Universität Stuttgart
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Item Open Access Patient‐specific simulation of brain tumour growth and regression(2023) Suditsch, Marlon; Ricken, Tim; Wagner, ArndtThe medical relevance of brain tumours is characterised by its locally invasive and destructive growth. With a high mortality rate combined with a short remaining life expectancy, brain tumours are identified as highly malignant. A continuum‐mechanical model for the description of the governing processes of growth and regression is derived in the framework of the Theory of Porous Media (TPM). The model is based on medical multi‐modal magnetic resonance imaging (MRI) scans, which represent the gold standard in diagnosis. The multi‐phase model is described mathematically via strongly coupled partial differential equations. This set of governing equations is transformed into their weak formulation and is solved with the software package FEniCS. A proof‐of‐concept simulation based on one patient geometry and tumour pathology shows the relevant processes of tumour growth and the results are discussed.Item Open Access Characterization of muscle weakness due to myasthenia gravis using shear wave elastography(2023) Zimmer, Manuela; Kleiser, Benedict; Marquetand, Justus; Ates, FilizMyasthenia gravis (MG) is often accompanied with muscle weakness; however, little is known about mechanical adaptions of the affected muscles. As the latter can be assessed using ultrasound shear wave elastography (SWE), this study characterizes the biceps brachii muscle of 11 patients with MG and compares them with that of 14 healthy volunteers. Simultaneous SWE, elbow torque and surface electromyography measurements were performed during rest, maximal voluntary contraction (MVC) and submaximal isometric contractions (up to 25%, 50% and 75% MVC) at different elbow angles from flexion to extension. We found that, with increasing elbow angle, maximum elbow torque decreased (p < 0.001), whereas muscle stiffness increased during rest (p = 0.001), MVC (p = 0.004) and submaximal contractions (p < 0.001). Muscle stiffness increased with increasing contraction intensities during submaximal contractions (p < 0.001). In comparison to the healthy cohort, muscle stiffness of MG patients was 2.1 times higher at rest (p < 0.001) but 8.93% lower in active state (75% MVC, p = 0.044). We conclude that (i) increased muscle stiffness shown by SWE during rest might be an indicator of MG, (ii) SWE reflects muscle weakness and (iii) SWE can be used to characterize MG muscle.Item Open Access Analysing the bone cement flow in the injection apparatus during vertebroplasty(2023) Trivedi, Zubin; Gehweiler, Dominic; Wychowaniec, Jacek K.; Ricken, Tim; Gueorguiev-Rüegg, Boyko; Wagner, Arndt; Röhrle, OliverVertebroplasty, a medical procedure for treating vertebral fractures, requires medical practitioners to inject bone cement inside the vertebra using a cannula attached to a syringe. The required injection force must be small enough for the practitioner to apply it by hand while remaining stable for a controlled injection. Several factors could make the injection force unintuitive for the practitioners, one of them being the non‐Newtonian nature of the bone cement. The viscosity of the bone cement varies as it flows through the different parts of the injection apparatus and the porous cancellous interior of the vertebra. Therefore, it is important to study the flow of bone cement through these parts. This work is a preliminary study on the flow of bone cement through the injection apparatus. Firstly, we obtained the rheological parameters for the power law model of bone cement using experiments using standard clinical equipment. These parameters were then used to obtain the shear rate, viscosity, and velocity profiles of the bone cement flow through the cannula. Lastly, an analysis was carried out to understand the influence of various geometrical parameters of the injection apparatus, in which the radius of the cannula was found to be the most influential parameter.Item Open Access How mechanics of individual muscle-tendon units define knee and ankle joint function in health and cerebral palsy : a narrative review(2023) Kaya Keles, Cemre Su; Ates, FilizThis study reviews the relationship between muscle-tendon biomechanics and joint function, with a particular focus on how cerebral palsy (CP) affects this relationship. In healthy individuals, muscle size is a critical determinant of strength, with muscle volume, cross-sectional area, and moment arm correlating with knee and ankle joint torque for different isometric/isokinetic contractions. However, in CP, impaired muscle growth contributes to joint pathophysiology even though only a limited number of studies have investigated the impact of deficits in muscle size on pathological joint function. As muscles are the primary factors determining joint torque, in this review two main approaches used for muscle force quantification are discussed. The direct quantification of individual muscle forces from their relevant tendons through intraoperative approaches holds a high potential for characterizing healthy and diseased muscles but poses challenges due to the invasive nature of the technique. On the other hand, musculoskeletal models, using an inverse dynamic approach, can predict muscle forces, but rely on several assumptions and have inherent limitations. Neither technique has become established in routine clinical practice. Nevertheless, identifying the relative contribution of each muscle to the overall joint moment would be key for diagnosis and formulating efficient treatment strategies for patients with CP. This review emphasizes the necessity of implementing the intraoperative approach into general surgical practice, particularly for joint correction operations in diverse patient groups. Obtaining in vivo data directly would enhance musculoskeletal models, providing more accurate force estimations. This integrated approach can improve the clinicians’ decision-making process and advance treatment strategies by predicting changes at the muscle and joint levels before interventions, thus, holding the potential to significantly enhance clinical outcomes.Item Open Access Botulinum toxin intervention in cerebral palsy-induced spasticity management : projected and contradictory effects on skeletal muscles(2022) Kaya Keles, Cemre Su; Ates, FilizSpasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This leads to functional limitations at the respective joint. Focal injection of botulinum toxin type-A (BTX-A) is effectively used to manage spasticity and improve the quality of life of the patients. By blocking acetylcholine release at the neuromuscular junction and causing temporary muscle paralysis, BTX-A aims to reduce spasticity and hereby improve joint function. However, recent studies have indicated some contradictory effects such as increased muscle stiffness or a narrower range of active force production. The potential of these toxin- and atrophy-related alterations in worsening the condition of spastic muscles that are already subjected to changes should be further investigated and quantified. By focusing on the effects of BTX-A on muscle biomechanics and overall function in children with CP, this review deals with which of these goals have been achieved and to what extent, and what can await us in the future.Item Open Access Quantifying the effects of achilles tendon lengthening surgery : an intraoperative approach(2023) Brendecke, Elena; Tsitlakidis, Stefanos; Götze, Marco; Hagmann, Sébastien; Ates, FilizAchilles tendon lengthening (ATL) is frequently used in the treatment of foot deformities. However, there is currently no objective method to determine the optimal muscle length during surgery. We developed an intraoperative approach to evaluate the passive and active forces of the triceps surae muscle group before and after ATL and aimed to test the following hypotheses: 1) the ankle passive range of motion (ROM) increases, 2) passive muscle forces decrease post-ATL, and 3) forces measured from patients with non-neurological and neurological conditions demonstrate different characteristics. Passive forces at various ankle joint positions were measured in ten patients (11.3 ± 3.0 years old) pre- and post-ATL using a force transducer attached to the Achilles tendon. In six patients, active isometric forces were measured by stimulating the triceps surae supramaximally. Passive forces decreased by 94.3% (p < 0.0001), and ROM increased by 89.4% (p < 0.0001) post-ATL. The pre-ATL passive forces were 70.8% ± 15.1% lower in patients with idiopathic foot deformities than in patients with neurological conditions (p < 0.001). The peak active force of 209.8 ± 114.3 N was achieved at an ankle angle of 38.3° ± 16.0°, where the passive force was 6.3 ± 6.7 N. The inter-individual variability was substantial in both groups. In conclusion, the hypotheses posed were supported. The present findings suggest that muscle passive and active force production as well as the inter-individual variability should be considered when planning further treatment.Item Open Access In vivo assessment of shear wave propagation in pennate muscles using an automatic ultrasound probe alignment system(2023) Zimmer, Manuela; Bunz, Elsa K.; Ehring, Tobias; Kaiser, Benedikt; Kienzlen, Annika; Schlüter, Henning; Zürn, ManuelItem Open Access Hepatectomy-induced alterations in hepatic perfusion and function : toward multi-scale computational modeling for a better prediction of post-hepatectomy liver function(2021) Christ, Bruno; Collatz, Maximilian; Dahmen, Uta; Herrmann, Karl-Heinz; Höpfl, Sebastian; König, Matthias; Lambers, Lena; Marz, Manja; Meyer, Daria; Radde, Nicole; Reichenbach, Jürgen R.; Ricken, Tim; Tautenhahn, Hans-MichaelLiver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery.Item Open Access Editorial - computational modeling for liver surgery and interventions(2022) Christ, Bruno; Dahmen, Uta; Radde, Nicole; Ricken, TimItem Open Access Quantifying fat zonation in liver lobules : an integrated multiscale in silico model combining disturbed microperfusion and fat metabolism via a continuum biomechanical bi-scale, tri-phasic approach(2024) Lambers, Lena; Waschinsky, Navina; Schleicher, Jana; König, Matthias; Tautenhahn, Hans-Michael; Albadry, Mohamed; Dahmen, Uta; Ricken, TimMetabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g., metabolic dysfunction-associated steatotic liver disease/MASLD). Zonated metabolic functions are influenced by zonal morphological abnormalities in the liver, such as periportal fibrosis and pericentral steatosis. We aim to analyze the interplay between microperfusion, oxygen gradient, fat metabolism and resulting zonated fat accumulation in a liver lobule. Therefore we developed a continuum biomechanical, tri-phasic, bi-scale, and multicomponent in silico model, which allows to numerically simulate coupled perfusion-function-growth interactions two-dimensionally in liver lobules. The developed homogenized model has the following specifications: (i) thermodynamically consistent, (ii) tri-phase model (tissue, fat, blood), (iii) penta-substances (glycogen, glucose, lactate, FFA, and oxygen), and (iv) bi-scale approach (lobule, cell). Our presented in silico model accounts for the mutual coupling between spatial and time-dependent liver perfusion, metabolic pathways and fat accumulation. The model thus allows the prediction of fat development in the liver lobule, depending on perfusion, oxygen and plasma concentration of free fatty acids (FFA), oxidative processes, the synthesis and the secretion of triglycerides (TGs). The use of a bi-scale approach allows in addition to focus on scale bridging processes. Thus, we will investigate how changes at the cellular scale affect perfusion at the lobular scale and vice versa. This allows to predict the zonation of fat distribution (periportal or pericentral) depending on initial conditions, as well as external and internal boundary value conditions.