TY - JOUR A1 - Sellmer, Andreas A1 - Stangl, Hubert A1 - Beyer, Mandy A1 - Grünstein, Elisabeth A1 - Leonhardt, Michel A1 - Pongratz, Herwig A1 - Eichhorn, Emerich A1 - Elz, Sigurd A1 - Striegl, Birgit A1 - Jenei-Lanzl, Zsuzsa A1 - Dove, Stefan A1 - Straub, Rainer H. A1 - Krämer, Oliver H. A1 - Mahboobi, Siavosh T1 - Marbostat-100 Defines a New Class of Potent and Selective Antiinflammatory and Antirheumatic Histone Deacetylase 6 Inhibitors JF - Journal of medicinal chemistry N2 - Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug. KW - Animals KW - anti-Inflammatory agent KW - chemical synthesis KW - pharmacology KW - therapeutic use KW - toxicity Y1 - 2018 U6 - https://doi.org/10.1021/acs.jmedchem.7b01593 VL - 61 IS - 8 SP - 3454 EP - 3477 PB - ACS Publications ER - TY - JOUR A1 - Schroeder, Florian A1 - Polzer, Stanislav A1 - Slažanský, Martin A1 - Man, Vojtěch A1 - Skácel, Pavel T1 - Predictive capabilities of various constitutive models for arterial tissue JF - Journal of the Mechanical Behavior of Biomedical Materials N2 - Introduction Aim of this study is to validate some constitutive models by assessing their capabilities in describing and predicting uniaxial and biaxial behavior of porcine aortic tissue. Methods 14 samples from porcine aortas were used to perform 2 uniaxial and 5 biaxial tensile tests. Transversal strains were furthermore stored for uniaxial data. The experimental data were fitted by four constitutive models: Holzapfel-Gasser-Ogden model (HGO), model based on generalized structure tensor (GST), Four-Fiber-Family model (FFF) and Microfiber model. Fitting was performed to uniaxial and biaxial data sets separately and descriptive capabilities of the models were compared. Their predictive capabilities were assessed in two ways. Firstly each model was fitted to biaxial data and its accuracy (in term of R2 and NRMSE) in prediction of both uniaxial responses was evaluated. Then this procedure was performed conversely: each model was fitted to both uniaxial tests and its accuracy in prediction of 5 biaxial responses was observed. Results Descriptive capabilities of all models were excellent. In predicting uniaxial response from biaxial data, microfiber model was the most accurate while the other models showed also reasonable accuracy. Microfiber and FFF models were capable to reasonably predict biaxial responses from uniaxial data while HGO and GST models failed completely in this task. Conclusions HGO and GST models are not capable to predict biaxial arterial wall behavior while FFF model is the most robust of the investigated constitutive models. Knowledge of transversal strains in uniaxial tests improves robustness of constitutive models. KW - Arterial biomechanics KW - Constitutive modeling KW - Mechanical testing KW - Uniaxial – biaxial tension Y1 - 2018 U6 - https://doi.org/10.1016/j.jmbbm.2017.11.035 VL - 78 IS - February SP - 369 EP - 380 PB - Elsevier ER - TY - JOUR A1 - Schmitz, Paul A1 - Neumann, Christoph Cornelius A1 - Neumann, Carsten A1 - Nerlich, Michael A1 - Dendorfer, Sebastian T1 - Biomechanical analysis of iliac crest loading following cortico-cancellous bone harvesting JF - Journal of Orthopaedic Surgery and Research N2 - Background Iliac crest bone harvesting is a frequently performed surgical procedure widely used to treat bone defects. The objective of this study is to assess the biomechanical quantities related to risk for pelvic fracture after harvesting an autologous bone graft at the anterior iliac crest. Methods Finite element models with a simulated harvest site (sized 15 × 20 mm, 15 × 35 mm, 30 × 20 mm and 30 × 35 mm) in the iliac wing are created. The relevant loading case is when the ipsilateral leg is lifted off the ground. Musculoskeletal analysis is utilized to compute the muscle and joint forces involved in this motion. These forces are used as boundary conditions for the finite element analyses. Bone tissue stress is analyzed. Results Critical stress peaks are located between the anterior superior iliac spine (ASIS) and the anterior edge of the harvest site. Irrespective of the graft size, the iliac wing does not show any significant stress peaks with the harvest site being 20 to 25 mm posterior to the ASIS. The harvest area itself inhibits the distribution of the forces applied on the ASIS to extend to the posterior iliac wing. This leads to a lack of stress posterior to the harvest site. A balanced stress distribution with no stress peaks appears when the bone graft is taken below the iliac crest. Conclusion A harvest site located at least 20 to 25 mm posterior to the ASIS should be preferred to minimize the risk of iliac fatigue fracture. KW - Bone harvesting KW - Autologous bone graft KW - Iliac crest KW - Fatigue fracture KW - Pelvis KW - ASIS KW - FEA KW - Biomechanical investigation KW - Beckenkammknochen KW - Knochenentnahme KW - Spongiosa KW - Biomechanische Analyse Y1 - 2018 U6 - https://doi.org/10.1186/s13018-018-0822-1 VL - 13 IS - 108 SP - 1 EP - 8 PB - Springer Nature ER - TY - CHAP A1 - Aurbach, Maximilian A1 - Jungtäubl, Dominik A1 - Spicka, Jan A1 - Dendorfer, Sebastian T1 - EMG-based validation of musculoskeletal models considering crosstalk T2 - World Congress Biomechanics, 28-30 June 2018, Dublin N2 - BACKGROUND: Validation and verification of multibody musculoskeletal models sEMG is a difficult process because of the reliability of sEMG data and the complex relationship of muscle force and sEMG. OBJECTIVE: This work aims at comparing experimentally recorded and simulated muscle activities considering a numerical model for crosstalk. METHODS: For providing an experimentally derived reference data set, subjects were performing elevations of the arm, where the activities of the contemplated muscle groups were measured by sEMG sensors. Computed muscle activities were further processed and transformed into an artificial electromyographical signal, which includes a numerical crosstalk model. In order to determine whether the crosstalk model provides a better agreement with the measured muscle activities, the Pearson correlation coefficient has been computed as a qualitative way of assessing the curve progression of the data sets. RESULTS: The results show an improvement in the correlation coefficient between the experimental data and the simulated muscle activities when taking crosstalk into account. CONCLUSIONS: Although the correlation coefficient increased when the crosstalk model was utilized, it is questionable if the discretization of both, the crosstalk and the musculoskeletal model, is accurate enough. Y1 - 2018 U6 - https://doi.org/10.1109/BIOMDLORE.2018.8467211 ER - TY - GEN A1 - Singh, Max Diamond T1 - Zusätzliche Anforderungen an Produktdaten und technische Dokumentation durch die MDR T2 - Medizintechnik Kongress 2018: Effizienz in der Medizinprodukteentwicklung vor dem Hintergrund von MDR und IVDR ; Frankfurt am Main, 08.11.2018, [Veranstalter: Velten Consulting & ILC Consulting] Y1 - 2018 ER - TY - GEN A1 - Singh, Max Diamond T1 - Notified Body Viewpoint : Preparing for MDR/IVDR T2 - MDR/IVDR - Status Report from Stakeholders. Where are we now in November 2018? - Bern, 22.11.2018 - [Veranstalter: RAPS : Regulatory Affairs Professionals Society] Y1 - 2018 ER - TY - GEN A1 - Singh, Max Diamond T1 - Overview of the Medical Device Regulation (MDR) BT - MDR-Roadshow TÜV SÜD MHS, San Diego & Minneapolis, 2018 Y1 - 2018 ER - TY - JOUR A1 - Raptis, Georgios T1 - Technischer Datenschutz in der telemedizinischen Versorgung JF - Der Krankenhaus-JUSTITIAR N2 - Die fortschreitende Digitalisierung des Gesundheitswesens ebnet auch den Weg einer stärkeren Verbreitung der telemedizinischen Versorgung in Deutschland. Die Politik erleichtert diesen Weg, z.B. mit dem eHealth-Gesetz oder mit der Lockerung des "Fernbehandlungsverbots" durch den Deutschen Ärztetag. Dabei wird schon aus der Definition (siehe z.B. die unten stehende Definition der AG Telemedizin) klar, dass Telemedizin keine neue medizinische Disziplin begründet. Bei Telemedizin handelt es sich nur um ein technisches Werkzeug in Kombination mit geeigneten klinischen Prozessen, damit bestehende medizinische Expertise unter Einsatz von Informations- und Kommunikationstechnologien räumliche Entfernungen oder einen zeitlichen Versatz überbrücken kann. Patientinnen und Patienten können also behandelt werden, auch wenn sie vom Arzt räumlich entfernt sind. KW - Telemedizin KW - Datenschutz Y1 - 2018 VL - 7 IS - 4 SP - 105 EP - 107 ER - TY - JOUR A1 - Benditz, Achim A1 - Auer, Simon A1 - Spörrer, J.F. A1 - Wolkerstorfer, S. A1 - Grifka, Joachim A1 - Süß, Franz A1 - Dendorfer, Sebastian T1 - Regarding loads after spinal fusion, every level should be seen separately: a musculoskeletal analysis JF - European Spine Journal N2 - The number of spinal fusion surgeries is steadily increasing and biomechanical consequences are still in debate. The aim of this study is to provide biomechanical insights into the sagittal balance of the spine and to compare spinal load before and after spinal fusion. METHOD: The joint reaction forces of 52 patients were analyzed in proximo-distal and antero-posterior direction from the levels T12-L1 to L5-S1 using musculoskeletal simulations. RESULTS: In 104 simulations, pre-surgical forces were equal to post-surgical. The levels L4-L5 and T12-L1, however, showed increased spinal forces compression forces with higher sagittal displacement. Improved restauration of sagittal balance was accompanied by lower spinal load. AP shear stress, interestingly decreased with sagittal imbalance. CONCLUSION: Imbalanced spines have a risk of increased compression forces at Th12-L1. L4-L5 always has increased spinal loads. These slides can be retrieved under Electronic Supplementary Material. KW - AnyBody Modeling System KW - Musculoskeletal analysis KW - Sagittal balance KW - Spinal fusion KW - Spine biomechanics KW - Biomechanische Analyse KW - Wirbelsäulenversteifung KW - Vergleichende Anatomie Y1 - 2018 U6 - https://doi.org/10.1007/s00586-018-5476-5 VL - 27 IS - 8 SP - 1905 EP - 1910 PB - Springer-Verlag ER - TY - CHAP A1 - Gross, Simon A1 - Verkerke, Gijsbertus Jacob A1 - Dendorfer, Sebastian T1 - Combined Experimental and Numerical Approach to Investigate Changes in Muscle Recruitment Pattern of the Back Muscles during Exhausting Exercise T2 - World Congress Biomechanics Dublin, 2018 N2 - In recent years, musculoskeletal computation has become a widely used tool to investigate joint and muscle forces within the human body. However, the issue of muscle fatigue is not considered adequately in most models and is a challenging task. One aspect that needs to be examined is the interaction of muscles during an exhausting task. Therefore, an experimental study was designed to analyze the changes of back muscle recruitment pattern during such exercises. In this study 38 subjects (27 male, 11 female, height = 177±8.5 cm, weight = 74.0±13.6 kg) participated. Each subject had to perform three static and three dynamic exhausting exercises where the back muscles were loaded with subject specific forces using a dynamometer adapter especially designed for the trunk muscles. To collect the muscle activity, twelve surface electromyography sensors were applied on the back, and four on the abdominal muscles. Muscle activity and fatigue were analyzed by calculating the maximum voluntary contraction normalized signal and the median frequency. At first the fatigue of m. erector spinae and m. multifidi was analyzed, since these muscles carry the main load during the exercises. Subsequently the activity of the m. trapezius, m. rectus abdominis and m. obliquus externus were investigated to determine recruitment patterns. To gain more detailed information of these patterns a numerical model was built using the AnyBody Modeling System™. Analyzing the measurements, we can observe an increasing muscle activity during isokinetic exercises while the force is constant. Since the activity in the simulation is defined as the current force output divided by the strength of the muscle, the strength parameter was scaled down based on the measured data, assuming a linear force – activity correlation, and using a numerical algorithm considering the influence of cross talk. The results show, that changes in recruitment pattern can be divided into three major subgroups. Prior to total exhaustion, some of the subjects show additional activation of muscles in the trapezius region, while other subjects show an additional activation of abdominal muscles, increasing the intra-abdominal pressure which supports the spine. In the third group an activation in both regions can be observed. The numerical simulations show an increasing activity of abdominal muscles as well as muscles in the upper back. Especially the m. latissimus dorsi shows a significantly higher activity. The results lead to the conclusion that prior to total exhaustion, additional muscles are recruited to support the main muscles. It was shown that abdominal muscles are activated to support back muscles by pressurizing the trunk cavity to delay total exhaustion as long as possible. In conclusion, the results show that changes in muscle recruitment pattern need to be considered when introducing muscle fatigue to musculoskeletal models. Y1 - 2018 ER - TY - CHAP A1 - Jungtäubl, Dominik A1 - Aurbach, Maximilian A1 - Melzner, Maximilian A1 - Spicka, Jan A1 - Süß, Franz A1 - Dendorfer, Sebastian T1 - EMG-Based Validation of Musculoskeletal Models Considering Crosstalk T2 - International Conference BIOMDLORE, June 28 - 30 2018, Białystok, Poland N2 - BACKGROUND: Validation and verification of multibody musculoskeletal models sEMG is a difficult process because of the reliability of sEMG data and the complex relationship of muscle force and sEMG. OBJECTIVE: This work aims at comparing experimentally recorded and simulated muscle activities considering a numerical model for crosstalk. METHODS: For providing an experimentally derived reference data set, subjects were performing elevations of the arm, where the activities of the contemplated muscle groups were measured by sEMG sensors. Computed muscle activities were further processed and transformed into an artificial electromyographical signal, which includes a numerical crosstalk model. In order to determine whether the crosstalk model provides a better agreement with the measured muscle activities, the Pearson correlation coefficient has been computed as a qualitative way of assessing the curve progression of the data sets. RESULTS: The results show an improvement in the correlation coefficient between the experimental data and the simulated muscle activities when taking crosstalk into account. CONCLUSIONS: Although the correlation coefficient increased when the crosstalk model was utilized, it is questionable if the discretization of both, the crosstalk and the musculoskeletal model, is accurate enough. KW - musculoskeletal modeling KW - validation KW - surface electromyography KW - crosstalk Y1 - 2018 U6 - https://doi.org/10.1109/BIOMDLORE.2018.8467211 ER - TY - CHAP A1 - Kubowitsch, Simone A1 - Süß, Franz A1 - Jansen, Petra A1 - Dendorfer, Sebastian T1 - Comparison of dynamic muscular imbalances in back pain patients and healthy controls T2 - World Congress Biomechanics Dublin, 2018 Y1 - 2018 ER - TY - CHAP A1 - Seefried, C. A1 - Aurbach, Maximilian A1 - Wyss, C. A1 - Dendorfer, Sebastian T1 - Achilles tendon lengthening alters stresses in the growth plate T2 - International Conference BIOMDLORE, June 28 - 30 2018, Białystok, Poland Y1 - 2018 ER - TY - CHAP A1 - Süß, Franz A1 - Kubowitsch, Simone A1 - Verkerke, Gijsbertus Jacob A1 - Dendorfer, Sebastian T1 - Investigation of cognitive stress induced changes in spinal disc forces due to altered kinematics and muscle activity T2 - World Congress Biomechanics, Dublin, 2018 Y1 - 2018 ER - TY - CHAP A1 - Kubowitsch, Simone A1 - Dendorfer, Sebastian T1 - Psychologie und Biomechanik – Integrierte Betrachtung von Muskelrekrutierung BT - Erkenntnisse und Ableitungen für Biofeedback T2 - Jahrestagung der Deutschen Gesellschaft für Biofeedback e. V., Regensburg, 2018 Y1 - 2018 ER - TY - GEN A1 - Wiesent, Lisa A1 - Hupke, Constantin A1 - Balk, Christian A1 - Schultheiss, Ulrich A1 - Schratzenstaller, Thomas T1 - Optimization of the cardiovascular stent design towards improved expansion behaviour and radial stiffness properties T2 - Biomedizinische Technik N2 - - Development of a FEA Tool for a realistic stent simulation - investigation on minor modification on the stent design on the expansion behaviour - analysis of three stent designs: classical stent design with pronounced dogbone effect, two modified stent design (non-dogbone-design) KW - Kardiovaskuläres System KW - Stent Y1 - 2018 U6 - https://doi.org/10.1515/bmt-2018-6031 VL - 63 IS - s1 ER - TY - GEN A1 - Geith, Markus A. A1 - Swidergal, Krzysztof A1 - Schratzenstaller, Thomas A1 - Holzapfel, Gerhard A. A1 - Wagner, Marcus T1 - Numerical analysis of stent delivery systems during pre- and intraoperative processes T2 - 15. Deutsches LS-DYNA Forum, 15.-17.10.2018, Bamberg Y1 - 2018 UR - https://www.researchgate.net/publication/335260823_Numerical_analysis_of_stent_delivery_systems_during_pre-_and_intraoperative_processes ER - TY - CHAP A1 - Singh, Max Diamond A1 - Capanni, Felix ED - Pfannstiel Mario A., ED - Da-Cruz, Patrick ED - Rasche, Christoph T1 - Medizintechnik-Spin-offs aus der Hochschule - Ein Prozessbeispiel T2 - Entrepreneurship im Gesundheitswesen II N2 - Die Aufmerksamkeit für Unternehmensgründungen hat in den letzten Jahren extrem zugenommen. Grundsätzlich muss ein Start-up in einem kompetitiven Umfeld erfolgreich sein, um bestehen zu können. Der Weg dorthin wird maßgeblich beeinflusst durch Planung und finanzielle Ressourcen, die die Gründer bereitstellen müssen. In der Medizinprodukteindustrie kommen zusätzlich große Hürden hinzu, die u. a. einen kurzen Produktlebenszyklus, lange Projektlaufzeiten, aufwendige klinische Studien und aktuell neue gesetzliche Verordnungen betreffen. Dieser Beitrag konzentriert sich zunächst auf mögliche Fördermittel und Beratung von Start-up-Projekten aus dem Hochschulbereich. Aus einer Analyse derzeit existierender Gründerwettbewerbe im Hinblick auf das Gesundheitswesen werden dem Leser entsprechende Adressen zum Einwerben von Fördermitteln geliefert. Darüber hinaus wird ein Pilot-Prozess vorgestellt, wie eine Ausgründungsberatung an der Hochschule Ulm im Studiengang Medizintechnik derzeit verläuft. Dies kann möglicherweise ein Anknüpfungspunkt für eine zukünftige Institutionalisierung von Spin-off-Vorhaben aus dem Hochschulbereich sein. Y1 - 2018 SN - 978-3-658-14781-5 SN - 978-3-658-14780-8 PB - Springer Gabler CY - Wiesbaden ER - TY - CHAP A1 - Franz, Daniela A1 - Dreher, Maria A1 - Prinzen, Martin A1 - Teßmann, Matthias A1 - Palm, Christoph A1 - Katzky, Uwe A1 - Perret, Jerome A1 - Hofer, Mathias A1 - Wittenberg, Thomas T1 - CT-basiertes virtuelles Fräsen am Felsenbein BT - Bild- und haptischen Wiederholfrequenzen bei unterschiedlichen Rendering Methoden T2 - Bildverarbeitung für die Medizin 2018; Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 11. bis 13. März 2018 in Erlangen N2 - Im Rahmen der Entwicklung eines haptisch-visuellen Trainingssystems für das Fräsen am Felsenbein werden ein Haptikarm und ein autostereoskopischer 3D-Monitor genutzt, um Chirurgen die virtuelle Manipulation von knöchernen Strukturen im Kontext eines sog. Serious Game zu ermöglichen. Unter anderem sollen Assistenzärzte im Rahmen ihrer Ausbildung das Fräsen am Felsenbein für das chirurgische Einsetzen eines Cochlea-Implantats üben können. Die Visualisierung des virtuellen Fräsens muss dafür in Echtzeit und möglichst realistisch modelliert, implementiert und evaluiert werden. Wir verwenden verschiedene Raycasting Methoden mit linearer und Nearest Neighbor Interpolation und vergleichen die visuelle Qualität und die Bildwiederholfrequenzen der Methoden. Alle verglichenen Verfahren sind sind echtzeitfähig, unterscheiden sich aber in ihrer visuellen Qualität. KW - Felsenbein KW - Fräsen KW - Virtualisierung KW - Computertomographie KW - Computerassistierte Chirurgie Y1 - 2018 SN - 978-3-662-56537-7 U6 - https://doi.org/10.1007/978-3-662-56537-7_51 SP - 176 EP - 181 PB - Springer CY - Berlin ER - TY - JOUR A1 - Wöhl, Rebecca A1 - Maier, Johannes A1 - Gehmert, Sebastian A1 - Palm, Christoph A1 - Riebschläger, Birgit A1 - Nerlich, Michael A1 - Huber, Michaela T1 - 3D Analysis of Osteosyntheses Material using semi-automated CT Segmentation BT - a case series of a 4 corner fusion plate JF - BMC Musculoskeletal Disorders N2 - Backround Scaphoidectomy and midcarpal fusion can be performed using traditional fixation methods like K-wires, staples, screws or different dorsal (non)locking arthrodesis systems. The aim of this study is to test the Aptus four corner locking plate and to compare the clinical findings to the data revealed by CT scans and semi-automated segmentation. Methods: This is a retrospective review of eleven patients suffering from scapholunate advanced collapse (SLAC) or scaphoid non-union advanced collapse (SNAC) wrist, who received a four corner fusion between August 2011 and July 2014. The clinical evaluation consisted of measuring the range of motion (ROM), strength and pain on a visual analogue scale (VAS). Additionally, the Disabilities of the Arm, Shoulder and Hand (QuickDASH) and the Mayo Wrist Score were assessed. A computerized tomography (CT) of the wrist was obtained six weeks postoperatively. After semi-automated segmentation of the CT scans, the models were post processed and surveyed. Results During the six-month follow-up mean range of motion (ROM) of the operated wrist was 60°, consisting of 30° extension and 30° flexion. While pain levels decreased significantly, 54% of grip strength and 89% of pinch strength were preserved compared to the contralateral healthy wrist. Union could be detected in all CT scans of the wrist. While X-ray pictures obtained postoperatively revealed no pathology, two user related technical complications were found through the 3D analysis, which correlated to the clinical outcome. Conclusion Due to semi-automated segmentation and 3D analysis it has been proved that the plate design can keep up to the manufacturers’ promises. Over all, this case series confirmed that the plate can compete with the coexisting techniques concerning clinical outcome, union and complication rate. KW - Handchirurgie KW - Osteosynthese KW - Arthrodese KW - 4FC KW - SLAC wrist KW - SNAC wrist KW - Semi-automated segmentation KW - 3D analysis KW - Computertomographie KW - Bildsegmentierung KW - Dreidimensionale Bildverarbeitung Y1 - 2018 U6 - https://doi.org/10.1186/s12891-018-1975-0 VL - 19 SP - 1 EP - 8 PB - Springer Nature ER - TY - CHAP A1 - Eixelberger, Thomas A1 - Wittenberg, Thomas A1 - Perret, Jerome A1 - Katzky, Uwe A1 - Simon, Martina A1 - Schmitt-Rüth, Stephanie A1 - Hofer, Mathias A1 - Sorge, M. A1 - Jacob, R. A1 - Engel, Felix B. A1 - Gostian, A. A1 - Palm, Christoph A1 - Franz, Daniela T1 - A haptic model for virtual petrosal bone milling T2 - 17. Jahrestagung der Deutschen Gesellschaft für Computer- und Roboterassistierte Chirurgie (CURAC2018), Tagungsband, 2018, Leipzig, 13.-15. September N2 - Virtual training of bone milling requires realtime and realistic haptics of the interaction between the ”virtual mill” and a ”virtual bone”. We propose an exponential abrasion model between a virtual one and the mill bit and combine it with a coarse representation of the virtual bone and the mill shaft for collision detection using the Bullet Physics Engine. We compare our exponential abrasion model to a widely used linear abrasion model and evaluate it quantitatively and qualitatively. The evaluation results show, that we can provide virtual milling in real-time, with an abrasion behavior similar to that proposed in the literature and with a realistic feeling of five different surgeons. KW - Osteosynthese KW - Simulation KW - Lernprogramm Y1 - 2018 UR - https://www.curac.org/images/advportfoliopro/images/CURAC2018/CURAC 2018 Tagungsband.pdf VL - 17 SP - 214 EP - 219 ER - TY - CHAP A1 - Maier, Johannes A1 - Huber, Michaela A1 - Katzky, Uwe A1 - Perret, Jerome A1 - Wittenberg, Thomas A1 - Palm, Christoph T1 - Force-Feedback-assisted Bone Drilling Simulation Based on CT Data T2 - Bildverarbeitung für die Medizin 2018; Algorithmen - Systeme - Anwendungen; Proceedings des Workshops vom 11. bis 13. März 2018 in Erlangen N2 - In order to fix a fracture using minimally invasive surgery approaches, surgeons are drilling complex and tiny bones with a 2 dimensional X-ray as single imaging modality in the operating room. Our novel haptic force-feedback and visual assisted training system will potentially help hand surgeons to learn the drilling procedure in a realistic visual environment. Within the simulation, the collision detection as well as the interaction between virtual drill, bone voxels and surfaces are important. In this work, the chai3d collision detection and force calculation algorithms are combined with a physics engine to simulate the bone drilling process. The chosen Bullet-Physics-Engine provides a stable simulation of rigid bodies, if the collision model of the drill and the tool holder is generated as a compound shape. Three haptic points are added to the K-wire tip for removing single voxels from the bone. For the drilling process three modes are proposed to emulate the different phases of drilling in restricting the movement of a haptic device. KW - Handchirurgie KW - Osteosynthese KW - Simulation KW - Lernprogramm Y1 - 2018 U6 - https://doi.org/10.1007/978-3-662-56537-7_78 SP - 291 EP - 296 PB - Springer CY - Berlin ER - TY - JOUR A1 - Graßmann, Felix A1 - Mengelkamp, Judith A1 - Brandl, Caroline A1 - Harsch, Sebastian A1 - Zimmermann, Martina E. A1 - Linkohr, Birgit A1 - Peters, Annette A1 - Heid, Iris M. A1 - Palm, Christoph A1 - Weber, Bernhard H. F. T1 - A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography JF - Ophtalmology N2 - Purpose Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Design Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. Participants. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. Methods. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. Main Outcome Measures. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. Results. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%–92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly. Conclusions Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age. KW - Senile Makuladegeneration KW - Krankheitsverlauf KW - Mustererkennung KW - Maschinelles Lernen Y1 - 2018 U6 - https://doi.org/10.1016/j.ophtha.2018.02.037 N1 - Corresponding authors: Bernhard H. F. Weber, University of Regensburg, and Christoph Palm VL - 125 IS - 9 SP - 1410 EP - 1420 PB - Elsevier ER - TY - GEN A1 - Birkenmaier, Clemens A1 - Krenkel, Lars T1 - Towards a realistic model of blood viscosity and coagulation in membrane oxygenators T2 - 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 N2 - 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. KW - Blood Viscosity KW - Shear Raed Induced Coagulation KW - Membrane Oxygenator Y1 - 2018 ER - TY - GEN A1 - Birkenmaier, Clemens A1 - Krenkel, Lars A1 - Lehle, Karla T1 - Linking flow conditions in membrane oxygenators to arrangements of multimeric von-Willebrand-factor as indication for coagulation T2 - World Congress of Biomechanics 2018, Convention Centre Dublin, 8.-12. Juli 2018 N2 - 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. Y1 - 2018 ER - TY - CHAP A1 - Birkenmaier, Clemens A1 - Steiger, Tamara A1 - Philipp, Alois A1 - Lehle, Karla A1 - Krenkel, Lars T1 - Flow-induced accumulations of von Willebrand factor inside oxygenators during extracorporeal life support therapy T2 - Proceedings of 12th International Conference BIOMDLORE 2018, June 28–30, 2018, Białystok, Poland N2 - BACKGROUND: Shear-induced conformational changes of von Willebrand factor (vWF) may be responsible for coagulation disorder and clot formation inside membrane oxygenators (MOs) during extracorporeal membrane oxygenation (ECMO) therapy. OBJECTIVE: The aim was to identify vWF structures inside clinically used MOs and employ computational fluid dynamics to verify the corresponding flow conditions. METHODS: Samples from gas exchange membranes (GEM) from MOs were analysed for accumulations of vWF and P-selectin-positive platelets using immunofluorescence techniques. Streamlines and shear rates of the flow around GEMs were computed using a laminar steady Reynolds-Averaged-Navier-Stokes approach. RESULTS: Most samples were colonized with equally distributed leukocytes, integrated in thin cobweb-like vWF-structures. Only 25 % of the samples showed extended accumulations of vWF. Computed streamlines showed considerable cross flow between interconnected neighbouring channels. Stagnation points were non-symmetric and contact faces were washed around closely. The occurring maximum shear rates ranged from 2,500 to 3,000 1/s. CONCLUSIONS: If pronounced vWF structures are present, shape and extent match the flow computations well. Computed shear rates bear a critical degree of uncertainty due to the improper viscosity model. If flow conditions inside the MO were sufficient to affect vWF, a more consistent distribution of vWF across the samples should be present. KW - Blood Viscosity KW - Shear Rate Induced Coagulation KW - Hemodynamics KW - Membrane Oxygenator KW - von Willebrand factor Y1 - 2018 SN - 978-1-5386-2396-1 U6 - https://doi.org/10.1109/BIOMDLORE.2018.8467205 PB - IEEE CY - Piscataway, NJ ER - TY - JOUR A1 - Philipp, Alois A1 - de Somer, Filip A1 - Foltan, Maik A1 - Bredthauer, Andre A1 - Krenkel, Lars A1 - Zeman, Florian A1 - Lehle, Karla T1 - Life span of different extracorporeal membrane systems for severe respiratory failure in the clinical practice JF - PLOS ONE N2 - 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. KW - Equipment Failure Analysis/statistics & numerical data KW - Extracorporeal Membrane Oxygenation/instrumentation KW - Membrane/classification/standards/statistics & numerical data KW - Primary Health Care/statistics & numerical data KW - Respiratory Distress Syndrome/therapy KW - Retrospective Studies KW - Severity of Illness Index KW - Time factors KW - MULTIDETECTOR COMPUTED-TOMOGRAPHY KW - THROMBOTIC DEPOSITS KW - ECMO SYSTEMS KW - Flow KW - OXYGENATION Y1 - 2018 U6 - https://doi.org/10.1371/journal.pone.0198392 VL - 13 IS - 6 SP - 1 EP - 10 PB - PLOS ER - TY - JOUR A1 - De Souza Jr., Luis Antonio A1 - Palm, Christoph A1 - Mendel, Robert A1 - Hook, Christian A1 - Ebigbo, Alanna A1 - Probst, Andreas A1 - Messmann, Helmut A1 - Weber, Silke A. T. A1 - Papa, João Paulo T1 - A survey on Barrett's esophagus analysis using machine learning JF - Computers in Biology and Medicine N2 - This work presents a systematic review concerning recent studies and technologies of machine learning for Barrett's esophagus (BE) diagnosis and treatment. The use of artificial intelligence is a brand new and promising way to evaluate such disease. We compile some works published at some well-established databases, such as Science Direct, IEEEXplore, PubMed, Plos One, Multidisciplinary Digital Publishing Institute (MDPI), Association for Computing Machinery (ACM), Springer, and Hindawi Publishing Corporation. Each selected work has been analyzed to present its objective, methodology, and results. The BE progression to dysplasia or adenocarcinoma shows a complex pattern to be detected during endoscopic surveillance. Therefore, it is valuable to assist its diagnosis and automatic identification using computer analysis. The evaluation of the BE dysplasia can be performed through manual or automated segmentation through machine learning techniques. Finally, in this survey, we reviewed recent studies focused on the automatic detection of the neoplastic region for classification purposes using machine learning methods. KW - Speiseröhrenkrankheit KW - Diagnose KW - Mustererkennung KW - Maschinelles Lernen KW - Literaturbericht KW - Barrett's esophagus KW - Machine learning KW - Adenocarcinoma KW - Image processing KW - Pattern recognition KW - Computer-aided diagnosis Y1 - 2018 U6 - https://doi.org/10.1016/j.compbiomed.2018.03.014 VL - 96 SP - 203 EP - 213 PB - Elsevier ER -