Imaging of the Breast

Early detection of breast cancer combined with targeted therapy offers the best outcome for breast cancer patients. This volume deal with a wide range of new technical innovations for improving breast cancer detection, diagnosis and therapy. There is a special focus on improvements in mammographic image quality, image analysis, magnetic resonance imaging of the breast and molecular imaging. A chapter on targeted therapy explores the option of less radical postoperative therapy for women with early, screen-detected breast cancers

Potilaan säteilyaltistuksen monitorointi ja säteilylaadut kaksiulotteisessa digitaalisessa röntgenkuvantamisessa

The methods for estimating patient exposure in x-ray imaging are based on the measurement of radiation incident on the patient. In digital imaging, the useful dose range of the detector is large and excessive doses may remain undetected. Therefore, real-time monitoring of radiation exposure is important. According to international recommendations, the measurement uncertainty should be lower than 7% (confidence level 95%). The kerma-area product (KAP) is a measurement quantity used for monitoring patient exposure to radiation. A field KAP meter is typically attached to an x-ray device, and it is important to recognize the effect of this measurement geometry on the response of the meter. In a tandem calibration method, introduced in this study, a field KAP meter is used in its clinical position and calibration is performed with a reference KAP meter. This method provides a practical way to calibrate field KAP meters. However, the reference KAP meters require comprehensive calibration. In the calibration laboratory it is recommended to use standard radiation qualities. These qualities do not entirely correspond to the large range of clinical radiation qualities. In this work, the energy dependence of the response of different KAP meter types was examined. According to our findings, the recommended accuracy in KAP measurements is difficult to achieve with conventional KAP meters because of their strong energy dependence. The energy dependence of the response of a novel large KAP meter was found out to be much lower than with a conventional KAP meter. The accuracy of the tandem method can be improved by using this meter type as a reference meter. A KAP meter cannot be used to determine the radiation exposure of patients in mammography, in which part of the radiation beam is always aimed directly at the detector without attenuation produced by the tissue. This work assessed whether pixel values from this detector area could be used to monitor the radiation beam incident on the patient. The results were congruent with the tube output calculation, which is the method generally used for this purpose. The recommended accuracy can be achieved with the studied method. New optimization of radiation qualities and dose level is needed when other detector types are introduced. In this work, the optimal selections were examined with one direct digital detector type. For this device, the use of radiation qualities with higher energies was recommended and appropriate image quality was achieved by increasing the low dose level of the system.Tässä työssä esitettiin menetelmiä, joilla potilaalle röntgenkuvauksesta aiheutuneen säteilyaltistuksen/annoksen mittauksen tarkkuutta voidaan parantaa ja kansainvälisten suositusten mukainen tarkkuustaso voidaan saavuttaa. Digitaalisessa kuvauksessa filmin ylivalottumista ei tapahdu ja liian suuret annokset saattavat jäädä huomaamatta. Sen vuoksi säteilyaltistuksen tosiaikainen mittaaminen (monitorointi) on tärkeää. Mittaussuuretta ilmakerman ja pinta-alan tulo (KAP) käytetään potilaan säteilyaltistuksen määrittämiseen. KAP-mittari on tyypillisesti kiinnitettynä röntgenlaitteeseen. Mittarin näyttämän oikeellisuus (kalibrointi) tulisi tarkistaa tässä samassa mittausasetelmassa. Tässä työssä esitetyssä tandem-kalibrointimenetelmässä, KAP-mittaria käytetään sen omalla paikallaan ja kalibrointi suoritetaan toisen KAP-vertailumittarin avulla. Tämä menetelmä tarjoaa käytännöllisen tavan kalibroida KAP-mittareita. Kuitenkin, KAP-vertailumittarin kalibroinnin tulisi kattaa tarvittavat säteilylaadut (energiajakaumat). Kalibrointilaboratoriossa suositellaan käytettävän standardin mukaisia säteilylaatuja. Nämä laadut eivät täysin vastaa potilaskuvauksissa käytettävien kliinisten säteilylaatujen laajaa valikoimaa. Tässä työssä tutkittiin kuinka paljon eri KAP-mittarityyppien vaste vaihtelee eri säteilylaaduilla. Tutkimuksemme perusteella perinteisillä KAP-mittareilla suositeltu tarkkuus on vaikea saavuttaa KAP-mittauksissa. Uuden tyyppisen ison KAP-mittarin vasteen säteilylaaturiippuvuus todettiin olevan pienempi. Tandem-menetelmän tarkkuutta voidaan parantaa käyttämällä tämän tyyppistä mittaria vertailumittarina. Tässä työssä esiteltiin uusi menetelmä mitata potilaan säteilyaltistusta mammografiassa, jossa KAP-mittaria ei voida käyttää. Mammografiassa osa säteilykeilasta osuu suoraan ilmaisimelle ja tutkittiin voisiko tältä alueelta saatua signaalia käyttää potilaaseen kohdistuvan säteilykeilan monitorointiin. Tämä mittausmenetelmä antaa tosiaikaista tietoa potilaan säteilyaltistuksesta ja suositeltu tarkkuus voidaan saavuttaa. Yhdellä digitaalisella mammografialaitteella selvitettiin optimaalisia säteilylaatuja ja annostasoja. Tutkitulla laitteella suurempi energisten säteilylaatujen käyttöä suositeltiin ja riittävä kuvanlaatu saavutettiin nostamalla laitteen matalaa annostasoa. Laitteiden säätöjen uusi optimointi on tarpeen, kun otetaan käyttöön uusia ilmaisintyyppejä

Model-Based Iterative Reconstruction in Cone-Beam Computed Tomography: Advanced Models of Imaging Physics and Prior Information

Cone-beam computed tomography (CBCT) represents a rapidly developing imaging modality that provides three-dimensional (3D) volumetric images with sub-millimeter spatial resolution and soft-tissue visibility from a single gantry rotation. CBCT tends to have small footprint, mechanical simplicity, open geometry, and low cost compared to conventional diagnostic CT. Because of these features, CBCT has been used in a variety of specialty diagnostic applications, image-guided radiation therapy (on-board CBCT), and surgical guidance (e.g., C-arm based CBCT). However, the current generation of CBCT systems face major challenges in low-contrast, soft-tissue image quality – for example, in the detection of acute intracranial hemorrhage (ICH), which requires a fairly high level of image uniformity, spatial resolution, and contrast resolution. Moreover, conventional approaches in both diagnostic and image-guided interventions that involve a series of imaging studies fail to leverage the wealth of patient-specific anatomical information available from previous scans. Leveraging the knowledge gained from prior images holds the potential for major gains in image quality and dose reduction. Model-based iterative reconstruction (MBIR) attempts to make more efficient use of the measurement data by incorporating a forward model of physical detection processes. Moreover, MBIR allows incorporation of various forms of prior information into image reconstruction, ranging from image smoothness and sharpness to patient-specific anatomical information. By leveraging such advantages, MBIR has demonstrated improved tradeoffs between image quality and radiation dose in multi-detector CT in the past decade and has recently shown similar promise in CBCT. However, the full potential of MBIR in CBCT is yet to be realized. This dissertation explores the capabilities of MBIR in improving image quality (especially low-contrast, soft-tissue image quality) and reducing radiation dose in CBCT. The presented work encompasses new MBIR methods that: i) modify the noise model in MBIR to compensate for noise amplification from artifact correction; ii) design regularization by explicitly incorporating task-based imaging performance as the objective; iii) mitigate truncation effects in a computationally efficient manner; iv) leverage a wealth of patient-specific anatomical information from a previously acquired image; and v) prospectively estimate the optimal amount of prior image information for accurate admission of specific anatomical changes. Specific clinical challenges are investigated in the detection of acute ICH and surveillance of lung nodules. The results show that MBIR can substantially improve low-contrast, soft-tissue image quality in CBCT and enable dose reduction techniques in sequential imaging studies. The thesis demonstrates that novel MBIR methods hold strong potential to overcome conventional barriers to CBCT image quality and open new clinical applications that would benefit from high-quality 3D imaging

Establishment of the Physical and Technical Prerequisites for the Determination of the Relative Biological Effectiveness of Low-energy Monochromatic X-rays

A superconducting electron linear accelerator of high brilliance and low emittance (ELBE) is under operation at Forschungszentrum Rossendorf since January 2003. The first stage of ELBE is based on an electron energy of 20 MeV, whereas in the future a 40 MeV beam will be provided. The relativistic electron beam is used to drive various kinds of secondary radiation sources. Among all, X-rays in a wide energy range can be obtained. One method for production of intensive, quasi-monochromatic Xrays in the energy range 10 - 100 keV, tunable in photon energy, is by channeling of relativistic electrons in a perfect crystal. This unconventional photon source with variable time structure will be optimised and used for radiobiological studies. Its first test operation was in October 2003. This thesis is part of the first radiobiological project – the determination of relative biological effectiveness (RBE) of the X-rays in this energy range. The most important aspects of medical application of low-energy X-rays are imaging and radiation therapy, but they can also be helpful in the study of radiation effects in living matter. However, the RBE depends on the photon energy, dose range, cell line and biological endpoint. Up to now no definitive conclusions can be made about their biological effectiveness due to the large spread of the published data. Therefore, in order to precisely determine the RBE, studies have to be performed at an intensive, tunable photon source, for several practically relevant cell lines and biological endpoints. The possibility of using channeling radiation (CR) for medical applications has been widely discussed in the literature, but building and optimisation of a dedicated source is for the first time performed at the ELBE accelerator

Dose and image quality in X-ray phase contrast breast imaging

Nowadays, mammographic examination is the gold standard technique for detecting breast cancer in asymptomatic women. However, it presents some limitations, mainly due to the superimposition of the tissues in the 2D mammograms, which may hide tumor lesions. Partially (digital breast tomosynthesis) and fully (CT dedicated to the breast) 3D breast imaging techniques have been developed in order to have a better tissues separation and to overcome such a limitation. Along with 3D breast imaging, the use of the X-ray beam phase shift, via so-called phase-contrast imaging techniques, has been shown to be a promising method in order to increase the image contrast between glandular tissue and tumor lesions. Indeed, in phase-contrast the image contrast is due to the X-ray wave phase-shift between different imaged materials, while in conventional imaging the image contrast arises from the different attenuation they introduce. Among all phase-contrast techniques, propagation based phase-contrast imaging does not need any special optical elements in the beam path, but only an X-ray beam with a certain degree of coherence and enough distance between imaged object and detector. It can be implemented either with synchrotron radiation source or with a compact X-ray tube. The 3D propagation based phase-contrast breast imaging devices are not yet employed in the routine clinical exams but they are available only at experimental level, and appropriate evaluations of image quality and dose are necessary. This is needed in order to optimize the various techniques and to understand the corresponding dose limitations. In this thesis, the dose paradigms in X-ray breast imaging are revisited and specific Monte Carlo simulation codes have been developed. A part of this work focuses on the breast dose aiming at studying the adopted breast models and the effects of the breast partial irradiation on the dose estimates, as occurs in 2D spot mammography clinical examinations as well as by adopting a narrow beam produced via synchrotron radiation. The second part of this work focuses on the image quality obtainable in 3D images of the breast by adopting propagation based phase-contrast imaging. We present the CT scanner dedicated to the breast developed within the SYRMA-CT project at Elettra synchrotron radiation facility. We evaluate its imaging performance in terms of spatial resolution, image noise properties and capability of showing breast lesions and microcalcification clusters. Finally, the CT scanner dedicated to the breast, developed at the University of Naples, which relies on compact X-ray source with a 7-μm focal spot is presented and its image performance at dose comparable to that adopted in two-view digital mammography is explored together with its capability of producing phase-contrast effects. This scanner was developed and studied in order to compare a scanner which is clinical feasible in terms of cost, setup dimension and scan time to the results obtainable via the high flux and monochromatic X-ray beam synchrotron based experimental scanner

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