3D Mapping of the DMEK Detachment Area from OCT Scans of the Anterior Segment of the Eye - Clinical Applications. / 3D-Kartierung der DMEK-Abhebungsfläche aus OCT-Scans des vorderen Augensegmentes mit klinischen Anwendungen.

Graft detachment is the most common complication after Descemet membrane endothelial keratoplasty (DMEK). To assess the amount of graft detachment, precision is limited when using slit-lamp biomicroscopy. Detachment of DMEK grafts can be assessed automatically on anterior segment optical coherence tomography (AS OCT) images and allows visualization of the area and volume of detachment using 3D maps. This article provides an overview of its applications such as accurately assessing the course of natural graft attachment, identification of potential risk factors for detachment and evaluation of the long-term effect of graft detachment. The 3D map of DMEK detachment may support researchers and clinicians in precise quantification of the area and volume of graft detachment even in large data sets, and the intuitive, fast and reliable evaluation.

Emergence of self-organized multivortex states in flocks of active rollers.

Active matter, both synthetic and biological, demonstrates complex spatiotemporal self-organization and the emergence of collective behavior. A coherent rotational motion, the vortex phase, is of great interest because of its ability to orchestrate well-organized motion of self-propelled particles over large distances. However, its generation without geometrical confinement has been a challenge. Here, we show by experiments and computational modeling that concentrated magnetic rollers self-organize into multivortex states in an unconfined environment. We find that the neighboring vortices more likely occur with the opposite sense of rotation. Our studies provide insights into the mechanism for the emergence of coherent collective motion on the macroscale from the coupling between microscale rotation and translation of individual active elements. These results may stimulate design strategies for self-assembled dynamic materials and microrobotics.

Targeted evolution of pinning landscapes for large superconducting critical currents.

The ability of type II superconductors to carry large amounts of current at high magnetic fields is a key requirement for future design innovations in high-field magnets for accelerators and compact fusion reactors, and largely depends on the vortex pinning landscape comprised of material defects. The complex interaction of vortices with defects that can be grown chemically, e.g., self-assembled nanoparticles and nanorods, or introduced by postsynthesis particle irradiation precludes a priori prediction of the critical current and can result in highly nontrivial effects on the critical current. Here, we borrow concepts from biological evolution to create a vortex pinning genome based on a genetic algorithm, naturally evolving the pinning landscape to accommodate vortex pinning and determine the best possible configuration of inclusions for two different scenarios: a natural evolution process initiating from a pristine system and one starting with preexisting defects to demonstrate the potential for a postprocessing approach to enhance critical currents. Furthermore, the presented approach is even more general and can be adapted to address various other targeted material optimization problems.

Emergence and dynamics of unconfined self-organised vortices in active magnetic roller liquids.

Actively driven colloids demonstrate complex out-of-equilibrium dynamics often rivaling self-organized patterns and collective behavior observed in living systems. Recent studies revealed the emergence of steady macroscopic states with multiple interacting vortices in an unconfined environment that emerge from the coupling between microscale particle rotation and translation. Yet, insights into the microscopic behavior during the vortex emergence, growth, and formation of a multi-vortical state remain lacking. Here, we investigate in experiments and simulations how the microscale magnetic roller behavior leads to the emergence of seed vortices, their aggregation or annihilation, and the formation of stable large-scale vortical structures. We reveal that the coupling of roller-induced hydrodynamic flows guides the local self-densifications and self-organization of the micro-rollers into seed vortices. The resulting multi-vortical state is sensitive to the external magnetic field amplitude and allows tuning the rollers' number density in a vortex and its characteristic size.

Parallel magnetic field suppresses dissipation in superconducting nanostrips.

The motion of Abrikosov vortices in type-II superconductors results in a finite resistance in the presence of an applied electric current. Elimination or reduction of the resistance via immobilization of vortices is the "holy grail" of superconductivity research. Common wisdom dictates that an increase in the magnetic field escalates the loss of energy since the number of vortices increases. Here we show that this is no longer true if the magnetic field and the current are applied parallel to each other. Our experimental studies on the resistive behavior of a superconducting Mo0.79Ge0.21 nanostrip reveal the emergence of a dissipative state with increasing magnetic field, followed by a pronounced resistance drop, signifying a reentrance to the superconducting state. Large-scale simulations of the 3D time-dependent Ginzburg-Landau model indicate that the intermediate resistive state is due to an unwinding of twisted vortices. When the magnetic field increases, this instability is suppressed due to a better accommodation of the vortex lattice to the pinning configuration. Our findings show that magnetic field and geometrical confinement can suppress the dissipation induced by vortex motion and thus radically improve the performance of superconducting materials.

[Deep Learning in Pathology: Applications and Challenges in Ophthalmic Pathology]. / Deep Learning in der Pathologie: Anwendungsmöglichkeiten und Herausforderungen in der Ophthalmopathologie.

INTRODUCTION: Deep learning has received increasing attention in recent years and is used in many different areas. Since image analysis is a strength of deep learning, it would be obvious to use it for histopathological questions too. Our goal is to identify possible deep learning approaches from general pathology which could be used in ophthalmic pathology. In addition, the data of the past year will be used to estimate the proportion of potentially interesting cases and the necessary technical effort. METHODS: Firstly, a literature search for deep learning models and their possible applications in the field of pathology was carried out. In order to estimate the potential benefit, technical challenges and feasibility, the number of suitable ophthalmopathology cases in our lab in 2019 for the identified models was determined and put in relation to the resulting amount of data and the scanning time. RESULTS: We identified 7 areas of particular interest: determination of regions of interest (ROI), classification of histological images in scoring systems, mapping of tumor fractions, differentiation of different types of inflammation, differentiation of various cutaneous tumors, classification of lymphomas and prediction of patient outcome-based on tumor histology. Within one year, a total of 831 cases (43%) would have been suitable for the above models. The creation of whole slide images (WSI) for all histological cases would have required a storage capacity of 630 GB with a scanning time of 35 h. CONCLUSION: There are several deep learning approaches which are also interesting for ophthalmic pathology. Most of them would have to be specially trained for the ophthalmopathological aspects. To be able to apply deep learning approaches, it is necessary to have a good IT infrastructure with the possibility to create and permanently store WSI, and this seems to be technically feasible. Future studies should focus on the specific practical implementation of current deep learning possibilities for ophthalmic pathology.

Diffusive ferromagnetic roller gas.

An ensemble of actively rotating ferromagnetic particles is used to realize an active roller gas. Here, we investigate the diffusive properties of such a gas in experiments and simulations. We reveal that ferromagnetic rollers demonstrate a normal (Fickian) diffusion with a characteristic linear growth of the mean-squared displacement, while statistics of displacements stay non-Gaussian. At short times the system has a bimodal distribution of the displacements that transitions with time to a quasi-Gaussian distribution (Gaussian core with overpopulated tails) for a range of studied particle number densities. Inert particles introduced into the active roller gas exhibit similar diffusive behavior. The results provide insights into diffusive properties of active colloidal systems with activity originating from spinning degrees of freedom.

Association between Striatal Brain Iron Deposition, Microbleeds and Cognition 1 Year After a Minor Ischaemic Stroke.

Brain iron deposits (IDs) are inversely associated with cognitive function in community-dwelling older people, but their association with cognition after ischemic stroke, and whether that differs from microbleeds, is unknown. We quantified basal ganglia IDs (BGID) and microbleeds (BMBs) semi-automatically on brain magnetic resonance images from patients with minor stroke (NIHSS < 7), at presentation and 12 months after stroke. We administered the National Adult Reading Test (NART, estimates premorbid or peak adult cognition) and the Revised Addenbrooke's Cognitive Examination (ACE-R; current cognition) at 1 and 12 months after stroke. We adjusted analyses for baseline cognition, age, gender, white matter hyperintensity (WMH) volume and vascular risk factors. In 200 patients, mean age 65 years, striatal IDs and BMBs volumes did not change over the 12 months. Baseline BGID volumes correlated positively with NART scores at both times (ρ = 0.19, p < 0.01). Baseline and follow-up BGID volumes correlated positively with age (ρ = 0.248, p < 0.001 and ρ = 0.271, p < 0.001 respectively), but only baseline (and not follow-up) BMB volume correlated with age (ρ = 0.129, p < 0.05). Both smoking and baseline WMH burden predicted verbal fluency and visuospatial abilities scores (B = -1.13, p < 0.02 and B = -0.22, p = 0.001 respectively) at 12 months after stroke. BGIDs and BMBs are associated differently with cognition post-stroke; studies of imaging and post-stroke cognition should adjust for premorbid cognition. The positive correlation of BGID with NART may reflect the lower premorbid cognition in patients with stroke at younger vs older ages.

MRI Relaxometry for Quantitative Analysis of USPIO Uptake in Cerebral Small Vessel Disease.

A protocol for evaluating ultrasmall superparamagnetic particles of iron oxide (USPIO) uptake and elimination in cerebral small vessel disease patients was developed and piloted. B1-insensitive R1 measurement was evaluated in vitro. Twelve participants with history of minor stroke were scanned at 3-T MRI including structural imaging, and R1 and R2* mapping. Participants were scanned (i) before and (ii) after USPIO (ferumoxytol) infusion, and again at (iii) 24⁻30 h and (iv) one month. Absolute and blood-normalised changes in R1 and R2* were measured in white matter (WM), deep grey matter (GM), white matter hyperintensity (WMH) and stroke lesion regions. R1 measurements were accurate across a wide range of values. R1 (p < 0.05) and R2* (p < 0.01) mapping detected increases in relaxation rate in all tissues immediately post-USPIO and at 24⁻30 h. R2* returned to baseline at one month. Blood-normalised R1 and R2* changes post-infusion and at 24⁻30 h were similar, and were greater in GM versus WM (p < 0.001). Narrower distributions were seen with R2* than for R1 mapping. R1 and R2* changes were correlated at 24⁻30 h (p < 0.01). MRI relaxometry permits quantitative evaluation of USPIO uptake; R2* appears to be more sensitive to USPIO than R1. Our data are explained by intravascular uptake alone, yielding estimates of cerebral blood volume, and did not support parenchymal uptake. Ferumoxytol appears to be eliminated at 1 month. The approach should be valuable in future studies to quantify both blood-pool USPIO and parenchymal uptake associated with inflammatory cells or blood-brain barrier leak.

Bedside Immune Monitoring: An Automated Immunoassay Platform for Quantification of Blood Biomarkers in Patient Serum within 20 Minutes.

This Article presents an automated, compact, and self-contained system for sensitive quantitative detection of blood biomarkers. A disposable microfluidic chip, prefilled with biomarker-specific reagents and magnetic beads, can be processed fully automatically by a readout platform, enabling an immunoassay-based analysis with a processing time from sample incubation to signal analysis of 20 min. Novel concepts for on-chip vortexing of the magnetic beads and on-chip reagent storage and actuation were developed. A lens-free photodiode readout system represents a cost-efficient approach for detecting the chemiluminescent signal. IL-8 spiked serum samples were measured with a high reproducibility and a limit of detection of 2.05 pg·mL-1. The system was validated with undiluted serum samples collected from trauma patients at the intensive care unit. The developed platform demonstrated good correlation with the clinical reference method, and the clinical trajectory course of IL-8 could be sufficiently followed. With an automated assay approach and an easily adaptable protocol, this portable platform has the potential to be utilized as a universal instrument for analyzing proteins in small sample volumes (<25 µL) in point-of-care settings.

Direct Lattice Shaking of Bose Condensates: Finite Momentum Superfluids.

We address band engineering in the presence of periodic driving by numerically shaking a lattice containing a bosonic condensate. By not restricting to simplified band structure models we are able to address arbitrary values of the shaking frequency, amplitude, and interaction strengths g. For "near-resonant" shaking frequencies with moderate g, a quantum phase transition to a finite momentum superfluid is obtained with Kibble-Zurek scaling and quantitative agreement with experiment. We use this successful calibration as a platform to support a more general investigation of the interplay between (one particle) Floquet theory and the effects associated with arbitrary g. Band crossings lead to superfluid destabilization, but where this occurs depends on g in a complicated fashion.

Tracer kinetic modelling for DCE-MRI quantification of subtle blood-brain barrier permeability.

There is evidence that subtle breakdown of the blood-brain barrier (BBB) is a pathophysiological component of several diseases, including cerebral small vessel disease and some dementias. Dynamic contrast-enhanced MRI (DCE-MRI) combined with tracer kinetic modelling is widely used for assessing permeability and perfusion in brain tumours and body tissues where contrast agents readily accumulate in the extracellular space. However, in diseases where leakage is subtle, the optimal approach for measuring BBB integrity is likely to differ since the magnitude and rate of enhancement caused by leakage are extremely low; several methods have been reported in the literature, yielding a wide range of parameters even in healthy subjects. We hypothesised that the Patlak model is a suitable approach for measuring low-level BBB permeability with low temporal resolution and high spatial resolution and brain coverage, and that normal levels of scanner instability would influence permeability measurements. DCE-MRI was performed in a cohort of mild stroke patients (n=201) with a range of cerebral small vessel disease severity. We fitted these data to a set of nested tracer kinetic models, ranking their performance according to the Akaike information criterion. To assess the influence of scanner drift, we scanned 15 healthy volunteers that underwent a "sham" DCE-MRI procedure without administration of contrast agent. Numerical simulations were performed to investigate model validity and the effect of scanner drift. The Patlak model was found to be most appropriate for fitting low-permeability data, and the simulations showed vp and K(Trans) estimates to be reasonably robust to the model assumptions. However, signal drift (measured at approximately 0.1% per minute and comparable to literature reports in other settings) led to systematic errors in calculated tracer kinetic parameters, particularly at low permeabilities. Our findings justify the growing use of the Patlak model in low-permeability states, which has the potential to provide valuable information regarding BBB integrity in a range of diseases. However, absolute values of the resulting tracer kinetic parameters should be interpreted with extreme caution, and the size and influence of signal drift should be measured where possible.

Vortices in high-performance high-temperature superconductors.

The behavior of vortex matter in high-temperature superconductors (HTS) controls the entire electromagnetic response of the material, including its current carrying capacity. Here, we review the basic concepts of vortex pinning and its application to a complex mixed pinning landscape to enhance the critical current and to reduce its anisotropy. We focus on recent scientific advances that have resulted in large enhancements of the in-field critical current in state-of-the-art second generation (2G) YBCO coated conductors and on the prospect of an isotropic, high-critical current superconductor in the iron-based superconductors. Lastly, we discuss an emerging new paradigm of critical current by design-a drive to achieve a quantitative correlation between the observed critical current density and mesoscale mixed pinning landscapes by using realistic input parameters in an innovative and powerful large-scale time dependent Ginzburg-Landau approach to simulating vortex dynamics.

Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities.

Multifocal basal ganglia T2*-weighted (T2*w) hypointensities, which are believed to arise mainly from vascular mineralization, were recently proposed as a novel MRI biomarker for small vessel disease and ageing. These T2*w hypointensities are typically segmented semi-automatically, which is time consuming, associated with a high intra-rater variability and low inter-rater agreement. To address these limitations, we developed a fully automated, unsupervised segmentation method for basal ganglia T2*w hypointensities. This method requires conventional, co-registered T2*w and T1-weighted (T1w) volumes, as well as region-of-interest (ROI) masks for the basal ganglia and adjacent internal capsule generated automatically from T1w MRI. The basal ganglia T2*w hypointensities were then segmented with thresholds derived with an adaptive outlier detection method from respective bivariate T2*w/T1w intensity distributions in each ROI. Artefacts were reduced by filtering connected components in the initial masks based on their standardised T2*w intensity variance. The segmentation method was validated using a custom-built phantom containing mineral deposit models, i.e. gel beads doped with 3 different contrast agents in 7 different concentrations, as well as with MRI data from 98 community-dwelling older subjects in their seventies with a wide range of basal ganglia T2*w hypointensities. The method produced basal ganglia T2*w hypointensity masks that were in substantial volumetric and spatial agreement with those generated by an experienced rater (Jaccard index = 0.62 ± 0.40). These promising results suggest that this method may have use in automatic segmentation of basal ganglia T2*w hypointensities in studies of small vessel disease and ageing.

Phase imprinting in equilibrating Fermi gases: the transience of vortex rings and other defects.

We present numerical simulations of phase imprinting experiments in ultracold trapped Fermi gases, which were obtained independently and are in good agreement with recent experimental results. Our focus is on the sequence and evolution of defects using the fermionic time-dependent Ginzburg-Landau equation, which contains dissipation necessary for equilibration. In contrast to other simulations, we introduce small, experimentally unavoidable symmetry breaking, particularly that associated with thermal fluctuations and with the phase-imprinting tilt angle, and we illustrate their dramatic effects. As appears consistent with experiment, the former causes vortex rings in confined geometries to move to the trap surface and rapidly decay into more stable vortex lines. The latter aligns the precessing and relatively long-lived vortex filaments, rendering them difficult to distinguish from solitons.

Differentiation of calcified regions and iron deposits in the ageing brain on conventional structural MR images.

PURPOSE: In the human brain, minerals such as iron and calcium accumulate increasingly with age. They typically appear hypointense on T2*-weighted MRI sequences. This study aims to explore the differentiation and association between calcified regions and noncalcified iron deposits on clinical brain MRI in elderly, otherwise healthy subjects. MATERIALS AND METHODS: Mineral deposits were segmented on co-registered T1- and T2*-weighted sequences from 100 1.5 Tesla MRI datasets of community-dwelling individuals in their 70s. To differentiate calcified regions from noncalcified iron deposits we developed a method based on their appearance on T1-weighted images, which was validated with a purpose-designed phantom. Joint T1- and T2*-weighted intensity histograms were constructed to measure the similarity between the calcified and noncalcified iron deposits using a Euclidean distance based metric. RESULTS: We found distinct distributions for calcified regions and noncalcified iron deposits in the cumulative joint T1- and T2*-weighted intensity histograms across all subjects (correlations ranging from 0.02 to 0.86; mean = 0.26 ± 0.16; t = 16.93; P < 0.001) consistent with differences in iron and calcium signal in the phantom. The mean volumes of affected tissue per subject for calcified and noncalcified deposits were 236.74 ± 309.70 mm(3) and 283.76 ± 581.51 mm(3); respectively. There was a positive association between the mineral depositions (ß = 0.32, P < 0.005), consistent with existing literature reports. CONCLUSION: Calcified mineral deposits and noncalcified iron deposits can be distinguished from each other by signal intensity changes on conventional 1.5T T1-weighted MRI and are significantly associated in brains of elderly, otherwise healthy subjects.

ZEISS PLEX Elite 9000 Widefield Optical Coherence Tomography Angiography as Screening Method for Early Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease.

Purpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting. Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated. Results: In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA. Conclusions: The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy. Translational Relevance: Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.

Characterization of multifocal T2*-weighted MRI hypointensities in the basal ganglia of elderly, community-dwelling subjects.

Multifocal T2*-weighted (T2*w) hypointensities in the basal ganglia, which are believed to arise predominantly from mineralized small vessels and perivascular spaces, have been proposed as a biomarker for cerebral small vessel disease. This study provides baseline data on their appearance on conventional structural MRI for improving and automating current manual segmentation methods. Using a published thresholding method, multifocal T2*w hypointensities were manually segmented from whole brain T2*w volumes acquired from 98 community-dwelling subjects in their early 70s. Connected component analysis was used to derive the average T2*w hypointensity count and load per basal ganglia nucleus, as well as the morphology of their connected components, while nonlinear spatial probability mapping yielded their spatial distribution. T1-weighted (T1w), T2-weighted (T2w) and T2*w intensity distributions of basal ganglia T2*w hypointensities and their appearance on T1w and T2w MRI were investigated to gain further insights into the underlying tissue composition. In 75/98 subjects, on average, 3 T2*w hypointensities with a median total volume per intracranial volume of 50.3ppm were located in and around the globus pallidus. Individual hypointensities appeared smooth and spherical with a median volume of 12mm(3) and median in-plane area of 4mm(2). Spatial probability maps suggested an association between T2*w hypointensities and the point of entry of lenticulostriate arterioles into the brain parenchyma. T1w and T2w and especially the T2*w intensity distributions of these hypointensities, which were negatively skewed, were generally not normally distributed indicating an underlying inhomogeneous tissue structure. Globus pallidus T2*w hypointensities tended to appear hypo- and isointense on T1w and T2w MRI, whereas those from other structures appeared iso- and hypointense. This pattern could be explained by an increased mineralization of the globus pallidus. In conclusion, the characteristic spatial distribution and appearance of multifocal basal ganglia T2*w hypointensities in our elderly cohort on structural MRI appear to support the suggested association with mineralized proximal lenticulostriate arterioles and perivascular spaces.

Spontaneous shock waves in pulse-stimulated flocks of Quincke rollers.

Active matter demonstrates complex spatiotemporal self-organization not accessible at equilibrium and the emergence of collective behavior. Fluids comprised of microscopic Quincke rollers represent a popular realization of synthetic active matter. Temporal activity modulations, realized by modulated external electric fields, represent an effective tool to expand the variety of accessible dynamic states in active ensembles. Here, we report on the emergence of shockwave patterns composed of coherently moving particles energized by a pulsed electric field. The shockwaves emerge spontaneously and move faster than the average particle speed. Combining experiments, theory, and simulations, we demonstrate that the shockwaves originate from intermittent spontaneous vortex cores due to a vortex meandering instability. They occur when the rollers' translational and rotational decoherence times, regulated by the electric pulse durations, become comparable. The phenomenon does not rely on the presence of confinement, and multiple shock waves continuously arise and vanish in the system.

Multiquanta flux jumps in superconducting fractal.

We study the magnetic field response of millimeter scale fractal Sierpinski gaskets (SG) assembled of superconducting equilateral triangular patches. Directly imaged quantitative induction maps reveal hierarchical periodic filling of enclosed void areas with multiquanta magnetic flux, which jumps inside the voids in repeating bundles of individual flux quanta Φ0. The number Ns of entering flux quanta in different triangular voids of the SG is proportional to the linear size s of the void, while the field periodicity of flux jumps varies as 1/s. We explain this behavior by modeling the triangular voids in the SG with effective superconducting rings and by calculating their response following the London analysis of persistent currents, Js, induced by the applied field Ha and by the entering flux. With changing Ha, Js reaches a critical value in the vertex joints that connect the triangular superconducting patches and allows the giant flux jumps into the SG voids through phase slips or multiple Abrikosov vortex transfer across the vertices. The unique flux behavior in superconducting SG patterns, may be used to design tunable low-loss resonators with multi-line high-frequency spectrum for microwave technologies.