Lebenswissenschaften und Ethik
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Tissue-engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof-of-concept study evaluated a contact-free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer-filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0-200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5-100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (-35%, p = 0.0061) and elastase (-45%, p < 0.001) treatments caused significant decreases of NF within 120 min. Decellularized HUV showed similar results, indicating that changes of the extracellular matrix were responsible for the observed shift in NF. Performing vibration response analysis on vessel grafts is feasible without compromising sterility or integrity of the samples. This technique allows direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright (C) 2016 John Wiley & Sons, Ltd.
This paper discusses modeling and nonlinear control of a joint antagonistically actuated by two pneumatic, artificial muscles. A single model of the whole system is obtained by a combined physical and phenomenological modeling approach. The combined model for the joint, the muscles and the proportional valves results in a nonlinear, affine-in-control system description. The model is used to derive control laws for an input/output linearization approach to linearize the plant. Modeling and parametrization errors are covered via an outer control loop consisting of a state-feedback which is extended by an additional feedback of error integral. Extensive experimental results show the quality of the model and the performance of the respective control laws.
Einleitung:
Blutdruck gilt als sogenannter Vitalparameter als einer der grundlegenden Indikatoren für den Gesundheitszustand einer Person. Sowohl zu niedriger als auch zu hoher Blutdruck kann lebensbedrohend sein, letzerer ist darüber hinaus ein Risikofaktor insbesondere für Herz-Kreislauferkrankungen, die trotz wichtiger Fortschritte in der Behandlung immer noch die häufigste Todesursache in Deutschland darstellen. Die Hämodynamik, also die raumzeitliche Dynamik des Blutflusses, und der Gefäßzustand sind eng verbunden mit dem Blutdruck und ebenfalls von hoher klinischer Relevanz, u.a. zur Identifikation von Durchblutungsstörungen und ungünstigen Druckverteilungen der Gefäßwand. Innovationen in der Messtechnik als auch in der Datenanalyse bieten heute neue Möglichkeiten der Erfassung und Bewertung von Blutdruck, Hämodynamik und Gefäßzustand [1], [2], [3], [4].
Methodik:
In einer gemeinsamen Workshopserie der AG Medizinische Bild- und Signalverarbeitung der GMDS und des Fachausschusses Biosignale der DGBMT werden wir neue Ansätze und Lösungen für Mess- und Analyseverfahren zu Blutdruck und -fluss sowie zum Gefäßzustand vorstellen und diskutieren. Dabei stehen im ersten Workshop auf der GMDS Jahrestagung Bildbasierte Verfahren im Zentrum, während der zweite Workshop auf der DGBMT Jahrestagung den Fokus auf Biosignalbasierten Verfahren legt. Es werden aktuelle Forschungsergebnisse vorgestellt und diskutiert. Es sind jeweils mehrere Vorträge geplant mit ausreichend Zeit zur Diskussion. Folgende Vorträge sind geplant (Arbeitstitel):
Sebastian Zaunseder: Videobasierte Erfassung des Blutdrucks
Anja Hennemuth: A Visualization Toolkit for the Analysis of Aortic Anatomy and Pressure Distribution
Lars Krenkel: Numerische Analyse der Rupturwahrscheinlichkeit zerebraler Aneurysmata
Susanne Schnell: Messung des Blutflusses und hämodynamischer Parameter mit 4D flow MRI: Möglichkeiten und Herausforderungen
Ergebnisse:
Ziel des Workshops ist die Identifikation von innovativen Ansätzen und neuen Methoden zur qualitativen und quantitativen Bestimmung von hämodynamischen Parametern sowie deren kritische Bewertung durch die Community für die Eignung in der klinischen Entscheidungsunterstützung.
Diskussion:
Der Workshop leistet inhaltlich einen Beitrag zu zentralen Aspekten für die Herz-Kreislauf-Medizin. Er bringt dabei Expertise aus verschiedenen Bereichen zusammen und schlägt die Brücke zwischen Kardiologie, Medizininformatik und Medizintechnik.
Schlussfolgerung:
Innovative Technologien aus Medizintechnik und Informatik ermöglichen zunehmend einfache und raumzeitlich aufgelöste Erfassung und Bewertung wichtiger Informationen zur Unterstützung von Diagnose und Therapieverfolgung.
[1] Zaunseder S, Trumpp A, Wedekind D, Malberg H. Cardiovascular assessment by imaging photoplethysmography - a review. Biomed Tech (Berl). 2018 Oct 25;63(5):617–34.
[2] Huellebrand M, Messroghli D, Tautz L, Kuehne T, Hennemuth A. An extensible software platform for interdisciplinary cardiovascular imaging research. Comput Methods Programs Biomed. 2020 Feb;184:105277.
[3] Schmitter S, Adriany G, Waks M, Moeller S, Aristova M, Vali A, et al. Bilateral Multiband 4D Flow MRI of the Carotid Arteries at 7T. Magn Reson Med. 2020 Oct;84(4):1947–60.
[4] Birkenmaier C, and Krenkel, L. Flow in Artificial Lungs. In: New Results in Numerical and Experimental Fluid Mechanics XIII. Contributions to the 22nd STAB/DGLR Symposium. Springer; 2021.
Convolutional Neural Networks for Approximation of Internal Non-Newtonian Multiphase Flow Fields
(2021)
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.
Anatomical differences between individuals are often neglected in musculoskeletal models, but they are necessary in case of subject-specific questions regarding the lumbar spine. A modification of models to each subject is complex and the effects on lumbar loading are difficult to assess. One objective of this work is to create a validated musculoskeletal human model, which facilitates a subject-specific modification of the lumbar geometry. In a second step, important parameters are identified in sensitivity studies and at last, a case study regarding multifidus muscle atrophy after a disc herniation is conducted.
The results of the studies indicate that lumbar motion and loading is dependent on lumbar ligament stiffness. Furthermore, subject-specific modelling of the lumbar spine should include at least the vertebral height, disc height and lumbar lordosis. The results of the case study suggest that an overloading of the multifidus muscle could follow disc herniation. Additionally, a subsequent atrophy of the muscles could expose adjacent levels to an increased loading, but these findings are highly dependent on the individual.
The implant stability and biomechanical response of periprosthetic bone in acetabulum around total hip joint replacement (THR) devices depend on a host of parameters, including design of articulating materials, gait cycle and subject parameters. In this study, the impact of shell design (conventional, finned, spiked, and combined design) and liner material on the biomechanical response of periprosthetic bone has been analyzed using finite element (FE) method. Two different liner materials: high density polyethylene-20% hydroxyapatite-20% alumina (HDPE-20%HA-20%Al2O3) and highly cross-linked ultrahigh molecular weight polyethylene (HC-UHMWPE) were used. The subject parameters included bone condition and bodyweight. Physiologically relevant load cases of a gait cycle were considered. The deviation of mechanical condition of the periprosthetic bone due to implantation was least for the finned shell design. No significant deviation was observed at the bone region adjacent to the spikes and the fins. This study recommends the use of the finned design, particularly for weaker bone conditions. For stronger bones, the combined design may also be recommended for higher stability. The use of HC-UHMWPE liner was found to be better for convensional shell design. However, similar biomechanical response was captured in our FE analysis for both the liner materials in case of other shell designs. Overall, the study establishes the biomechanical response of periprosthetic bone in the acetabular with preclinically tested liner materials together with new shell design for different subject conditions.
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.
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.
Degradation and release of tannic acid from an injectable tissue regeneration bead matrix in vivo
(2021)
The development of multifunctional biomaterials as both tissue regeneration and drug delivery devices is currently a major focus in biomedical research. Tannic Acid (TA), a naturally occurring plant polyphenol, displays unique medicinal abilities as an antioxidant, an antibiotic, and as an anticancer agent. TA has applications in biomaterials acting as a crosslinker in polymer hydrogels improving thermal stability and mechanical properties. We have developed injectable cell seeded collagen beads crosslinked with TA for breast reconstruction and anticancer activity following lumpectomy. This study determined the longevity of the bead implants by establishing a degradation time line and TA release profile in vivo. Beads crosslinked with 0.1% TA and 1% TA were compared to observe the differences in TA concentration on degradation and release. We found collagen/TA beads degrade at similar rates in vivo, yet are resistant to complete degradation after 16 weeks. TA is released over time in vivo through diffusion and cellular activity. Changes in mechanical properties in collagen/TA beads before implantation to after 8 weeks in vivo also indicate loss of TA over a longer period of time. Elastic moduli decreased uniformly in both 0.1% and 1% TA beads. This study establishes that collagen/TA materials can act as a drug delivery system, rapidly releasing TA within the first week following implantation. However, the beads retain TA long term allowing them to resist degradation and remain in situ acting as a cell scaffold and tissue filler. This confirms its potential use as an anticancer and minimally invasive breast reconstructive device following lumpectomy.