In vivo und ex vivo MR-Elastographie der Leber – Quantitative Bildgebung zur biophysikalischen Diagnostik von chronischen Lebererkrankungen

In dieser Habilitationsschrift zur MR Elastographie (MRE) der Leber wurden in vivo und ex vivo Untersuchungen mit einem Top Down Ansatz durchgeführt. Zunächst wurden allgemeine Erkenntnisse zur diagnostischen Genauigkeit der in vivo Leber-MRE bei verschiedenen chronischen Lebererkrankungen gewonnen. Anschließend wurden diese Erkenntnisse bei spezifischen chronischen Lebererkrankungen angewandt – Alpha-1-Antitrypsinmangel (AATD) und primär sklerosierende Cholangitis (PSC). Ein Hauptergebnis der vorliegenden Schrift ist die Etablierung diagnostischer Referenzwerte zur nichtinvasiven Graduierung der Leberfibrose. In Originalarbeit 1 wurden 45 Patient:innen mit chronischen Lebererkrankungen und 16 freiwillige Proband:innen prospektiv untersucht. Die Referenzwerte der Steifigkeit zur Fibrosegraduierung zeigten exzellente AUC-Werte (95%-Konfidenzintervall) wie folgt für die Tomoelastographie: F1, 1,52 m/s und 0,89 (0,81-0,95); F2, 1,55 m/s und 0,94 (0,89-0,99); F3, 1,67 m/s und 0,98 (0,96-1,00); und F4, 1,72 m/s und 0,98 (0,96-1,00). Diese Referenzwerte kommen seit dem Jahr 2019 in der klinischen Routine der Charité – Universitätsmedizin Berlin und in allen weltweiten Zentren, die über die Technik der Tomoelastographie verfügen, zum Einsatz. Dadurch kann die Anzahl invasiver Leberbiopsien gesenkt werden. Darauf aufbauend wurde in Originalarbeit 2 mit der Fluidität ein weiterer potenzieller Biomarker für die Erkennung von pathologischen Prozessen im Zusammenhang mit Fibrose und Zirrhose unabhängig von der Steifigkeit evaluiert. Die Fluidität basiert auf einem scheinbaren Fließverhalten eines Materials, dass mit φ zunimmt, jedoch nicht zwingendermaßen mit dem Wassergehalt zusammenhängt. Während die Steifigkeit mit dem Fibrosegrad zunahm (F0: 1,53 ± 0,11 m/s; F1-F3: 1,71 ± 0,17 m/s; F4: 2,50 ± 0,39 m/s; p < 0,001), blieb die Fluidität bei leichter bis schwerer Fibrose unverändert (F0: 0,63 ± 0,05 rad; F1-F3: 0,60 ± 0,05 rad; p = 0.21), stieg aber bei Zirrhose an (F4: 0,81 ± 0,16 rad; p < 0,001). Eine signifikante Korrelation mit dem Child-Pugh-Score zur klinischen Graduierung der Zirrhose wurde für die Fluidität (r = 0,60; p = 0,01), aber nicht für die Steifigkeit gefunden. Diese biophysikalischen Gewebeeigenschaften könnten einen prognostischen Biomarker für die Erkennung von pathologischen Prozessen im Zusammenhang mit Fibrose bzw. Zirrhose unabhängig von der Steifigkeit darstellen. In Originalarbeit 3 wurden 15 klinisch asymptomatische AATD-Patient:innen und 16 freiwilligen Proband:innen mittels MRE, Acoustic radiation force impulse (ARFI) und 2Dshear wave elastography (2D-SWE) prospektiv untersucht. Für die verschiedenen elastographischen Methoden konnte eine hohe Pearson-Korrelation gezeigt werden: 2DSWE/MRE mit r = 0,86; ARFI/2D-SWE mit r = 0,74; ARFI/MRE mit r = 0,69; jeweils p ≤ 0.009. Die hohe Korrelation und eine konsistente Identifizierung von Patient:innen mit pathologisch erhöhter Lebersteifigkeit mittels MRE und verschiedenen Ultraschallelastographiemethoden lassen vermuten, dass die MRE ein geeignetes bildgebendes Instrument zur Beurteilung der AATD-bedingten Leberfibrose ist. In Originalarbeit 4 wurden 20 Patient:innen mit PSC und 26 Patient:innen mit Virushepatitis prospektiv untersucht. Die Mittelwerte von Steifigkeit und Variationskoeffizient betrugen 1,70 m/s und 21 % für PSC und 1,84 m/s und 18 % für Virushepatitis. Dabei war die mittels Variationskoeffizient bestimmte Fibrose-Heterogenität bei PSC signifikant erhöht (p = 0,04), während für die Steifigkeit kein signifikanter Unterschied festgestellt wurde (p = 0,17). Obwohl die globale Lebersteifigkeit in beiden Gruppen ähnlich war, konnte die Heterogenitätsbestimmung räumliche Muster von Steifigkeitsveränderungen aufzeigen, die zu einer verbesserten biophysikalischen Diagnose mittels MRT führen könnten. Darüber hinaus konnten in Originalarbeit 5 die mechanischen Auswirkungen des Gefrier-TauZyklus auf ex vivo Leberproben mittels Tabletop-MRE charakterisiert werden. Hierbei konnte gezeigt werden, dass das 3-Parameter-Zener-Rheologiemodell die beste Übereinstimmung zwischen Experiment und Modell vor und nach dem Gefrier-Tau-Zyklus erreichte. Dies ermöglicht die Erforschung eines breiten Spektrums von pathologischem Lebergewebe aus Tiefkühl-Gewebebanken, für die histopathologische und biochemische Referenzdaten zur Verfügung stehen. In Zukunft können dadurch mit geringem Aufwand wertvolle Informationen über das diagnostische Potenzial elastographischer Methoden gewonnen werden. Die Erkenntnisse dieser Habilitationsschrift sind ein Beitrag zur Reduktion invasiver Leberbiopsien und zum Fortschritt der quantitativen Bildgebung zur biophysikalischen Diagnostik von chronischen Lebererkrankungen mit Umsetzung in der klinischen Routine der Charité – Universitätsmedizin Berlin und weltweit

Using NLG and sensors to support personal narrative for children with complex communication needs

We would like to express our thanks to the children, their parents and staff and the special school where this project had its base. Without their valuable contributions and feedback this research would not have been possible. We would also like to thank DynaVox Systems Ltd for supplying the communication devices to run our system on. This research was supported by the UK Engineering and Physical Sciences Research Council under grants EP/F067151/1, EP/F066880/1, EP/E011764/1, EP/H022376/1, and EP/H022570/1Publisher PD

A probable Keplerian disk feeding an optically revealed massive young star.

The canonical picture of star formation involves disk-mediated accretion, with Keplerian accretion disks and associated bipolar jets primarily observed in nearby, low-mass young stellar objects (YSOs). Recently, rotating gaseous structures and Keplerian disks have been detected around several massive (M > 8 M ) YSOs (MYSOs) , including several disk-jet systems . All the known MYSO systems are in the Milky Way, and all are embedded in their natal material. Here we report the detection of a rotating gaseous structure around an extragalactic MYSO in the Large Magellanic Cloud. The gas motion indicates that there is a radial flow of material falling from larger scales onto a central disk-like structure. The latter exhibits signs of Keplerian rotation, so that there is a rotating toroid feeding an accretion disk and thus the growth of the central star. The system is in almost all aspects comparable to Milky Way high-mass YSOs accreting gas from a Keplerian disk. The key difference between this source and its Galactic counterparts is that it is optically revealed rather than being deeply embedded in its natal material as is expected of such a massive young star. We suggest that this is the consequence of the star having formed in a low-metallicity and low-dust content environment. Thus, these results provide important constraints for models of the formation and evolution of massive stars and their circumstellar disks. [Abstract copyright: © 2023. The Author(s).

A probable Keplerian disk feeding an optically revealed massive young star

The canonical picture of star formation involves disk-mediated accretion, with Keplerian accretion disks and associated bipolar jets primarily observed in nearby, low-mass young stellar objects (YSOs). Recently, rotating gaseous structures and Keplerian disks have been detected around a number of massive (M > 8 solar masses) YSOs (MYSOs) including several disk-jet systems. All of the known MYSO systems are located in the Milky Way, and all are embedded in their natal material. Here we report the detection of a rotating gaseous structure around an extragalactic MYSO in the Large Magellanic Cloud. The gas motions show radial flow of material falling from larger scales onto a central disk-like structure, the latter exhibiting signs of Keplerian rotation, i.e., a rotating toroid feeding an accretion disk and thus the growth of the central star. The system is in almost all aspects comparable to Milky Way high-mass young stellar objects accreting gas via a Keplerian disk. The key difference between this source and its Galactic counterparts is that it is optically revealed, rather than being deeply embedded in its natal material as is expected of such a young massive star. We suggest that this is the consequence of the star having formed in a low-metallicity and low-dust content environment, thus providing important constraints for models of the formation and evolution of massive stars and their circumstellar disks.Comment: 20 pages, 9 page

High temperature particle jet erosion of nickel- and cobalt-based alloys

Higher operating temperatures can increase the effectiveness of different technical processes, e.g. turbines, combustion furnaces and cyclone separators. The combination of the increasedtemperatures with the stresses and strains necessitate new hardwearing materials. Theresearch of the influence of high temperatures and oxidation on the wear resistance hasmainly been conducted on single-phase materials. In the current research, the influences of temperature, impact angle and kinetic energy of theparticles are examined. Therefore, high temperature particle jet erosion tests of a nickel-basedand a cobalt-based alloy were conducted. Hastealloy® C22 and Ultimet® Alloy were chosen,due to the high resistances against both corrosion and abrasion. The specimens are PTA-welded layers on steel plates, partially reinforced with different carbides, including fusedtungsten carbides and titanium carbides. Initially, only carbides of the same grain size wereused. Further tests were conducted on alloys with a mixture of carbides, varying in type andsize. These tests were conducted in a specially designed testing machine with a variety ofparameters. This includes temperatures of 750 °C, different particle velocities and impactangles. Oxidation tests were used to isolate the influence of the corrosion on the wearresistance at high temperatures. The results of this research provide a better understanding of the properties and capabilities ofthe alloys and carbides

Parasitic Absorption in Polycrystalline Si-layers for Carrier-selective Front Junctions

We investigate the optical properties of n- and p-type polycrystalline silicon (poly-Si) layers. We determine the optical constants n and k of the complex refractive index of polycrystalline silicon by using variable-angle spectroscopic ellipsometry. Moreover, we investigate the effect of different doping levels in the poly-Si on free carrier absorption (FCA). Thereby, we demonstrate that the FCA in poly-Si can be described by a model developed for crystalline silicon (c-Si) at a first approximation. The optical properties of hydrogenated amorphous silicon layers (a-Si:H) are also investigated as a reference. With ray tracing simulations the absorption losses of poly-Si and of the a-Si:H layers are quantified with respect to the film thickness. Based on this approach we find that the short-circuit current density losses due to parasitic absorption of poly-Si layers are significantly lower when compared to a-Si:H layers of the same thickness. For example the short-circuit current density loss due to a 20 nm thick p-type poly-Si layer is around 1.1 mA/cm2, whereas a 20 nm thick p-type a-Si:H layer leads to a loss of around 3.5 mA/cm2.BMWi/032570

Personal storytelling: Using Natural Language Generation for children with complex communication needs, in the wild...

This paper describes a Natural Language Generation system (NLG), How was School Today? that automatically creates a personal narrative from sensor data and other media (photos and audio). It can be used by children with complex communication needs in schools to support interactive narrative about personal experiences. The robustness of story generation to missing data was identified as a key area for improvement in a feasibility study of the system at a first special needs school. This paper therefore suggests three possible methods for generating stories from unstructured data: clustering by voice recording, by location, or by time. Clustering based on voice recordings resulted in stories that were perceived as most easy to read, and to make most sense, by parents in a quantitative evaluation. This method was implemented in the live system, which was developed and evaluated iteratively at a second special needs school with children with different usage profiles. Open challenges and possibilities for NLG in augmented and alternative communication are also discussed

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis vs. viral hepatitis assessed by MR elastography

Spatial heterogeneity of hepatic fibrosis in primary sclerosing cholangitis (PSC) in comparison to viral hepatitis was assessed as a potential new biomarker using MR elastography (MRE). In this proof-of-concept study, we hypothesized a rather increased heterogeneity in PSC and a rather homogeneous distribution in viral hepatitis. Forty-six consecutive subjects (PSC: n=20, viral hepatitis: n=26) were prospectively enrolled between July 2014 and April 2017. Subjects underwent multifrequency MRE (1.5 T) using drive frequencies of 35-60 Hz and generating shear-wave speed (SWS in m/s) maps as a surrogate of stiffness. The coefficient of variation (CV in %) was determined to quantify fibrosis heterogeneity. Mean SWS and CV were 1.70 m/s and 21% for PSC, and 1.84 m/s and 18% for viral hepatitis. Fibrosis heterogeneity was significantly increased for PSC (P=0.04) while no difference was found for SWS of PSC and viral hepatitis (P=0.17). Global hepatic stiffness was similar in PSC and viral hepatitis groups, but spatial heterogeneity may reveal spatial patterns of stiffness changes towards enhanced biophysics-based diagnosis by MRI

Multifrequency magnetic resonance elastography-based tomoelastography of the parotid glands–feasibility and reference values

Objectives: Accurate radiological differentiation of parotid tumors remains challenging despite recent technical advances in quantitative medical imaging. Multifrequency magnetic resonance elastography (MRE) could provide additional information on viscoelastic properties of normal and abnormal biological tissues. This study investigates the feasibility of MRE of the parotid glands in healthy participants and provides first reference values. Methods: 20 healthy participants underwent multifrequency MRE of both parotid glands at 3 Tesla. Shear waves at frequencies of 25, 30, 40, and 50 Hz were introduced into the participants' heads through the occiput using pressurized-air actuators. Shear wave speed (SWS) and loss angle of the shear modulus (φ) were reconstructed by tomoelastography post-processing as surrogate parameters for tissue stiffness and viscosity or fluidity. 10 participants underwent repeated MRE to determine test-retest reliability based on intraclass correlation coefficients. Results: All MRE datasets acquired could be included in the analysis. Mean SWS was 0.97 ± 0.13 m/s, and mean φ was 0.59 ± 0.05 rad, each for both sides combined and without notable lateral difference (p = 0.88/0.87). Test-retest reliability was good for SWS (ICC = 0.84 for both sides/ICC = 0.77 for the right side/ICC = 0.79 for the left side) and good to excellent for φ(ICC = 0.94/0.86/0.90). Conclusions: Multifrequency MRE of the parotid glands is feasible and reliable. This technique, therefore, is a promising method for investigating the viscoelastic properties of salivary gland tumors in future studies