Using synchrotron imaging techniques to solve problems in neurosurgery

Objective: The purpose of the research presented in this thesis is to explore new biomedical applications of synchrotron imaging in the field of neurosurgery. Methods: Four different studies were performed, all using advanced biomedical synchrotron imaging techniques. In the first two experiments, diffraction enhanced imaging (DEI) and analyzer based imaging (ABI) were utilized to study the anatomy of the rat spine and a novel rat model of spinal fusion. In a third experiment, K-edge digital subtraction angiography (KEDSA) was used to study the cerebral vasculature in a rabbit model. In a fourth experiment, rapid scanning X-ray fluorescence spectroscopy (RS-XRF) was used to study stem cell migration in a rat stroke model. Results: DEI had superior visualization of ligamentous and boney anatomy in a rat model. Analyzer based imaging was able to visualize physiologic amounts of bone graft material and progressive incorporation into the spine. Intravenous KEDSA showed excellent visualization of the cerebral vasculature in a rabbit model. Finally, RS-XRF was used to track iron labeled stem cells implanted in a rat stroke model. The technique was able to visualize the iron that represented the stem cell migration. This was correlated with histology and magnetic resonance imaging information. Conclusions: 1) Diffraction enhanced imaging has excellent contrast for the study of boney and ligamentous anatomy. 2) Analyzer based imaging is an excellent tool to study animal models of boney fusion. 3) Intravenous KEDSA is able to clearly visualize the arterial vasculature in a rabbit model. 4) RS-XRF can be used to study the migration patterns of implanted iron labeled stem cells

Micro Soft Tissues Visualization Based on X-Ray Phase-Contrast Imaging

The current imaging methods have a limited ability to visualize microstructures of biological soft tissues. Small lesions cannot be detected at the early stage of the disease. Phase contrast imaging (PCI) is a novel non-invasive imaging technique that can provide high contrast images of soft tissues by the use of X-ray phase shift. It is a new choice in terms of non-invasively revealing soft tissue details. In this study, the lung and hepatic fibrosis models of mice and rats were used to investigate the ability of PCI in microstructures observation of soft tissues. Our results demonstrated that different liver fibrosis stages could be distinguished non-invasively by PCI. The three-dimensional morphology of a segment of blood vessel was constructed. Noteworthy, the blood clot inside the vessel was visualized in three dimensions which provided a precise description of vessel stenosis. Furthermore, the whole lung airways including the alveoli were obtained. We had specifically highlighted its use in the visualization and assessment of the alveoli. To our knowledge, this was the first time for non-invasive alveoli imaging using PCI. This finding may offer a new perspective on the diagnosis of respiratory disease. All the results confirmed that PCI will be a valuable tool in biological soft tissues imaging

Interpretation of refraction images in synchrotron based imaging techniques using growth plate injury specimens in an animal model

Typical clinical radiography uses the variable absorption of x-radiation of different tissues within the object to produce contrast in the image. The interpretation of this image is based on understanding the anatomy and pathology as well as understanding how the image is produced. One needs to understand what features of the image are representative of the anatomy/pathology, what is inherent to the imaging process and what is artefact. The correlation of contrast in the image with absorption contrast in the object is fairly intuitive. Diffraction Enhanced Imaging (DEI) uses the bending or refraction of radiation as it passes through a tissue interface to produce the contrast in the image in addition to absorption. The ability to interpret the refraction contrast image is not as intuitive as the absorption image. Edges are enhanced and tissues with different densities can look similar. Understanding the image acquisition of refraction based radiography also is not as intuitive as typical absorption radiography. One potential advantage of DEI is the ability to visualize small structures that may not be visible using absorption radiography. The growth plate of long bones and the premature closure or bone bridge/bar formation across the growth plate associated with a fracture was targeted as a study sample. An animal model (juvenile rat) was used for inducing a fracture through the proximal metaphysis of the tibia. The animal was then sacrificed at variable times of healing which is described below. The specimens were then imaged using DEI techniques at Brookhaven National Lab, Upton, New York, at the Biomedical Imaging and Therapy (BMIT) beamline at the Canadian Light Source and using a laboratory based DEI system at Nesch, LLC, Crown Point, Indiana. High resolution absorption images were obtained using a SkyScan micro-CT from Prof. Cooper’s laboratory for comparison of DEI and absorption images. Histological slides were also prepared for correlation of image anatomy. The reason for imaging these specimens using different techniques was to determine potential translation of synchrotron based techniques with lab based or conventional techniques as well as determining what features of imaging could be uniquely done at a synchrotron. Since access to synchrotron biomedical imaging facilities is limited, the potential for some work to be done outside of synchrotron facilities would make research progress more efficient. A detailed analysis of the images was performed. The detail of the bone as well as the fracture was exquisite with the CT data. With the planar images the orientation of the trabeculae of the bone relative to the direction of the analyser crystal (direction of diffraction) changes the appearance and texture of the bone image. It was hoped to visualize the layers of the growth plate (variable calcification) and perhaps the initiation of bone spicules leading to bone bridges across the growth plates at the site of fracture. However, the small size of the object limited observable detail. This work was originally intended to apply a unique imaging technique for the study of growth plate fracture pathophysiology. However, it became clear that the technical image production and interpretation was more important to the project than the individual analysis of each specimen. As a result not all specimens were used, but those selected were used to refine the technique and interpret the synchrotron based images compared to conventional images. The use of DEI for assessing bone bridge formation was promising, but the specimen size limited detail and resolution. This has led to the conclusion that a larger animal model would be more appropriate for this type of study. Further, it was discovered that the bone (growth plate) orientation affected the planar image contrast of the bone / cartilage interface based on long axis orientation relative to the refraction sensitive direction of the DEI system. To more fully exploit this effect, more images at different object orientations would be necessary for interpretation in future work with larger animal models

Development of X-ray phase-contrast imaging techniques for medical diagnostics

The X-Ray phase-contrast techniques are innovative imaging methods allowing overtaking the limitations of classic radiology. In addition to the differential X-ray absorption on which standard radiology relies, in phase-contrast imaging the contrast is given by the effects of the refraction of X-rays inside the tissues. The combination of phase-contrast with quantitative computer tomography (CT) allows for a highly accurate reconstruction of the tissues’ index of refraction. Thanks to the high sensitivity of the method, tomographic images can be obtained at clinically compatible dose. For all these reasons phase-contrast imaging is a very promising approach, which can potentially revolutionize diagnostic X-Ray imaging. Several techniques are classified under the name of X-Ray phase-contrast imaging. This Thesis focused on the so-called analyzer-based imaging (ABI) method. ABI uses a perfect crystal, placed between the sample and the detector, to visualize the phase effects occurred within the sample. The quantitative reconstruction of the refraction index from CT data is not trivial and before this Thesis work it was documented only for small size objects. This Thesis has focused on two main scientific problems: (1) the development of theoretical and calculation strategies to determine the quantitative map of the refraction index of large biological tissues/organs (>10 cm) using the ABI technique; and (2) the preparation of accurate and efficient tools to estimate and simulate the dose deposited in CT imaging of large samples. For the determination of the refraction index, two CT geometries were considered and studied: the out-of-plane and the in-plane configurations. The first one, the most used in the works reported in the literature, foresees that the rotation axis of the sample occurs in a plane parallel to that of the sensitivity of the analyzer crystal; while, in the second CT geometry, the rotation axis is perpendicular to that plane. The theoretical study, technical design and experimental implementation of the in-plane geometry have been main tasks of this Thesis. A first experiment has been performed in order to compare the results obtained with in-plane quantitative phase contrast CT with the absorption-based CT ones. An improved accuracy and a better agreement with the theoretical density values have been obtained by exploiting the refraction effect while keeping the dose to sample low. A second campaign of experiments has been performed on large human breasts to investigate the efficiency of the in-plane and out-of-plane CT geometries and the performances of the associated image reconstruction procedures. The same experimental conditions were also studied by numerical simulations and the results were compared. This analysis shows that the in-plane geometry allows producing more accurate quantitative three dimensional maps of the index of refraction, while the out-of-plane case is preferable for qualitative investigations. A study for developing advanced procedures for improving the quality of the obtained CT images has been also conducted. As a result, a two-step procedure has been tested and identified: first the noise level of the experimental images is reduced by applying a wavelet decomposition algorithm and then a deconvolution procedure. The obtained images show an enhanced sharpness of the interfaces and of the object edges and high signal to noise ratio values are preserved. The second problem of this Thesis was to find strategies to calculate, in a fast way, the delivered dose in CT imaging of complex biological samples. For this purpose an acceleration method to speed-up the convergence of Monte Carlo simulations based on the Track Length Estimator method has been computed and included in the open-source software GATE. Results show that this method can lead to the same accuracy of conventional Monte Carlo methods while reducing the required computation time of up to two orders of magnitude, with the respect to the considered geometry. A database of dose curves for the case of monochromatic breast CT has been produced: it allows for a quick estimation of the delivered dose. A way to choose the best energy and the optimal photon flux was also proposed, which leads to a significant reduction of the delivered dose without any loss in terms of image quality. Most of the experimental and data reconstruction methods developed within this Thesis work can be applied also to other phase-contrast techniques. This Thesis shows that high resolution three dimensional diagnostic imaging of large and complex biological organs can, in principle, be performed at clinical compatible doses; this is the most significant contribution of the Thesis towards the clinical implementation of phase-contrast CT.Auf Phasenkontrast basierende Röntgentechniken sind innovative bildgebende Methoden, welche die Limitierungen der klassischen Radiologie überschreiten. Auβer der differentiellen Röntgenabsorption, auf der die herkömmliche Radiologie beruht, ist der Kontrast bei Phasenkontrast-Bildgebung durch die Brechungseffekte der Röntgenstrahlen innerhalb eines Gewebes gegeben. Die Kombination zwischen Phasenkontrast und quantitativer Computertomographie (CT) erlaubt eine höchstgenaue Rekonstruktion der Brechzahl der Gewebe. Aufgrund der hohen Empfindlichkeit dieser Methode, können tomographische Bilder mit einer klinisch verträglichen Dosis erzeugt werden. Aus all diesen Gründen, stellt Phasenkontrast-Bildgebung einen vielversprechenden Ansatz dar, welcher die diagnostische Röntgenbildgebung revolutionieren könnte. Verschiedene röntgenbildgebende Techniken werden als Phasenkontrast-Verfahren bezeichnet. Die vorliegende Doktorarbeit befasst sich mit der sogenannten Bildgebungsmethode mithilfe eines Analysatorkristalls (auf englisch: analyser-based imaging (ABI) ). ABI benutzt ein perfektes, zwischen der Probe und dem Detektor angeordnetes Kristall, um in der Probe stattfindenden Phaseneffekte zu veranschaulichen. Die quantitative Rekonstruktion des Brechungsindizes aus den CT-Daten ist jedoch nicht trivial und war vor dieser Arbeit nur für kleine Gegenstände beschrieben. Im Mittelpunkt dieser Dissertation stehen folgende wissenschaftliche Fragestellungen: (1) die Entwicklung theoretischer und rechnerischer Strategien, um die quantitative räumliche Verteilung des Brechungsindizes in größeren Organen aus biologischen Geweben (10 cm) unter Verwendung der ABI-Technik zu bilden und (2) die Vorbereitung von genauen und leistungsfähigen Rechenmitteln zur Abschätzung und Simulation der in größeren Proben bei einem CT-Bildgebungsversuch abgelagerten Strahlendosis zu treffen. Für die Bestimmung des Brechungsindizes wurden zwei geometrische Anordnungen in Betracht gezogen und untersucht, und zwar die Konfiguration auβerhalb (out-of-plane) bzw. in der Ebene (in-plane) der Probe. Erstere wird am häufigsten in der Fachliteratur zitiert und sieht vor, dass die Probe-Drehachse sich in der parallelen Ebene zur Achse des Analysatorkristalls befindet, wobei in der zweiteren Geometrie die Drehachse orthogonal zu jener Ebene ist. Die theoretische Studie, der technische Entwurf und die experimentelle Umsetzung der geometrischen Anordnung in der Probe-Ebene stellen die Hauptaufgaben dieser Arbeit dar. Ein erstes Experiment wurde durchgeführt, um die durch quantitative Phasenkontrast-CT nach in-plane-Modus erlangten Ergebnisse mit entsprechenden, auf Absorption basierenden CT-Versuchen zu vergleichen. Eine höhere Genauigkeit sowie eine bessere Übereinstimmung mit den theoretischen Dichtewerten wurden dadurch erzielt, dass man sich die Brechungseffekte zunutze macht, indem man die an die Probe gelieferte Dosis niedrig hält. Eine zweite Versuchsreihe wurde auβerdem auf menschliche Brüste ausgeführt, um die Effizienz sowohl der in-plane- als auch der out-of-plane-CT-Geometrien sowie die Leistungsfähigeit der entsprechenden Bildrekonstruktionsverfahren zu überprüfen. Die gleichen Experimentalbedingungen wurden auch anhand von numerischen Simulationen untersucht und die Ergebnisse miteinander verglichen. Diese Analyse zeigt, dass die in-plane-Geometrie die Erstellung genauerer dreidimensionaler Verteilungen der Brechzahl ermöglicht, während der out-of-plane-Fall eher für die Zwecke qualitativer Untersuchungen vorzuziehen ist. Fortschrittliche Prozeduren zur Verbesserung der Qualität von aufgezeichneten CT-Bildern wurden im Rahmen dieser Doktorarbeit konzipiert und entwickelt. Das Fazit: eine zweistufige Vorgehensweise wurde ermittelt und geprüft. Zunächst wird der Rauschpegel der Meβdaten über die Anwendung eines Zerlegungsalgorithmus mittels Wavelets gesenkt, anschlieβend gefolgt von einem Entfaltung-Verfahren. Die damit gewonnenen Bilder weisen eine erhöhte Schärfe der Schnittstellen auf. Die Objektkanten und das Signal-zu-Rausch-Verhältnis bleiben damit erhalten. Die zweite Fragestellung dieser Arbeit war es, Lösungansätze zu erarbeiten, um die während CT-Bildgebung-Messungen über complexe biologische Proben abgegebene Dosis möglichst rapide zu berechnen. Zu diesem Zweck wurde ein Verfahren zur Beschleunigung der Konvergenz von Monte-Carlo-Simulationen auf der Grundlage der Track-Length-Estimator-Methode entwickelt und in die Open-Source-Software GATE eingegliedert. Die bisherigen Ergebnisse zeigen, dass dieses Verfahren zur selben Genauigkeit der herkömmlichen Monte-Carlo-Methoden bei gleichzeitiger Minderung bis zu zwei Gröβenordnungen der zur Berechnung einer und der selben Geometrie notwendigen Rechenzeit führt. Eine Datenbank von Dosiskurven für den Fall von monochromatischer Brust-CT ist erzeugt worden, die eine schnelle Schätzung der abgegebenen Dosis erlaubt. Darüber hinaus wurde ein Lösungsweg zur Auswahl der besten Energie und des optimalen Photonenflusses vorgeschlagen, welcher eine bedeutende Abnahme der abgelieferten Dosis zur Folge hat, und zwar ohne Bildqualitätsverluste. Die meisten, im Rahmen dieser Doktorarbeit entwickelten Experimental- und Datenrekonstruktion-Verfahren können freilich auch an andere Phasenkontrast-Techniken angewendet werden. Es wird hiermit gezeigt, dass hochauflösende dreidimensionale bildgebende Verfahren zur Diagnostik gröβerer und komplexer biologischer Gegenstände bei klinisch verträglichen Dosen grundsätzlich eingesetzt werden können. Dies ist der nennenwerteste Beitrag dieser Dissertation zur klinischen Umsetzung der Phasenkontrast-CT

Compressed Sensing Based Reconstruction Algorithm for X-ray Dose Reduction in Synchrotron Source Micro Computed Tomography

Synchrotron computed tomography requires a large number of angular projections to reconstruct tomographic images with high resolution for detailed and accurate diagnosis. However, this exposes the specimen to a large amount of x-ray radiation. Furthermore, this increases scan time and, consequently, the likelihood of involuntary specimen movements. One approach for decreasing the total scan time and radiation dose is to reduce the number of projection views needed to reconstruct the images. However, the aliasing artifacts appearing in the image due to the reduced number of projection data, visibly degrade the image quality. According to the compressed sensing theory, a signal can be accurately reconstructed from highly undersampled data by solving an optimization problem, provided that the signal can be sparsely represented in a predefined transform domain. Therefore, this thesis is mainly concerned with designing compressed sensing-based reconstruction algorithms to suppress aliasing artifacts while preserving spatial resolution in the resulting reconstructed image. First, the reduced-view synchrotron computed tomography reconstruction is formulated as a total variation regularized compressed sensing problem. The Douglas-Rachford Splitting and the randomized Kaczmarz methods are utilized to solve the optimization problem of the compressed sensing formulation. In contrast with the first part, where consistent simulated projection data are generated for image reconstruction, the reduced-view inconsistent real ex-vivo synchrotron absorption contrast micro computed tomography bone data are used in the second part. A gradient regularized compressed sensing problem is formulated, and the Douglas-Rachford Splitting and the preconditioned conjugate gradient methods are utilized to solve the optimization problem of the compressed sensing formulation. The wavelet image denoising algorithm is used as the post-processing algorithm to attenuate the unwanted staircase artifact generated by the reconstruction algorithm. Finally, a noisy and highly reduced-view inconsistent real in-vivo synchrotron phase-contrast computed tomography bone data are used for image reconstruction. A combination of prior image constrained compressed sensing framework, and the wavelet regularization is formulated, and the Douglas-Rachford Splitting and the preconditioned conjugate gradient methods are utilized to solve the optimization problem of the compressed sensing formulation. The prior image constrained compressed sensing framework takes advantage of the prior image to promote the sparsity of the target image. It may lead to an unwanted staircase artifact when applied to noisy and texture images, so the wavelet regularization is used to attenuate the unwanted staircase artifact generated by the prior image constrained compressed sensing reconstruction algorithm. The visual and quantitative performance assessments with the reduced-view simulated and real computed tomography data from canine prostate tissue, rat forelimb, and femoral cortical bone samples, show that the proposed algorithms have fewer artifacts and reconstruction errors than other conventional reconstruction algorithms at the same x-ray dose

A multi-scale imaging approach to understand osteoarthritis development

X-ray phase-contrast imaging is an innovative and advanced imaging method. Contrary to conventional radiology, where the image contrast is primarily determined by X-ray attenuation, phase-contrast images contain additional information generated by the phase shifts or refraction of the X-rays passing through matter. The refractive effect on tissue samples is orders of magnitude higher than the absorption effect in the X-ray energy range used in biomedical imaging. This technique makes it possible to produce excellent and enhanced image contrast, particularly when examining soft biological tissues or features with similar X-ray attenuation properties. In combination with high spatial resolution detector technology and computer tomography, X-ray phase-contrast imaging has been proved to be a powerful method to examine tissue morphology and the evolution of pathologies three-dimensionally, with great detail and without the need of contrast agents. This Thesis work has focused on developing an accurate, multi-scale X-ray-based methodology for imaging and characterizing the early stages of osteoarthritis. X-ray phase-contrast images acquired at different spatial resolutions provide unprecedented insights into cartilage and the development of its degeneration, i.e., osteoarthritis. Other types of X-ray phase-contrast imaging techniques and setups using spatial resolutions ranging from micrometer down to nanometer were applied. Lower spatial resolutions allow large sample coverage and comprehensive representations, while the nanoscale analysis provides a precise depiction of anatomical details and pathological signs. X-ray phase-contrast results are correlated to data obtained, on the same specimens, by standard laboratory methods, such as histology and transmission electron microscopy. Furthermore, X-ray phase-contrast images of cartilage were acquired using different X-ray sources and results were compared in terms of image quality. It was shown that with the use of synchrotron radiation, more detailed images and much faster data acquisitions could be achieved. A second focus in this Thesis work has been the investigation of the reaction of healthy and degenerated cartilage under different physical pressures, simulating the different levels of stress to which the tissue is subject during daily movements. A specifically designed setup was used to dynamically study cartilage response to varying pressures with X-ray phase-contrast micro-computed tomography, and a fully volumetric and quantitative methodology to accurately describe the tissue morphological variations. This study revealed changes in the behavior of the cartilage cell structure, which differ between normal and osteoarthritic cartilage tissues. The third focus of this Thesis is the realization of an automated evaluation procedure for the discrimination of healthy and cartilage images with osteoarthritis. In recent years, developments in neural networks have shown that they are excellently suited for image classification tasks. The transfer learning method was applied, in which a pre-trained neural network with cartilage images is further trained and then used for classification. This enables a fast, robust and automated grouping of images with pathological findings. A neural network constructed in this way could be used as a supporting instrument in pathology. X-ray phase-contrast imaging computed tomography can provide a powerful tool for a fully 3D, highly accurate and quantitative depiction and characterization of healthy and early stage-osteoarthritic cartilage, supporting the understanding of the development of osteoarthritis.Röntgen-Phasenkontrast-Bildgebung ist eine innovative und weiterführende Bildgebungsmethode. Im Gegensatz zu herkömlichen Absorptions-Röntgenaufnahmen, wie sie in der Radiologie verwendet werden, wird der Kontrast bei dieser Methode aus dem Effekt der Phasenverschiebung oder auch Brechung der Röngtenstrahlen gebildet. Der Brechungseffekt bei Gewebeproben ist um ein Vielfaches höher als der Absorptionseffekt des elektromagnetischen Spektrums der Röntgenstrahlen. Diese Methode ermöglicht die Darstellung von großen Kontraste im Gewebe. Unter Verwendung eines hochauflösenden Detektors und in Kombination mit der Computer-Tomographie, ist Phasenkontrast-Bildgebung eine sehr gute Methode um Knorpelgewebe und Arthrose im Knorpel zu untersuchen. Diese Arbeit beschreibt primär ein Verfahren zur Darstellung arthrotischen Knorpels im Anfangsstadium. Die mit verschiedenen Auflösungen und 3D-Phasen-Kontrast-Methoden produzierten Aufnahmen ermöglichen einen noch nie dagewesenen Einblick in den Knorpel und die Entwicklung von Arthrose im Anfangsstadium. Hierbei kam die propagationsbasierte Phasenkontrastmethode mit einer Auflösung im mikrometer Bereich und die (Nano)-Holotomographie-Methode mit einer Auflösung im Submicrometer Bereich zum Einsatz. Durch Auflösung im mikrometer Bereich kann ein großes Volumen im Knorpel gescannt werden, während die Nano-Holotomographie Methode eine sehr große Detailauflösung aufweißt. Die Phasenkontrast-Aufnahmen werden mit zwei anderen wissenschaftlichen Methoden verglichen: mikroskopische Abbildungen histologisch aufgearbeiteter Knorpelproben und Aufnahmen eines Transmissionselektroskop zeigen sehr große Übereinstimmungen zur Röntgen-Phasenkontrast-Bildgebung. Desweiteren wurden Phasenkontrast-Aufnahmen von Knorpel aus unterschiedlichen Röntgenquellen verglichen. Hierbei zeigte sich, dass mit Hilfe des Teilchenbeschleunigers (Synchrotron) detailreichere und schnellere Aufnahmen erzielt werden können. Bilder aus Flüssig-Metall-Quellen zeigen sich durchaus von guter Qualität, erfordern jedoch sehr lange Aufnahmezeiten. In dieser Arbeit wird zudem das Verhalten von Knorpelgewebe, welches ein Anfangsstadium von Arthrose aufweist, unter physikalischem Druck untersucht. Hierfür wurden 3D-Computertomographie-Aufnahmen von komprimiertem Knorpelgewebe angefertig und mit Aufnahmen ohne Komprimierung verglichen. Ein quantitativer Vergleich machte Veränderungen des Verhaltens der Knorpelzellstruktur (Chondronen) sichtbar. Es konnte gezeigt werden, dass Chondrone bei arthrotischem Knorpel ein verändertes Kompressionsverhalten haben. Der dritte Fokus dieser Arbeit liegt auf der automatisierten Auswertung von Aufnahmen gesunden und arthrotischen Knorpelgewebes. Die Entwicklungen im Bereich der Neuronale Netze zeigten in den letzten Jahren, dass diese sich hervoragend für Bildklassifizierungsaufgaben eignen. Es wurde die Methode des transferierenden Lernens angewandt, bei der ein vortrainiertes Neuronales Netz mit Knorpelbildern weitertrainiert und anschließend zur Klassifizierung eingesetzt wird. Dadurch ist eine schnelle, robuste und automatisierte Gruppierung von Bildern mit pathologischen Befunden möglich. Ein derart konstruiertes Neuronales Netz könnte als unterstützendes Instrument in der Pathologie angewandt werden. Röntgen-Phasenkontrast-CT kann ein leistungsstarkes Werkzeug für eine umfassende, hochpräzise und quantitative 3D-Darstellung und Charakterisierung von gesundem Knorpel und athrotischem Knorpel im Frühstadium bieten, um das Verständnis der Entwicklung von Osteoarthritis zu erweitern

Modern Breast Cancer Detection: A Technological Review

Breast cancer is a serious threat worldwide and is the number two killer of women in the United States. The key to successful management is screening and early detection. What follows is a description of the state of the art in screening and detection for breast cancer as well as a discussion of new and emerging technologies. This paper aims to serve as a starting point for those who are not acquainted with this growing field

Evaluation of a diffraction-enhanced imaging (DEI) prototype and exploration of novel applications for clinical implementation of DEI

Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging due to monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. Although laboratory breast imaging studies have demonstrated excellent breast imaging, important clinical translation and application studies are needed before the DEI system can be established as a useful breast imaging modality. This dissertation focuses on several important studies toward the development of a clinical DEI system. First, contrast-enhanced DEI was explored using commercially available contrast agents. Phantoms were imaged at a range of x-ray energies and relevant contrast agent concentrations. Second, we performed a reader study to determine if superior DEI contrast mechanisms preserve image quality as tissue thickness increases. Breast specimens were imaged at several thicknesses, and radiologist perception of lesion visibility was recorded. Lastly, a prototype DEI system utilizing an x-ray tube source was evaluated through a reader study. Breast tissue specimens were imaged on the traditional and prototype DEI systems, and expert radiologists evaluated image quality and pathology correlation. This dissertation will demonstrate proof-of-principle for contrast-enhanced DEI, establishing the feasibility of contrast-enhanced DEI using commercially available contrast agents. Further, it will show that DEI might be able to reduce breast compression, and thus the perception of pain during mammography, without significantly decreasing breast lesion visibility. Finally, this research shows the successful implementation of a DEI prototype, displaying breast features with approximately statistically equivalent visibility to the traditional DEI system. Together, this research is an important step toward the clinical translation of DEI, a technology with the potential to facilitate early breast cancer detection and diagnosis

Sironta ja taittuminen kontrastimekanismeina röntgenkuvantamisessa

Differentiation of various types of soft tissues is of high importance in medical imaging, because changes in soft tissue structure are often associated with pathologies, such as cancer. However, the densities of different soft tissues may be very similar, making it difficult to distinguish them in absorption images. This is especially true when the consideration of patient dose limits the available signal-to-noise ratio. Refraction is more sensitive than absorption to changes in the density, and small angle x-ray scattering on the other hand contains information about the macromolecular structure of the tissues. Both of these can be used as potential sources of contrast when soft tissues are imaged, but little is known about the visibility of the signals in realistic imaging situations. In this work the visibility of small-angle scattering and refraction in the context of medical imaging has been studied using computational methods. The work focuses on the study of analyzer based imaging, where the information about the sample is recorded in the rocking curve of the analyzer crystal. Computational phantoms based on simple geometrical shapes with differing material properties are used. The objects have realistic dimensions and attenuation properties that could be encountered in real imaging situations. The scattering properties mimic various features of measured small-angle scattering curves. Ray-tracing methods are used to calculate the refraction and attenuation of the beam, and a scattering halo is accumulated, including the effect of multiple scattering. The changes in the shape of the rocking curve are analyzed with different methods, including diffraction enhanced imaging (DEI), extended DEI (E-DEI) and multiple image radiography (MIR). A wide angle DEI, called W-DEI, is introduced and its performance is compared with that of the established methods. The results indicate that the differences in scattered intensities from healthy and malignant breast tissues are distinguishable to some extent with reasonable dose. Especially the fraction of total scattering has large enough differences that it can serve as a useful source of contrast. The peaks related to the macromolecular structure come to angles that are rather large, and have intensities that are only a small fraction of the total scattered intensity. It is found that such peaks seem to have only limited usefulness in medical imaging. It is also found that W-DEI performs rather well when most of the intensity remains in the direct beam, indicating that dark field imaging methods may produce the best results when scattering is weak. Altogether, it is found that the analysis of scattered intensity is a viable option even in medical imaging where the patient dose is the limiting factor.Lääketieteellisessä kuvantamisessa on usein tarve erottaa toisistaan tiheydeltään hyvin samankaltaisia kudoksia, erityisesti pehmytkudoksista tehtävien tutkimusten yhteydessä, kuten mammografiassa. Tavallinen röntgensäteiden vaimenemiseen perustuva kuvantaminen ei kykene erottelemaan tiheydeltään samankaltaisia kudoksia toisistaan erityisen hyvin. Aiemmin on havaittu röntgensäteiden taittumisen olevan paljon herkempi kudosten välisille tiheyseroille kuin vaimenemisen. Myös röntgensäteiden sirontakuviot, jotka johtuvat säteiden suunnan hajautumisesta, riippuvat kudostyypistä. Sirontaa kudoksista on tutkittu pääasiassa ohuilla kudosnäytteillä, käyttämällä hyvin voimakasta röntgensäteilyä. Todellisissa lääketieteellisissä kuvantamisessa kohteet ovat selvästi paksumpia kuin ohuet kudosnäytteet, ja röntgensäteen voimakkuutta on rajoitettava potilaaseen kohdistuvan säteilyannoksen takia. Tässä työssä tutkittiin sirontakuvioiden näkymistä kun nämä käytännön tilanteissa rajoittavat tekijät otetaan huomioon. Kudokset sirottavat ja taittavat röntgensäteitä hyvin pienelle kulma-alueelle, joten havaintojen tekemiseen tarvitaan erityisen herkkiä laitteita. Eräs tapa havaita nämä pienet suunnanmuutokset säteiden kulussa on käyttää kidehilaa heijastamaan tiettyyn kulmaan tulevat röntgensäteet. Tällaista hilaa kutsutaa analysaattorikiteeksi, ja sen asentoa muuttamalla saadaan mitattua eri kulmissa tulevien röntgensäteiden voimakkuuksia. Analysaattoriin perustuva kuvantaminen (engl. analyzer based imaging, ABI) mahdollistaa säteen kulkusuunnassa tapahtuneiden muutosten mittaamisen mikroradiaania paremmalla tarkkuudella. Tässä tutkimuksessa mallinnettiin tietokoneella ABI-kuvausmenetelmää, ja tutkittiin laskennallisesti eri tyyppisistä näytteistä tulevan sironnan näkymistä. Erityisesti kiinnitettiin huomiota siihen, kuinka suuri potilaaseen kohdistuva säteilyannos tarvitaan sironnan luotettavan näkymisen mahdollistamiseksi. Sironnan kokonaisvoimakkuuden muutosten havaittiin näkyvän melko selkeästi. Sirontakuvion yksityiskohtien, kuten esimerkiksi sirontapiikkien paikkojen ja leveyksien, havaittiin puolestaan näkyvän huonosti. Tulokset osoittavat, että sironnan kokonaismäärässä tapahtuvat muutokset voivat olla hyvä kontrastin lähde lääketieteellisen kuvantamisen kannalta, mahdollistaen sellaisten kudosten erottamisen toisistaan, jotka eivät tavallisessa vaimenemiseen perustuvassa kuvantamisessa erotu