TY - CHAP A1 - Birkenmaier, Clemens A1 - Steiger, Tamara A1 - Philipp, Alois A1 - Lehle, Karla A1 - Krenkel, Lars T1 - Flow-induced accumulations of von Willebrand factor inside oxygenators during extracorporeal life support therapy T2 - Proceedings of 12th International Conference BIOMDLORE 2018, June 28–30, 2018, Białystok, Poland N2 - BACKGROUND: Shear-induced conformational changes of von Willebrand factor (vWF) may be responsible for coagulation disorder and clot formation inside membrane oxygenators (MOs) during extracorporeal membrane oxygenation (ECMO) therapy. OBJECTIVE: The aim was to identify vWF structures inside clinically used MOs and employ computational fluid dynamics to verify the corresponding flow conditions. METHODS: Samples from gas exchange membranes (GEM) from MOs were analysed for accumulations of vWF and P-selectin-positive platelets using immunofluorescence techniques. Streamlines and shear rates of the flow around GEMs were computed using a laminar steady Reynolds-Averaged-Navier-Stokes approach. RESULTS: Most samples were colonized with equally distributed leukocytes, integrated in thin cobweb-like vWF-structures. Only 25 % of the samples showed extended accumulations of vWF. Computed streamlines showed considerable cross flow between interconnected neighbouring channels. Stagnation points were non-symmetric and contact faces were washed around closely. The occurring maximum shear rates ranged from 2,500 to 3,000 1/s. CONCLUSIONS: If pronounced vWF structures are present, shape and extent match the flow computations well. Computed shear rates bear a critical degree of uncertainty due to the improper viscosity model. If flow conditions inside the MO were sufficient to affect vWF, a more consistent distribution of vWF across the samples should be present. KW - Blood Viscosity KW - Shear Rate Induced Coagulation KW - Hemodynamics KW - Membrane Oxygenator KW - von Willebrand factor Y1 - 2018 SN - 978-1-5386-2396-1 U6 - https://doi.org/10.1109/BIOMDLORE.2018.8467205 PB - IEEE CY - Piscataway, NJ ER - TY - JOUR A1 - Birkenmaier, Clemens A1 - Dornia, Christian A1 - Lehle, Karla A1 - Müller, Thomas A1 - Gruber, Michael A1 - Philipp, Alois A1 - Krenkel, Lars T1 - Analysis of Thrombotic Deposits in Extracorporeal Membrane Oxygenators by High-resolution Microcomputed Tomography: A Feasibility Study JF - ASAIO Journal / American Society for Artificial Internal Organs N2 - Coagulative disorders, especially clotting during extracorporeal membrane oxygenation, are frequent complications. Direct visualization and analysis of deposits in membrane oxygenators using computed tomography (CT) may provide an insight into the underlying mechanisms causing thrombotic events. However, the already established multidetector CT1 (MDCT) method shows major limitations. Here, we demonstrate the feasibility of applying industrial micro-CT (μCT) to circumvent these restrictions. Three clinically used membrane oxygenators were investigated applying both MDCT and μCT. The scans were analyzed in terms of clot volume and local clot distribution. As validation, the clot volume was also determined from the fluid volume, which could be filled into the respective used oxygenator compared to a new device. In addition, cross-sectional CT images were compared with crosscut oxygenators. Based on the μCT findings, a morphological measure (sphericity) for assessing clot structures in membrane oxygenators is introduced. Furthermore, by comparing MDCT and μCT results, an augmentation of the MDCT method is proposed, which allows for improved clot volume determination in a clinical setting. Y1 - 2020 U6 - https://doi.org/10.1097/MAT.0000000000001089 SN - 1538-943X VL - 66 IS - 8 SP - 922 EP - 928 PB - Lippincott Williams & Wilkins ER - TY - CHAP A1 - Markus Rütten, A1 - Krenkel, Lars A1 - Kessler, Roland T1 - Secondary Flow Effects as Physical Mechanism of Molecular Species Transport in Highly Oscillating Generic-Trachea Flows T2 - 83rd Annual Scientific Conference of the International Association of Applied Mathematics and Mechanics, 26.-30. März 2012, Darmstadt, Germany N2 - The high frequency oscillation artificial respiration technique is often the last hope for patients to survive highly damaged lung tissue. The mortality can significantly be reduced. In comparison to conventional artificial respiration the applied volume flow rate and pressure is significantly lowered in order to avoid further damaging of lung tissue and remaining intact alveolae. However, the physical mechanism of transport of oxygen to the aeriols under high frequency oscillation is not well understood. In the upper part of the lung convection is dominant, in contrast, the gas exchange in the lower parts of the lung is mainly driven by diffusion. It is not clear how associated gradients of concentrations of different molecular species are then achieved. Highly oscillating fluid flows has been a long research topic in fluid dynamics. It is known that oscillating pressure fluctuations are able to induce secondary flows, in particular, in curved ducts and pipes. The question is, whether the trachea enforces the generation of secondary flow by its kidney like cross section geometry. The influence of molecular species of different densities onto the formation of secondary flows and the convectional transport within the trachea is investigated. In order to clarify the physical mechanisms behind flow simulations have been conducted by using state of the art CFD techniques. KW - CFD KW - Generic-Trachea Flows Y1 - 2012 UR - https://elib.dlr.de/75733/ ER - TY - CHAP A1 - Friedrich, Janet A1 - Feldmann, Daniel A1 - Krenkel, Lars A1 - Wagner, Claus A1 - Schreiber, Laura Maria T1 - 19F Gas Flow Measurement of C3F7H During Constant Flow and High Frequency Oscillatory Ventilation T2 - Discovery, innovation & application - advancing mr for improved health : ISMRM 21st Annual Meeting & Exhibition ; SMRT 22nd Annual Meeting Salt Lake City, Utah, USA 20-26 April 2013 N2 - The aim of the current study is the development of MRI methods that enable the investigation of gas flow mechanisms during high frequency oscillatory ventilation. This work includes flow measurements during three constant flows (19.9, 30.6 and 41.4 L min-1) and the comparison to direct numerical simulations (DNS) using a second-order-acurate finite-volume method and to data measured with a volume flow meter. 19F-MRI, DNS and flow meter data are in good agreement. Flow measurements during HFOV of 4 Hz were successfully performed and velocity profiles could be recorded at different phases of the ventilation cycle. Y1 - 2013 UR - https://archive.ismrm.org/2013/1482.html VL - 21 ER - TY - CHAP A1 - Birkenmaier, Clemens A1 - Krenkel, Lars ED - Dillmann, Andreas ED - Heller, Gerd ED - Krämer, Ewald ED - Wagner, Claus T1 - Convolutional Neural Networks for Approximation of Blood Flow in Artificial Lungs T2 - New Results in Numerical and Experimental Fluid Mechanics XIII: Contributions to the 22nd STAB/DGLR Symposium N2 - Blood flow in channels of varying diameters <500μm exhibits strong non-linear effects. Multiphase finite volume approaches are feasible, but still computationally costly. Here, the feasibility of applying convolutional neural networks for blood flow prediction in artificial lungs is investigated. Training targets are precomputed using an Eulerian two-phase approach. To match with experimental data, the interphase drag and lift, as well as intraphase shear-thinning are adapted. A recursively branching regression network and convolution/deconvolution networks with plain skip connections and densely connected skips are investigated. A priori knowledge is incorporated in the loss functional to prevent the network from learning non-physical solutions. Inference from neural networks is approximately six orders of magnitude faster than the classical finite volume approach. Even if resulting in comparably coarse flow fields, the neural network predictions can be used as close to convergence initial solutions greatly accelerating classical flow computations. KW - Deep learning fluid mechanics KW - Multiphase blood flow Y1 - 2021 SN - 978-3-030-79560-3 U6 - https://doi.org/10.1007/978-3-030-79561-0_43 IS - 1. Auflage SP - 451 EP - 460 PB - Springer International Publishing CY - Cham ER - TY - CHAP A1 - Tauwald, Sandra Melina A1 - Quadrio, Maurizio A1 - Rütten, Markus A1 - Stemmer, Christian A1 - Krenkel, Lars T1 - High Spatial Resolution Tomo-PIV of the Trachea Focussing on the Physiological Breathing Cycle T2 - New Results in Numerical and Experimental Fluid Mechanics XIV - Contributions to the 23nd STAB/DGLR Symposium N2 - Investigations of complex patient-specific flow in the nasopharynx requires high resolution numerical calculations validated by reliable experiments. When building the validation base and the benchmark of computational fluid dynamics, an experimental setup of the nasal airways was developed. The applied optical measurement technique of tomo-PIV supplies information on the governing flow field in three dimensions. This paper presents tomo-PIV measurements of the highly complex patient-specific geometry of the human trachea. A computertomographic scan of a person’s head builds the basis of the experimental silicone model of the nasal airways. An optimised approach for precise refractive index matching avoids optical distortions even in highly complex non-free-of-sight 3D geometries. A linear-motor-driven pump generates breathing scenarios, based on measured breathing cycles. Adjusting of the CCD cameras‘ double-frame-rate PIV-Δt enables the detailed analysis of flow structures during different cycle phases. Merging regions of interest enables high spatial resolution acquisition of the flow field. KW - Tomographic PIV KW - Flow visualisation KW - Breathing cycle KW - Nasal airflow Y1 - 2023 N1 - Accepted for publication, not yet published PB - Springer ER - TY - JOUR A1 - Kriegl, Raphael A1 - Krenkel, Lars A1 - Shamonin (Chamonine), Mikhail T1 - Preservation of wetting ridges using field-induced plasticity of magnetoactive elastomers JF - Journal of Colloid and Interface Science N2 - Hypothesis. The presence of a wetting ridge is crucial for many wetting phenomena on soft substrates. Conventional experimental observations of a wetting ridge require permanent presence of a droplet. The magnetic field-induced plasticity effect (FIPE) of soft magnetoative elastomers (MAEs) allows one to overcome this limitation. Depositing a droplet onto an MAE surface and applying a magnetic field fixes the wetting ridge in place due to the FIPE. The droplet can be removed to investigate the ridge with ease using conventional optical methods. Experiments. The wetting ridge is observed on MAEs with different shear moduli and different material thicknesses by confocal laser scanning microscopy (LSM). The preservation quality of the ridge is analyzed for several values of magnetic field from 10 mT to 270 mT. To verify the plausibilty of results obtained, the measured shape is compared to a theoretical model by Style & Dufresne. Findings. Upon removal of the sessile droplet, the deformation remains embossed onto the MAE surface as long as the magnetic field remains applied. The height of the ridge peak on soft samples (effective shear modulus kPa) is close to the theoretical prediction for a magnetic flux density of 50 mT. The magnitude of the external magnetic field magnifies the height of the wetting ridge. KW - Wetting ridge KW - Droplet KW - Magnetoactive elastomer KW - Magnetorheological elastomer KW - Field-induced plasticity KW - Confocal laser scanning microscopy Y1 - 2025 U6 - https://doi.org/10.1016/j.jcis.2024.12.132 SN - 0021-9797 N1 - Corresponding author der OTH Regensburg: Raphael Kriegl VL - 683 SP - 1019 EP - 1027 PB - Elsevier ER - TY - GEN A1 - Birkenmaier, Clemens A1 - Dornia, Christian A1 - Lehle, Karla A1 - Krenkel, Lars T1 - Feasibility of detecting thrombotic deposits in membrane oxygenators using micro computed tomography T2 - 25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria Y1 - 2019 UR - https://esbiomech.org/conference/archive/2019vienna/Contribution_129.pdf ER - TY - CHAP A1 - Tschurtschenthaler, Karl A1 - Krenkel, Lars A1 - Schreiner, Rupert T1 - Mechano-optical micro pillar sensor for biofluidmechanic wall shear stress measurements T2 - 25th Congress of the European Society of Biomechanics (ESB), July 7-10, 2019, Vienna, Austria Y1 - 2019 UR - https://esbiomech.org/conference/archive/2019vienna/Contribution_608.pdf ER - TY - GEN A1 - Tauwald, Sandra Melina A1 - Krenkel, Lars T1 - Elementary experimental setup for flow visualization in upper human respiratory tract T2 - 25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria Y1 - 2019 UR - https://esbiomech.org/conference/archive/2019vienna/Contribution_195.pdf ER - TY - GEN A1 - Wagner, Thomas A1 - Krenkel, Lars A1 - Dönitz, Christian A1 - Brawanski, Alexander T1 - Influence of CFD Strategy on WSS and OSI Determination for Intracranial Aneurysm Rupture Assessment T2 - 25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria Y1 - 2019 ER - TY - GEN A1 - Krenkel, Lars T1 - Relevanz von Aerosolen im klinischen Kontext T2 - Innovationstag Hygiene 2021, Continental Arena, Regensburg, Deutschland Y1 - 2021 ER - TY - JOUR A1 - Tauwald, Sandra Melina A1 - Erzinger, Florian A1 - Quadrio, Maurizio A1 - Rütten, Markus A1 - Stemmer, Christian A1 - Krenkel, Lars T1 - Tomo-PIV in a patient-specific model of human nasal cavities: a methodological approach JF - Measurement Science and Technology N2 - The human nose serves as the primary gateway for air entering the respiratory system and plays a vital role in breathing. Nasal breathing difficulties are a significant health concern, leading to substantial healthcare costs for patients. Understanding nasal airflow dynamics is crucial for comprehending respiratory mechanisms. This article presents a detailed study using tomo-Particle Image Velocimetry (PIV) to investigate nasal airflow dynamics while addressing its accuracy. Embedded in the OpenNose project, the work described aims to provide a validation basis for different numerical approaches to upper airway flow. The study includes the manufacturing of a transparent silicone model based on a clinical CT scan, refractive index matching to minimize optical distortions, and precise flow rate adjustments based on physiological breathing cycles. This method allows for spatial high-resolution investigations in different regions of interest within the nasopharynx during various phases of the breathing cycle. The results demonstrate the accuracy of the investigations, enabling detailed analysis of flow structures and gradients. This spatial high-resolution tomo-PIV approach provides valuable insights into the complex flow phenomena occurring during the physiological breathing cycle in the nasopharynx. The study's findings contribute to advancements in non-free-of-sight experimental flow investigation of complex cavities under nearly realistic conditions. Furthermore, reliable and accurate experimental data is crucial for properly validating numerical approaches that compute this patient-specific flow for clinical purposes. Y1 - 2024 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:898-opus4-70393 N1 - Corresponding author: Sandra Melina Tauwald VL - 35 IS - 5 PB - IOP Publishing ER - TY - INPR A1 - Thaus, Christopher A1 - Hofrichter, Elena A1 - Lubnow, Matthias A1 - Krenkel, Lars A1 - Lehle, Karla T1 - Hemocompatibility of Membrane Lung Components from Extracorporeal Membrane Oxygenation with Different Antithrombogenic Coatings N2 - Thrombus formation within extracorporeal membrane oxygenation (ECMO) devices remained a critical complication. One reason seems to be the contact of blood with large artificial surfaces within the membrane lung (ML). The aim was to test the hemocompatibility of different naïve ECMO materials. Blood and platelets from five healthy volunteers were incubated with gas exchange (GF) and heat exchange fibers (HE) from four different commercial available new MLs representing different antithrombogenic coatings. Adherent platelets were stained with rhodamine-phalloidin. Surface coverage was quantified with ImageJ. Non-adherent platelets were stained with antibodies (CD62P, PAC-1, CD61) and fibrinogen to detect platelet activation with flow cytometry. Hemolysis of red blood cells after material contact was detected. All ECMO-materials were non-hemolytic and did not induce platelet activation. However, platetelet adhesion (median (IQR)) was significantly elevated on uncoated GFs made of polymethylpentene (GF-PMP; 12 (7-19)%) and on GFs from the Hilite-MLs (GF-Hilite; 13 ((8-19)%) compared to the other materials. In vitro testing of platelet adhesion disclosed significant differences of ECMO-materials with different antithrombogenic surface coatings. Instead, circulating platelets remained non-activated. ECMO-materials and its coatings were non-hemolytic. Finally, this study confirmed the good hemocompatibility of GFs and HEs from commerciall available MLs. KW - ECMO KW - platelet activation KW - platelet adhesion KW - hemolysis KW - hemocompatibility Y1 - 2024 U6 - https://doi.org/10.20944/preprints202412.0615.v1 SP - 1 EP - 11 ER - TY - JOUR A1 - Wagner, Maria Stella A1 - Kranz, Michael A1 - Krenkel, Lars A1 - Pointner, Daniel A1 - Foltan, Maik A1 - Lubnow, Matthias A1 - Lehle, Karla ED - Becatti, Matteo T1 - Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs JF - Frontiers in Medicine N2 - Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-oftherapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4′, 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs. KW - ECMO KW - membrane lung KW - µCT KW - MDCT KW - shear induced clotting KW - vWF KW - histological evaluation Y1 - 2024 U6 - https://doi.org/10.3389/fmed.2024.1416319 IS - 11 PB - Frontiers ER - TY - JOUR A1 - Lingel, Maximilian P. A1 - Haus, Moritz A1 - Paschke, Lukas A1 - Foltan, Maik A1 - Lubnow, Matthias A1 - Gruber, Michael A1 - Krenkel, Lars A1 - Lehle, Karla T1 - Clinical relevance of cell-free DNA during venovenous extracorporeal membrane oxygenation JF - Artificial organs N2 - BACKGROUND: Thrombosis remains a critical complication during venovenous extracorporeal membrane oxygenation (VV ECMO). The involvement of neutrophil extracellular traps (NETs) in thrombogenesis has to be discussed. The aim was to verify NETs in the form of cell-free DNA (cfDNA) in the plasma of patients during ECMO. METHODS: A fluorescent DNA-binding dye (QuantifFluor®, Promega) was used to detect cell-free DNA in plasma samples. cfDNA concentrations from volunteers (n = 21) and patients (n = 9) were compared and correlated with clinical/technical data before/during support, ECMO end and time of a system exchange. RESULTS: Before ECMO, patients with a median (IQR) age of 59 (51/63) years, SOFA score of 11 (10/15), and ECMO run time of 9.0 (7.0/19.5) days presented significantly higher levels of cfDNA compared to volunteers (6.4 (5.8/7.9) ng/μL vs. 5.9 (5.4/6.3) ng/μL; p = 0.044). Within 2 days after ECMO start, cfDNA, inflammatory, and hemolysis parameters remained unchanged, while platelets decreased (p = 0.005). After ECMO removal at the end of therapy, cfDNA, inflammation, and coagulation data (except antithrombin III) remained unchanged. The renewal of a system resulted in known alterations in fibrinogen, d-dimers, and platelets, while cfDNA remained unchanged. CONCLUSION: Detection of cfDNA in plasma of ECMO patients was not an indicator of acute and circuit-induced thrombogenesis. KW - blood KW - cell- free DNA KW - coagulation KW - ECMO KW - inflammation KW - neutrophil extracellular traps Y1 - 2023 U6 - https://doi.org/10.1111/aor.14616 SN - 1525-1594 VL - 47 IS - 11 SP - 1720 EP - 1731 PB - Wiley ER - TY - JOUR A1 - Foltan, Maik A1 - Dinh, D. A1 - Gruber, Michael A1 - Müller, Thomas A1 - Hart, C. A1 - Krenkel, Lars A1 - Schmid, C. A1 - Lehle, Karla T1 - Incidence of neutrophil extracellular traps (NETs) in different membrane oxygenators: pilot in vitro experiments in commercially available coated membranes JF - Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs N2 - Neutrophil extracellular traps (NETs) were detected in blood samples and in cellular deposits of oxygenator membranes during extracorporeal membrane oxygenation (ECMO) therapy and may be responsible for thrombogenesis. The aim was to evaluate the effect of the base material of gas fiber (GF, polymethylpentene) and heat exchange (HE) membranes and different antithrombogenic coatings on isolated granulocytes from healthy volunteers under static culture conditions. Contact of granulocytes with membranes from different ECMO oxygenators (with different surface coatings) and uncoated-GFs allowed detection of adherent cells and NETotic nuclear structures (normal, swollen, ruptured) using nuclear staining. Flow cytometry was used to identify cell activation (CD11b/CD62L, oxidative burst) of non-adherent cells. Uncoated-GFs were used as a reference. Within 3 h, granulocytes adhered to the same extent on all surfaces. In contrast, the ratio of normal to NETotic cells was significantly higher for uncoated-GFs (56-83%) compared to all coated GFs (34-72%) (p < 0.001) with no difference between the coatings. After material contact, non-adherent cells remained vital with unchanged oxidative burst function and the proportion of activated cells remained low. The expression of activation markers was independent of the origin of the GF material. In conclusion, the polymethylpentene surfaces of the GFs already induce NET formation. Antithrombogenic coatings can already reduce the proportion of NETotic nuclei. However, it cannot be ruled out that NET formation can induce thrombotic events. Therefore, new surfaces or coatings are required for future ECMO systems and long-term implantable artificial lungs. Y1 - 2025 U6 - https://doi.org/10.1007/s10047-024-01486-4 ER - TY - JOUR A1 - Paschke, Lukas A1 - Foltan, Maik A1 - Wagner, Maria S. A1 - Lubnow, Matthias A1 - Gruber, Michael A1 - Krenkel, Lars A1 - Lehle, Karla T1 - Clinical Relevance of Platelet-Leukocyte Aggregates and Platelet P-Selectin Expression During Venovenous Extracorporeal Membrane Oxygenation JF - ASAIO Journal N2 - Thrombosis continues to be a significant complication during venovenous extracorporeal membrane oxygenation (V-V ECMO). Platelet activation markers might serve as indicators of inflammation and thrombogenesis. The aim was to identify these markers in ECMO patients. Blood from 10 ECMO patients (before, during, after ECMO) and 11 healthy volunteers were collected to determine platelet-neutrophil-aggregates (PNAs), platelet-monocyte-aggregates (PMAs), fibrinogen-binding, and P-selectin-expression on platelets by flow cytometry. Critical illness was associated with significantly elevated levels of PNAs and PMAs, increased P-selectin expression, reduced fibrinogen-binding, and restricted activation of platelets. Although PNAs and PMAs decreased significantly within 2 hours after the initiation of ECMO and remained at those levels, ECMO did not affect basal P-selectin expression and fibrinogen-binding. These results correlated with coagulation activation. Platelet markers before ECMO were not indicators for an imminent system exchange and end of therapy. In conclusion, platelet dysfunction during ECMO was mainly attributed to the critical illness. Extracorporeal membrane oxygenation support strengthened the restricted response of platelets to exogenous agonists (P-selectin). Furthermore, a decrease in PNAs/PMAs after ECMO started identified a reduced inflammatory response. There was no correlation of analyzed platelet parameters with the incidence of thrombotic complications. Y1 - 2025 U6 - https://doi.org/10.1097/MAT.0000000000002421 SN - 1058-2916 IS - April 03 PB - Wolters Kluwer ER - TY - JOUR A1 - Steiger, Tamara A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Gruber, Michael A1 - Bredthauer, Andre A1 - Krenkel, Lars A1 - Birkenmaier, Clemens A1 - Lehle, Karla T1 - Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients? JF - Artificial Organs N2 - Clot formation within membrane oxygenators (MOs) remains a critical problem during extracorporeal membrane oxygenation (ECMO). The composition of the clots-in particular, the presence of von Willebrand factor (vWF)-may be an indicator for prevalent nonphysiological flow conditions, foreign body reactions, or coagulation abnormalities in critically ill patients. Mats of interwoven gas exchange fibers from randomly collected MOs (PLS, Maquet, Rastatt, Germany) of 21 patients were stained with antibodies (anti-vWF and anti-P-selectin) and counterstained with 4 ',6-diamidino-2-phenylindole. The extent of vWF-loading was correlated with patient and technical data. While 12 MOs showed low vWF-loadings, 9 MOs showed high vWF-loading with highest accumulations close to crossing points of adjacent gas fibers. The presence and the extent of vWF-fibers/"cobwebs," leukocytes, platelet-leukocyte aggregates (PLAs), and P-selectin-positive platelet aggregates were independent of the extent of vWF-loading. However, the highly loaded MOs were obtained from patients with a significantly elevated SOFA score, severe thrombocytopenia, and persistent liver dysfunction. The coagulation abnormalities of these critically ill patients may cause an accumulation of the highly thrombogenic and elongated high-molecular-weight vWF multimers in the plasma which will be trapped in the MOs during the ECMO therapy. KW - ECMO KW - PLATELET ACTIVATION KW - THROMBOSIS KW - BLOOD FLOW KW - INFLAMMATION Y1 - 2019 U6 - https://doi.org/10.1111/aor.13513 SN - 1525-1594 VL - 43 IS - 11 SP - 1065 EP - 1076 PB - Wiley CY - Hoboken ER - TY - GEN A1 - Krenkel, Lars A1 - Michel, Johanna A1 - Keil, Niklas A1 - Daschner, Jan T1 - Experimental Investigation of Logitudinal Folds in Endotracheal Tube Cuffs and their Correlation to Silent Breathing T2 - 23. DGLR Fach-Symposium Strömungen mit Ablösung, 09./10. November 2022, Berlin, Deutschland N2 - Air leakage past High-Volume-Low-Pressure (HVLP) endotracheal tube (ETT) cuffs creates a potential infection risk for health care professionals during ventilation of patients suffering from contagious airborne diseases. However, unlike silent aspiration, a phenomenon where fluids enter the airways of intubated patients, the aspect of aerosol emergence through cuff folds -what we called accordingly “silent breathing” (SB)- has not been investigated in detail so far. This study investigates air leakage past HVLP cuffs with varying cuff pressures under realistic artificial breathing scenarios experimentally and in addition numerically. The focus was laid on the parametric investigation of the occurrence and furthermore on different influencing factors of silent breathing. The morphology of the folds responsible for the leakage was captured using high-resolution 3D microcomputed tomography (μCT). For the numerical investigations (Com-putational Fluid Dynamics - CFD), the commercial CFD Software package FLUENT 2021 R2 (ANSYS, Inc., Canonsburg, PA, US), as well as the DLR in-house research code THETA has been used. KW - Silent Breathing KW - Aerosols KW - CFD KW - Endotracheal Intubation Y1 - 2022 UR - https://www.dlr.de/as/Portaldata/5/Resources/dokumente/veranstaltungen/stab_workshop/Jahresbericht2022.pdf CY - Göttingen ER - TY - JOUR A1 - Haus, Moritz A1 - Foltan, Maik A1 - Philipp, Alois A1 - Müller, Thomas A1 - Lingel, Maximilian P. A1 - Krenkel, Lars A1 - Gruber, Michael A1 - Lehle, Karla T1 - Neutrophil extracellular traps -a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation N2 - Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased iL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients. KW - Neutrophil extracellular traps (NET) KW - Immunoflorescence KW - Thrombocytopenia KW - Extracorporeal membrane oxygenation (ECMO) KW - Sepsis KW - immunothrombosis KW - Coagulation disorder Y1 - 2024 UR - https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1339235/abstract U6 - https://doi.org/10.3389/fimmu.2024.1339235 VL - 15 PB - frontiers ER - TY - JOUR A1 - Broser, Christian A1 - Falter, Thomas A1 - Ławrowski, Robert Damian A1 - Altenbuchner, Amelie A1 - Vögele, Daniel A1 - Koss, Claus A1 - Schlamp, Matthias A1 - Dunnweber, Jan A1 - Steffens, Oliver A1 - Heckner, Markus A1 - Jaritz, Sabine A1 - Schiegl, Thomas A1 - Corsten, Sabine A1 - Lauer, Norina A1 - Guertler, Katherine A1 - Koenig, Eric A1 - Haug, Sonja A1 - Huber, Dominik A1 - Birkenmaier, Clemens A1 - Krenkel, Lars A1 - Wagner, Thomas A1 - Justus, Xenia A1 - Saßmannshausen, Sean Patrick A1 - Kleine, Nadine A1 - Weber, Karsten A1 - Braun, Carina N. A1 - Giacoppo, Giuliano A1 - Heinrich, Michael A1 - Just, Tobias A1 - Schreck, Thomas A1 - Schnabl, Andreas A1 - Gilmore, Amador Téran A1 - Roeslin, Samuel A1 - Schmid, Sandra A1 - Wellnitz, Felix A1 - Malz, Sebastian A1 - Maurial, Andreas A1 - Hauser, Florian A1 - Mottok, Jürgen A1 - Klettke, Meike A1 - Scherzinger, Stefanie A1 - Störl, Uta A1 - Heckner, Markus A1 - Bazo, Alexander A1 - Wolff, Christian A1 - Kopper, Andreas A1 - Westner, Markus A1 - Pongratz, Christian A1 - Ehrlich, Ingo A1 - Briem, Ulrich A1 - Hederer, Sebastian A1 - Wagner, Marcus A1 - Schillinger, Moritz A1 - Görlach, Julien A1 - Hierl, Stefan A1 - Siegl, Marco A1 - Langer, Christoph A1 - Hausladen, Matthias A1 - Schreiner, Rupert A1 - Haslbeck, Matthias A1 - Kreuzer, Reinhard A1 - Brückl, Oliver A1 - Dawoud, Belal A1 - Rabl, Hans-Peter A1 - Gamisch, Bernd A1 - Schmidt, Ottfried A1 - Heberl, Michael A1 - Gänsbauer, Bianca A1 - Bick, Werner A1 - Ellermeier, Andreas A1 - Monkman, Gareth J. A1 - Prem, Nina A1 - Sindersberger, Dirk A1 - Tschurtschenthaler, Karl A1 - Aurbach, Maximilian A1 - Dendorfer, Sebastian A1 - Betz, Michael A. A1 - Szecsey, Tamara A1 - Mauerer, Wolfgang A1 - Murr, Florian ED - Baier, Wolfgang T1 - Forschung 2018 T3 - Forschungsberichte der OTH Regensburg - 2018 KW - Forschung KW - Forschungsbericht Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:898-opus4-13826 SN - 978-3-9818209-5-9 CY - Regensburg ER - TY - JOUR A1 - Deuter, Daniel A1 - Haj, Amer A1 - Brawanski, Alexander A1 - Krenkel, Lars A1 - Schmidt, Nils Ole A1 - Doenitz, Christian T1 - Fast simulation of hemodynamics in intracranial aneurysms for clinical use JF - Acta Neurochirurgica N2 - BACKGROUND: A widely accepted tool to assess hemodynamics, one of the most important factors in aneurysm pathophysiology, is Computational Fluid Dynamics (CFD). As current workflows are still time consuming and difficult to operate, CFD is not yet a standard tool in the clinical setting. There it could provide valuable information on aneurysm treatment, especially regarding local risks of rupture, which might help to optimize the individualized strategy of neurosurgical dissection during microsurgical aneurysm clipping. METHOD: We established and validated a semi-automated workflow using 3D rotational angiographies of 24 intracranial aneurysms from patients having received aneurysm treatment at our centre. Reconstruction of vessel geometry and generation of volume meshes was performed using AMIRA 6.2.0 and ICEM 17.1. For solving ANSYS CFX was used. For validational checks, tests regarding the volumetric impact of smoothing operations, the impact of mesh sizes on the results (grid convergence), geometric mesh quality and time tests for the time needed to perform the workflow were conducted in subgroups. RESULTS: Most of the steps of the workflow were performed directly on the 3D images requiring no programming experience. The workflow led to final CFD results in a mean time of 22 min 51.4 s (95%-CI 20 min 51.562 s-24 min 51.238 s, n = 5). Volume of the geometries after pre-processing was in mean 4.46% higher than before in the analysed subgroup (95%-CI 3.43-5.50%). Regarding mesh sizes, mean relative aberrations of 2.30% (95%-CI 1.51-3.09%) were found for surface meshes and between 1.40% (95%-CI 1.07-1.72%) and 2.61% (95%-CI 1.93-3.29%) for volume meshes. Acceptable geometric mesh quality of volume meshes was found. CONCLUSIONS: We developed a semi-automated workflow for aneurysm CFD to benefit from hemodynamic data in the clinical setting. The ease of handling opens the workflow to clinicians untrained in programming. As previous studies have found that the distribution of hemodynamic parameters correlates with thin-walled aneurysm areas susceptible to rupture, these data might be beneficial for the operating neurosurgeon during aneurysm surgery, even in acute cases. Y1 - 2025 U6 - https://doi.org/10.1007/s00701-025-06469-9 VL - 167 PB - Springer ER - TY - CHAP A1 - Rütten, Markus A1 - Krenkel, Lars A1 - Quadrio, Maurizio T1 - Simulation and Analyis of the Unsteady Flow within Nasal Airways T2 - 9th European Congress on Computational Methods in Applied Sciences and Engineering - ECCOMAS Congress, 3-7 June 2024, Lisbon, Portugal Y1 - 2024 UR - https://re.public.polimi.it/handle/11311/1269952 ER - TY - CHAP A1 - Krenkel, Lars A1 - Wagner, Claus A1 - Wolf, Ursula A1 - Scholz, Alexander-Wigbert K. A1 - Terekhov, Maxim A1 - Rivoire, Julien A1 - Schreiber, W. ED - Hirschel, Ernst Heinrich ED - Schröder, Wolfgang ED - Fujii, Kozo ED - Haase, Werner ED - Leer, Bram ED - Leschziner, Michael A. ED - Pandolfi, Maurizio ED - Periaux, Jacques ED - Rizzi, Arthur ED - Roux, Bernard ED - Shokin, Yurii I. ED - Dillmann, Andreas ED - Heller, Gerd ED - Klaas, Michael ED - Kreplin, Hans-Peter ED - Nitsche, Wolfgang T1 - Protective Artificial Lung Ventilation: Impact of an Endotracheal Tube on the Flow in a Generic Trachea T2 - New Results in Numerical and Experimental Fluid Mechanics VII : Contributions to the 16th STAB/DGLR Symposium Aachen, Germany 2008 N2 - Computational Fluid Dynamics (CFD) and experimental investigations on a generic model of the trachea have been carried out focusing on the impact of an endotracheal tube (ETT) on the resulting flow regime. It could be shown that detailed modelling of the airway management devices is essential for proper flow prediction, but secondary details as Murphy Eyes can be neglected. Models with bending and connector promote the formation of stronger secondary flows and disturbances which persist for a longer time. KW - computational fluid dynamics KW - Computational Fluid Dynamics Simulation KW - Endotracheal Tube KW - Particle Image Velocimetry KW - Turbulent Kinetic Energy Y1 - 2010 SN - 978-3-642-14242-0 U6 - https://doi.org/10.1007/978-3-642-14243-7_62 SP - 505 EP - 512 PB - Springer Berlin Heidelberg CY - Berlin, Heidelberg ER - TY - GEN A1 - Friedrich, Janet A1 - Rivoire, Julien A1 - Scholz, Alexander-Wigbert K. A1 - Wiegbert, A1 - Terekov, Maxim A1 - Kbrich, Rainer A1 - Krenkel, Lars A1 - Wagner, Claus A1 - Schreiber, Laura Maria T1 - Exploration of Gas Flow During High Frequency Oscillated Ventilation by 19F-Gas-MRI T2 - Proceedings of the International Society for Magnetic Resonance in Medicine N2 - To detect convective gas flow inside the large airways during high frequency oscillated ventilation (HFOV) the fluorinated contrast gas Heptafluoropropane was used for 19F-MRI. In a first study the comparison between constant flow measurements and Computational Fluid Dynamics (CFD) simulations provided a good agreement. In a following experiment oscillated flow was applied to a lung phantom consisting of ventilation bag and long pipe. The pressure wave inside the pipe was explored point-by-point and corresponding velocities were determined. With these experiments it could be shown for the first time that flow measurement during HFOV using fluorinated contrast gas is feasible. Y1 - 2010 UR - https://archive.ismrm.org/2010/2527.html VL - 18 ER - TY - GEN A1 - Krefting, Dagmar A1 - Zaunseder, Sebastian A1 - Säring, Dennis A1 - Wittenberg, Thomas A1 - Palm, Christoph A1 - Schiecke, Karin A1 - Krenkel, Lars A1 - Hennemuth, Anja A1 - Schnell, Susanne A1 - Spicher, Nicolai T1 - Blutdruck, Hämodynamik und Gefäßzustand: Innovative Erfassung und Bewertung – Schwerpunkt bildbasierte Verfahren T2 - 66. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS), 12. Jahreskongress der Technologie- und Methodenplattform für die vernetzte medizinische Forschung e. V. (TMF), 26. - 30.09.2021, online N2 - Einleitung: Blutdruck gilt als sogenannter Vitalparameter als einer der grundlegenden Indikatoren für den Gesundheitszustand einer Person. Sowohl zu niedriger als auch zu hoher Blutdruck kann lebensbedrohend sein, letzerer ist darüber hinaus ein Risikofaktor insbesondere für Herz-Kreislauferkrankungen, die trotz wichtiger Fortschritte in der Behandlung immer noch die häufigste Todesursache in Deutschland darstellen. Die Hämodynamik, also die raumzeitliche Dynamik des Blutflusses, und der Gefäßzustand sind eng verbunden mit dem Blutdruck und ebenfalls von hoher klinischer Relevanz, u.a. zur Identifikation von Durchblutungsstörungen und ungünstigen Druckverteilungen der Gefäßwand. Innovationen in der Messtechnik als auch in der Datenanalyse bieten heute neue Möglichkeiten der Erfassung und Bewertung von Blutdruck, Hämodynamik und Gefäßzustand [1], [2], [3], [4]. Methodik: In einer gemeinsamen Workshopserie der AG Medizinische Bild- und Signalverarbeitung der GMDS und des Fachausschusses Biosignale der DGBMT werden wir neue Ansätze und Lösungen für Mess- und Analyseverfahren zu Blutdruck und -fluss sowie zum Gefäßzustand vorstellen und diskutieren. Dabei stehen im ersten Workshop auf der GMDS Jahrestagung Bildbasierte Verfahren im Zentrum, während der zweite Workshop auf der DGBMT Jahrestagung den Fokus auf Biosignalbasierten Verfahren legt. Es werden aktuelle Forschungsergebnisse vorgestellt und diskutiert. Es sind jeweils mehrere Vorträge geplant mit ausreichend Zeit zur Diskussion. Folgende Vorträge sind geplant (Arbeitstitel): Sebastian Zaunseder: Videobasierte Erfassung des Blutdrucks Anja Hennemuth: A Visualization Toolkit for the Analysis of Aortic Anatomy and Pressure Distribution Lars Krenkel: Numerische Analyse der Rupturwahrscheinlichkeit zerebraler Aneurysmata Susanne Schnell: Messung des Blutflusses und hämodynamischer Parameter mit 4D flow MRI: Möglichkeiten und Herausforderungen Ergebnisse: Ziel des Workshops ist die Identifikation von innovativen Ansätzen und neuen Methoden zur qualitativen und quantitativen Bestimmung von hämodynamischen Parametern sowie deren kritische Bewertung durch die Community für die Eignung in der klinischen Entscheidungsunterstützung. Diskussion: Der Workshop leistet inhaltlich einen Beitrag zu zentralen Aspekten für die Herz-Kreislauf-Medizin. Er bringt dabei Expertise aus verschiedenen Bereichen zusammen und schlägt die Brücke zwischen Kardiologie, Medizininformatik und Medizintechnik. Schlussfolgerung: Innovative Technologien aus Medizintechnik und Informatik ermöglichen zunehmend einfache und raumzeitlich aufgelöste Erfassung und Bewertung wichtiger Informationen zur Unterstützung von Diagnose und Therapieverfolgung. [1] Zaunseder S, Trumpp A, Wedekind D, Malberg H. Cardiovascular assessment by imaging photoplethysmography - a review. Biomed Tech (Berl). 2018 Oct 25;63(5):617–34. [2] Huellebrand M, Messroghli D, Tautz L, Kuehne T, Hennemuth A. An extensible software platform for interdisciplinary cardiovascular imaging research. Comput Methods Programs Biomed. 2020 Feb;184:105277. [3] Schmitter S, Adriany G, Waks M, Moeller S, Aristova M, Vali A, et al. Bilateral Multiband 4D Flow MRI of the Carotid Arteries at 7T. Magn Reson Med. 2020 Oct;84(4):1947–60. [4] Birkenmaier C, and Krenkel, L. Flow in Artificial Lungs. In: New Results in Numerical and Experimental Fluid Mechanics XIII. Contributions to the 22nd STAB/DGLR Symposium. Springer; 2021. KW - Bildbasierte Verfahren KW - Blutdruck KW - Hämodynamik KW - Blutgefäß KW - Bildgebendes Verfahren Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0183-21gmds0167 ER - TY - JOUR A1 - Lehle, Karla A1 - Philipp, Alois A1 - Krenkel, Lars A1 - Gruber, Michael A1 - Hiller, Karl-Anton A1 - Müller, Thomas A1 - Lubnow, Matthias T1 - Thrombocytopenia During Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Bacterial, Viral, and COVID-19 Pneumonia JF - ASAIO Journal N2 - Contact of blood with artificial surfaces triggers platelet activation. The aim was to compare platelet kinetics after venovenous extracorporeal membrane oxygenation (V-V ECMO) start and after system exchange in different etiologies of acute lung failure. Platelet counts and coagulation parameters were analyzed from adult patients with long and exchange-free (≥8 days) ECMO runs (n = 330) caused by bacterial (n = 142), viral (n = 76), or coronavirus disease 2019 (COVID-19) (n = 112) pneumonia. A subpopulation requiring a system exchange and with long, exchange-free runs of the second oxygenator (≥7 days) (n = 110) was analyzed analogously. Patients with COVID-19 showed the highest platelet levels before ECMO implantation. Independent of the underlying disease and ECMO type, platelet counts decreased significantly within 24 hours and reached a steady state after 5 days. In the subpopulation, at the day of a system exchange, platelet counts were lower compared with ECMO start, but without differences between underlying diseases. Subsequently, platelets remained unchanged in the bacterial pneumonia group, but increased in the COVID-19 and viral pneumonia groups within 2–4 days, whereas D-dimers decreased and fibrinogen levels increased. Thus, overall platelet counts on V-V ECMO show disease-specific initial dynamics followed by an ongoing consumption by the ECMO device, which is not boosted by new artificial surfaces after a system exchange. Y1 - 2025 U6 - https://doi.org/10.1097/MAT.0000000000002383 SN - 1058-2916 SN - 1538-943X PB - Wolters Kluwer ER - TY - JOUR A1 - Bartsch, Alexander A1 - Eigenberger, Andreas A1 - Felthaus, Oliver A1 - Booth, Brian W. A1 - Krenkel, Lars A1 - Schratzenstaller, Thomas A1 - Prantl, Lukas T1 - Quantification of Cannula Influence on Negative Pressure in Syringe Assisted Liposuction JF - Plastic & Reconstructive Surgery N2 - To make the results of the autologous fat transfer more satisfactory, all parameters of suction, preparation, and reapplication must be well understood. Since syringe-assisted liposuction is frequently used for small-volume procedures, we quantified the influence of the cannula on negative pressure. For these experiments, we used a digital manometer to which a syringe and one of seven different cannulas were connected. Data was collected and analyzed using LabVIEW and Matlab. The volume of our measurement setup was calculated using Boyle-Mariotte's law to ease interpretation, which revealed a volume of 2.82 ± 0.03 mL. We demonstrate that the volume of the measurement setup significantly affects the measurement results. Consequently, we accounted for this factor and calculated the theoretical values accordingly. Statistical analysis shows a significant influence on negative pressure across different cannulas, except for two pairs, which had minimal volume differences. Exemplary, for cannulas with volumes under 1.75 mL, a 2 mL syringe plunger pull was sufficient to create a - 0.5 bar (- 14.8 inHg) negative pressure. The present data indicate that the size of the suction cannula must be considered in syringe-assisted suction to ensure a specific negative pressure is not exceeded. Other research groups have demonstrated that adipocyte vitality and the amount of stromal vascular fraction are reduced by excessively strong negative pressure. Y1 - 2025 U6 - https://doi.org/10.1097/PRS.0000000000012477 SN - 0032-1052 PB - American Society of Plastic Surgeons ER - TY - JOUR A1 - Kranz, Michael A1 - Wagner, Maria Stella A1 - Pointner, Daniel A1 - Haus, Moritz A1 - Lubnow, Matthias A1 - Lehle, Karla A1 - Krenkel, Lars T1 - Polymer embedding of membrane lungs for histological investigations of intra-device clot formation JF - Cardiovascular Medicine N2 - Extracorporeal membrane oxygenation (ECMO) is an invasive but potentially lifesaving treatment option for severe cardiac or respiratory failure. Despite its beneficial effect, coagulation-related complications, mainly due to clot formation, excessive bleeding and the accumulation of deposits in the membrane lung (ML) remain common, causing higher mortality. In this context, the formation of clots and other deposits in the ML is of particular interest. Previous histological examinations of the polymethylpentene fiber mats inside the ML could only be performed in a top view, prohibiting valid quantification and examination of the multi-layered deposits or fiber mat spanning structures. Our objective was the establishment of a polymer embedding to increase the mechanical stability of the deposits and thus enable cross-sectional microtome cutting through the ML hollow-fibers. Clinically used MLs (PLS, Getinge, Rastatt, Germany) were stabilized with a polymer resin (HistoCURE 8100). Specimens were cut out of the embedded MLs and microtome sections with a thickness of 10 µm were performed. In addition to standard histological staining with hematoxylin-eosin (HE) and Pappenheim (May-Grunwald-Giemsa), fluorescence DNA staining for nucleated cells with 4′,6-diamidino-2-phenylindole (DAPI) and SYTOX™ Green as well as immunohistochemical and immunofluorescence staining for the lysosomal enzyme myeloperoxidase (MPO) and von Willebrand factor (vWF) were established. The protocol provides a method for large volume embedding (400 mL). The cellular and extracellular deposits were securely fixed by the polymer scaffold allowing the examination of clots in MLs in native position which was not possible with conventional paraffin embedding. Multi-layered deposits and fiber mat spanning structures are no longer disrupted during specimen extraction and can now be quantified. Staining with HE, Pappenheim, DAPI, SYTOX™ Green, MPO, and vWF was successfully tested with this protocol. This method may be the foundation for new insights into the complex clotting phenomena observed in MLs KW - clot formation KW - ECMO KW - HistoCURE 8100 KW - histology KW - membrane lungs KW - polymer embedding KW - Technovit 8100 Y1 - 2026 U6 - https://doi.org/10.3389/fcvm.2026.1650978 VL - 13 PB - Frontiers CY - Lausanne ER - TY - GEN A1 - Michel, Johanna A1 - Krenkel, Lars T1 - Experimental Investigation of Shear-Induced Generation of Respiratory Aerosol: Simultaneous Measurements of Particle Quantities and Wave Topology T2 - 2nd European Fluid Dynamics Conference (EFDC2), 26-29 August 2025, Dublin, Ireland N2 - Despite the high level of attention on infectious respiratory aerosol during the Covid19 pandemic, little is known about the processes how these particles form inside the respiratory system. Understanding the underlying fluid mechanical processes and their influencing factors would enable the development of drugs to suppress the generation of infectious aerosol. In the proposed work, we focus on the shear-induced mechanism of aerosol generation, which is supposed to occur mostly in the larger airways during coughing. In this process, high air velocities trigger Kelvin-Helmholtz waves in the mucus film, which lines the air vessels. Through a series of instabilities, particles detach from the crest of these waves. In the proposed work, we investigate the process of shear-induced aerosol generation in idealized experiments where we vary the air-flow characteristics and the properties of the mucus fluid. Our central aim here is to deduct an empirical model of the quantity and size distribution of generated particles depending on the mucus rheology and the local shear flow. Further, we observe the wave topology to better understand the coupling between the air flow and the waves. In our experimental setup, we measure the quantity of created particles and the emerging waves simultaneously. To ensure controllable conditions, we simplify the complex flow conditions in the airways. We use a rectangular channel with the bottom wall covered in a mucus mimetic. The mucus mimetic fluid is a synthetic hydrogel developed to recreate the viscoelastic properties and low surface tensions of the mucus. Filtered pressurized air is guided through the channel to trigger shear-induced aerosol generation. After passing the mucus mimetic, the air enters into a collection chamber from where particles are sampled continuously by an aerosol spectrometer. To measure wave topology, we use planar laser induced fluorescence. For this, we stain the mucus mimetic with fluorescent dyes and illuminate a line on the surface of the fluid film with a 532 nm laser. A high-resolution camera captures the resulting fluorescent glow of the mucus mimetic. Figure 1 presents exemplary wave topology results from the experiments, employing varying air flow volume rates, mucus mimetic gel properties, and different configurations of the laser and camera. The resulting wave topologies exhibit significant variation. For the conference, we will conduct parameter studies of the particle quantities and wave topology while varying the mucus mimetic properties and the flow rate of the air. Additionally, we will present grid projection-based techniques to extend the single-line wave measurements and asses the entire surface of the mucus film. Y1 - 2025 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:898-opus4-88593 ER -