Tesis sobre el tema "High-Resolution X-Ray imaging"

The primary aim of the work presented in this thesis is to elucidate novel information regarding the uptake, storage, distributions, and functions of both copper and zinc in mammalian cells by predominantly using a combination of the high resolution imaging modalities, synchrotron radiation X-ray fluorescence microscopy (SXRF) and standard fluorescence imaging. Results from studies using cell permeable, metal ion selective fluorescent probes suggested the presence of labile pools of copper and zinc localized within the mitochondria and Golgi apparatus. Furthermore, SXRF imaging of a cell line defective in the copper transporter, Atox1, revealed intriguing differences in the Cu distribution of Atox1-/- cells compared to the corresponding wild-type cells. Finally, spatially well-resolved SXRF elemental maps of single, adherent mouse cells revealed remarkable changes in the distributions of both zinc and copper as the cells progressed through the cell cycle. Taken together, findings suggested major roles for copper and zinc within a native biological setting.

Coherent imaging is a promising method in the field of x-ray microscopy allowing for the nondestructive determination of the interior structure of radiation-hard samples with a spatial resolution that is only limited by the fluence on the sample and the scattering strength of the sample. Ultimately, the achievable spatial resolution is limited by the wavelength of the incoming x-ray radiation. Combining coherent imaging with scanning microscopy to a method called ptychography enables one to also probe extended objects. In this method, a sample is scanned through a defined coherent x-ray beam and at each scan point a diffraction pattern is recorded with a diffraction camera located in the far field of the sample. Neighboring illuminated areas must have a certain overlap to guarantee the collection of sufficient information about the object for a subsequent successful and unique computational reconstruction of the object. Modern ptychographic reconstruction algorithms are even able to reconstruct the complex-valued transmission function of the sample and the complex illumination wave field at the same time. Once the 2D transmission function of a sample is known, it is an obvious step forward to combine ptychography with tomographic techniques yielding the 3D internal structure of an object with unprecedented spatial resolution. Here, projections at varying angular positions of the sample are generated via ptychographic scans and are subsequently used for the tomographic reconstruction. In this thesis the development of 3D ptychography is described. It includes the description of the required experimental environment, the numerical implementation of ptychographic phase retrieval and tomographic reconstruction routines, and a detailed analysis of the performance of 3D ptychography using an example of an experiment carried out at beamline P06 of PETRA III at DESY in Hamburg. In that experiment the investigated object was a Mo/UO2 thin film, which is a simplified model for spent nuclear fuel from nuclear power plant reactors. Such models find application in systematic scientific investigations related to the safe disposal of nuclear waste. We determined the three-dimensional interior structure of this sample with an unprecedented spatial resolution of at least 18 nm. The measurement of the fluorescence signal at each scan point of the ptychograms delivers the two- and three-dimensional elemental distribution of the sample with a spatial resolution of 80 nm. Using the fluorescence data, we assigned the chemical element to the area of the corresponding phase shift in the ptychographic reconstruction of the object phase and to the corresponding refractive index decrement in the tomographic reconstruction. The successful demonstration of the feasibility of the 3D ptychography motivates further applications, for instance, in the field of medicine, of material science, and of basic physical research
Kohärente Bildgebung ist eine vielversprechende Methode der Röntgenmikroskopie. Sie ermöglicht die zerstörungsfreie Bestimmung der inneren Struktur von strahlenharten Untersuchungsobjekten mit einer räumlichen Auflösung, die im Prinzip nur von der integralen Anzahl der Photonen auf der Probe sowie deren Streukraft abhängt. Letztendlich stellt die Wellenlänge der verwendeten Röntgenstrahlung eine Grenze für die erreichbare räumliche Auflösung dar. Die Kombination der kohärenten Bildgebung mit der Rastermikroskopie zur sogenannten Ptychographie eröffnet die Möglichkeit, auch ausgedehnte Objekte mit hoher Auflösung zu untersuchen. Dabei wird die Probe mit einem räumlich begrenzten, kohärenten Röntgenstrahl abgerastert und an jedem Rasterpunkt ein Beugungsbild von einer im Fernfeld platzierten Beugungskamera registriert. Die Beleuchtungen benachbarter Rasterpunkte müssen dabei zu einem bestimmten Prozentsatz überlappen, um genügend Informationen für eine anschließende computergestützte und eindeutige Rekonstruktion des Objektes sicherzustellen. Moderne Rekonstruktionsalgorithmen ermöglichen sogar die gleichzeitige Rekonstruktion der Transmissionsfunktion des Objektes und der Beleuchtungsfunktion des eintreffenden Röntgenstrahls. Die Verknüpfung der Ptychographie mit der Tomographie zur 3D-Ptychographie ist der nahe liegende Schritt, um nun auch die dreidimensionale innere Struktur von Objekten mit hoher räumlicher Auflösung zu bestimmen. Die Projektionen an den verschiedenen Winkelpositionen der Probe werden dabei mittels ptychographischer Abrasterung der Probe erzeugt und anschließend der tomographischen Rekonstruktion zugrunde gelegt. In dieser Arbeit wird die Entwicklung der 3D-Ptychographie beschrieben. Das beinhaltet die Beschreibung der experimentellen Umgebung, der numerischen Implementierung des ptychographischen und des tomographischen Rekonstruktionsalgorithmus als auch eine detaillierte Darstellung der Durchführung der 3D-Ptychographie am Beispiel eines Experiments, welches unter Verwendung des modernen Nanoprobe-Aufbaus des Strahlrohres P06 am PETRA III Synchrotronring des DESY in Hamburg durchgeführt wurde. Als Untersuchungsobjekt diente dabei ein dünner Mo/UO2-Film, der ein vereinfachtes Modell für die in Reaktoren von Atomkraftwerken verbrauchten Brennstäbe darstellt und deshalb im Bereich des Umweltschutzes Anwendung findet. Die dreidimensionale Struktur der Probe wurde mit einer - für diese Methode bisher einmaligen - räumlichen Auflösung von 18 nm bestimmt. Die Messung des von der Probe kommenden Fluoreszenz-Signals an jedem Rasterpunkt der Ptychogramme ermöglichte zusätzlich die Bestimmung der zwei- und dreidimensionalen Elementverteilung innerhalb der Probe mit einer räumlichen Auflösung von 80 nm. Anhand der Fluoreszenzdaten konnte sowohl den Bereichen verschiedener Phasenschübe in den ptychographischen Rekonstruktionen der Objektphase als auch den verschiedenen Werten des Dekrementes des Brechungsindex in der tomographischen Rekonstruktion, das entsprechende chemische Element zugeordnet werden. Die erfolgreiche Demonstration der Durchführbarkeit der 3D-Ptychographie motiviert weitere zukünftige Anwendungen, z. B. auf dem Gebiet der Medizin, der Materialforschung und der physikalischen Grundlagenforschung

Over the past couple of decades there has been tremendous advancements in the field of medicine and engineering technology. Increases in the level of integration between these two branches of science has led to better understanding of physiology and anatomy of a living organism, thus allowing for better understanding of diseases along with their cures and treatments. The work presented in this dissertation aims at improving the imaging aspects of x-ray image guided interventions with endovascular image guided intervention as the primary area of application.

Minimally invasive treatments for neurovascular conditions such as aneurysms, stenosis, etc involve guidance of catheters to the treatment area, and deployment of treatment devices such as stents, coils, balloons, etc, all under x-ray image guidance. The features in these device are in the order of a few 10 µm's to a few 100 µm's and hence demand higher resolution imaging than the current state of the art flat panel detector. To address this issue three high resolution x-ray cameras were developed. The Micro Angiography Fluoroscope (MAF) based on a Charge Coupled Device (MAF-CCD), the MAF based on Complementary Metal Oxide Semiconductors (MAF-CMOS) and the Solid State X-ray Image Intensifier based on Electron Multiplying CCDs. The construction details along with performance evaluations are presented. The MAF-CCD was successfully used in a few interventions on human patient to treat neurovascular conditions, primarily aneurysm. Images acquired by the MAF-CCD during these procedures are presented.

A software platform CAPIDS was previously developed to facilitate the use of the high resolution MAF-CCD in a clinical environment. In this work the platform was modified to be used with any camera. The upgrades to CAPIDS, along with parallel programming including both the Graphics Processing Unit (GPU) and Central Processing Unit (CPU) are presented.

With increasing use of x-ray guidance for minimally invasive interventions, a major cause of concern is that of prolonged exposure to x-ray radiation that can cause biological damage to the patient. Hence during x-ray guided procedures necessary steps must be taken to minimize the dose to the patient. In this work a novel dose reduction technique, using a combination of Region of Interest (ROI) fluoroscopy to reduce dose along with spatially different temporal filtering to restore image quality is presented.

Finally a novel ROI imaging technique for biplane imaging in interventional suites, combining the use of high resolution detector along with dose reduction technique using ROI fluoroscopy with spatially different temporal filtering is presented.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Physics, 2000.
Includes bibliographical references (p. 203-206).
In this thesis high resolution soft x-ray measurements from the Alcator C-Mod plasma edge are presented for a variety of different plasma conditions. These measurements provide radial profiles of the soft x-ray emissivity with 1.5 mm resolution or better, and temporal resolution down to 12 [mu]s. These profiles show a distinct and very narrow pedestal shape in H-mode, indicative of the H-mode transport barrier. The soft x-ray emissivity pedestal at the outboard edge is typically 10 mm inside the last closed flux surface, near the top of the electron density and temperature pedestals. Modelling shows that the inward shift of the x-ray pedestal implies an inward shift of the impurity density pedestal. This inward shift is explained by an inward impurity pinch located in the region of strong electron density gradient, as predicted by neoclassical impurity transport theory. Calculations using the impurity transport code MIST support the existence of a neoclassical-like inward pinch. Changes in the soft x-ray pedestal width can be interpreted as changes in the edge impurity diffusion coefficient. We find several scaling laws of the edge diffusion coefficient with various plasma parameters in EDA H-mode. A second array views the top of the plasma. The x-ray emissivity measured with this array also shows a distinct and narrow pedestal in H-mode. However, it is located significantly closer to the separatrix and is often narrower. Both of these differences increase with the safety factor at the edge, q95 . Thus, there is a significant poloidal asymmetry in the impurity density in the H-mode edge region, which increases with q95 . Therefore, the impurity transport in the H-mode edge is highly two-dimensional. The strong poloidal asymmetries measured show some quantitative agreement with theories developed to explain poloidal impurity asymmetries. However, none of the theories are strictly applicable to the Alcator C-Mod edge, and they all significantly underestimate the actual asymmetries that we observe.
by Thomas Sunn Pedersen.
Ph.D.

A new closed cell is presented for in situ X-ray ptychography which allows studies under gas flow and at elevated temperature. In order to gain complementary information by transmission and scanning electron microscopy, the cell makes use of a Protochips E-chipTM which contains a small, thin electron transparent window and allows heating. Two gold-based systems, 50 nm gold particles and nanoporous gold as a relevant catalyst sample, were used for studying the feasibility of the cell. Measurements showing a resolution around 40 nm have been achieved under a flow of synthetic air and during heating up to temperatures of 933 K. An elevated temperature exhibited little influence on image quality and resolution. With this study, the potential of in situ hard X-ray ptychography for investigating annealing processes of real catalyst samples is demonstrated. Furthermore, the possibility to use the same sample holder for ex situ electron microscopy before and after the in situ study underlines the unique possibilities available with this combination of electron microscopy and X-ray microscopy on the same sample.

L'apparition des détecteurs à comptage de photons X à base de CdTe avec des capacités de discrimination de l'énergie des photons ouvre de nouvelles perspectives pour l'imagerie radiographique. Les applications médicales et en contrôle de bagages X sont caractérisées par un flux de photons X très élevé, et exigent par conséquent une mise en forme très rapide du photo-courant mesuré pour limiter les empilements. Cependant, si cette mise en forme est plus courte que le temps de transit des électrons dans le semi-conducteur, la charge mesurée devient inférieure à la charge déposée : c’est le déficit balistique. Par ailleurs, la variation dans le temps du profil du champ électrique dans le volume du détecteur entraîne une augmentation du temps de transit des électrons. En conséquence, la charge mesurée diminue dans le temps, faussant la mesure de l’énergie des photons X. L’objectif de ce travail est de caractériser cette instabilité et de développer une méthode de correction de son effet sur les spectres en énergie. Nous avons proposé un algorithme de correction basé sur l'utilisation de deux Lignes à Retard (LAR). Une LAR rapide (50ns ?) permet de mesurer les spectres X à très fort flux sans compromis sur le taux de comptage. Une LAR lente (200ns ?) est utilisée pour mesurer intégralement la charge déposée sans déficit balistique. Un facteur de correction est évalué et utilisé pour stabiliser la mesure de l’énergie des X avec la LAR rapide. Une étape importante de cet algorithme consiste à trier les impulsions traitées pour rejeter celles qui peuvent dégrader la mesure de ce facteur de correction, notamment les empilements. La méthode proposée a été implémentée dans un FPGA pour fonctionner en temps réel et a été testée avec un détecteur CdTe de 3mm d'épaisseur avec 4×4 pixels au pas de 800 microns, capable de mesurer des spectres X dans la gamme d'énergie 20-160 keV avec 256 canaux d'énergie. La méthode développée a été initialement testée à faible taux de comptage avec des sources gamma Co-57 et Am-241, puis à fort taux de comptage jusqu'à ~2 Mc/s avec un tube à rayons X. Cet algorithme innovant a montré sa capacité de fournir une réponse stable du détecteur dans le temps sans affecter la résolution d'énergie (7 % à 122 keV) et le temps mort (~70 ns)
The emergence of CdTe Photon Counting Detectors (PCD) with energy discrimination capabilities, opens up new perspectives in X-ray imaging. Medical and security applications are characterized by very high X-ray fluxes and consequently require a very fast shaper in order to limit dead time losses due to pile-up. However, if the shaper is faster than the collection of the charges in the semiconductor, there is a loss of charge called ballistic deficit. Moreover, variations of the electric field profile in the detector over time cause a change in the collection time of the charges. As a result, the conversion gain of the detector will be affected by these variations. The instability of the response is visible over time as a channel shift of the spectra, resulting in a false information of the photon energy. The aim of this work is to characterize this instability in order to understand the mechanisms behind them and to develop a method to correct its effect. We proposed a correction algorithm based on the use of two Single Delay Line (SDL) shaping amplifiers. A fast SDL is used to measure the X-ray spectra at high count rates with limited count rate losses. A slow SDL is used to measure the full collected charge in order estimate a correction factor for the compensation of the ballistic deficit fluctuations of the fast SDL. An important step is to sort the processed pulses in order to reject pile-up and other undesirable effects that may degrade the measurement of the correction factor. The proposed method was implemented in an FPGA in order to correct the ballistic deficit in real-time and to give a stable response of the detector at very high fluxes. The method was tested with a 4x4 pixels detector (CdTe) of 3 mm thickness and 800 micron pitch, which is able to measure transmitted X-ray spectra in the energy range of 20-160 kV on 256 energy bins. The developed method was initially tested at low count rate with a Co-57 and an Am-241 gamma-ray sources, then at high count rates up to ~2 Mc/s with an X-ray source. With the characterization and the validation of this innovative algorithm we prove its ability in providing a stable response of the detector over time without affecting the energy resolution (~7% at 122 keV) and the dead time (~70 ns)

Les détecteurs de rayon-X utilisés pour l'imagerie à haute résolution (micromètrique ou submicronique) utilisés aux synchrotrons sont pour la plupart basés sur un système de détection indirecte. Les rayons X ne sont pas directement convertis en signal électrique. Ils sont absorbés par un scintillateur qui est un matériau émettant de la lumière à la suite de l'absorption d'un rayonnement ionisant. L'image émise sous forme de lumière visible est ensuite projetée par des optiques de microscopie sur une camera 2D de type CCD ou CMOS. De nos jours, il existe différents types des scintillateurs. On distingue entre autres des scintillateurs en poudre compactée, micro structurés, céramique poly-cristalline et monocristalline. L’obtention d’une image de très bonne qualité avec une résolution spatiale au-dessous du micromètre requiert le choix d’une couche mince (1-20 µm) monocristalline. Ces types des scintillateurs peuvent être déposes sur un substrat par épitaxie en phase liquide. La très faible efficacité d’absorption dans une couche mince en fait sa faiblesse, surtout pour des énergies au-dessus de 20 keV. A l’ESRF (le synchrotron européen) des énergies jusqu'à 120 keV peuvent être exploitées pour l’imagerie. Des nouveaux scintillateurs sont donc toujours recherchés pour pouvoir améliorer le compromis entre l’efficacité d’absorption et la résolution spatiale. Dans la première partie de cet travail, un model qui décrit les détecteurs indirects pour la haute résolution, est présenté. Cet model permet de calculer la MTF (fonction de transfert de modulation) du système et peut être utilisé pour trouver la combinaison optimal de scintillateur et d’optique selon l’énergie des rayons X. Les simulations ont guidées le choix des scintillateurs à développer par épitaxie.Dans la deuxième partie, deux nouveaux types de scintillateurs développés et caractérisés dans le cadre de ce projet de thèse sont introduits : les couches minces basées sur des monocristaux de gadolinium lutétium aluminium pérovskite (GdLuAP:Eu) et d’oxyde de lutétium (Lu2O3:Eu)
X-ray detectors for high spatial resolution imaging are mainly based on indirect detection. The detector consists of a converter screen (scintillator), light microscopy optics and a CCD or CMOS camera. The screen converts part of the absorbed X-rays into visible light image, which is projected onto the camera by means of the optics. The detective quantum efficiency of the detector is strongly influenced by the properties of the converter screen (X-ray absorption, spread of energy deposition, light yield and emission wavelength). To obtain detectors with micrometer and sub-micrometer spatial resolution, thin (1-20 µm) single crystal film scintillators are required. These scintillators are grown on a substrate by liquid phase epitaxy. The critical point for these layers is their weak absorption, especially at energies exceeding 20 keV. At the European Synchrotron radiation Facility (ESRF), X-ray imaging applications can exploit energies up to 120 keV. Therefore, the development of new scintillating materials is currently investigated. The aim is to improve the contradictory compromise between absorption and spatial resolution, to increase the detection efficiency while keeping a good image contrast even at high energies.The first part of this work presents a model describing high-resolution detectors which was developed to calculate the modulation transfer function (MTF) of the system as a function of the X-ray energy. The model can be used to find the optimal combination of scintillator and visible light optics for different energy ranges, and it guided the choice of the materials to be developed as SCF scintillators. In the second part, two new kinds of scintillators for high-resolution are presented: the gadolinium-lutetium aluminum perovskite (Gd0.5Lu0.5AlO3:Eu) and the lutetium oxide (Lu2O3:Eu) SCFs

Deux approches ont été employées pour développer des scintillateurs couche mince à haut pouvoir d’arrêt. Ceux-ci sont utilisés pour l'imagerie à rayons X à haute résolution spatiale dans les synchrotrons. • La première approche a consisté à faire croître par Epitaxie en Phase Liquide (EPL) des films monocristallins (SCF) à densité et nombre atomique effectif (Z) élevés. L'objectif est ainsi d'atteindre une résolution spatiale élevée, tout en maximisant l'efficacité d'absorption au rayons X des films. Avant de mettre au point les procédures d'épitaxie en phase liquide, les composés potentiels ont été étudiés à l'aide d'un outil de simulation Monte Carlo (Geant4), combiné à des calculs analytiques, afin d'évaluer leur résolution spatiale intrinsèque ainsi que leur efficacité d’absorption aux rayons X. A la suite de cette étude, différentes couches épitaxiées basées sur les hafnates ont été mises au point sur des substrats de ZrO2 :Y. Plus particulièrement, le Lu2Hf2O7 a été développé avec succès. Les structures atomiques des films se sont confirmées comme étant iso-structurelles par rapport au substrat et présentant un faible désaccord paramétrique cristallin. Il a été constaté que divers éléments pouvaient entrer facilement dans la structure, révélant ainsi une flexibilité surprenante du système hafnate pour la croissance LPE. Par ailleurs les films de Lu2Hf2O7 dopés à l'europium présentent une luminescence caractéristique de l’ion Eu3+. Le substrat de ZrO2 :Y quant à lui présente une émission de faible intensité, du fait de la présence de défauts de vacances en oxygène. Les films ont un rendement lumineux plutôt faible mais offrent une bonne réponse spatiale, validée par les mesures de Fonction de Transfert de Modulation (MTF) ainsi que par des radiographies et tomographies rayon X réalisées sur ces échantillons.• La deuxième approche a consisté à faire croître des scintillateurs SCF de manière micro-structurée par EPL. L'objectif est ainsi de pouvoir augmenter le pouvoir d’arrêt des scintillateurs tout en conservant une bonne résolution spatiale. Dans un premier temps des substrats de GGG et de LYSO :Ce ont subis un traitement laser ultra-rapide (ps), permettant de modifier la surface de ces substrats, et ce afin de réduire le taux de croissance LPE dans les zones ainsi altérées. Ensuite, la croissance de scintillateurs LSO :Tb et GGG :Eu a été réalisée sur ces substrats respectifs de LYSO :Ce et GGG, mettant en évidence la croissance de ‘’piliers’’, résultant en une surface micro-structurée. La morphologie des ‘’piliers’’ varie en fonction du composé et de l'orientation du substrat. Les structures atomiques et les propriétés luminescentes sont comparables à celles de leurs homologues SCF non micro- structurés. Une preuve de concept a ainsi été démontrée
The development of scintillators with high stopping power for high spatial resolution X-ray imaging at synchrotrons has been performed by employing two approaches. The first approach was to grow thin Single Crystalline Films (SCFs) of high density and effective Z number by Liquid Phase Epitaxy (LPE). This is to reach ultimate high spatial resolution while maximizing the absorption efficiency of the films. Before attempting to develop the LPE procedures, the compounds were investigated with a Geant4, Monte Carlo simulation tool combined with subsequent analytical calculations to evaluate their scintillating spatial response. Ultimate high-density compound, Lu2Hf2O7, and other hafnates have in this framework been successfully grown on ZrO2:Y substrates. The atomic structures of the films were confirmed to be iso-structural with the substrate and have a low lattice mismatch. It was experienced that various elements could enter the structure, and a surprising flexibility of the hafnate system for LPE growth is thereby realized. The grown films of Lu2Hf2O7 doped with Europium are discovered to scintillate. However, the substrate itself displays low-intensity emission. The films have a rather low light output but deliver a good spatial response validated by MTFs as well as when performing radiography and tomography. The second approach was to grow state-of-the-art SCF scintillators in a micro-structured manner by LPE. The aim is to increase the stopping power by having tall pillars containing light and maintaining a good spatial response. LSO:Tb and GGG:Eu, were grown micro-structured onto laser-treated LYSO:Ce and GGG substrates, respectively. The morphology of the pillars varies depending on the compound and the substrate orientation. The atomic structures and luminescent properties are comparable to their normal SCF counterparts. Thereby a proof of concept has been demonstrated

The combination of X-ray imaging and diffraction techniques provides a unique tool for structural and mechanical analysis of engineering components. A variety of modes can be employed in terms of the spatial resolution (length-scale), time resolution (frequency), and the nature of the physical quantity being interrogated. This thesis describes my contributions towards the development of novel X-ray “rich” imaging experimental techniques and data interpretation. The experimental findings have been validated via comparison with other experimental methods and numerical modelling. The combination of fast acquisition rate and high penetration properties of X-ray beams allows the collection of high-resolution 3-D tomographic data sets at submicron resolution during in situ deformation experiments. Digital Volume Correlation analysis tools developed in this study help understand crack propagation mechanisms in quasi-brittle materials and elasto-plastic deformation in co-sprayed composites. For the cases of crystalline specimens where the knowledge of “live” or residual elastic strain distributions is required, diffraction techniques have been advanced. Diffraction Strain Tomography (DST) allows non-destructive reconstruction of the 2-D (in-plane) variation of the out-of-plane strain component. Another diffraction modality dubbed Laue Orientation Tomography (LOT), a grain mapping approach has been proposed and developed based on the translate-rotate tomographic acquisition strategy. It allows the reconstruction of grain shape and orientation within polycrystalline samples, and provides information about intragranular lattice strain and distortion. The implications of this method have been thoroughly investigated. State-of-the-art engineering characterisation techniques evolve towards scrutinising submicron scale structural features and strain variation using the complementarity of X-ray imaging and diffraction. The first successful feasibility study is reported of in operando stress analysis in an internal combustion engine. Finally, further advancement of ‘rich’ imaging techniques is illustrated via the first successful application of Time-of-Flight Neutron Diffraction Strain (TOF-NDST) tomography for non-destructive reconstruction of the complete strain tensor using an inverse eigenstrain formulation.

In der Arbeit haben wir die Grenzen der weit verbreiteten tomographischen Rekonstruktion von 3D-Proben mittels Transmissionsröntgenmikroskopie charakterisiert. Wir zeigen, dass die 3D-Auflösung mit diesem Ansatz durch die Schärfentiefe begrenzt ist. Zur Untersuchung von Alternativen führten wir Simulationen zur Bildentstehung in einem konfokalen Röntgenmikroskop und einem FIB-SXM durch. Wir zeigen, dass FIB-SXM ein vielversprechender Ansatz ist, der eine isotrope 3D-Aulösung um die 10 nm erreichen kann und zusätzlich ein drastisch verbessertes Signal-Rausch-Verhältnis bieten könnte. Wir stellen auch eine neue Holographiemethode vor, die sich für Vollfeldabbildungen mit kurzen kohärenten Röntgenpulsen als vorteilhaft erweisen und neue Einsichten in die ultraschnelle Physik liefern könnte.
We have characterized the limitations of the most powerful and widely used 3D X-ray imaging approach, transmission X-ray microscopy with tomographic reconstruction. We show that 3D resolution in this approach is limited by the depth of field. To investigate alternatives, we perform simulations of a confocal transmission X-ray microscope and a FIB-SXM. We show that FIB-SXM is a very promising approach that could o er 3D isotropic resolution at 10 nm with dramatically improved signal to noise. We also introduce a new holography method that could prove bene cial for full eld imaging with short coherent X-ray pulses and yield new insights into ultrafast physics.

The SNR spectra model and measurement method developed in this work yield reliable application-specific optima for image quality. This optimization can either be used to understand image quality, find out how to build a good imaging device or to (automatically) optimize the parameters of an existing setup. SNR spectra are here defined as a fraction of power spectra instead of a product of device properties. In combination with the newly developed measurement method for this definition, a close correspondence be- tween theory and measurement is achieved. Prior approaches suffer from a focus on theoretical definitions without fully considering if the defined quantities can be measured correctly. Additionally, discrepancies between assumptions and reality are common. The new approach is more reliable and complete, but also more difficult to evaluate and interpret. The signal power spectrum in the numerator of this fraction allows to model the image quality of different contrast mechanisms that are used in high-resolution x-ray imaging. Superposition equations derived for signal and noise enable understanding how polychromaticity (or superposition in general) affects the image quality. For the concept of detection energy weighting, a quantitative model for how it affects im- age quality was found. It was shown that—depending on sample properties—not detecting x-ray photons can increase image quality. For optimal computational energy weighting, more general formula for the optimal weight was found. In addition to the signal strength, it includes noise and modulation transfer. The novel method for measuring SNR spectra makes it possible to experimentally optimize image quality for different contrast mechanisms. This method uses one simple measurement to obtain a measure for im- age quality for a specific experimental setup. Comparable measurement methods typically require at least three more complex measurements, where the combination may then give a false result. SNR spectra measurements can be used to: • Test theoretical predictions about image quality optima. • Optimize image quality for a specific application. • Find new mechanisms to improve image quality. The last item reveals an important limitation of x- ray imaging in general: The achievable image quality is limited by the amount of x-ray photons interacting with the sample, not by the amount incident per detector area (see section 3.6). If the rest of the imaging geometry is fixed, moving the detector only changes the field of view, not the image quality. A practical consequence is that moving the sample closer to the x-ray source increases image quality quadratically. The results of a SNR spectra measurement represent the image quality only on a relative scale, but very reliable. This relative scale is sufficient for an optimization problem. Physical effects are often already clearly identifiable by the shape of the functional relationship between input parameter and measurement result. SNR spectra as a quantity are not well suited for standardization, but instead allow a reliable optimization. Not satisfying the requirements of standardization allows to use methods which have other advantages. In this case, the SNR spectra method describes the image quality for a specific application. Consequently, additional physical effects can be taken into account. Additionally, the measurement method can be used to automate the setting of optimal machine parameters. The newly proposed image quality measure detection effectiveness is better suited for standardization or setup comparison. This quantity is very similar to measures from other publications (e.g. CNR(u)), when interpreted monochromatically. Polychromatic effects can only be modeled fully by the DE(u). The measurement processes of both are different and the DE(u) is fundamentally more reliable. Information technology and digital data processing make it possible to determine SNR spectra from a mea- sured image series. This measurement process was designed from the ground up to use these technical capabilities. Often, information technology is only used to make processes easier and more exact. Here, the whole measurement method would be infeasible without it. As this example shows, using the capabilities of digital data processing much more extensively opens many new possibilities. Information technology can be used to extract information from measured data in ways that analog data processing simply cannot. The original purpose of the SNR spectra optimization theory and methods was to optimize high resolution x-ray imaging only. During the course of this work, it has become clear that some of the results of this work affect x-ray imaging in general. In the future, these results could be applied to MI and NDT x-ray imaging. Future work on the same topic will also need to consider the relationship between SNR spectra or DE(u) and sufficient image quality.This question is about the minimal image quality required for a specific measurement task
Das in dieser Arbeit entwickelte Modell und die Messmethode für SNR Spektren ergeben zuverlässige anwendungsspezifische Optima für die Bildqualität. Diese Optimierung kann verwendet werden, entweder um Bildqualität zu verstehen, um herauszufinden wie ein gutes Bildgebungsgerät gebaut werden kann oder um die Parameter eines existierenden Aufbaus (automatisch) festzulegen.

With increasing miniaturization in industry and medical technology, non-destructive testing techniques are an area of everincreasing importance. In this framework, X-ray microscopy offers an efficient tool for the analysis, understanding and quality assurance of microscopic species, in particular as it allows reconstructing three-dimensional data sets of the whole sample’s volumevia computed tomography (CT). The following thesis describes the conceptualization, design, construction and characterization of a compact laboratory-based X-ray microscope in the hard X-ray regime around 9 keV, corresponding to a wavelength of 0.134 nm. Hereby, the main focus is on the optimization of resolution and contrast at relatively short exposure times. For this, a novel liquid-metal-jet anode source is the basis. Such only recently commercially available X-ray source reaches a higher brightness than other conventional laboratory sources, i.e. the number of emitted photons (X-ray quanta) per area and solid angle is exceptionally high. This is important in order to reach low exposure times. The reason for such high brightness is the usage of the rapidly renewing anode out of liquid metal which enables an effective dissipation of heat, normally limiting the creation of high intensities on a small area. In order to cover a broad range of different samples, the microscope can be operated in two modes. In the “micro-CT mode”, small pixels are realized with a crystal-scintillator and an optical microscope via shadow projection geometry. Therefore, the resolution is limited by the emitted wavelength of the scintillator, as well as the blurring of the screen. However, samples in the millimeter range can be scanned routinely with low exposure times. Additionally, this mode is optimized with respect to in-line phase contrast, where edges of an object are enhanced and thus better visible. In the second “nano-CT mode”, a higher resolution can be reached via X-ray lenses. However, their production process is due to the physical properties of the hard X-ray range - namely high absorption and low diffraction - extremely difficult, leading typically to low performances. In combination with a low brightness, this leads to long exposure times and high requirements in terms of stability, which is one of the key problems of laboratory-based X-ray microscopy. With the here-developed setup and the high brightness of its source, structures down to 150 nm are resolved at moderate exposure times (several minutes per image) and nano-CTs can be obtained
Mit zunehmender Miniaturisierung in Industrie und Medizintechnik werden zerstörungsfreie Prüfverfahren immer wichtiger. In diesem Umfeld bietet Röntgenmikroskopie ein effizientes Instrument zu Analyse, Verständnis und Qualitätssicherung mikroskopischer Proben, insbesondere da sie im Rahmen der Computer-Tomografie (CT) die Aufnahme dreidimensionaler Datensätze des gesamten Probenvolumens ermöglicht. Die vorliegende Arbeit befasst sich mit Konzeption, Design, Aufbau und Charakterisierung eines kompakten Labor-Röntgenmikroskops im harten Röntgenbereich bei 9 keV, bzw. einer Wellenlänge von 0.134 nm. Im Fokus liegt dabei die Optimierung von Auflösung und Kontrast bei möglichst kurzen Belichtungszeiten. Hier für bildet die Basis eine neuartige Flüssig-Metall- Anoden Röntgenquelle. Solche erst seit kurzem kommerziell verfügbare Quellen erreichen eine höhere Brillianz als konventionelle Laborquellen, d.h. dass die Anzahl der emittierten Photonen (Röntgenquanten) pro Fläche und Raumwinkel außergewöhnlich hoch ist. Dies ist ein entscheidender Faktor, um nötige Belichtungszeiten zu verringern. Der Grund für die hohe Brillianz ist die Verwendung einer sich sehr schnell erneuernden Anode aus flüssigem Metall. Diese ermöglicht die effektive Abfuhr von Wärme, welche normalerweise die Erzeugung von höheren Intensitäten auf kleinerer Fläche limitiert. Um ein möglichst großes Spektrum an Proben abzubilden, kann das Mikroskop in zwei Modi betrieben werden. Im ”Mikro-CT Modus“ werden kleine Pixel mit Hilfe eines Kristall-Leuchtschirms und einem Lichtmikroskop über das Schattenwurfprinzip erreicht, weswegen dessen Auflösung durch die Wellenlänge des emittierten Lichts und die Unschärfe des Schirms beschränkt ist. Dafür können Proben im Millimeterbereich bei geringen Belichtungszeiten standardmäßig aufgenommen werden. Zudem wurde dieser Modus auf inline Phasen-Kontrast optimiert, bei welchem die Kanten eines Objekts durch Interferenz überhöht dargestellt werden und somit besser sichtbar sind. Im zweiten ”Nano-CT Modus“ kann eine erhöhte Auflösung mit Hilfe von Röntgenlinsen erreicht werden. Deren Herstellung ist aber aufgrund der physikalische Eigenschaften im harten Röntgenbereichs - nämlich starke Absorption und schwache Brechung - technisch extrem schwierig und meist mit einer sehr geringe optischen “Leistung” verbunden. Dies führt in Kombination mit einer geringen Brillianz zu sehr langen Belichtungszeiten und hohen Anforderungen an die Stabilität, was ein Kernproblem der auf Laborquellen basierenden Röntgenmikroskope darstellt. Mit der hier entwickelten Anlage können durch die hohe Brillianz der verwendeten Quelle bei moderaten Belichtungszeiten (wenige Minuten pro Bild) Strukturen der Größe 150 nm voneinander getrennt, sowie Nano-CTs aufgenommen werden

Research using mice and rats has gained interest because they are robust test beds for clinical drug development and are used to elucidate disease etiologies. Blood vessel visualization and blood flow measurements are important anatomic and physiologic indicators to drug/disease stimuli or genetic modification. Cardio-pulmonary blood flow is an important indicator of heart and lung performance. Small animal functional imaging provides a way to measure physiologic changes minimally-invasively while the animal is alive, thereby allowing for multiple measurements in the same animal with little physiologic perturbation. Current methods of measuring cardio-pulmonary blood flow suffer from some or all of these limitations-they produce relative measurements, are limited to global or whole animal or organ regions, do not provide vasculature visualization, limited to a few or singular samples per animal, are not able to measure acute changes, or are very invasive or requires animal sacrifice. The focus of this work was the development of a small animal x-ray imaging system capable of minimally invasive real-time, high resolution vascular visualization, and cardio-pulmonary blood flow measurements in the live animal. The x-ray technique used was digital subtraction angiography (DSA). This technique is a particularly appealing approach because it is easy to use, can capture rapid physiological changes on a heart beat-to-beat basis, and provides anatomical and functional vasculature information. This DSA system is special because it was designed and implemented from the ground up to be optimized for small animal imaging and functional measurements. This system can perform: 1) minimally invasive in vivo blood flow measurements, 2) multiple measurements in the same animal in a rapid succession (every 30 seconds-a substantial improvement over singular measurements that require minutes to acquire by the Fick method), 3) very high resolution (up to 46 micron) vascular visualization, 4) quantitative blood flow measurements in absolute metrics (mL/min instead of arbitrary units or velocity) and relative blood volume dynamics from discrete ROIs, and 5) relative mean transit time dynamics on a pixel-by-pixel basis (100 µm x 100 µm). The end results are 1) anatomical vessel time course images showing the contrast agent flowing through the vasculature, 2) blood flow information of the live rat cardio-pulmonary system in absolute units and relative blood volume information at discrete ROIs of enhanced blood vessels, and 3) colormaps of relative transit time dynamics. This small animal optimized imaging system can be a useful tool in future studies to measure drug or disease modulated blood flow dynamics in the small animal.

Dissertation

Coherent imaging is a promising method in the field of x-ray microscopy allowing for the nondestructive determination of the interior structure of radiation-hard samples with a spatial resolution that is only limited by the fluence on the sample and the scattering strength of the sample. Ultimately, the achievable spatial resolution is limited by the wavelength of the incoming x-ray radiation. Combining coherent imaging with scanning microscopy to a method called ptychography enables one to also probe extended objects. In this method, a sample is scanned through a defined coherent x-ray beam and at each scan point a diffraction pattern is recorded with a diffraction camera located in the far field of the sample. Neighboring illuminated areas must have a certain overlap to guarantee the collection of sufficient information about the object for a subsequent successful and unique computational reconstruction of the object. Modern ptychographic reconstruction algorithms are even able to reconstruct the complex-valued transmission function of the sample and the complex illumination wave field at the same time. Once the 2D transmission function of a sample is known, it is an obvious step forward to combine ptychography with tomographic techniques yielding the 3D internal structure of an object with unprecedented spatial resolution. Here, projections at varying angular positions of the sample are generated via ptychographic scans and are subsequently used for the tomographic reconstruction. In this thesis the development of 3D ptychography is described. It includes the description of the required experimental environment, the numerical implementation of ptychographic phase retrieval and tomographic reconstruction routines, and a detailed analysis of the performance of 3D ptychography using an example of an experiment carried out at beamline P06 of PETRA III at DESY in Hamburg. In that experiment the investigated object was a Mo/UO2 thin film, which is a simplified model for spent nuclear fuel from nuclear power plant reactors. Such models find application in systematic scientific investigations related to the safe disposal of nuclear waste. We determined the three-dimensional interior structure of this sample with an unprecedented spatial resolution of at least 18 nm. The measurement of the fluorescence signal at each scan point of the ptychograms delivers the two- and three-dimensional elemental distribution of the sample with a spatial resolution of 80 nm. Using the fluorescence data, we assigned the chemical element to the area of the corresponding phase shift in the ptychographic reconstruction of the object phase and to the corresponding refractive index decrement in the tomographic reconstruction. The successful demonstration of the feasibility of the 3D ptychography motivates further applications, for instance, in the field of medicine, of material science, and of basic physical research.
Kohärente Bildgebung ist eine vielversprechende Methode der Röntgenmikroskopie. Sie ermöglicht die zerstörungsfreie Bestimmung der inneren Struktur von strahlenharten Untersuchungsobjekten mit einer räumlichen Auflösung, die im Prinzip nur von der integralen Anzahl der Photonen auf der Probe sowie deren Streukraft abhängt. Letztendlich stellt die Wellenlänge der verwendeten Röntgenstrahlung eine Grenze für die erreichbare räumliche Auflösung dar. Die Kombination der kohärenten Bildgebung mit der Rastermikroskopie zur sogenannten Ptychographie eröffnet die Möglichkeit, auch ausgedehnte Objekte mit hoher Auflösung zu untersuchen. Dabei wird die Probe mit einem räumlich begrenzten, kohärenten Röntgenstrahl abgerastert und an jedem Rasterpunkt ein Beugungsbild von einer im Fernfeld platzierten Beugungskamera registriert. Die Beleuchtungen benachbarter Rasterpunkte müssen dabei zu einem bestimmten Prozentsatz überlappen, um genügend Informationen für eine anschließende computergestützte und eindeutige Rekonstruktion des Objektes sicherzustellen. Moderne Rekonstruktionsalgorithmen ermöglichen sogar die gleichzeitige Rekonstruktion der Transmissionsfunktion des Objektes und der Beleuchtungsfunktion des eintreffenden Röntgenstrahls. Die Verknüpfung der Ptychographie mit der Tomographie zur 3D-Ptychographie ist der nahe liegende Schritt, um nun auch die dreidimensionale innere Struktur von Objekten mit hoher räumlicher Auflösung zu bestimmen. Die Projektionen an den verschiedenen Winkelpositionen der Probe werden dabei mittels ptychographischer Abrasterung der Probe erzeugt und anschließend der tomographischen Rekonstruktion zugrunde gelegt. In dieser Arbeit wird die Entwicklung der 3D-Ptychographie beschrieben. Das beinhaltet die Beschreibung der experimentellen Umgebung, der numerischen Implementierung des ptychographischen und des tomographischen Rekonstruktionsalgorithmus als auch eine detaillierte Darstellung der Durchführung der 3D-Ptychographie am Beispiel eines Experiments, welches unter Verwendung des modernen Nanoprobe-Aufbaus des Strahlrohres P06 am PETRA III Synchrotronring des DESY in Hamburg durchgeführt wurde. Als Untersuchungsobjekt diente dabei ein dünner Mo/UO2-Film, der ein vereinfachtes Modell für die in Reaktoren von Atomkraftwerken verbrauchten Brennstäbe darstellt und deshalb im Bereich des Umweltschutzes Anwendung findet. Die dreidimensionale Struktur der Probe wurde mit einer - für diese Methode bisher einmaligen - räumlichen Auflösung von 18 nm bestimmt. Die Messung des von der Probe kommenden Fluoreszenz-Signals an jedem Rasterpunkt der Ptychogramme ermöglichte zusätzlich die Bestimmung der zwei- und dreidimensionalen Elementverteilung innerhalb der Probe mit einer räumlichen Auflösung von 80 nm. Anhand der Fluoreszenzdaten konnte sowohl den Bereichen verschiedener Phasenschübe in den ptychographischen Rekonstruktionen der Objektphase als auch den verschiedenen Werten des Dekrementes des Brechungsindex in der tomographischen Rekonstruktion, das entsprechende chemische Element zugeordnet werden. Die erfolgreiche Demonstration der Durchführbarkeit der 3D-Ptychographie motiviert weitere zukünftige Anwendungen, z. B. auf dem Gebiet der Medizin, der Materialforschung und der physikalischen Grundlagenforschung.

This work extends the technology of amorphous silicon (a-Si) thin film transistors (TFTs) from traditional switching applications to on-pixel signal amplification for large area digital imaging and in particular, is aimed towards enabling emerging low noise, high resolution and high frame rate medical diagnostic imaging modalities such as digital tomosynthesis. A two transistor (2T) pixel amplifier circuit based on a novel charge-gate thin film transistor (TFT) device architecture is introduced to shrink the TFT based pixel readout circuit size and complexity and thus, improve the imaging array resolution and reliability of the TFT fabrication process. The high resolution pixel amplifier results in improved electrical performance such as on-pixel amplification gain, input referred noise and faster readouts. In this research, a charge-gated TFT that operates as both a switched amplifier and driver is used to replace two transistors (the addressing switch and the amplifier transistor) of previously reported three transistor (3T) APS pixel circuits.. In addition to enabling smaller pixels, the proposed 2T pixel amplifier results in better signal-to-noise (SNR) by removing the large flicker noise source associated with the switched TFT and increased pixel transconductance gain since the large ON-state resistance of the switched TFT is removed from the source of the amplifier TFT. Alternate configurations of 2T APS architectures based on source or drain switched TFTs are also investigated, compared, and contrasted to the gate switched architecture using charge-gated TFT. A new driving scheme based on multiple row resetting is introduced which combined with the on-pixel gain of the APS, offers considerable improvements in imaging frame rates beyond those feasible for PPS based pixels. The novel developed 2T APS architectures is implemented in single pixel test structures and in 88 pixel test arrays with a pixel pitch of 100 µm. The devices were fabricated using an in-house developed top-gate TFT fabrication process. Measured characteristics of the test devices confirm the performance expectations of the 2T architecture design. Based on parameters extracted from fabricated TFTs, the input referred noise is calculated, and the instability in pixel transconductance gain over prolonged operation tine is projected for different imaging frame rates. 2T APS test arrays were packaged and integrated with an amorphous selenium (a-Se) direct x-ray detector, and the x-ray response of the a-Se detector integrated with the novel readout circuit was evaluated. The special features of the APS such as non-destructive readout and voltage programmable on-pixel gain control are verified. The research presented in this thesis extends amorphous silicon pixel amplifier technology into the area of high density pixel arrays such as large area medical X-ray imagers for digital mammography tomosynthesis. It underscores novel device and circuit design as an effective method of overcoming the inherent shortcomings of the a-Si material . Although the developed device and circuit ideas were implemented and tested using a-Si TFTs, the scope of the device and circuit designs is not limited to amorphous silicon technology and has the potential to be applied to more mainstream technologies, for example, in CMOS active pixel sensor (APS) based digital cameras.