Multi‐layered tissue models in patient‐specific simulations of aortic dissection

In aortic dissections blood flows not only in the regular, true lumen but also between separated lamellae within the media of the aortic wall, in the so-called false lumen. Both lumina are separated by a dissection membrane, which may move substantially during the cardiac cycle, linking blood flow and vessel deformation. We employ strongly coupled fluid-structure interaction simulations incorporating an anisotropic, fiber-reinforced, hyperelastic continuum including layer-specific tissue parameters

Detection of CD33 expression on monocyte surface is influenced by phagocytosis and temperature

CD33 is a myeloid-associated marker and belongs to the sialic acid-binding immunoglobulin (Ig)-like lectin (Siglec) family. Such types of receptors are highly expressed in acute myeloid leukemia, which could be used in its treatment. CD33 shows high variability in its expression levels with still unknown reasons. Here, we investigated the CD33 expression of monocytes in human blood samples processed at different temperatures and in dependence on their phagocytic activity against opsonized Escherichia coli. The samples were stained by fluorescently labelled anti-human CD14 to specify the monocyte population, anti-human CD33 antibodies to evaluate CD33 expression and analyzed by flow cytometry and confocal laser scanning microscopy. In blood samples kept at 37°C or first pre-chilled at 0°C with subsequent warming up to 37°C, the percentage of CD33-positive monocytes as well as their relative fluorescence intensity was up-regulated compared to samples kept constantly at 0°C. After exposure to E. coli the CD33 relative fluorescence intensity of the monocytes activated at 37°C was 3 to 4 times higher than that of those cells kept inactive at 0°C. Microscopic analysis showed internalisation of CD33 due to its enhanced expression on the surface followed by engulfment of E. coli

On the role of tissue mechanics in fluid–structure interaction simulations of patient‐specific aortic dissection

Modeling an aortic dissection represents a particular challenge from a numerical perspective, especially when it comes to the interaction between solid (aortic wall) and liquid (blood flow). The complexity of patient-specific simulations requires a variety of parameters, modeling assumptions and simplifications that currently hinder their routine use in clinical settings. We present a numerical framework that captures, among other things, the layer-specific anisotropic properties of the aortic wall, the non-Newtonian behavior of blood, patient-specific geometry, and patient-specific flow conditions. We compare hemodynamic indicators and stress measurements in simulations with increasingly complex material models for the vessel tissue ranging from rigid walls to anisotropic hyperelastic materials. We find that for the present geometry and boundary conditions, rigid wall simulations produce different results than fluid–structure interaction simulations. Considering anisotropic fiber contributions in the tissue model, stress measurements in the aortic wall differ, but shear stress-based biomarkers are less affected. In summary, the increasing complexity of the tissue model enables capturing more details. However, an extensive parameter set is also required. Since the simulation results depend on these modeling choices, variations can lead to different recommendations in clinical applications

Hemodynamic Effects of Entry and Exit Tear Size in Aortic Dissection Evaluated with In Vitro Magnetic Resonance Imaging and Fluid-Structure Interaction Simulation

Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid-structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (-17.8 and -18.5 %, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (-16.0 and -17.3 %). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (-20.6 and -13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.Comment: Judith Zimmermann and Kathrin B\"aumler contributed equall

Inter-observer Variability of Expert-derived Morphologic Risk Predictors in Aortic Dissection

OBJECTIVES: Establishing the reproducibility of expert-derived measurements on CTA exams of aortic dissection is clinically important and paramount for ground-truth determination for machine learning. METHODS: Four independent observers retrospectively evaluated CTA exams of 72 patients with uncomplicated Stanford type B aortic dissection and assessed the reproducibility of a recently proposed combination of four morphologic risk predictors (maximum aortic diameter, false lumen circumferential angle, false lumen outflow, and intercostal arteries). For the first inter-observer variability assessment, 47 CTA scans from one aortic center were evaluated by expert-observer 1 in an unconstrained clinical assessment without a standardized workflow and compared to a composite of three expert-observers (observers 2-4) using a standardized workflow. A second inter-observer variability assessment on 30 out of the 47 CTA scans compared observers 3 and 4 with a constrained, standardized workflow. A third inter-observer variability assessment was done after specialized training and tested between observers 3 and 4 in an external population of 25 CTA scans. Inter-observer agreement was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Pre-training ICCs of the four morphologic features ranged from 0.04 (-0.05 to 0.13) to 0.68 (0.49-0.81) between observer 1 and observers 2-4 and from 0.50 (0.32-0.69) to 0.89 (0.78-0.95) between observers 3 and 4. ICCs improved after training ranging from 0.69 (0.52-0.87) to 0.97 (0.94-0.99), and Bland-Altman analysis showed decreased bias and limits of agreement. CONCLUSIONS: Manual morphologic feature measurements on CTA images can be optimized resulting in improved inter-observer reliability. This is essential for robust ground-truth determination for machine learning models. KEY POINTS: • Clinical fashion manual measurements of aortic CTA imaging features showed poor inter-observer reproducibility. • A standardized workflow with standardized training resulted in substantial improvements with excellent inter-observer reproducibility. • Robust ground truth labels obtained manually with excellent inter-observer reproducibility are key to develop reliable machine learning models

Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) in Uncomplicated Type B Aortic Dissection: Study Design and Rationale

PURPOSE To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD). MATERIALS AND METHODS The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model. Clinical and imaging data from eight ROADMAP centers will be used for external validation. Patients with uTBAD who survived the initial hospitalization between January 1, 2001, and December 31, 2013, with follow-up until 2020, will be retrospectively identified. Clinical and imaging data from the index hospitalization and all follow-up encounters will be collected at each center and transferred to the coordinating center for analysis. Baseline and follow-up CT scans will be evaluated by cardiovascular imaging experts using a standardized technique. RESULTS The primary end point is the occurrence of late adverse events, defined as aneurysm formation (≥6 cm), rapid expansion of the aorta (≥1 cm/y), fatal or nonfatal aortic rupture, new refractory pain, uncontrollable hypertension, and organ or limb malperfusion. The previously derived multivariable model will be externally validated by using Cox proportional hazards regression modeling. CONCLUSION This study will show whether a recent clinical and imaging-based risk prediction model for patients with uTBAD can be generalized to a larger population, which is an important step toward individualized risk stratification and therapy.Keywords: CT Angiography, Vascular, Aorta, Dissection, Outcomes Analysis, Aortic Dissection, MRI, TEVAR© RSNA, 2022See also the commentary by Rajiah in this issue

Effects of a cognitive training on spatial learning and associated functional brain activations

BACKGROUND: Both cognitive and physical exercise have been discussed as promising interventions for healthy cognitive aging. The present study assessed the effects of cognitive training (spatial vs. perceptual training) and physical training (endurance training vs. non-endurance training) on spatial learning and associated brain activation in 33 adults (40–55 years). Spatial learning was assessed with a virtual maze task, and at the same time neural correlates were measured with functional magnetic resonance imaging (fMRI). RESULTS: Only the spatial training improved performance in the maze task. These behavioral gains were accompanied by a decrease in frontal and temporal lobe activity. At posttest, participants of the spatial training group showed lower activity than participants of the perceptual training group in a network of brain regions associated with spatial learning, including the hippocampus and parahippocampal gyrus. No significant differences were observed between the two physical intervention groups. CONCLUSIONS: Functional changes in neural systems associated with spatial navigation can be induced by cognitive interventions and seem to be stronger than effects of physical exercise in middle-aged adults

Simulation von Einzeltropfen unter dem Einfluss variabler Grenzflächenspannung

In der vorliegenden Arbeit wird eine numerische Unterraumprojektionsmethode zur Behandlung von Zweiphasenströmungen mit gleichzeitigem Stofftransport und Marangonikonvektion unter Berücksichtigung deformierbarer Grenzflächen vorgestellt. Das Wissen über Kenngrößen wie Aufstiegsgeschwindigkeiten und Stoffübergangskoeffizienten von Einzeltropfen ist beispielsweise notwendig zur Planung von Flüssig/flüssig–Extraktionsprozessen, und damit eine zentrale Fragestellung in der Verfahrenstechnik. Die komplexen Grenzflächeneffekte am Einzeltropfen (durch Marangonikonvektion sind der Stofftransport und die Fluidynamik nichtlinear gekoppelt) machen deren Untersuchung auch aus numerischer Sicht interessant und erfordern den Einsatz neuer numerischer Methoden. Zunächst wird ein –im Hinblick auf die anschließende Diskretisierung– geeignetes mathematisches Modell des umströmten Einzeltropfens entwickelt. Dieses Modell basiert auf der Verwendung spezieller Unterräume, einer zweiphasenspezifischen Entdimensionalisierung, sowie eines beschleunigten Koordinatensystems, das dem Aufstieg des Einzeltropfens folgt. Basierend auf der variationellen Formulierung wird eine Energieabschätzung des umströmten Einzeltropfens, die Wohlgestelltheit des Oseen–Problems (das Oseen–Problem ist ein erweitertes Stokes–Problem, das durch Zeitdiskretisierung und Linearisierung der Navier–Stokes Gleichungen entsteht), sowie die Inf–sup Stabilit ̈at nachgewiesen. Kernbestandteil der Unterraumprojektionsmethode ist die Realisierung der Grenzflächenbedingungen durch den Einsatz von Projektionen, die je nach gewünschter Anwendung (starre Kugel, sphärischer Tropfen, deformierbarer Tropfen, sphärische “Stagnant cap” – ein Spezialfall in der Behandlung tensidbehafteter Systeme) zugeschaltet werden können. Die hohe Approximationsgüte in der Darstellung komplexer Grenzflächenphänomene durch die Anwendung einer “aligned mesh method” wird durch unstetige Druck– und Konzentrations– Ansatzfunktionen weiter erhöht. Insbesondere die Darstellung eines unstetigen Druckes ist unerlässlich zur Vermeidung der sogenannten “spurious oscillations”. Für die Unterraumprojektionsmethode kann leicht die Inf–sup Stabilitätsbedingung für den Fall der Zweiphasenströmung nachgewiesen werden. In der Simulation umströmter Einzeltropfen ist die numerische Behandlung der gekoppelten Impuls– und Stofftransportgleichungen durch konzentrationsinduzierte Marangonikonvektion hervorzuheben. Hierbei wird von der bisherigen Methode zur Implementierung der Grenzflächeneffekte abgewichen, und auf die Darstellung der Grenzflächenspannungen in Divergenzform zurückgegriffen. Vorteilhaft bei der Behandlung in Divergenzform ist die Formulierung der Schubspannungsbilanz ohne tangentiale Ableitungen der Grenzflächenspannung. In der Praxis treten häufig konvektionsdominante Systeme auf, wie beispielsweise das Stoffsystem Toluol/Aceton/Wasser. Hierbei ergeben sich im Zusammenhang mit der Finiten Elemente Methode numerische Schwierigkeiten. Wir untersuchen residuenbasierte Stabilisierungsmethoden im Hinblick auf ihre Anwendbarkeit in der Simulation von Zweiphasenströmungen. Desweiteren werden allgemeine Aspekte der Implementierung, wie beispielsweise die Parallelisierung mit Open MP, behandelt. Die numerische Methode wird in verschiedenen achsensymmetrischen Anwendungen validiert, beispielsweise in der Simulation binärer Systeme (Einzeltropfen ohne zusätzlichen Stofftransport) mit niedriger, mittlerer, und hoher Grenzflächenspannung im Bereich nicht oszillierender Tropfen. Aufstiegsgeschwindigkeiten, Widerstandsbeiwerte sowie Tropfendeformation zeigen eine exzellente Übereinstimmung mit experimentellen Daten, beispielsweise weichen Endaufstiegsgeschwindigkeiten um weniger als 4% von den experimentellen Daten ab. In der Simulation von starren Kugeln, sphärischen Tropfen, sphärischen Tropfen mit Stagnant caps und thermokapillarer Strömung kann ebenfalls eine gute Übereinstimmung mit bestehenden Korrelationen (oder – soweit vorhanden – analytischen Lösungen) aus der Literatur gezeigt werden. Die numerische Simulation der Aufstiegsgeschwindigkeit der thermokapillaren Strömung weicht um weniger als 0.2% von der Vorhersage von Young, Goldstein und Block (1959) ab. Eine qualitative Untersuchung des Effekts der variablen Grenzflächensspannung wird im tertiären System Toluol/Aceton/Wasser durchgeführt. Eine quantitative Validierung der Ergebnisse ist hier nicht möglich. Ursache ist die ausgeprägte Konvektionsdominanz des betrachteten Systems, sowie die Annahme von Rotationssymmetrie trotz der inhärent dreidimensionalen Effekte der Marangonikonvektion. Dennoch zeigen die numerischen Simulationen, dass qualitativ der Einfluss der konzentrationsinduzierten Marangonikonvektion dargestellt werden kann.In this thesis, a numerical method for the simulation of two–phase flow problems with a deformable interface and coupled species transport is investigated. The coupling of species concentration and fluid dynamics originates from a concentration–dependent interfacial tension coefficient – an effect known as concentration–induced Marangoni convection. For this purpose, a mathematical model of a single drop was formulated using subspaces of the conventional function spaces, a problem–specific nondimensionalization, an accelerated frame of reference, and a divergence formulation of interfacial stresses. The numerical method is based on a finite element method within an arbitrary Lagrangian– Eulerian framework. This class of methods results in an explicit interface representation, and forms the basis of the subspace projection method, a novel method for the implementation of various interface conditions in two–phase flow problems via problem–specific projections. Interface conditions that are investigated in this thesis comprise the flow around a rigid body, the simulation of spherically–shaped fluid particles, interface conditions of deformable drops with and without Marangoni convection, and the simulation of spherical stagnant caps – a limiting case observed in single drop flow under the presence of surfactants. An essential feature of the subspace projection method is its ability to represent discontinuous functions, enabled by using a computational grid with doubled interfacial nodes. Spurious oscillations –often observed in two–phase flow problems where the pressure is approximated by globally continuous functions– are considerably reduced. Concentration–induced Marangoni convection (resulting from a non–vanishing tangential gradient of interfacial stresses) is a challenging application in the numerical simulation of two– phase flows with a deforming interface. The implementation of interfacial stresses is based on a divergence formulation. This formulation accounts for normal and tangential stresses without the necessity of approximating surface derivatives of the interfacial tension. A validation of the numerical method is performed for different axisymmetric single drop flow applications. Different binary systems (single, buoyant, deformable drops with constant interfacial tension) are numerically investigated in terms of terminal rise velocities, drag coefficients, and deformation, comprising the range from low to high interfacial tension coefficients and drop diameters below the onset of shape oscillations. An excellent agreement of simulation results and experimental data is obtained. In case of terminal rise velocities, the deviation is below 4%. Simulations of ternary systems (binary systems with species transport) are performed with and without Marangoni convection. In case of high Peclet numbers, finite element simulations often suffer from instabilities due to convection dominance. Stabilizing methods are investigated with special regard to two–phase flow applications. Simulations of fluid dynamics and species transport in single drop flow applications like rigid particles, spherically shaped drops, spherical stagnant caps, and thermocapillary migration, show good to excellent agreement to correlations from literature in systems with moderate Peclet numbers. The deviation of the thermocapillary rise velocity is below 0.2% to the prediction by Young, Goldstein and Block (1959). The ternary system toluene/acetone/water with concentration–induced Marangoni convection is numerically investigated and the results are compared to experimental data. In spite of the convection dominance of the corresponding species transport problem and the assumption of axisymmetry despite the inherent three–dimensional nature of the Marangoni effect, a reasonable qualitative agreement was achieved

Numerical Benchmarking for 3D Multiphase Flow: New Results for a Rising Bubble

Based on the benchmark results in [1] for a 2D rising bubble, we present the extension towards 3D providing test cases with corresponding reference results, following the suggestions in [2]. Additionally, we include also an axisymmetric configuration which allows 2.5D simulations and which provides further possibilities for validation and evaluation of numerical multiphase flow components and software tools in 3D

Failure of omalizumab (Xolair®) in the treatment of a case of solar urticaria caused by ultraviolet A and visible light

Solar urticaria is a rare photodermatosis probably caused by a chromophore, that - if activated by light of a specific spectrum - binds to mast cell-bound IgE and elicits degranulation. In our patient an action spectrum in ultraviolet A and visible light range was found, in the autologous serum test the presence of a serum chromophore for the same action spectra could be demonstrated, which may underline this pathogenetic hypothesis. Symptoms did not improve using antihistamines and sun protection. Photo hardening was denied from the patient, immunosuppression and plasmapheresis were discussed but not considered. So a treatment with Omalizumab was started that recently was successfully used in 4 case reports. After 3 doses of Xolair® there was no changing in the phototesting results and after 4 doses no subjective improvement