionsalgorithmus zur intuitiven Betrachtung der Bilddatensätze etabliert. Im Teilprojekt Phasenkontrast-Computertomographie wurde im Rahmen einer Feasibility Studie die Anwendbarkeit der Phasenkontrast-Computertomographie am Brustgewebe an einer konventionellen Röntgenröhre untersucht. Weitere Teilprojekte befassten sich mit der Darstellbarkeit typischer Strukturen von Fibroadenomen und post-therapeutischen Veränderungen der Brust im Rahmen einer Chemotherapie. Ergebnisse: Die Phasenkontrast-Mammographie akquiriert in einer einzigen Messung drei verschiedene Datensätze: Das Phasenkontrastbild, das Absorptionsbild (vergleichbar mit dem konventionellen Röntgenbild) und das Dunkelfeldbild. Die Dunkelfeld-Radiographie stellt mikrokalkbesetzte Tumorherde kontrastreicher dar als die Standard-Mammographie, wobei die Größe der Mikroverkalkungen zum Teil unterhalb der Detektionsgrenze der konventionellen Mammographie lag. Die Phasenkontrast-Mammographie bildete Tumorausläufer kontrastreich ab, was für das operative Management von Bedeutung sein kann. Der im Rahmen des Habilitationsprojektes entwickelte intuitive Fusionsalgorithmus bietet die Möglichkeit die jeweiligen diagnostisch wertvollen Informationen der drei Datensätze in einem Bild zusammenzuführen, welches einer konventionellen Mammographie ähnelt bei allerdings deutlich verbesserter Darstellbarkeit diagnostisch relevanter Bildmerkmale. Die Phasenkontrast-CT ist in der Lage mit hoher Auflösung kleinste Strukturen kontrastreich abzubilden, die in der konventionellen CT nicht darstellbar sind, beispielsweise dilatierte Gänge, Fibrose-Areale und Binnenstrukturen von Fibroadenomen. Ausblick: Die Phasenkontrastmammographie liefert komplementäre Bildinformationen zur konventionellen Mammographie. Dabei bietet die Phasenkontrastbildgebung potentiell die Möglichkeit einer verbesserten diagnostischen Qualität bei gleicher Dosis bzw. einer Dosisreduktion bei gleicher Auflösung. Die Methode ist grundsätzlich auch auf die Tomosynthese anwendbar. Die Phasenkontrast-CT bietet ein dreidimensionales, nichtinvasives diagnostisches Zusatztool, mit dem ohne die vorhergehende Applikation von Kontrastmitteln in hoher Auflösung Gewebs-Binnenstrukturen akkurat dargestellt werden können. Im Rahmen einer ex-vivo Anwendung bietet die Phasenkontrast CT die Möglichkeit der ergänzenden Diagnostik im Rahmen der histopathologischen Befundung, um durch die damit verbundene 3D Darstellung beispielsweise eines Tumors diagnostisch relevante Bereiche innerhalb großer Tumoren zu identifizieren

Toward Clinically Compatible Phase-Contrast Mammography

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom

Toward Clinically Compatible Phase-Contrast Mammography

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom

Assessment of intraductal carcinoma in situ (DCIS) using grating-based X-ray phase-contrast CT at conventional X-ray sources: An experimental ex-vivo study

Background The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. Materials and methods GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. Results Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. Conclusions GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins

Improved Diagnostics by Assessing the Micromorphology of Breast Calcifications via X-Ray Dark-Field Radiography

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures

Improved Diagnostics by Assessing the Micromorphology of Breast Calcifications via X-Ray Dark-Field Radiography

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures

Bi-Directional X-Ray Phase-Contrast Mammography

Phase-contrast x-ray imaging is a promising improvement of conventional absorption-based mammography for early tumor detection. This potential has been demonstrated recently, utilizing structured gratings to obtain differential phase and dark-field scattering images. However, the inherently anisotropic imaging sensitivity of the proposed mono-directional approach yields only insufficient diagnostic information, and has low diagnostic sensitivity to highly oriented structures. To overcome these limitations, we present a two-directional x-ray phase-contrast mammography approach and demonstrate its advantages by applying it to a freshly dissected, cancerous mastectomy breast specimen. We illustrate that the two-directional scanning procedure overcomes the insufficient diagnostic value of a single scan, and reliably detects tumor structures, independently from their orientation within the breast. Our results indicate the indispensable diagnostic necessity and benefit of a multi-directional approach for x-ray phase-contrast mammography

Underneath the Arches, no. 61, October 24, 1968

Underneath the Arches was Grand Valley State\u27s faculty and staff newsletter, published from 1963 to 1971. It was a precursor to the Forum

Деякі проблеми використання тимчасово зайнятих земель

<div><p>Glucocorticoid induced-leucine zipper (GILZ) has been shown to be induced in cells by different stimuli such as glucocorticoids, IL-10 or deprivation of IL-2. GILZ has anti-inflammatory properties and may be involved in signalling modulating apoptosis. Herein we demonstrate that wildtype <em>Yersinia enterocolitica</em> which carry the pYV plasmid upregulated GILZ mRNA levels and protein expression in epithelial cells. Infection of HeLa cells with different <em>Yersinia</em> mutant strains revealed that the protease activity of YopT, which cleaves the membrane-bound form of Rho GTPases was sufficient to induce GILZ expression. Similarly, <em>Clostridium difficile</em> toxin B, another bacterial inhibitor of Rho GTPases induced GILZ expression. YopT and toxin B both increased transcriptional activity of the GILZ promoter in HeLa cells. GILZ expression could not be linked to the inactivation of an individual Rho GTPase by these toxins. However, forced expression of RhoA and RhoB decreased basal <em>GILZ</em> promoter activity. Furthermore, MAPK activation proved necessary for profound GILZ induction by toxin B. Promoter studies and gel shift analyses defined binding of upstream stimulatory factor (USF) 1 and 2 to a canonical c-Myc binding site (E-box) in the <em>GILZ</em> promoter as a crucial step of its trans-activation. In addition we could show that USF-1 and USF-2 are essential for basal as well as toxin B induced GILZ expression. These findings define a novel way of <em>GILZ</em> promoter trans-activation mediated by bacterial toxins and differentiate it from those mediated by dexamethasone or deprivation of IL-2.</p> </div

Visualizing Typical Features of Breast Fibroadenomas Using Phase-Contrast CT: An Ex-Vivo Study

Background: Fibroadenoma is the most common benign solid breast lesion type and a very common cause for histologic assessment. To justify a conservative therapy, a highly specific discrimination between fibroadenomas and other breast lesions is crucial. Phase-contrast imaging offers improved soft-tissue contrast and differentiability of fine structures combined with the potential of 3-dimensional imaging. In this study we assessed the potential of grating-based phase-contrast CT imaging for visualizing diagnostically relevant features of fibroadenomas. Materials and Methods: Grating-based phase-contrast CT was performed on six ex-vivo formalin-fixed breast specimens containing a fibroadenoma and three samples containing benign changes that resemble fibroadenomas using Talbot Lau interferometry and a polychromatic X-ray source. Phase-contrast and simultaneously acquired absorption-based 3D-datasets were manually matched with corresponding histological slices. The visibility of diagnostically valuable features was assessed in comparison with histology as the gold-standard. Results: In all cases, matching of grating-based phase-contrast CT images and histology was successfully completed. Grating-based phase-contrast CT showed greatly improved differentiation of fine structures and provided accurate depiction of strands of fibrous tissue within the fibroadenomas as well as of the diagnostically valuable dilated, branched ductuli of the fibroadenomas. A clear demarcation of tumor boundaries in all cases was provided by phase- but not absorption-contrast CT. Conclusions: Pending successful translation of the technology to a clinical setting and considerable reduction of the required dose, the data presented here suggest that grating-based phase- contrast CT may be used as a supplementary non-invasive diagnostic tool in breast diagnostics. Phase-contrast CT may thus contribute to the reduction of false positive findings and reduce the recall and core biopsy rate in population-based screening. Phase-contrast CT may further be used to assist during histopathological workup, offering a 3D view of the tumor and helping to identify diagnostically valuable tissue sections within large tumors