Forward model for quantitative pulse-echo speed-of-sound imaging

Computed ultrasound tomography in echo mode (CUTE) allows determining the spatial distribution of speed-of-sound (SoS) inside tissue using handheld pulse-echo ultrasound (US). This technique is based on measuring the changing phase of beamformed echoes obtained under varying transmit (Tx) and/or receive (Rx) steering angles. The SoS is reconstructed by inverting a forward model describing how the spatial distribution of SoS is related to the spatial distribution of the echo phase shift. CUTE holds promise as a novel diagnostic modality that complements conventional US in a single, real-time handheld system. Here we demonstrate that, in order to obtain robust quantitative results, the forward model must contain two features that were not taken into account so far: a) the phase shift must be detected between pairs of Tx and Rx angles that are centred around a set of common mid-angles, and b) it must account for an additional phase shift induced by the error of the reconstructed position of echoes. In a phantom study mimicking liver imaging, this new model leads to a substantially improved quantitative SoS reconstruction compared to the model that has been used so far. The importance of the new model as a prerequisite for an accurate diagnosis is corroborated in preliminary volunteer results

Early stage phase separation of AlCoCr_0.75Cu_0.5FeNi high-entropy powder at the nanoscale

High entropy alloys are generally considered to be single phase material. This state is, however, typically a non-equilibrium state after fabrication at high cooling rates. Phase constitution after fabrication or heat treatment is mostly known for isothermal annealing only and for casts as well as rapidly quenched alloys. Knowledge on early phase separation stages of high entropy alloys and their mechanisms are missing so far. Here, we present results on phase separation at intermediate cooling rates, by characterization of gas atomized powder of the AlCoCr0.75Cu0.5FeNi alloy. Although investigation by X-ray diffraction and Electron Backscatter Diffraction indicates a single-phase nature of the powder particles, aberration-corrected scanning transmission electron microscopy and atom probe tomography reveal a nanoscale phase separation into Ni-Al-rich B2 and Fe-Cr-rich A2 regions as well as a high number density of 3.1x1024 Cu-rich clusters per m3 in the B2 matrix. The observed phase separation and cluster formation are linked to spinodal decomposition and nucleation processes, respectively. The study highlights that adequate characterization techniques need to be chosen when making statements about phase stability and structural evolution in compositionally complex alloys.Comment: 33 pages, 12 figure

On Open and Strong-Scaling Tools for Atom Probe Crystallography: High-Throughput Methods for Indexing Crystal Structure and Orientation

Volumetric crystal structure indexing and orientation mapping are key data processing steps for virtually any quantitative study of spatial correlations between the local chemistry and the microstructure of a material. For electron and X-ray diffraction methods it is possible to develop indexing tools which compare measured and analytically computed patterns to decode the structure and relative orientation within local regions of interest. Consequently, a number of numerically efficient and automated software tools exist to solve the above characterisation tasks. For atom probe tomography (APT) experiments, however, the strategy of making comparisons between measured and analytically computed patterns is less robust because many APT datasets may contain substantial noise. Given that general enough predictive models for such noise remain elusive, crystallography tools for APT face several limitations: Their robustness to noise, and therefore, their capability to identify and distinguish different crystal structures and orientation is limited. In addition, the tools are sequential and demand substantial manual interaction. In combination, this makes robust uncertainty quantifying with automated high-throughput studies of the latent crystallographic information a difficult task with APT data. To improve the situation, we review the existent methods and discuss how they link to those in the diffraction communities. With this we modify some of the APT methods to yield more robust descriptors of the atomic arrangement. We report how this enables the development of an open-source software tool for strong-scaling and automated identifying of crystal structure and mapping crystal orientation in nanocrystalline APT datasets with multiple phases.Comment: 36 pages, 19 figures, preprin

High-Resolution 3D Ptychography

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

Absolute surface topography measurement with polarisation sensitive coherence scanning interferometry

Traditionally, surface topography measurement was in the domain of quality control of engineering parts. With the advancement of manufacturing technology and affordable computational costs, different types of surfaces are produced with varied shapes and surface textures. These pose significant measurement problems, therefore, surface topography research is gaining momentum to achieve a better control of the surface. Coherence scanning interferometry (CSI) is one of the most common techniques used for measurement of surface topography. It is preferred over tactile and other non-contact techniques since it provides fast and accurate measurement with high vertical (~ 1 nm) and lateral (~1 μm) resolutions over larger areas without any damage to the surface. Essentially, CSI is treated as one dimensional (1D) superposition of the light waves from an object and a reference that generates a three dimensional (3D) interferogram. Secondly, despite the advantages, there is no standard configuration of CSI that can provide absolute surface topography measurement of an engineering part with multiple materials. An effective solution to this problem will be particularly useful in the field of semiconductor and bio-related industries where chips and instruments are made of many materials. In this Thesis, first, the CSI technique is analysed in terms of a wider theoretical framework of 3D linear filtering technique which shows the similarities among other seemingly disparate techniques such as confocal and optical coherence tomography. Due consideration to the spectral characteristic of the source and the effect of numerical aperture are given and important parameters such as vertical and lateral resolutions are computed to compare this theory with standard analysis methods. Additionally, it is shown that the 3D fringe pattern can be considered to be a superposition of a reference field and the scattered field from the top foil-like layer on the top the object. The scattered field from this foil object is dependent on the normal Fresnel reflection coefficients. Therefore, it explains the phase offset and the proportional height offset introduced by different materials, especially, metals. In an object, where multiple materials are present, each material introduces different phase to the fringe pattern and therefore, the surface topography of the entire object is altered. To overcome this problem, the optical polarising properties of the material are exploited. A novel configuration of polarisation sensitive CSI is presented where interferograms with orthogonal circular polarisations are recorded and analysed. The configuration, initially, needs to be calibrated with a material and after that at each point on the object, the refractive index and height offset can be calculated. Therefore, it can be dually used to identify unknown materials present on the object and also to compensate for the height offset introduced by each material to produce absolute surface topography of the entire object. The configuration provides good agreement with ellipsometric results for metals. Additionally, it retains the advantages of high vertical and lateral resolution same as other standard coherence scanning interferometers

Hyperspectral interferometry for single-shot profilometry and depth-resolved displacement field measurement

A new approach to the absolute measurement of two-dimensional optical path differences is presented in this thesis. The method, which incorporates a white light interferometer and a hyperspectral imaging system, is referred to as Hyperspectral Interferometry. A prototype of the Hyperspectral Interferometry (HSI) system has been designed, constructed and tested for two types of measurement: for surface profilometry and for depth-resolved displacement measurement, both of which have been implemented so as to achieve single shot data acquisition. The prototype has been shown to be capable of performing a single-shot 3-D shape measurement of an optically-flat step-height sample, with less than 5% difference from the result obtained by a standard optical (microscope) based method. The HSI prototype has been demonstrated to be able to perform single-shot measurement with an unambiguous 352 (m depth range and a rms measurement error of around 80 nm. The prototype has also been tested to perform measurements on optically rough surfaces. The rms error of these measurements was found to increase to around 4× that of the smooth surface. For the depth-resolved displacement field measurements, an experimental setup was designed and constructed in which a weakly-scattering sample underwent simple compression with a PZT actuator. Depth-resolved displacement fields were reconstructed from pairs of hyperspectral interferograms. However, the experimental results did not show the expected result of linear phase variation with depth. Analysis of several possible causes has been carried out with the most plausible reasons being excessive scattering particle density inside the sample and the possibility of insignificant deformation of the sample due to insufficient physical contact between the transducer and the sample

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

Fiber Orientation Tensors and Mean Field Homogenization: Application to Sheet Molding Compound

Effective mechanical properties of fiber-reinforced composites strongly depend on the microstructure, including the fibers\u27 orientation. Studying this dependency, we identify the variety of fiber orientation tensors up to fourth-order using irreducible tensors and material symmetry. The case of planar fiber orientation tensors, relevant for sheet molding compound, is presented completely. Consequences for the reconstruction of fiber distributions and mean field homogenization are presented

Uncertainty Quantification in Biophotonic Imaging using Invertible Neural Networks

Owing to high stakes in the field of healthcare, medical machine learning (ML) applications have to adhere to strict safety standards. In particular, their performance needs to be robust toward volatile clinical inputs. The aim of the work presented in this thesis was to develop a framework for uncertainty handling in medical ML applications as a way to increase their robustness and trustworthiness. In particular, it addresses three root causes for lack of robustness that can be deemed central to the successful clinical translation of ML methods: First, many tasks in medical imaging can be phrased in the language of inverse problems. Most common ML methods aimed at solving such inverse problems implicitly assume that they are well-posed, especially that the problem has a unique solution. However, the solution might be ambiguous. In this thesis, we introduce a data-driven method for analyzing the well-posedness of inverse problems. In addition, we propose a framework to validate the suggested method in a problem-aware manner. Second, simulation is an important tool for the development of medical ML systems due to small in vivo data sets and/or a lack of annotated references (e. g. spatially resolved blood oxygenation (sO 2 )). However, simulation introduces a new uncertainty to the ML pipeline as ML performance guarantees generally rely on the testing data being sufficiently similar to the training data. This thesis addresses the uncertainty by quantifying the domain gap between training and testing data via an out-of-distribution (OoD) detection approach. Third, we introduce a new paradigm for medical ML based on personalized models. In a data-scarce regime with high inter-patient variability, classical ML models cannot be assumed to generalize well to new patients. To overcome this problem, we propose to train ML models on a per-patient basis. This approach circumvents the inter-patient variability, but it requires training without a supervision signal. We address this issue via OoD detection, where the current status quo is encoded as in-distribution (ID) using a personalized ML model. Changes to the status quo are then detected as OoD. While these three facets might seem distinct, the suggested framework provides a unified view of them. The enabling technology is the so-called invertible neural network (INN), which can be used as a flexible and expressive (conditional) density estimator. In this way, they can encode solutions to inverse problems as a probability distribution as well as tackle OoD detection tasks via density-based scores, like the widely applicable information criterion (WAIC). The present work validates our framework on the example of biophotonic imaging. Biophotonic imaging promises the estimation of tissue parameters such as sO 2 in a non-invasive way by evaluating the “fingerprint” of the tissue in the light spectrum. We apply our framework to analyze the well-posedness of the tissue parameter estimation problem at varying spectral and spatial resolutions. We find that with sufficient spectral and/or spatial context, the sO 2 estimation problem is well-posed. Furthermore, we examine the realism of simulated biophotonic data using the proposed OoD approach to gauge the generalization capabilities of our ML models to in vivo data. Our analysis shows a considerable remaining domain gap between the in silico and in vivo spectra. Lastly, we validate the personalized ML approach on the example of non-invasive ischemia monitoring in minimally invasive kidney surgery, for which we developed the first-in-human laparoscopic multispectral imaging system. In our study, we find a strong OoD signal between perfused and ischemic kidney spectra. Furthermore, the proposed approach is video-rate capable. In conclusion, we successfully developed a framework for uncertainty handling in medical ML and validated it using a diverse set of medical ML tasks, highlighting the flexibility and potential impact of our approach. The framework opens the door to robust solutions to applications like (recording) device design, quality control for simulation pipelines, and personalized video-rate tissue parameter monitoring. In this way, this thesis facilitates the development of the next generation of trustworthy ML systems in medicine