@misc{BirkenmaierKrenkelLehle, author = {Birkenmaier, Clemens and Krenkel, Lars and Lehle, Karla}, title = {Linking flow conditions in membrane oxygenators to arrangements of multimeric von-Willebrand-factor as indication for coagulation}, series = {World Congress of Biomechanics 2018, Convention Centre Dublin, 8.-12. Juli 2018}, journal = {World Congress of Biomechanics 2018, Convention Centre Dublin, 8.-12. Juli 2018}, abstract = {Introduction Shear induced multimerisation of von-Willebrand-factor (vWF) is supposed to play an important role in coagulation inside extracorporeal membrane oxygenators. However, there is no proof that links observed vWF structures to computed or measured flow conditions. Methods The structures of multimeric vWF fibers, observed in clinically used membrane oxygenators is examined using immunofluorescence microscopy (IFM) using Carstairs' staining method (positive ethics committee vote). The flow around the membrane fibres inside the oxygenator is investigated in terms of shear rate, wall shear velocity and streamlines by using CFD (RANS, Carreau-Yasuda viscosity, geometry remodelled after high-resolution µCT-scans). By interpreting the histological and numerical results in this common context, indications for shear induced coagulation mechanisms can be identified. Results The fibre structures of multimeric vWF build regular but not exactly symmetric formations around the contact face (CF) between the crosswise stacked oxygenator fibres (OF), see fig.1B, vWF marked red. Annular around the CF arranged, cells are likely to be found, see fig.1B, nuclei marked blue. The computed streamlines around the OF show attached flow around the circular fibres. However, the irregular arrangement of real OF produce considerable cross flow between the interconnected neighbouring channels, in contrast to previous 2D-simulations. Thus, the CF are washed around closely by blood, also from neighbouring channels. The wall shear velocity streamlines form regular, slightly asymmetric shapes around the contact faces. The occurring maximum shear rates are in the range of 1,000 1/s. Discussion The shapes of vWF structures found in clinically used oxygenators match the computational results in terms of wall shear velocity and streamlines well. The accumulation of cells close to the CF can also be explained by fluid mechanics, as there are small shear gradients and slow velocities. However, occurring shear rates between OFs are too low to trigger multimerisation of vWF. That raises the question where in the circuit the actual activation of vWF is started and how, at least partly chained, vWF multimeres are attracted towards the OF surface. A next step will be the investigation of the actual shear rate triggered (or mediated) multimerisation of vWF. Towards this end, microfluidic experiments with shear triggered coagulation will be performed. Also of big interest is the computation of the flow situation in the oxygenator in proximity to chaining threads, which have been ignored in computations so far. However, first a realistic representation of the effective viscosity in computations is needed, which is not available yet.}, language = {en} } @inproceedings{BirkenmaierKrenkel, author = {Birkenmaier, Clemens and Krenkel, Lars}, title = {Convolutional Neural Networks for Approximation of Internal Non-Newtonian Multiphase Flow Fields}, series = {14th World Congress on Computational Mechanics (WCCM), ECCOMAS Congress 2020: 19-24 July 2020, Paris, France}, booktitle = {14th World Congress on Computational Mechanics (WCCM), ECCOMAS Congress 2020: 19-24 July 2020, Paris, France}, editor = {Chinesta, F. and Abgrall, R. and Allix, O. and Kalistke, M}, publisher = {CIMNE}, doi = {10.23967/wccm-eccomas.2020.107}, abstract = {Neural networks (NNs) as an alternative method for universal approximation of differential equations have proven to be computationally efficient and still sufficiently accurate compared to established methods such as the finite volume method (FVM). Additionally, analysing weights and biases can give insights into the underlying physical laws. FVM and NNs are both based upon spacial discretisation. Since a Cartesian and equidistant grid is a raster graphics, image-to-image regression techniques can be used to predict phase velocity fields as well as particle and pressure distributions from simple mass flow boundary conditions. The impact of convolution layer depth and number of channels of a ConvolutionDeconvolution Regression Network (CDRN), on prediction performance of internal non-Newtownian multiphase flows is investigated. Parametric training data with 2055 sets is computed using FVM. To capture significant non-Newtownian effects of a particle-laden fluid (e.g. blood) flowing through small and non-straight channels, an Euler-Euler multiphase approach is used. The FVM results are normalized and mapped onto an equidistant grid as supervised learning target. The investigated NNs consist of n= {3, 5, 7} corresponding encoding/decoding blocks and different skip connections. Regardless of the convolution depth (i.e. number of blocks), the deepest spacial down-sampling via strided convolution is adjusted to result in a 1 × 1 × f · 2nfeature map, with f = {8, 16, 32}. The prediction performance expressed is as channel-averaged normalized root mean squared error (NRMSE). With a NRMSE of < 2 · 10-3, the best preforming NN has f = 32 initial feature maps, a kernel size of k = 4, n = 5 blocks and dense skip connections. Average inference time from this NN takes < 7 · 10-3s. Worst accuracy at NRMSE of approx 9 · 10-3is achieved without any skips, at k = 2, f = 16 and n = 3, but deployment takes only < 2 · 10-3s Given an adequate training, the prediction accuracy improves with convolution depth, where more features have higher impact on deeper NNs. Due to skip connections and batch normalisation, training is similarly efficient, regardless of the depth. This is further improved by blocks with dense connections, but at the price of a drastically larger model. Depending on geometrical complexity, spacial resolution is critical, as it increases the number of learnables and memory requirements massively.}, language = {en} } @article{PhilippdeSomerFoltanetal., author = {Philipp, Alois and de Somer, Filip and Foltan, Maik and Bredthauer, Andre and Krenkel, Lars and Zeman, Florian and Lehle, Karla}, title = {Life span of different extracorporeal membrane systems for severe respiratory failure in the clinical practice}, series = {PLOS ONE}, volume = {13}, journal = {PLOS ONE}, number = {6}, publisher = {PLOS}, doi = {10.1371/journal.pone.0198392}, pages = {1 -- 10}, abstract = {Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010-2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30\%. The median (IQR) life span was 9 (6-12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange.}, language = {en} } @techreport{Krenkel, author = {Krenkel, Lars}, title = {Investigation of the impact of vortex generators on the shock/boundary-layer interaction}, issn = {1434-8454}, abstract = {Comprehensive experimental and numerical parameter studies on the impact of isolated vortex generator pairs and complex vortex generator arrays onto a strong shock-/boundary layer interaction are presented within the context of this thesis. The effects of vortices, especially as they interact with each other are discussed in terms of their impact on the boundary layer development, the shock characteristics and the overall aerodynamic performance of the aerofoil. The presented results have been obtained from wind tunnel experiments with a simple flat plate with superimposed pressure gradient as well as with a more comprehensive model of a supercritical transonic aerofoil. In addition complex numerical parameter studies on a supercritical aerofoil in free stream conditions have been conducted. This work is designed for gaining a better understanding of the fundamental mechanisms of vortex generator/shock/boundary-layer interaction in order to achieve improved flight performance in terms of drag reduction, avoidance or at least postponement of separation onset and shock oscillation as well as lift improvement by application of optimised vortex generator configurations.}, language = {en} } @article{DiermeierSindersbergerKrenkeletal., author = {Diermeier, Andreas and Sindersberger, Dirk and Krenkel, Lars and Rosell, X. C. and Monkman, Gareth J.}, title = {Controllable Magnetoactive Polymer Conduit}, series = {The Open Mechanical Engineering Journal}, volume = {12}, journal = {The Open Mechanical Engineering Journal}, number = {1}, publisher = {Bentham}, pages = {192 -- 200}, abstract = {Objective: Magneto-active Polymers (MAP) are smart materials whose mechanical characteristics, such as elastic and shear moduli, may be controllable by means of an externally applied magnetic field. Methods: Various additives may be used to influence the characteristics of the polymer matrix whilst a suspension of soft and/or hard magnetic particles determine the magnetic properties of the composite. Both pre-cure and post-cure magnetization is possible. Results: A range of control strategies have been investigated for evaluation of the system using fluids of differing kinematic viscosity. Conclusion: Depending on the degree of magnetic field homogeneity, magneto-deformation and magnetostriction contribute to MAP actuation. This paper presents a novel application in the form of a peristaltic MAP tube system, applicable to flow control and pumping of hemorheological fluids in blood circulatory systems for biomedical research purposes.}, language = {en} } @incollection{ScholzKrenkelTerekhovetal., author = {Scholz, Alexander-Wigbert K. and Krenkel, Lars and Terekhov, Maxim and Friedrich, Janet and Rivoire, Julien and K{\"o}brich, Rainer and Wolf, Ursula and Kalthoff, Daniel and David, Matthias and Wagner, Claus and Schreiber, Laura Maria}, title = {Magnetic Resonance Imaging and Computational Fluid Dynamics of High Frequency Oscillatory Ventilation (HFOV)}, series = {Fundamental Medical and Engineering Investigations on Protective Artificial Respiration}, volume = {116}, booktitle = {Fundamental Medical and Engineering Investigations on Protective Artificial Respiration}, editor = {Hirschel, Ernst Heinrich and Schr{\"o}der, Wolfgang and Fujii, Kozo and Haase, Werner and Leer, Bram and Leschziner, Michael A. and Pandolfi, Maurizio and Periaux, Jacques and Rizzi, Arthur and Roux, Bernard and Shokin, Yurii I. and Klaas, Michael and Koch, Edmund and Schr{\"o}der, Wolfgang}, publisher = {Springer}, address = {Berlin, Heidelberg}, isbn = {978-3-642-20325-1}, doi = {10.1007/978-3-642-20326-8_7}, pages = {107 -- 128}, abstract = {In order to better understand the mechanisms of gas transport during High Frequency Oscillatory Ventilation (HFOV) Magnetic Resonance Imaging (MRI) with contrast gases and numerical flow simulations based on Computational Fluid Dynamics(CFD) methods are performed. Validation of these new techniques is conducted by comparing the results obtained with simplified models of the trachea and a first lung bifurcation as well as in a cast model of the upper central airways with results achieved from conventional fluid mechanical measurement techniques like e.g. Laser Doppler Anemometry (LDA). Further it is demonstrated that MRI of experimental HFOV is feasible and that Hyperpolarized 3He allows for imaging the gas re-distribution inside the lung. Finally, numerical results of oscillatory flow in a 3rd generation model of the lung as well as the impact of endotracheal tubes on the flow regime development in a trachea model are presented.}, language = {en} } @techreport{SteigerFoltanPhilippetal., type = {Working Paper}, author = {Steiger, Tamara and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Gruber, Michael and Bredthauer, Andre and Krenkel, Lars and Birkenmaier, Clemens and Lehle, Karla}, title = {Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?}, abstract = {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.}, language = {en} } @inproceedings{StelzerTauwaldVielsmeieretal., author = {Stelzer, Vera and Tauwald, Sandra Melina and Vielsmeier, Veronika and Cieplik, Fabian and Kandulski, Arne and Schneider-Brachert, Wulf and W{\"u}nsch, Olaf and R{\"u}tten, Markus and Krenkel, Lars}, title = {Generation and Distribution of Surgical Smoke During High Frequency Electrocauterization}, series = {New Results in Numerical and Experimental Fluid Mechanics XIV. STAB/DGLR Symposium 2022}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics XIV. STAB/DGLR Symposium 2022}, editor = {Dillman, Andreas and Heller, Gerd and Kraemer, Ewald and Wagner, Claus and Weiss, Julien}, publisher = {Springer Nature Switzerland AG}, address = {Cham, Switzerland}, isbn = {978-3-031-40481-8}, doi = {10.1007/978-3-031-40482-5_53}, pages = {559 -- 568}, abstract = {Surgical Smoke is generated during the cauterization of tissue with high-frequency (HF) devices and consists of 95\% water vapor and 5\% cellular debris. When the coagulation tweezers, which are supplied with HF voltage by the HF device, touch tissue, the electric circuit is closed, and smoke is generated by the heat. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during coagulation of tissue. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. With higher power of the HF device, the particles generated are larger in size and the total number of particles generated is also higher. Adding artificial saliva to the tissue shows even higher particle counts. The study by laser light sheet also confirms this. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms considering the risk arising from surgical smoke. Furthermore, the experiments will provide the database for further numerical investigations.}, language = {en} } @incollection{RuettenKrenkel, author = {R{\"u}tten, Markus and Krenkel, Lars}, title = {Vortex-Generator Pairs for Vortex-Induced Heat-Transfer Enhancement in Heat-Exchanger Channels}, series = {New Results in Numerical and Experimental Fluid Mechanics VII : Contributions to the 16th STAB/DGLR Symposium Aachen, Germany 2008}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics VII : Contributions to the 16th STAB/DGLR Symposium Aachen, Germany 2008}, editor = {Hirschel, Ernst Heinrich and Schr{\"o}der, Wolfgang and Fujii, Kozo and Haase, Werner and Leer, Bram and Leschziner, Michael A. and Pandolfi, Maurizio and Periaux, Jacques and Rizzi, Arthur and Roux, Bernard and Shokin, Yurii I. and Dillmann, Andreas and Heller, Gerd and Klaas, Michael and Kreplin, Hans-Peter and Nitsche, Wolfgang}, publisher = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, isbn = {978-3-642-14242-0}, doi = {10.1007/978-3-642-14243-7_68}, pages = {555 -- 562}, abstract = {The objective of the presented work is to investigate possibilities for increasing the heattransfer in heat-exchanger channels for aircraft applications by using flow-manipulating devices. Focal point of the investigation are different arrangements of vortex-generator pairs within a generic heat-exchanger channel. The DLR URANS CFD solver THETA has been used to carry out numerical simulations of the laminar flow within a rectangular channel with integrated vortex generators. In particular, the analysis of the interaction of generated vortices with the stratified thermal boundary layer, the impact of vortical flow structures on heated walls and the enforced mixed-convection flow is of special interest. The final goal is the evaluation of the applicability of oppositely arranged vortex-generator pairs for the enhancement of vortex-induced heat-transfer.}, language = {en} } @book{Krenkel, author = {Krenkel, Lars}, title = {Untersuchung des Einflusses von Wirbelgeneratoren auf die Stoß-/Grenzschicht-Wechselwirkung}, publisher = {Rheinisch-Westf{\"a}lische Technische Hochschule Aachen}, address = {Aachen}, issn = {1434-8454}, abstract = {Im Rahmen dieser Arbeit werden experimentelle und numerische Parameterstudien von einzelnen Wirbelgeneratorpaaren und komplexeren Wirbelgeneratoranordnungen bez{\"u}glich ihres Einflusses auf eine starke Stoß-/Grenzschicht-Wechselwirkung vorgestellt. Dabei werden die Einfl{\"u}sse von Wirbeln, insbesondere die Auswirkungen ihrer Wechselwirkungen untereinander, auf das Grenzschichtverhalten, die Stoßcharakteristik und insgesamt auf die aerodynamische Leistung des betrachteten Profils diskutiert. Dazu wurden sowohl Windkanalversuche am einfachen Modell einer ebenen Platte mit aufgepr{\"a}gtem Druckgradienten sowie an einem Modell eines superkritischen transsonischen Profils durchgef{\"u}hrt. Erg{\"a}nzend wurden komplexe nume-rische Parameteruntersuchungen an einem Profil in freier Anstr{\"o}mung ausgef{\"u}hrt. Es ist das Ziel, ein besse-res Verst{\"a}ndnis der Mechanismen der Wirbelgenerator-/Stoß-/Grenzschicht-Wechselwirkung zu gewinnen, um durch optimierte Anwendung von Wirbelgeneratoren eine Verbesserung der Flugleistungen erzielen zu k{\"o}nnen. Die Schwerpunkte liegen dabei auf der Reduktion des Widerstandes, der Vermeidung bzw. Verz{\"o}ge-rung von Str{\"o}mungsabl{\"o}sung und Stoßschwingung sowie auf der Erh{\"o}hung des Auftriebs.}, language = {de} } @inproceedings{KrenkelPennecotLenzetal., author = {Krenkel, Lars and Pennecot, Julien and Lenz, Christian and Feldmann, Daniel and Wagner, Claus}, title = {Optimierung der Hochfrequenz-Oszillationsventilation mittels str{\"o}mungsmechanischer Methoden und kontrastgasgest{\"u}tzter Magnetresonanztomografie - Teilprojekt: Rekonstruktion von Geometrien aus medizinischen Bilddaten und Erstellung von Modellen f{\"u}r experimentelle Str{\"o}mungsuntersuchungen}, series = {Laseranwendung in der Medizin, Erfassen und Verarbeiten kardiovaskul{\"a}rer Signale, protektive Beatmungskonzepte : 3. Dresdner Medizintechnik-Symposium - mit DFG-Forschungsschwerpunkt Protektive Beatmungskonzepte, 6. bis 9. Dezember 2010, Dresden}, booktitle = {Laseranwendung in der Medizin, Erfassen und Verarbeiten kardiovaskul{\"a}rer Signale, protektive Beatmungskonzepte : 3. Dresdner Medizintechnik-Symposium - mit DFG-Forschungsschwerpunkt Protektive Beatmungskonzepte, 6. bis 9. Dezember 2010, Dresden}, editor = {F{\"u}ssel, Jens and Koch, Edmund and Malberg, Hagen}, publisher = {TUDpress}, address = {Dresden}, isbn = {978-3-942710-02-2}, pages = {107 -- 114}, abstract = {Der vorliegende Artikel skizziert die neu entwickelte Prozesskette f{\"u}r detailgenaue Rekonstruktion von Geometrien anhand medizinischer Bilddaten sowie die Herstellung von transparenten Modellen f{\"u}r experimentelle Untersuchungen mit bildgebenden Str{\"o}mungsmessverfahren. Die Geometriedaten und Modelle werden f{\"u}r systematische Untersuchungen der komplexen Transportvorg{\"a}nge in den Atemwegen bei k{\"u}nstlicher Beatmung mittels Hochfrequenzoszillationsventilation (HFOV) verwendet.}, language = {en} } @misc{TauwaldQuadrioRuettenetal., author = {Tauwald, Sandra Melina and Quadrio, Maurizio and R{\"u}tten, Markus and Stemmer, Christian and Krenkel, Lars}, title = {High Spatial Resolution Tomo-PIV of the Nasopharynx Focussing on the Physiological Breathing Cycle}, series = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, journal = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, address = {G{\"o}ttingen}, organization = {Deutsche Gesellschaft f{\"u}r Luft- und Raumfahrt e.V. / Arbeitsgemeinschaft Str{\"o}mungen mit Abl{\"o}sung, AG STAB}, abstract = {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.}, language = {en} } @misc{StelzerTauwaldVielsmeieretal., author = {Stelzer, Vera and Tauwald, Sandra Melina and Vielsmeier, Veronika and Cieplik, Fabian and Kandulski, Arne and Schneider-Brachert, Wulf and Wuensch, Olaf and R{\"u}tten, Markus and Krenkel, Lars}, title = {Generation, Distribution, and Contagiousness of Surgical Smoke during Tracheotomies}, series = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, journal = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, address = {G{\"o}ttingen}, organization = {Deutsche Gesellschaft f{\"u}r Luft- und Raumfahrt e.V. / Arbeitsgemeinschaft Str{\"o}mungen mit Abl{\"o}sung, AG STAB}, abstract = {Surgical smoke has been a little discussed topic in the context of the current pandemic. Surgical smoke is generated during the cauterization of tissue with heat-generating devices and consists of 95\% water vapor and 5\% cellular debris in the form of particulate matter. In-vivo investigations are performed during tracheotomies where surgical smoke is produced during tissue electrocautery. Furthermore, in-vitro parametric studies to investigate the particle number and size distribution and the spatial distribution of surgical smoke with laser light sheet technique are conducted. The higher the power of the high-frequency-device the larger the particles in size and the higher the resulting particle counts. The images taken show the densest smoke at 40W with artificial saliva. The resulting characteristic size distribution, which may include viruses and bacterial components, confirms that the risk arising from surgical smoke should be considered. Furthermore, the experiments will provide the database for further numerical investigations.}, language = {en} } @article{StelzerKrenkel, author = {Stelzer, Vera and Krenkel, Lars}, title = {2D numerical investigations derived from a 3D dragonfly wing captured with a high-resolution micro-CT}, series = {Technology and health care : official journal of the European Society for Engineering and Medicine}, volume = {30}, journal = {Technology and health care : official journal of the European Society for Engineering and Medicine}, number = {1}, publisher = {IOS Press}, doi = {10.3233/THC-219010}, pages = {283 -- 289}, abstract = {BACKGROUND: Due to their corrugated profile, dragonfly wings have special aerodynamic characteristics during flying and gliding. OBJECTIVE: The aim of this study was to create a realistic 3D model of a dragonfly wing captured with a high-resolution micro-CT. To represent geometry changes in span and chord length and their aerodynamic effects, numerical investigations are carried out at different wing positions. METHODS: The forewing of a Camacinia gigantea was captured using a micro-CT. After the wing was adapted an error-free 3D model resulted. The wing was cut every 5 mm and 2D numerical analyses were conducted in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, USA). RESULTS: The highest lift coefficient, as well as the highest lift-to-drag ratio, resulted at 0 mm and an angle of attack (AOA) of 5∘. At AOAs of 10∘ or 15∘, the flow around the wing stalled and a K{\´a}rm{\´a}n vortex street behind the wing becomes CONCLUSIONS: The velocity is higher on the upper side of the wing compared to the lower side. The pressure acts vice versa. Due to the recirculation zones that are formed in valleys of the corrugation pattern the wing resembles the form of an airfoil.}, language = {en} } @article{SchecklmannSchmausserKlingeretal., author = {Schecklmann, Martin and Schmausser, Maximilian and Klinger, Felix and Kreuzer, Peter M. and Krenkel, Lars and Langguth, Berthold}, title = {Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil}, series = {scientific reports}, volume = {10}, journal = {scientific reports}, number = {1}, publisher = {Nature}, doi = {10.1038/s41598-020-58034-2}, abstract = {The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27\%) in contrast to the DC coil (about 15\%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.}, language = {en} } @misc{Krenkel, author = {Krenkel, Lars}, title = {Maskenpflicht f{\"u}r Aerosole - wie wir medizinisches Personal in der Pandemie sch{\"u}tzen}, series = {TRIOKON Digital 2021 : Zukunft Ostbayern, 29.09.2021, Weiden, Deutschland}, journal = {TRIOKON Digital 2021 : Zukunft Ostbayern, 29.09.2021, Weiden, Deutschland}, language = {de} } @misc{StelzerRuettenKrenkel, author = {Stelzer, Vera and R{\"u}tten, Markus and Krenkel, Lars}, title = {Numerical Investigation of a 3D Dragonfly Wing Captured with a High-Resolution Micro-CT}, series = {8th European Congress on Computational Methods in Applied Sciences and Engineering, ECCOMAS Congress 2022, 5-9 June 2022, Oslo, Norway}, journal = {8th European Congress on Computational Methods in Applied Sciences and Engineering, ECCOMAS Congress 2022, 5-9 June 2022, Oslo, Norway}, abstract = {The special wing geometry of dragonflies consisting of veins and a membrane forming a corrugated profile leads to special aerodynamic characteristics. To capture the governing flow regimes of a dragonfly wing in detail, a realistic wing model has to be investigated. Therefore, this study aimed to analyze the aerodynamic characteristics of a 3D dragonfly wing reconstructed from a high-resolution micro-CT scan. Afterwards, a spatially high discretized mesh was generated using the mesh generator CENTAUR™ 14.5.0.2 (CentaurSoft, Austin, TX, US) to finally conduct Computational Fluid Dynamics (CFD) investigations in Fluent® 2020 R2 (ANSYS, Inc., Canonsburg, PA, US). Due to the small dimensions of the wing membrane, only the vein structure of a Camacinia Gigantea was captured at a micro-CT voxel size of 7 microns. The membrane was adapted and connected to the vein structure using a Boolean union operation. Occurring nconsistencies after combining the veins and the membrane were corrected using an adapted pymesh script [1]. As an initial study, only one quarter of the wing (outer wing section) was investigated to reduce the required computational effort. The resulting hybrid mesh consisting of 10 pseudo-structured prism layers along the wing surface and tetrahedra in the farfield area has 43 mio. nodes. The flow around the wing was considered to be incompressible and laminar using transient calculations. When the flow passes the vein structures, steady vortices occur in the corrugation valleys leading to recirculation zones. Therefore, the dragonfly wing resembles the profile of an airfoil. This leads to comparable lift coefficients of dragonfly wings and airfoil profiles at significantly reduced structural weight. The reconstructed geometry also included naturally occurring triangular prismlike serrated structures at the leading edge of the wing, which have comparable effects to micro vortex generators and might stabilize the recirculation zones. Further work aims to investigate the aerodynamic properties of a complete dragonfly wing during wing flapping.}, language = {en} } @misc{BirkenmaierKrenkel, author = {Birkenmaier, Clemens and Krenkel, Lars}, title = {Towards a realistic model of blood viscosity and coagulation in membrane oxygenators}, series = {6th European Conference on Computational Mechanics (Solids, Structures and Coupled Problems) - ECCM 6; 7th European Conference on Computational Fluid Dynamics - ECFD 7 : Glasgow, Scotland, UK, June 11-15, 2018}, journal = {6th European Conference on Computational Mechanics (Solids, Structures and Coupled Problems) - ECCM 6; 7th European Conference on Computational Fluid Dynamics - ECFD 7 : Glasgow, Scotland, UK, June 11-15, 2018}, abstract = {Modelling blood flow an shear induced coagulation in membraene oxygenators (MO) is challenging. The relevant geometry of oxygenator fibers (OF) and chaining threads is complex and spans several length scales. In relevant scales and regimes blood shows several significant non-Newtonian effects. Existing models are only capable of accounting for some, but not all relevant effects. Additionally, coagulation processes are influencing fluid properties and geometry significantly. Due to the enormous size of the discretised geometries highly detailed viscosity and coagulation properties of blodd flow in MOs. First step is to find a gemoetry dependent viscosity representation on basis of parametric micro channel experiments with anti-coagulated blood. Next step is a statistic coagulation model, based on micro channel experiments with human (re-calcified citrated) whole blood an evaluation of clinically used osygenators. Since shear rate dependent (i.e. viscosity dependet) coagulation in return influences the viscosity, a combined model with suitable implementation in a RANS framework is necessary. Towards this end, micro channel experiments with new and used single OFs triggering coagulation are performed. Structures of multimeric von Willebrand fibers (vWF), as indicator for shear induced coagulation, are compared to computed and measured flow conditions, using immunofluorescence microscopy, RANS-computations and µPIV, respectively. Preliminary examinations in clinically used MOs show good agreement between occurring structures of vWF, cell depositions and computed flow patterns (geometry form µCT-Scans). However, computed shear rates might be to low to actually trigger activation of vWF. The complex geometry of MOs results in huge meshes, which makes RANS with statistical modelling of viscosity and coagulation a reasonable approach. Towards this end, experimental data on micro channel level with evaluation on real application level is crucial. Especially regarding clotting processes, micro fluidic experiments are powerful research tool.}, language = {en} } @article{TauwaldMichelBrandtetal., author = {Tauwald, Sandra Melina and Michel, Johanna and Brandt, Marie and Vielsmeier, Veronika and Stemmer, Christian and Krenkel, Lars}, title = {Experimental studies and mathematical modeling of the viscoelastic rheology of tracheobronchial mucus from respiratory healthy patients}, series = {Multidisciplinary Respiratory Medicine}, volume = {18}, journal = {Multidisciplinary Respiratory Medicine}, number = {1}, publisher = {PAGEPress}, address = {Pavia, Italy}, issn = {2049-6958}, doi = {10.4081/mrm.2023.923}, pages = {12}, abstract = {BACKGROUND: Tracheobronchial mucus plays a crucial role in pulmonary function by providing protection against inhaled pathogens. Due to its composition of water, mucins, and other biomolecules, it has a complex viscoelastic rheological behavior. This interplay of both viscous and elastic properties has not been fully described yet. In this study, we characterize the rheology of human mucus using oscillatory and transient tests. Based on the transient tests, we describe the material behavior of mucus under stress and strain loading by mathematical models. METHODS: Mucus samples were collected from clinically used endotracheal tubes. For rheological characterization, oscillatory amplitude-sweep and frequency-sweep tests, and transient creep-recovery and stress-relaxation tests were performed. The results of the transient test were approximated using the Burgers model, the Weibull distribution, and the six-element Maxwell model. The three-dimensional microstructure of the tracheobronchial mucus was visualized using scanning electron microscope imaging. RESULTS: Amplitude-sweep tests showed storage moduli ranging from 0.1 Pa to 10000 Pa and a median critical strain of 4 \%. In frequency-sweep tests, storage and loss moduli increased with frequency, with the median of the storage modulus ranging from 10 Pa to 30 Pa, and the median of the loss modulus from 5 Pa to 14 Pa. The Burgers model approximates the viscoelastic behavior of tracheobronchial mucus during a constant load of stress appropriately (R2 of 0.99), and the Weibull distribution is suitable to predict the recovery of the sample after the removal of this stress (R2 of 0.99). The approximation of the stress-relaxation test data by a six-element Maxwell model shows a larger fit error (R2 of 0.91). CONCLUSIONS: This study provides a detailed description of all process steps of characterizing the rheology of tracheobronchial mucus, including sample collection, microstructure visualization, and rheological investigation. Based on this characterization, we provide mathematical models of the rheological behavior of tracheobronchial mucus. These can now be used to simulate mucus flow in the respiratory system through numerical approaches.}, language = {en} } @inproceedings{BirkenmaierSteigerPhilippetal., author = {Birkenmaier, Clemens and Steiger, Tamara and Philipp, Alois and Lehle, Karla and Krenkel, Lars}, title = {Flow-induced accumulations of von Willebrand factor inside oxygenators during extracorporeal life support therapy}, series = {Proceedings of 12th International Conference BIOMDLORE 2018, June 28-30, 2018, Białystok, Poland}, booktitle = {Proceedings of 12th International Conference BIOMDLORE 2018, June 28-30, 2018, Białystok, Poland}, publisher = {IEEE}, address = {Piscataway, NJ}, isbn = {978-1-5386-2396-1}, doi = {10.1109/BIOMDLORE.2018.8467205}, pages = {3}, abstract = {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.}, language = {en} } @article{BirkenmaierDorniaLehleetal., author = {Birkenmaier, Clemens and Dornia, Christian and Lehle, Karla and M{\"u}ller, Thomas and Gruber, Michael and Philipp, Alois and Krenkel, Lars}, title = {Analysis of Thrombotic Deposits in Extracorporeal Membrane Oxygenators by High-resolution Microcomputed Tomography: A Feasibility Study}, series = {ASAIO Journal / American Society for Artificial Internal Organs}, volume = {66}, journal = {ASAIO Journal / American Society for Artificial Internal Organs}, number = {8}, publisher = {Lippincott Williams \& Wilkins}, issn = {1538-943X}, doi = {10.1097/MAT.0000000000001089}, pages = {922 -- 928}, abstract = {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.}, language = {en} } @inproceedings{MarkusRuettenKrenkelKessler, author = {Markus R{\"u}tten, and Krenkel, Lars and Kessler, Roland}, title = {Secondary Flow Effects as Physical Mechanism of Molecular Species Transport in Highly Oscillating Generic-Trachea Flows}, series = {83rd Annual Scientific Conference of the International Association of Applied Mathematics and Mechanics, 26.-30. M{\"a}rz 2012, Darmstadt, Germany}, booktitle = {83rd Annual Scientific Conference of the International Association of Applied Mathematics and Mechanics, 26.-30. M{\"a}rz 2012, Darmstadt, Germany}, abstract = {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.}, language = {en} } @inproceedings{FriedrichFeldmannKrenkeletal., author = {Friedrich, Janet and Feldmann, Daniel and Krenkel, Lars and Wagner, Claus and Schreiber, Laura Maria}, title = {19F Gas Flow Measurement of C3F7H During Constant Flow and High Frequency Oscillatory Ventilation}, series = {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}, volume = {21}, booktitle = {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}, organization = {International Society for Magnetic Resonance in Medicine}, abstract = {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.}, language = {en} } @inproceedings{BirkenmaierKrenkel, author = {Birkenmaier, Clemens and Krenkel, Lars}, title = {Convolutional Neural Networks for Approximation of Blood Flow in Artificial Lungs}, series = {New Results in Numerical and Experimental Fluid Mechanics XIII: Contributions to the 22nd STAB/DGLR Symposium}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics XIII: Contributions to the 22nd STAB/DGLR Symposium}, number = {1. Auflage}, editor = {Dillmann, Andreas and Heller, Gerd and Kr{\"a}mer, Ewald and Wagner, Claus}, publisher = {Springer International Publishing}, address = {Cham}, isbn = {978-3-030-79560-3}, doi = {10.1007/978-3-030-79561-0_43}, pages = {451 -- 460}, abstract = {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.}, language = {en} } @inproceedings{TauwaldQuadrioRuettenetal., author = {Tauwald, Sandra Melina and Quadrio, Maurizio and R{\"u}tten, Markus and Stemmer, Christian and Krenkel, Lars}, title = {High Spatial Resolution Tomo-PIV of the Trachea Focussing on the Physiological Breathing Cycle}, series = {New Results in Numerical and Experimental Fluid Mechanics XIV - Contributions to the 23nd STAB/DGLR Symposium}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics XIV - Contributions to the 23nd STAB/DGLR Symposium}, publisher = {Springer}, abstract = {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.}, language = {en} } @article{KrieglKrenkelShamoninChamonine, author = {Kriegl, Raphael and Krenkel, Lars and Shamonin (Chamonine), Mikhail}, title = {Preservation of wetting ridges using field-induced plasticity of magnetoactive elastomers}, series = {Journal of Colloid and Interface Science}, volume = {683}, journal = {Journal of Colloid and Interface Science}, publisher = {Elsevier}, issn = {0021-9797}, doi = {10.1016/j.jcis.2024.12.132}, pages = {1019 -- 1027}, abstract = {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.}, language = {en} } @misc{BirkenmaierDorniaLehleetal., author = {Birkenmaier, Clemens and Dornia, Christian and Lehle, Karla and Krenkel, Lars}, title = {Feasibility of detecting thrombotic deposits in membrane oxygenators using micro computed tomography}, series = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, journal = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, language = {en} } @inproceedings{TschurtschenthalerKrenkelSchreiner, author = {Tschurtschenthaler, Karl and Krenkel, Lars and Schreiner, Rupert}, title = {Mechano-optical micro pillar sensor for biofluidmechanic wall shear stress measurements}, series = {25th Congress of the European Society of Biomechanics (ESB), July 7-10, 2019, Vienna, Austria}, booktitle = {25th Congress of the European Society of Biomechanics (ESB), July 7-10, 2019, Vienna, Austria}, language = {en} } @misc{TauwaldKrenkel, author = {Tauwald, Sandra Melina and Krenkel, Lars}, title = {Elementary experimental setup for flow visualization in upper human respiratory tract}, series = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, journal = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, language = {en} } @misc{WagnerKrenkelDoenitzetal., author = {Wagner, Thomas and Krenkel, Lars and D{\"o}nitz, Christian and Brawanski, Alexander}, title = {Influence of CFD Strategy on WSS and OSI Determination for Intracranial Aneurysm Rupture Assessment}, series = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, journal = {25th Congress of the European Society of Biomechanics, July 7-10, 2019, Vienna, Austria}, language = {en} } @misc{Krenkel, author = {Krenkel, Lars}, title = {Relevanz von Aerosolen im klinischen Kontext}, series = {Innovationstag Hygiene 2021, Continental Arena, Regensburg, Deutschland}, journal = {Innovationstag Hygiene 2021, Continental Arena, Regensburg, Deutschland}, language = {de} } @article{TauwaldErzingerQuadrioetal., author = {Tauwald, Sandra Melina and Erzinger, Florian and Quadrio, Maurizio and R{\"u}tten, Markus and Stemmer, Christian and Krenkel, Lars}, title = {Tomo-PIV in a patient-specific model of human nasal cavities: a methodological approach}, series = {Measurement Science and Technology}, volume = {35}, journal = {Measurement Science and Technology}, number = {5}, publisher = {IOP Publishing}, doi = {10.1088/1361-6501/ad282c}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:898-opus4-70393}, abstract = {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.}, language = {en} } @unpublished{ThausHofrichterLubnowetal., author = {Thaus, Christopher and Hofrichter, Elena and Lubnow, Matthias and Krenkel, Lars and Lehle, Karla}, title = {Hemocompatibility of Membrane Lung Components from Extracorporeal Membrane Oxygenation with Different Antithrombogenic Coatings}, doi = {10.20944/preprints202412.0615.v1}, pages = {1 -- 11}, abstract = {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 na{\"i}ve 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.}, language = {en} } @article{WagnerKranzKrenkeletal., author = {Wagner, Maria Stella and Kranz, Michael and Krenkel, Lars and Pointner, Daniel and Foltan, Maik and Lubnow, Matthias and Lehle, Karla}, title = {Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs}, series = {Frontiers in Medicine}, journal = {Frontiers in Medicine}, number = {11}, editor = {Becatti, Matteo}, publisher = {Frontiers}, doi = {10.3389/fmed.2024.1416319}, abstract = {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.}, language = {en} } @article{LingelHausPaschkeetal., author = {Lingel, Maximilian P. and Haus, Moritz and Paschke, Lukas and Foltan, Maik and Lubnow, Matthias and Gruber, Michael and Krenkel, Lars and Lehle, Karla}, title = {Clinical relevance of cell-free DNA during venovenous extracorporeal membrane oxygenation}, series = {Artificial organs}, volume = {47}, journal = {Artificial organs}, number = {11}, publisher = {Wiley}, issn = {1525-1594}, doi = {10.1111/aor.14616}, pages = {1720 -- 1731}, abstract = {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.}, language = {en} } @article{FoltanDinhGruberetal., author = {Foltan, Maik and Dinh, D. and Gruber, Michael and M{\"u}ller, Thomas and Hart, C. and Krenkel, Lars and Schmid, C. and Lehle, Karla}, title = {Incidence of neutrophil extracellular traps (NETs) in different membrane oxygenators: pilot in vitro experiments in commercially available coated membranes}, series = {Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs}, journal = {Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs}, doi = {10.1007/s10047-024-01486-4}, abstract = {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.}, language = {en} } @article{PaschkeFoltanWagneretal., author = {Paschke, Lukas and Foltan, Maik and Wagner, Maria S. and Lubnow, Matthias and Gruber, Michael and Krenkel, Lars and Lehle, Karla}, title = {Clinical Relevance of Platelet-Leukocyte Aggregates and Platelet P-Selectin Expression During Venovenous Extracorporeal Membrane Oxygenation}, series = {ASAIO Journal}, journal = {ASAIO Journal}, number = {April 03}, publisher = {Wolters Kluwer}, issn = {1058-2916}, doi = {10.1097/MAT.0000000000002421}, abstract = {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.}, language = {en} } @article{SteigerFoltanPhilippetal., author = {Steiger, Tamara and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Gruber, Michael and Bredthauer, Andre and Krenkel, Lars and Birkenmaier, Clemens and Lehle, Karla}, title = {Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients?}, series = {Artificial Organs}, volume = {43}, journal = {Artificial Organs}, number = {11}, publisher = {Wiley}, address = {Hoboken}, issn = {1525-1594}, doi = {10.1111/aor.13513}, pages = {1065 -- 1076}, abstract = {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.}, language = {en} } @misc{KrenkelMichelKeiletal., author = {Krenkel, Lars and Michel, Johanna and Keil, Niklas and Daschner, Jan}, title = {Experimental Investigation of Logitudinal Folds in Endotracheal Tube Cuffs and their Correlation to Silent Breathing}, series = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, journal = {23. DGLR Fach-Symposium Str{\"o}mungen mit Abl{\"o}sung, 09./10. November 2022, Berlin, Deutschland}, address = {G{\"o}ttingen}, organization = {Deutsche Gesellschaft f{\"u}r Luft- und Raumfahrt e.V. / Arbeitsgemeinschaft Str{\"o}mungen mit Abl{\"o}sung, AG STAB}, abstract = {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.}, language = {en} } @article{HausFoltanPhilippetal., author = {Haus, Moritz and Foltan, Maik and Philipp, Alois and M{\"u}ller, Thomas and Lingel, Maximilian P. and Krenkel, Lars and Gruber, Michael and Lehle, Karla}, title = {Neutrophil extracellular traps -a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation}, volume = {15}, publisher = {frontiers}, doi = {10.3389/fimmu.2024.1339235}, abstract = {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.}, language = {en} } @misc{BroserFalterŁawrowskietal., author = {Broser, Christian and Falter, Thomas and Ławrowski, Robert Damian and Altenbuchner, Amelie and V{\"o}gele, Daniel and Koss, Claus and Schlamp, Matthias and Dunnweber, Jan and Steffens, Oliver and Heckner, Markus and Jaritz, Sabine and Schiegl, Thomas and Corsten, Sabine and Lauer, Norina and Guertler, Katherine and Koenig, Eric and Haug, Sonja and Huber, Dominik and Birkenmaier, Clemens and Krenkel, Lars and Wagner, Thomas and Justus, Xenia and Saßmannshausen, Sean Patrick and Kleine, Nadine and Weber, Karsten and Braun, Carina N. and Giacoppo, Giuliano and Heinrich, Michael and Just, Tobias and Schreck, Thomas and Schnabl, Andreas and Gilmore, Amador T{\´e}ran and Roeslin, Samuel and Schmid, Sandra and Wellnitz, Felix and Malz, Sebastian and Maurial, Andreas and Hauser, Florian and Mottok, J{\"u}rgen and Klettke, Meike and Scherzinger, Stefanie and St{\"o}rl, Uta and Heckner, Markus and Bazo, Alexander and Wolff, Christian and Kopper, Andreas and Westner, Markus and Pongratz, Christian and Ehrlich, Ingo and Briem, Ulrich and Hederer, Sebastian and Wagner, Marcus and Schillinger, Moritz and G{\"o}rlach, Julien and Hierl, Stefan and Siegl, Marco and Langer, Christoph and Hausladen, Matthias and Schreiner, Rupert and Haslbeck, Matthias and Kreuzer, Reinhard and Br{\"u}ckl, Oliver and Dawoud, Belal and Rabl, Hans-Peter and Gamisch, Bernd and Schmidt, Ottfried and Heberl, Michael and G{\"a}nsbauer, Bianca and Bick, Werner and Ellermeier, Andreas and Monkman, Gareth J. and Prem, Nina and Sindersberger, Dirk and Tschurtschenthaler, Karl and Aurbach, Maximilian and Dendorfer, Sebastian and Betz, Michael A. and Szecsey, Tamara and Mauerer, Wolfgang and Murr, Florian}, title = {Forschung 2018}, editor = {Baier, Wolfgang}, address = {Regensburg}, organization = {Ostbayerische Technische Hochschule Regensburg}, isbn = {978-3-9818209-5-9}, doi = {10.35096/othr/pub-1382}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:898-opus4-13826}, pages = {98}, subject = {Forschung}, language = {de} } @article{DeuterHajBrawanskietal., author = {Deuter, Daniel and Haj, Amer and Brawanski, Alexander and Krenkel, Lars and Schmidt, Nils Ole and Doenitz, Christian}, title = {Fast simulation of hemodynamics in intracranial aneurysms for clinical use}, series = {Acta Neurochirurgica}, volume = {167}, journal = {Acta Neurochirurgica}, publisher = {Springer}, doi = {10.1007/s00701-025-06469-9}, pages = {14}, abstract = {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.}, language = {en} } @inproceedings{RuettenKrenkelQuadrio, author = {R{\"u}tten, Markus and Krenkel, Lars and Quadrio, Maurizio}, title = {Simulation and Analyis of the Unsteady Flow within Nasal Airways}, series = {9th European Congress on Computational Methods in Applied Sciences and Engineering - ECCOMAS Congress, 3-7 June 2024, Lisbon, Portugal}, booktitle = {9th European Congress on Computational Methods in Applied Sciences and Engineering - ECCOMAS Congress, 3-7 June 2024, Lisbon, Portugal}, language = {en} } @inproceedings{KrenkelWagnerWolfetal., author = {Krenkel, Lars and Wagner, Claus and Wolf, Ursula and Scholz, Alexander-Wigbert K. and Terekhov, Maxim and Rivoire, Julien and Schreiber, W.}, title = {Protective Artificial Lung Ventilation: Impact of an Endotracheal Tube on the Flow in a Generic Trachea}, series = {New Results in Numerical and Experimental Fluid Mechanics VII : Contributions to the 16th STAB/DGLR Symposium Aachen, Germany 2008}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics VII : Contributions to the 16th STAB/DGLR Symposium Aachen, Germany 2008}, editor = {Hirschel, Ernst Heinrich and Schr{\"o}der, Wolfgang and Fujii, Kozo and Haase, Werner and Leer, Bram and Leschziner, Michael A. and Pandolfi, Maurizio and Periaux, Jacques and Rizzi, Arthur and Roux, Bernard and Shokin, Yurii I. and Dillmann, Andreas and Heller, Gerd and Klaas, Michael and Kreplin, Hans-Peter and Nitsche, Wolfgang}, publisher = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, isbn = {978-3-642-14242-0}, doi = {10.1007/978-3-642-14243-7_62}, pages = {505 -- 512}, abstract = {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.}, language = {en} } @misc{FriedrichRivoireScholzetal., author = {Friedrich, Janet and Rivoire, Julien and Scholz, Alexander-Wigbert K. and Wiegbert, and Terekov, Maxim and Kbrich, Rainer and Krenkel, Lars and Wagner, Claus and Schreiber, Laura Maria}, title = {Exploration of Gas Flow During High Frequency Oscillated Ventilation by 19F-Gas-MRI}, series = {Proceedings of the International Society for Magnetic Resonance in Medicine}, volume = {18}, journal = {Proceedings of the International Society for Magnetic Resonance in Medicine}, abstract = {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.}, language = {en} } @misc{KreftingZaunsederSaeringetal., author = {Krefting, Dagmar and Zaunseder, Sebastian and S{\"a}ring, Dennis and Wittenberg, Thomas and Palm, Christoph and Schiecke, Karin and Krenkel, Lars and Hennemuth, Anja and Schnell, Susanne and Spicher, Nicolai}, title = {Blutdruck, H{\"a}modynamik und Gef{\"a}ßzustand: Innovative Erfassung und Bewertung - Schwerpunkt bildbasierte Verfahren}, series = {66. Jahrestagung der Deutschen Gesellschaft f{\"u}r Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS), 12. Jahreskongress der Technologie- und Methodenplattform f{\"u}r die vernetzte medizinische Forschung e. V. (TMF), 26. - 30.09.2021, online}, journal = {66. Jahrestagung der Deutschen Gesellschaft f{\"u}r Medizinische Informatik, Biometrie und Epidemiologie e. V. (GMDS), 12. Jahreskongress der Technologie- und Methodenplattform f{\"u}r die vernetzte medizinische Forschung e. V. (TMF), 26. - 30.09.2021, online}, doi = {10.3205/21gmds016}, url = {http://nbn-resolving.de/urn:nbn:de:0183-21gmds0167}, abstract = {Einleitung: Blutdruck gilt als sogenannter Vitalparameter als einer der grundlegenden Indikatoren f{\"u}r den Gesundheitszustand einer Person. Sowohl zu niedriger als auch zu hoher Blutdruck kann lebensbedrohend sein, letzerer ist dar{\"u}ber hinaus ein Risikofaktor insbesondere f{\"u}r Herz-Kreislauferkrankungen, die trotz wichtiger Fortschritte in der Behandlung immer noch die h{\"a}ufigste Todesursache in Deutschland darstellen. Die H{\"a}modynamik, also die raumzeitliche Dynamik des Blutflusses, und der Gef{\"a}ßzustand sind eng verbunden mit dem Blutdruck und ebenfalls von hoher klinischer Relevanz, u.a. zur Identifikation von Durchblutungsst{\"o}rungen und ung{\"u}nstigen Druckverteilungen der Gef{\"a}ßwand. Innovationen in der Messtechnik als auch in der Datenanalyse bieten heute neue M{\"o}glichkeiten der Erfassung und Bewertung von Blutdruck, H{\"a}modynamik und Gef{\"a}ßzustand [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 Ans{\"a}tze und L{\"o}sungen f{\"u}r Mess- und Analyseverfahren zu Blutdruck und -fluss sowie zum Gef{\"a}ßzustand vorstellen und diskutieren. Dabei stehen im ersten Workshop auf der GMDS Jahrestagung Bildbasierte Verfahren im Zentrum, w{\"a}hrend der zweite Workshop auf der DGBMT Jahrestagung den Fokus auf Biosignalbasierten Verfahren legt. Es werden aktuelle Forschungsergebnisse vorgestellt und diskutiert. Es sind jeweils mehrere Vortr{\"a}ge geplant mit ausreichend Zeit zur Diskussion. Folgende Vortr{\"a}ge 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 h{\"a}modynamischer Parameter mit 4D flow MRI: M{\"o}glichkeiten und Herausforderungen Ergebnisse: Ziel des Workshops ist die Identifikation von innovativen Ans{\"a}tzen und neuen Methoden zur qualitativen und quantitativen Bestimmung von h{\"a}modynamischen Parametern sowie deren kritische Bewertung durch die Community f{\"u}r die Eignung in der klinischen Entscheidungsunterst{\"u}tzung. Diskussion: Der Workshop leistet inhaltlich einen Beitrag zu zentralen Aspekten f{\"u}r die Herz-Kreislauf-Medizin. Er bringt dabei Expertise aus verschiedenen Bereichen zusammen und schl{\"a}gt die Br{\"u}cke zwischen Kardiologie, Medizininformatik und Medizintechnik. Schlussfolgerung: Innovative Technologien aus Medizintechnik und Informatik erm{\"o}glichen zunehmend einfache und raumzeitlich aufgel{\"o}ste Erfassung und Bewertung wichtiger Informationen zur Unterst{\"u}tzung 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.}, subject = {Blutdruck}, language = {de} } @article{LehlePhilippKrenkeletal., author = {Lehle, Karla and Philipp, Alois and Krenkel, Lars and Gruber, Michael and Hiller, Karl-Anton and M{\"u}ller, Thomas and Lubnow, Matthias}, title = {Thrombocytopenia During Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Bacterial, Viral, and COVID-19 Pneumonia}, series = {ASAIO Journal}, journal = {ASAIO Journal}, publisher = {Wolters Kluwer}, issn = {1058-2916}, doi = {10.1097/MAT.0000000000002383}, abstract = {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.}, language = {en} } @article{BartschEigenbergerFelthausetal., author = {Bartsch, Alexander and Eigenberger, Andreas and Felthaus, Oliver and Booth, Brian W. and Krenkel, Lars and Schratzenstaller, Thomas and Prantl, Lukas}, title = {Quantification of Cannula Influence on Negative Pressure in Syringe Assisted Liposuction}, series = {Plastic \& Reconstructive Surgery}, journal = {Plastic \& Reconstructive Surgery}, publisher = {American Society of Plastic Surgeons}, issn = {0032-1052}, doi = {10.1097/PRS.0000000000012477}, abstract = {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.}, language = {en} } @article{KranzWagnerPointneretal., author = {Kranz, Michael and Wagner, Maria Stella and Pointner, Daniel and Haus, Moritz and Lubnow, Matthias and Lehle, Karla and Krenkel, Lars}, title = {Polymer embedding of membrane lungs for histological investigations of intra-device clot formation}, series = {Cardiovascular Medicine}, volume = {13}, journal = {Cardiovascular Medicine}, publisher = {Frontiers}, address = {Lausanne}, doi = {10.3389/fcvm.2026.1650978}, pages = {21}, abstract = {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}, language = {en} } @misc{MichelKrenkel, author = {Michel, Johanna and Krenkel, Lars}, title = {Experimental Investigation of Shear-Induced Generation of Respiratory Aerosol: Simultaneous Measurements of Particle Quantities and Wave Topology}, series = {2nd European Fluid Dynamics Conference (EFDC2), 26-29 August 2025, Dublin, Ireland}, journal = {2nd European Fluid Dynamics Conference (EFDC2), 26-29 August 2025, Dublin, Ireland}, doi = {10.35096/othr/pub-8859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:898-opus4-88593}, pages = {1}, abstract = {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.}, language = {en} } @inproceedings{KranzPointnerWagneretal., author = {Kranz, Michael and Pointner, Daniel and Wagner, Maria Stella and Lubnow, Matthias and Lehle, Karla and Krenkel, Lars}, title = {High-Resolution Flow Investigations in Membrane-Lungs for Understanding Shear-Induced Blood Clot Formation}, series = {New Results in Numerical and Experimental Fluid Mechanics XV : Contributions to the 24th STAB/DGLR Symposium, Regensburg, Germany, 2024}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics XV : Contributions to the 24th STAB/DGLR Symposium, Regensburg, Germany, 2024}, editor = {Dillmann, Andreas and Heller, Gerd and Kr{\"a}mer, Ewald and Breitsamter, Christian and Wagner, Claus and Krenkel, Lars}, publisher = {Springer}, address = {Cham}, doi = {10.1007/978-3-032-11115-9_12}, pages = {125 -- 134}, abstract = {Complex blood flow phenomena in membrane lungs (MLs) play a crucial role in intra-device clot formation and the occurrence of thromboembolic events. At present, however, the local flow conditions within an ML are not yet sufficiently known. The aim was to gain a deeper understanding of local flow regimes inside MLs by performing highly resolved computational fluid dynamics (CFD) of generic and native fiber mat bundles. Straight cylinders with a diameter of 380 μm in parallel arrangement were the foundation of the generic model. For validation, a method for reconstructing a native geometry from a microcomputed tomography (μCT) scan was established, with both models used for CFD. While the generic model showed a symmetrical flow regime without indicating any pathological flow, the native model did show an irregular fiber arrangement and no symmetrical flow regime. In conclusion, the fiber arrangement significantly affects the local flow regimes inside MLs.}, language = {en} } @misc{KranzPointnerLehleetal., author = {Kranz, Michael and Pointner, Daniel and Lehle, Karla and Lubnow, Matthias and Krenkel, Lars}, title = {High-resolution flow field investigations in membrane lungs, considering the complex blood rheology}, series = {1st European Fluid Dynamics Conference (EFDC1), 16-20.September 2024, Aachen}, journal = {1st European Fluid Dynamics Conference (EFDC1), 16-20.September 2024, Aachen}, doi = {10.35096/othr/pub-8921}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:898-opus4-89214}, pages = {2}, abstract = {Despite major improvements over the last years, coagulative disorders and clotting phenomena in membrane lungs (MLs) are still considerable complications in extracorporeal membrane oxygenation (ECMO). ECMO is an increasingly used treatment for patients with severe respiratory failure or cardiac arrest [1]. For both, evaluation of therapeutic decisions and fundamental research on patient specific intra-device clotting phenomena, the direct visualization and analysis of clot formation in combination with a detailed flow field correlation is highly desirable and therefore an intensively followed research topic. Modelling blood flow and shear induced coagulation in MLs is challenging. The relevant geometry of oxygenator fibers and chaining threads is complex and spans several length scales. In relevant scales and regimes, blood shows several significant non-Newtonian effects. Viscosity impacts shear rate, which is important in several coagulation mechanisms. Additionally, coagulation processes are influencing fluid properties and geometry significantly. Existing approaches of previous research work are only able to consider some, but not all relevant effects and geometrical details. Due to the enormous size of the discretized geometries, highly detailed viscosity and coagulations models are not applicable. Our goal is to develop a model for combined viscosity and coagulation properties of blood flow in MLs. In our work, we compare the influence of different levels of detail of the ML geometry as well as the influence of considering realistic blood flow behavior (viscosity change by considering the local hematocrit distribution within the F{\aa}hraeus-Lindqvist-Effect) on the resulting flow field in relevant subsections of a ML. High-resolution micro-CT geometry reconstructions [1] are compared to idealized generic fiber representations. For realistic blood flow modelling, Newtonian representation is compared to the established Carreau-Yasuda and a multiphase Euler-Euler approach. Results are presented for relevant subsections as well as for the complete ML.}, language = {en} } @misc{KranzWagnerPointneretal., author = {Kranz, Michael and Wagner, Maria Stella and Pointner, Daniel and Waldbauer, Selina and M{\"u}ller, Thomas and Lubnow, Matthias and Foltan, Maik and Krenkel, Lars and Lehle, Karla}, title = {Polymeric Embedding of Membrane Lungs: A Novel Method for Histological Investigations of Intra-Device Clot Formation}, series = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, journal = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, language = {en} } @misc{KranzWagnerKrenkeletal., author = {Kranz, Michael and Wagner, Maria Stella and Krenkel, Lars and M{\"u}ller, Thomas and Lubnow, Matthias and Philipp, Alois and Lehle, Karla}, title = {Clot Localization within Membrane Lungs using different Imaging Methods and Histological Clot Characterization as a way to prevent Thrombosis in Extracorporeal Membrane Oxygenation}, volume = {2023}, language = {en} } @misc{KoesterKranzWagneretal., author = {K{\"o}ster, Leonie and Kranz, Michael and Wagner, Maria Stella and Foltan, Maik and M{\"u}ller, Thomas and Lubnow, Matthias and Krenkel, Lars and Lehle, Karla}, title = {Histological Investigations of Intra-Device Clot Formation in ECMO Pumps}, series = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, journal = {12th EuroELSO Congress, 24-27. April 2024, Krakow}, language = {en} } @article{PointnerKranzWagneretal., author = {Pointner, Daniel and Kranz, Michael and Wagner, Maria Stella and Haus, Moritz and Lehle, Karla and Krenkel, Lars}, title = {Automated deep learning based detection of cellular deposits on clinically used ECMO membrane lungs}, series = {Frontiers in Bioinformatics}, volume = {6}, journal = {Frontiers in Bioinformatics}, publisher = {Frontiers}, doi = {10.3389/fbinf.2026.1771574}, pages = {18}, abstract = {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.}, language = {en} } @inproceedings{MichelKrenkel, author = {Michel, Johanna and Krenkel, Lars}, title = {Towards Experimental Validation of Models of Shear-Induced Aerosol Generation in the Human Respiratory System}, series = {New Results in Numerical and Experimental Fluid Mechanics XV : Contributions to the 24th STAB/DGLR Symposium, Regensburg, Germany, 2024}, booktitle = {New Results in Numerical and Experimental Fluid Mechanics XV : Contributions to the 24th STAB/DGLR Symposium, Regensburg, Germany, 2024}, editor = {Dillmann, Andreas and Heller, Gerd and Kr{\"a}mer, Ewald and Breitsamter, Christian and Wagner, Claus and Krenkel, Lars}, publisher = {Springer Nature}, address = {Cham}, isbn = {978-3-032-11114-2}, doi = {10.1007/978-3-032-11115-9_13}, pages = {135 -- 144}, abstract = {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.}, language = {en} }