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 - 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 - 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 - 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 - Pointner, Daniel A1 - Kranz, Michael A1 - Wagner, Maria Stella A1 - Haus, Moritz A1 - Lehle, Karla A1 - Krenkel, Lars T1 - Automated deep learning based detection of cellular deposits on clinically used ECMO membrane lungs JF - Frontiers in Bioinformatics N2 - Introduction: Despite the promising application of extracorporeal membrane oxygenation (ECMO) in the treatment of critically ill patients, coagulation-associated technical complications, primarily clot formation and critical bleeding, remain a major challenge during ECMO therapy. The deposition of nucleated cells on the surface has been shown, yet the role of these cells towards complication development is still matter of ongoing research. In particular, the membrane lung (MemL) is prone to clot formation. Therefore, the investigation of nuclear deposits on its hollow-fibers may provide insights for a better understanding of the cellular mechanisms involved in the development of ECMO complications. Methods: To support current research, this study aimed to develop a deep learning–based tool for the automated detection and quantitative analysis of nuclear depositions on MemL hollow-fiber mats. A customized fluorescence microscopy workflow, combined with a semi-automated iterative labeling strategy, was used to generate a high-quality dataset for model training. Results: Six configurations of instance segmentation models were evaluated, with a Mask R-CNN with ResNet 101 backbone using dilated convolution providing the most balanced performance in both nuclei count and area accuracy. Compared with U-Net–based approaches such as Cellpose or StarDist, the proposed model demonstrated superior segmentation of overlapping and low-intensity nuclei, maintaining accuracy even in densely packed cellular regions. Discussion: We present an automated image analysis tool for clinically used MemLs, which exhibit complex three-dimensional hollow-fiber architectures and irregular cellular deposits that challenge conventional tools. A dedicated graphical user interface enables streamlined detection, morphometric analysis, and spatial clustering of nuclei, establishing a reproducible workflow for high-throughput analysis of fluorescence microscopy images. This approach eliminates labor-intensive manual counting and facilitates large-scale studies on cell-fiber interactions and disease-related correlations. Y1 - 2026 U6 - https://doi.org/10.3389/fbinf.2026.1771574 N1 - Corresponding author der OTH Regensburg: Daniel Pointner, Lars Krenkel VL - 6 PB - Frontiers ER - TY - CHAP A1 - Michel, Johanna A1 - Krenkel, Lars ED - Dillmann, Andreas ED - Heller, Gerd ED - Krämer, Ewald ED - Breitsamter, Christian ED - Wagner, Claus ED - Krenkel, Lars T1 - Towards Experimental Validation of Models of Shear-Induced Aerosol Generation in the Human Respiratory System T2 - New Results in Numerical and Experimental Fluid Mechanics XV : Contributions to the 24th STAB/DGLR Symposium, Regensburg, Germany, 2024 N2 - Numerical modeling is a valuable tool to research shear-induced aerosol generation inside the human respiratory system. While the volume of fluid method and Eulerian wall film models have been used to predict the stripping of particles from the mucus film, sufficient validation data is lacking. Here, we present an experimental method to create such validation data. A film of mucus mimetic hydrogel with an initial thickness of 1 mm covering the floor of a rectangular channel (75.5 mm 25.5 mm 3 mm) was exposed to an airflow with a flow rate of 9.5 and 21.6 L/min. The number of created particles and the emergence of waves on the mucus surface were measured. Shear-induced aerosol generation was triggered successfully and caused an increase of mean particle flow. Different wave profiles were observed at varying film depths. Y1 - 2026 SN - 978-3-032-11114-2 U6 - https://doi.org/10.1007/978-3-032-11115-9_13 SP - 135 EP - 144 PB - Springer Nature CY - Cham ER -