bluuebunny/crossref_metadata_2025 huggingface dataset:
Implantomics: A Paradigm Shift in Implantology
Authors: Jennissen H. P.
Published: September 2019

Implantomics is the science of the implantome. The implantome is a blend of the two terms implant and proteome. The proteome is defined as the protein complement of the genome. The term proteome also implies the mass screening of proteins for the determination of all proteins - and indirectly of all genes - involved in a certain tissue or organ response. In this sense the term proteome is employed here in a new way to specify the totality of proteins associated with a foreign body inserted into the human body. It will be addressed, why the determination of the implanttome is important and which role the implantome may play in the bone-implant interface.
Industrial robots for teleoperated surgery – a systematic review of existing approaches
Authors: Schäfer Max B. , Stewart Kent W. , Pott Peter P.
Published: September 2019

Robotic assistance in surgical interventions has been shown to improve both the surgical outcome and the surgeon’s performance. However, cost-efficient implementation of such systems in an operating room workflow is not yet resolved. Most of the current approaches use highly specialized and purpose-built robotic components, resulting in large costs. This paper presents an investigation into the usage of off-the-shelf robots as cost-efficient basis for teleoperated surgery. In addition, the modifications required of the robot and/or operating environment to make it suitable for the medical setting are assessed. The considered systems are found via a literature search and the MERODA-database, specifically focusing on systems designed for teleoperated surgery which use industrial robots. Among the 126 telemanipulated systems found, only 10 use industrial robots for surgical procedures. Overall, due to the better availability, reduced costs, and increased performance, current industrial robots should be further considered for new and versatile lowcost approaches to teleoperated surgery.
Towards automated and painless venipuncture – vibratory needle insertion techniques
Authors: Liu Jan , Stewart Kent W. , Pott Peter P.
Published: September 2019

The insertion of a needle into soft inhomogeneous tissue is required for many medical procedures. It has been shown that vibratory needle insertion methods have the ability to reduce insertion forces, which are correlated with increased needle placement precision, and reduced frequency and intensity of pain and trauma felt. This paper reviews different vibratory needle insertion methods that have been studied experimentally, addressing vibration generation, vibration frequency and amplitude, and force measurement. Reductions of up to 73 % in peak insertion force (150 Hz), and 37 % in placement error (15 Hz) were reported. Additionally, ultrasonic vibration (84 kHz) reduced the force by up to 28 %. The results of vibratory insertion show promise, specifically in regard to automated needle devices.
Cytotoxicity of Catalysed Silicone Resin Coatings for Smart Biomedical Devices
Authors: Werner Valerie M. K. , Kist Arian , Eblenkamp Markus
Published: September 2019

Equipping medical devices with smart technologies holds great potential for the development of modern medical products. The development requires the identification of new integration strategies and the research of new material combinations due to the miniaturization of systems and increasing production figures. The realization of Smart Biomedical Devices requires a sufficient barrier effect (bioprotection) by appropriate encapsulation of the electronic components. Thinnest polymer coatings have proven to be suitable for conformal encapsulation. The aim of the study was to investigate the fundamental suitability of thin-film lacquers added with catalysts as coating materials for electronic systems with regard to their biological use. Due to long curing times of up to 14 days, eight different catalysts based on different chemical structures were added to the coating materials and their influence on a cytotoxic effect was investigated. A non-cytotoxic effect was observed for the organometallic catalysts based on tin, zirconium, titanium, bismuth, and tertiary amine. Most were resistant to steam sterilization. The curing time of the non-cytotoxic coatings could be significantly reduced by the addition of catalysts. The shortening of process times is an important economic aspect in the production of mass-produced Smart Biomedical Devices.
Automatic Orientation Estimation of Inertial Sensors in C-Arm CT Projections
Authors: Thies Mareike , Maier Jennifer , Eskofier Björn , Maier Andreas , Levenston Marc , Gold Garry , Fahrig Rebecca
Published: September 2019

To obtain CT images of the knee joint in a more lifelike position, data acquisition can be performed with patients in standing rather than in lying position. However, in that situation, people tend to show involuntary motion. One possibility to compensate for that motion is the use of Inertial Measurement Units, that capture the accelerations during the scan. For this purpose, their local coordinate system needs to be known. An estimation based on the SIFT algorithm was implemented and compared to an existing approach that uses the Fast Radial Symmetry transform and to expert labels for evaluation. The SIFT method showed to be superior to the existing approach as it could extract stable feature points from the projections that were used to estimate the three-dimensional coordinate system in a reliable manner. The final algorithm achieved a mean euclidean distance of 2.61 mm between the calculated position of the origin and the assumed ground truth by the expert labels.
Dynamic image analysis of transparent particles released during the simulated use test of cardiovascular devices
Authors: Kurzhals Anja , Brandt-Wunderlich Christoph , Grabow Niels , Schmidt Wolfram , Schmitz Klaus-Peter
Published: September 2019

For product approval of coated cardiovascular devices, the assessment of particle release is essential. Particularly challenging are delivery systems equipped with hydrophilic coatings releasing highly transparent particles. The aim of this study was to compare two different methods of particle counting, namely the light obscuration method and the dynamic image analysis (DIA), with respect to optical transparent particles. The particles were collected during the simulated use of cardiovascular catheters and analysed in suspension with a dynamic imaging device (FlowCam, Fluid Imaging Technologies). Particles were detected by a greyscale threshold and imaged to analyse their shape and transparency. The statistical influence of the threshold on particle counts and size distribution was determined and compared to light obscuration particle counting (Model 9703 with sensor HRLD 400CE, HIAC ROYCO). The light obscuration method provided lower particle counts in suspensions containing a high amount of transparent particles. The lower the detection threshold, the higher the particle counts were. In conclusion, it is important to adapt the threshold value for samples that are expected to contain a high amount of transparent particles. DIA may be suggested as a valuable additional method for particulate analysis.
Construction of a novel microfluidic experimental setup for testing recent glaucoma drainage devices
Authors: Kara Emre , İhsan Kutlar Ahmet , Güngör Kıvanç
Published: September 2019

Glaucoma is an eye disorder in which the optic nerve is damaged over time due to a sustained elevation of the intraocular pressure (IOP). Being the second leading cause of blindness according to the reports of the World Health Organization, glaucoma is not only a serious ocular disease that threatens individuals, but also a community health problem. In recent years, great improvement has been achieved in the technology of implants used in the treatment of the disease. Despite the great effort dedicated to the design and implementation of the glaucoma drainage devices (GDD), they still have unsolved problems and weaknesses. Most of the currently employed GDDs are very simple and have major problems such as reversed flow, choking and a coarse interval of pressure control. Experiments must be devised to investigate the flow behavior inside these devices. In this study, an accurate microfluidics experimental setup is constructed to analyze and characterize the in-vitro performance of actively employed GDDs on the glaucoma treatment. Proposed setup includes a pressurized fluid reservoir, ELVEFLOW microfluidics flow rate measurement/control unit, microfluidics flow/pressure sensors, and data analysis system. In the setup, more precise measurements than experimental setups in literature is planned to be provided. It is estimated that the results showing consistency with in-vivo measurements will be obtained, behavior of the fluid passing through the GDDs will be observed and issues with design flaws will be addressed.
Quantifying the uncertainty of deep learning-based computer-aided diagnosis for patient safety
Authors: Laves Max-Heinrich , Ihler Sontje , Ortmaier Tobias , Kahrs Lüder A.
Published: September 2019

In this work, we discuss epistemic uncertainty estimation obtained by Bayesian inference in diagnostic classifiers and show that the prediction uncertainty highly correlates with goodness of prediction. We train the ResNet-18 image classifier on a dataset of 84,484 optical coherence tomography scans showing four different retinal conditions. Dropout is added before every building block of ResNet, creating an approximation to a Bayesian classifier. Monte Carlo sampling is applied with dropout at test time for uncertainty estimation. In Monte Carlo experiments, multiple forward passes are performed to get a distribution of the class labels. The variance and the entropy of the distribution is used as metrics for uncertainty. Our results show strong correlation with ρ = 0.99 between prediction uncertainty and prediction error. Mean uncertainty of incorrectly diagnosed cases was significantly higher than mean uncertainty of correctly diagnosed cases. Modeling of the prediction uncertainty in computer-aided diagnosis with deep learning yields more reliable results and is therefore expected to increase patient safety. This will help to transfer such systems into clinical routine and to increase the acceptance of machine learning in diagnosis from the standpoint of physicians and patients.
Computer Aided Detection of Polyps in Whitelight- Colonoscopy Images using Deep Neural Networks
Authors: Wittenberg Thomas , Zobel Pascal , Rathke Magnus , Mühldorfer Steffen
Published: September 2019

Early detection of polyps is one central goal of colonoscopic screening programs. To support gastroenterologists during this examination process, deep convolutional neural network can be applied for computer-assisted detection of neoplastic lesions. In this work, a Mask R-CNN architecture was applied. For training and testing, three independent colonoscopy data sets were used, including 2484 HD labelled images with polyps from our clinic, as well as two public image data sets from the MICCAI 2015 polyp detection challenge, consisting of 612 SD and 194 HD labelled images with polyps. After training the deep neural network, best results for the three test data sets were achieved in the range of recall = 0.92, precision = 0.86, F1 = 0.89 (data set A), rec = 0.86, prec = 0.80, F1 = 0.82 (data set B) and rec = 0.83, prec = 0.74, F1 = 0.79 (data set C).
Development and manufacturing of a custom made implant regarding the new European Medical Device Regulation
Authors: Schonhoff Mareike , Heinze Astrid , Carrillo Juliette , Lopinski Annika , Großkreutz Damian , Hanusek Stefan
Published: September 2019

New technologies are great opportunities for personalized medicine. Custom made implants can be very helpful for patients with severe bone defects or in case of bone tumor. Through the European Union it is regulated how many possibilities and restrictions all medical devices have. Because of critical vulnerabilities a new European Medical Device Regulation (MDR) was published in May 2017 and it will enter into force in May 2020. For the manufacturers of customized products it will change the documentation of the manufacturing and tracking of serious incidents. Patients with a pelvis defect of Paprosky IIb and higher can benefit from a custom made pelvis implant, because all planning steps according to biomechanic and bone contact to the implant can be designed and proofed during a reconstruction process. With regular modular implant systems, it probably can be a trial and error procedure during the surgery according to biomechanic and a stable position of the implant. Based on the 3D-Reconstruction of CT-Scans of a patient with a Paprosky 2b pelvis defect, a personalized acetabulum implant was designed. To maintain as much bone as possible, the implant was shaped to the remaining pelvic bone stock. Additive manufacturing gives the opportunity to produce custom made single items even in a quality that ful-fills the requirements of the MDR. Modern Selective Laser Melting (SLM) and Electron Beam melting (EBM) Systems are able to produce Titanium or CoCr parts in the ISO standards for Implants (ISO 5832 ff). In this study the process chain, starting from the reconstruction, to the design and the production of a custom made acetabulum cup was run through on an exemplary CTData of one patient. With this example, it was shown that it is possible, to establish a process, that is able to address surgical needs for patients that benefit from those techniques.
A Piezoelectric Flexural Plate Wave (FPW) Bio-MEMS Sensor with Improved Molecular Mass Detection for Point-of-Care Diagnostics
Authors: Walk Christian , Wiemann Matthias , Görtz Michael , Weidenmüller Jens , Jupe Andreas , Seidl Karsten
Published: September 2019

A piezoelectric FPW-sensor has been developed for a point of care device in this work. The Bio- MEMS FPW-sensor consists of an electrode configuration termed as an interdigital transducer (IDT) placed on a membrane. An input IDT excites and an output IDT detects the propagating acoustic waves through a PZT layer. Design optimizations and fabrication improvements of the FPW-sensor led to significantly reduced attenuation of the wave signal and the damping of the propagating waves between the IDTs. The working principle of mass loading is shown using different low-viscous liquids. A densitydependent sensitivity of -0.39 MHz/g/cm³ was evaluated. After the membrane was functionalized, the Bio-MEMS FPW-sensor was used to measure a specific chemokine in complex solution. By design improvements, the resolution was significantly increased from 0.7 Hz/nM to 14 Hz/nM.
Automated detection of bone splinters in DEXA phantoms using deep neural networks
Authors: Rüger Steffen , Firsching Markus , Lucic Julija , Ennen Alexander , Uhlmann Norman , Wittenberg Thomas
Published: September 2019

Dual energy radiographic imaging is a method to provide material information and can be used to differentiate between various tissue types. Dual energy X-ray absorption (DEXA) can be applied for breast density, osteoporosis or bone fracture analysis. To support radiologists with the assessment of DEXA images, machine learning can be applied. Specifically, deep convolutional neural networks (DCNNs) can be used for medical image analysis. In this work a DCNN is proposed and evaluated for automated detection of bone splinters in DEXA phantom images. The image data consists of 47 phantoms with (35) and without (12) bone splinters. Material decomposition and energy weighting results in additional image channels. Various DCNN architectures and parameters were explored. A classification rate in regions with 90 % and without 99 % bone splinters was achieved.
Catheter pose-dependent virtual angioscopy images visualized on augmented reality glasses
Authors: Haxthausen Felix von , Jäckle Sonja , Strehlow Jan , Ernst Floris , García-Vázquez Verónica
Published: September 2019

Fluoroscopy and digital subtraction angiography provide guidance in endovascular aortic repair (EVAR) but introduce radiation exposure and require the administration of contrast agent. To overcome these disadvantages, previous studies proposed to display the pose of an electromagnetically (EM) tracked catheter tip within a three-dimensional virtual aorta on augmented reality (AR) glasses. For further guidance, we propose to create virtual angioscopy images based on the catheter tip pose within the aorta and to display them on HoloLens. The aorta was segmented from the computed tomography (CT) data using MeVisLab software. A landmarkbased registration allowed the calculation of the pose of the EM sensor in the CT coordinate system. The sensor pose was sent to MeVisLab running on a computer and a virtual angioscopy image was created at runtime based on the segmented aorta. When requested by HoloLens, the last encoded image was sent from MeVisLab to the AR glasses via Wi-Fi using a remote procedure call (gRPC), and then decoded and displayed on HoloLens. For evaluation purposes, the latency of transmitting and displaying the images was measured using two different lossy compression formats (namely JPEG and DXT1). A mean latency of 82 ms was measured for the JPEG format. On the other hand, using the DXT1 format, the mean latency was reduced by 87 %. This study proved the feasibility of creating pose-dependent virtual angioscopy images and displaying them on HoloLens. Additionally, the results showed that the DXT1 format outperformed the JPEG format regarding latency. The virtual angioscopy may add valuable additional information for guidance in radiation-sparing EVAR procedure approaches.
Application of 3R principles in small animal GLP testing of biomaterials
Authors: Kischkel Sabine , Brietzke Andreas , Schmidt Wolfram , Eickner Thomas , Grabow Niels , Matschegewski Claudia
Published: September 2019

On the protection of animals used for scientific purposes, the EU Parliament adopted Directive 2010/63/EU. The essential factor is the 3R principle: Replacement, Reduction and Refinement. In 2013, the third amendment to the German Animal Welfare Act was revised and adapted to the European Directive. The majority of animals in science are used in basic research, as well as in translational and applied research. In medical research, animal experimentation is conducted to clarify previously unknown life processes and basic biological relationships, in order to improve diagnostics and treatment of human diseases. Before an animal experiment can be performed, it must be reported to and approved by the responsible authorities. The planned research project must be justified scientifically, and it must be demonstrated that the personnel and spatial/ technical prerequisites are in place to successfully complete the project. If all conditions are met, the approval can be granted, but may be subject to conditions. The guiding principle of essentiality also affects the procedure of the experiments: The number of animals used and the pain, suffering and damage caused to these animals must be limited to what is absolutely necessary. In this context, the 3R principle has to be applied. To obtain reliable results, it is essential that the laboratory animals are in normal physiological conditions and free of pain and fear. Scientific interest and animal welfare are therefore not in opposition, but rather mutually dependent. In our GLP (Good Laboratory Practice) laboratory we test new drug release systems for different biomedical applications in rabbits after careful selection of the animal model. Stress during animal experiments must be avoided as far as possible. Providing pain-killers and ensuring the best possible husbandry and care conditions are crucial for the animal’s wellbeing and absence of pain and anxiety. In the present work we report our different experience in a GLPcertified biomaterial test laboratory.
Electrical Dipole Source Localization using Hybrid Least Squares Method in combination with ICA
Authors: Samann Fars , Rausch Andreas , Schanze Thomas
Published: September 2019

In biomedical engineering, dipole source localization is commonly used to identify brain activities from scalp recorded potentials, which is known as inverse problem of electroencephalography (EEG) source localization. However, this problem is fundamental in biomedical engineering, medicine and neuroscience. The EEG inverse problem is non-linear, in addition, it is ill-posed and the solver can be unstable, i.e. the solution is non-unique and it is highly sensitive to small changes of the measured signal (noise). For solving the EEG inverse problem iterative methods, like Levenberg-Marquardt algorithm, are usually considered. However, these techniques require good initial values and many electrodes N, since a large redundancy supports the finding of the right solution. Therefore, in this paper, a hybrid method of linear and non-linear modelling and least squares approach are proposed to overcome of these problems: the solutions calculated by means of a linear approximation of EEG inverse problems serve as initial values for solving the original non-linear model. In addition, independent component analysis (ICA) is combined with the proposed hybrid least squares method to separate different dipole sources from multiple EEG signals. The performance of the hybrid least squares method with and without ICA is measured in term of root mean square error. The simulation results show that the proposed method can estimate the location of dipole source with acceptable accuracy under high noise condition and small N comparing with linear least squares method considering larger N. Finally, it should be mentioned that the proposed method promises advantages in finding solutions of the EEG inverse problem effectively.
Multiscale Parameter Estimation (msPE) of QRS complexes distorted by magnetohydrodynamic effects at 7 Tesla
Authors: Spicher Nicolai , Kukuk Markus , Maderwald Stefan , Ladd Mark E.
Published: September 2019

During ultra-high-field magnetic resonance imaging, the acquisition of electrocardiography is impeded by artifacts. This poses a challenge in examinations where the QRS complex is used as a trigger for activating image acquisition. In this work, we customize a framework for multiscale parameter estimation for processing electrocardiography signals acquired inside and outside an ultra-high-field scanner bore: The parameters of a QRS complex modeled by a Gaussian function were estimated using scale-dependent algebraic expressions for 600 heartbeats from three subjects. Sensitivity ≥ 94% and accuracy ≤ 5ms in each experiment indicate feasibility of this approach, and, additionally, run time is within the acceptable range for triggering latency in the majority of cases. Hence, we see a real-time implementation as an avenue for future work.
Local blood flow analysis and visualization from RGB-video sequences
Authors: Kossack Benjamin , Wisotzky Eric L. , Hilsmann Anna , Eisert Peter , Hänsch Ronny
Published: September 2019

The extraction of heart rate and other vital parameters from video recordings of a person has attracted much attention over the last years. In this paper, we examine time differences between distinct spatial regions using remote photoplethysmography (rPPG) in order to extract the blood flow path through human skin tissue in the neck and face. We can show that the visualization of the blood flow path corresponds to the physiologically defined path.
Foetal heart rate assessment by empirical mode decomposition and spectral analysis
Authors: Fuentealba Patricio , Illanes Alfredo , Ortmeier Frank
Published: September 2019

This paper focuses on studying the time-variant dynamics involved in the foetal heart rate (FHR) response resulting from the autonomic nervous system modulation. It provides a comprehensive analysis of such dynamics by relating the spectral information involved in the FHR signal with foetal physiological characteristics. This approach is based on two signal processing methods: the complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and time-varying autoregressive (TV-AR) modelling. First, the CEEMDAN allows to decompose the signal into intrinsic mode functions (IMFs). Then, the TV-AR modelling allows to analyse their spectral dynamics. Results reveal that the IMFs can involve significant spectral information (p -value < 0.05) that can help to assess the foetal condition.
Generation of an azide-modified extracellular matrix by adipose-derived stem cells using metabolic glycoengineering
Authors: Nellinger Svenja , Keller Silke , Southan Alexander , Wittmann Valentin , Volz Ann-Cathrin , Kluger Petra J.
Published: September 2019

Natural extracellular matrix (ECM) represents an ideal biomaterial for tissue engineering and regenerative medicine approaches. For further functionalization, there is a need for specific addressable functional groups within this biomaterial. Metabolic glycoengineering (MGE) provides a technique to incorporate modified monosaccharide derivatives into the ECM during their assembly, which was shown by us earlier for the production of a modified fibroblast-derived dermal ECM. In this study, adipose-derived stem cells (ASCs) were treated with the azide-modified monosaccharide derivate 1,3,4,6-tetra-O-acetyl-N-azidoacetylgalactosamine (Ac4GalNAz). Toxicity and viability assays after 24 h and 72 h incubation revealed high biocompatibility of Ac4GalNAz in contact with ASCs. The successful incorporation of the functional azide groups into the glycocalyx and the ECM of the ASCs was proven by conjugation with a fluorescent dye via a copper-catalyzed click reaction. Thus, Ac4GalNAz in combination with ASCs was confirmed to achieve an azidemodified ECM as a multifunctional biomaterial for further applications.
A Hybrid Mock Circulation for Control Algorithms of Ventricular Assist Devices
Authors: Salesch Tobias , Gesenhues Jonas , Abel Dirk
Published: September 2019

This paper deals with the design, simulation and control of a new lightweight hybrid Mock-Loop (MCL) concept. The proof of concept is evaluated by two simulation approaches. First, the design parameters are chosen by an optimal control problem. Second, a cascading controller structure is evaluated in a simulation. Both show that with a suitable range of the design parameter the new lightweight concept can be used as a MCL. To validate these findings, further investigations with the MCL under realistic test conditions are required.
Protective role of vitamin E to reduce oxidative degradation of soft implantable polyurethanes: In vitro study
Authors: Kutuzova Larysa , Molentor Olga , Wu Feng , Song Wenyao , Kandelbauer Andreas , Lorenz Günter
Published: September 2019

Vitamin E (VitE) additives are important in treating osteoarthritis inclusive cartilage regeneration due to their antioxidant and anti-inflammatory properties. The present research study focuses on the ability of biological antioxidant VitE (alpha-tocopherol isoform) to reduce or minimize oxidative degradation of soft implantable polyurethane (PU) elastomers after extended periods of time (5 months) in vitro. The effect of the oxidation storage media on the morphology of the segmented PUs was evaluated by mechanical softening, crystallization and melting behavior of both soft and hard segments (SS, HS) using dynamic mechanical analysis (DMA). Bulk mechanical properties of the potential implant materials during ageing were predicted from comprehensive mechanical testing of the biomaterials under tension and compression cyclic loads. 5-months in vitro data suggest that the prepared siloxane-poly(carbonate-urethane) formulations have sufficient resistance against degradation to be suitable materials for chondral long-term bio-stable implants. Most importantly, the positive effect of incorporating VitE (0.5 or 1.0% w/w) as bio-antioxidant and lubricant on the bio-stability was observed for all PU-types. VitE-additives protected the surface layer from erosion and cracking during chemical oxidation in vitro as well as from thermal oxidation during extrusion re-processing.
Support function of self-expanding nitinol stents – Are radial resistive force and crush resistance comparable?
Authors: Brandt-Wunderlich Christoph , Schmidt Wolfram , Grabow Niels , Stiehm Michael , Siewert Stefan , Andresen Reimer , Schmitz Klaus-Peter
Published: September 2019

The main task of any vascular stent is the mechanical support of the re-opened vessel. This support function may be quantified by the compressive properties of the stent in radial outer loading conditions. Different test methods are standardized and are accepted to provide relevant data. Six commercially available self-expanding stents were investigated with regard to their forcedeformation behavior during radial as well as elliptical deformation. The measured radial resistive force and crush resistance were not qualitatively congruent for all stents. As a conclusion both test methods should be considered when describing the compressive properties of self-expanding stents.
Extrusion as a manufacturing process for polymer micro-tubes for various bio-medical applications
Authors: Sahmel Olga , Siewert Stefan , Schmitz Klaus-Peter , Arbeiter Daniela , Grabow Niels , Kreiner Christine Friederike , Guthoff Rudolf
Published: September 2019

In various biomedical applications extrusion represents a common manufacturing process for polymeric semi-finished products. Extrusion allows the processing of a wide range of biomaterials, as well as different cross-sectional geometries. The present work focuses on the development of an extrusion process for polymer micro-tubes used for medical devices manufacturing, e.g. microstents for minimally invasive glaucoma therapy. Semi-finished products were manufactured by means of extrusion and dip-coating. Morphology was investigated using biaxial laser measurement and scanning electron microscopy (SEM). For the analysis of mechanical and thermal properties of the specimens uniaxial tensile testing and differential scanning calorimetry (DSC) were performed. While dip-coated micro-tubes reveal a smooth and homogeneous surface, SEM micrographs of extruded micro-tubes exhibit some longitudinal grooves. Mechanical properties of extruded and dip-coated micro-tubes are comparable, so that the presented extrusion process can be regarded suitable for the manufacturing of polymer microtubes in a sub-millimeter scale. A future improvement of nozzle design will allow for a smooth surface of extruded semi-finished products.
Technical Support of Wound Healing Processes: Project Status
Authors: Dawn Parente Jacquelyn , Möller Knut , Hensler Sabine , Kühlbach Claudia , Mueller Margareta M. , Belloni Paola , Chase J. Geoffrey
Published: September 2019

The optimized wound healing (OWID) project provides technical support of wound healing processes. Advanced biophysical treatment therapies using light (photobiomodulation), negative pressure wound therapy (NPWT), and electrical stimulation show biological effects. Specifically, a biphasic dose-response curve is observed where lower doses activate cells, while above a threshold, higher doses are inhibitory. However, no standard protocols and no multi-modal treatment studies determine specific therapy needs. The OWID project aims to develop a multi-modal treatment device and modelbased therapy for individualized wound healing. This work presents the OWID project status. Currently, a photobiomodulation prototype delivers red, green, and blue light ‘medicine’ at prescribed therapeutic ‘doses’. The calculation of incident light necessarily considers transmission properties of the intervening cell culture plate. Negative pressure wound therapy (NPWT) and electrical impedance tomography (EIT) hardware are being adapted for use in vitro. Development of mathematical models of wound healing and therapy control are supported by treatment experiment outcome measures conducted in a wounded 3D tissue model. Parameter sensitivity analysis conducted on an existing mathematical model of reepithelialization results in changing parameter values influencing cellular movement rates. Thus, the model is robust to fit model parameters to observed reepithelialization rates under treatment conditions impacting cellular activation, inhibition, and untreated controls. Developed image analysis techniques have not captured changes in wound area after photobiomodulation treatment experiments. Alternatively, EIT will be tested for wound area analysis. Additionally, live dyes will be introduced to non-invasively visualize the reepithelialization front on a smaller, cellular scale. Finally, an overall therapeutic feedback control model uses model reference adaptive control to incorporate the intrinsic biological reepithelialization mechanism, treatment loops, and treatment controller modulation at a wound state. Currently, the OWID project conducts photobiomodulation treatment experiments in vitro and has developed mathematical models. Future work includes the incorporation of multi-modal wound healing treatment experiments.
Generation of a Simplified Brain Geometry for the Calculation of Local Cerebral Temperature using a 1D Hemodynamic Model
Authors: Daschner Rosa , Krames Lorena , Lutz Yannick , Loewe Axel , Dössel Olaf , Cattaneo Giorgio
Published: September 2019

In Western countries, stroke is the third-most cause of death; 35- 55% of the survivors experience permanent disability. Mild therapeutic hypothermia (TH) showed neuroprotective effect in patients returning from cardiac arrest and is therefore assumed to decrease stroke induced cerebral damage. Recently, an intracarotid cooling sheath was developed to induce local TH in the penumbra using the cooling effect of cerebral blood flow via collaterals. Computational modeling provides unique opportunities to predict the resulting cerebral temperature without invasive procedures. In this work, we generated a simplified brain model to establish a cerebral temperature calculation using Pennes’ bio-heat equation and a 1D hemodynamics model of the cranial artery tree. In this context, we performed an extensive literature research to assign the terminal segments of the latter to the corresponding perfused tissue. Using the intracarotid cooling method, we simulated the treatment with TH for different degrees of stenosis in the middle cerebral artery (MCA) and analyzed the resulting temperature spatialtemporal distributions of the brain and the systemic body considering the influence of the collaterals on the effect of cooling.
Plug-in circuit board for the Raspberry-Pi microcomputer to reproduce multi-channel original electrocardiograms
Authors: Haber Tobias , Striebel Pascal , Ismer Bruno , Melichercik Juraj
Published: September 2019

Commercial simulators can only reproduce electrocardiograms (ECG) of the normal and diseased heart rhythm in a simplified waveform and with a low number of channels. With the presented project, the variety of digitally archived ECGs, recorded during electrophysiological examinations, should be made usable as original analogue signals for research and teaching purposes by the development of a special printed circuit board for the minicomputer “Raspberry-Pi “.
Establishment and initial characterization of a simple 3D wound healing model
Authors: Hensler Sabine , Kühlbach Claudia , Dawn Parente Jacquelyn , Moeller Knut , Mueller Margareta M.
Published: September 2019

Poor wound healing as consequence of malfunctions in the regulation of the healthy tissue repair response affects millions of people worldwide. The number of therapies available to successfully treat chronic wound is still very limited and their development is costly and time consuming. Therefore simple to use 3D systems, reflecting the in vivo tissue complexity, are urgently needed. We introduce a novel 3D organotypic model (OTC) containing the major cell components active during wound healing i.e. keratinocytes, fibroblasts and inflammatory cells that allows to determine the effects of different therapeutic approaches on wound closure, cell differentiation and cytokine secretion in chronic wounds. There are first reports on irradiation with visible light of different wave length (Low Level Light Therapy) as a means to enhance wound closure. However the mechanisms underlying this therapy as well as optimized irradiation wavelength and dose are not clear and were therefore analyzed using our 3D organotypic model. In the standardized OTC model we could demonstrate epithelial closure under control conditions as well as differential effects of red and blue light irradiation with respect to stability of the newly formed epithelium and time until epithelial closure. First results show differential cytokine profiles upon different wavelength irradiation e.g. high expression of TGF beta and IL-1 beta in red light irradiated cultures and increased GM-CSF expression in blue light irradiated and control cultures.
Influence of 12-bit and 16-bit CT values of metals on dose calculation in radiotherapy using PRIMO, a Monte Carlo code for clinical linear accelerators
Authors: Ese Zehra , Zylka Waldemar
Published: September 2019

In this paper, the effect of computed tomography (CT) values of metals in 12-bit and 16-bit extended Hounsfield Unit (EHU) scale on dose calculations in radiotherapy treatment planning systems (TPS) were quantified. Dose simulations for metals in water environment were performed with the software PRIMO in 6MV photon mode. The depth dose profiles were analysed and the relative dose differences between the metals determined with 12-bit and 16-bit CT imaging, respectively, were calculated. Maximum dose differences of ΔAl = 3.0%, ΔTi = 4.5%, ΔCr = 6.2% and ΔCu = 11.6% were measured. In order to increase the accuracy of dose calculation on patients with implants, CT imaging in the EHU scale is recommended.
Robust motion tracking of deformable targets in the liver using binary feature libraries in 4D ultrasound
Authors: Wulff Daniel , Kuhlemann Ivo , Ernst Floris , Schweikard Achim , Ipsen Svenja
Published: September 2019

In radiation therapy of abdominal targets, optimal tumor irradiation can be challenging due to intrafractional motion. Current target localization methods are mainly indirect, surrogate-based and the patient is exposed to additional radiation due to X-ray imaging. In contrast, 4D ultrasound (4DUS) imaging provides volumetric images of soft tissue tumors in real-time without ionizing radiation, facilitating a non-invasive, direct tracking method. In this study, the target was defined by features located in its local neighborhood. Features were extracted using the FAST detector and the BRISK descriptor, which were extended to 3D. To account for anatomical variability, a feature library was generated that contains manually annotated target information and relative locations of the features. During tracking, features were extracted from the current 4DUS volume and compared to the feature library. Recognized features are used to estimate feature position and shape. The developed method was evaluated in 4DUS sequences of the liver of three healthy subjects. For each dataset, a target was defined and manually contoured in a training and a test sequence. Training was used for library creation, the test sequence for target tracking. The target estimations are compared to the annotations to quantify a tracking error. The results show that binary feature libraries can be used for robust target localization in 4DUS data of the liver and could potentially serve as a tracking method less sensitive to target deformation.
Comparison of approval procedures for medical devices in Europe and the USA
Authors: Vila Wagner Marcel , Schanze Thomas
Published: September 2019

Important achievements such as the discovery of penicillin increased life expectancy in the 19th century. At the beginning of the 20th century, the influence of technical equipment and biomedical research led to a further leap in life expectancy. The use of computer devices with sophisticated software also improved the quality of life. This is linked to the fact that all these achievements have now led to the emergence of one of the largest import and export markets in the USA, alongside the european union (EU), which is an association of European states. In order to guarantee a uniform quality of this abundance of different products and therapies, there are worldwide corresponding regulations, to which all manufacturers must adhere. The entry into force of these regulations, with the associated approval and testing obligations for each individual medical device, ensures that a consistently high quality of products is used on patients. Of course, high quality as well as high functionality and safety levels of medical products are a must. However, the implementation of these regulations is realized differently in the various markets, as there is no global harmonization. This work focuses on approval procedures for medical devices in Europe (EU) and the USA and compares significant differences in the approval procedures, which are shown as a graphical comparison. An example is an approval of medical devices by the U.S. Food and Drug Administration (FDA), which is an US government agency. In Europe (EU) there is a manufacturer’s declaration of conformity for the approval.
Mobile compressed gas supply for active orthoses and exo-skeletons
Authors: Pott Peter P. , Schwenkel Laura , Janzen Swantje , Mühlbauer Pia
Published: September 2019

In this study a basic principle for the gas supply of a pneumatic actuation for a mobile active knee joint orthosis is described. Instead of using a compressor or a bulky pressure reservoir, the system is supplied with pressurized gas directly from a thermodynamic process to reduce size and weight of the device. To achieve this goal a literature search was performed identifying chemical processes. These options were then analysed and evaluated considering the aspects energy density, safety, eco-friendliness, and technical feasibility of the construction. The expansion of liquified carbon dioxide with phase change achieves the best result due to its high level of safety and the simple technical feasibility of the system. However, CO2cools down considerably during the expansion, so heating up again to room temperature is necessary. Therefore, the technical construction includes a passive and an active heat exchanger.
Automated alignment detection of an additively manufactured Z-frame marker to process instrument targeting signals in interventional MRI
Authors: Odenbach Robert , Parsanejad Parisa , Friebe Michael
Published: September 2019

MRI-guided interventions (iMRI, e.g. prostate biopsy) are usually performed under a free-hand instrument targeting approach to guide and feed the instrument (e.g. biopsy needle) along the desired trajectory. However, this technique requires many iterative movements either from the interventionist or of the patient (with the MRI table) in and out of the MRI tunnel, which is cumbersome, time-consuming and expensive. To overcome these downsides, interventional MRI procedures can be facilitated with remotely controllable assistance systems for instrument alignment. Such systems require an accurate registration and tracking of the position and orientation of the instrument. Passive fiducial marker frames (e.g. additively manufactured Z-frame marker) are capable of providing full information about a device´s orientation within the image. In this paper, we present an automated alignment detection algorithm to track a Z-marker from system-independent screen-captured images. We evaluated the precision of the detection algorithm by analysing its computation results from schematic gold standard images in different marker orientations in comparison to MR-images with the same orientations. Our combined setup consists of a precise alignment system, an additively manufactured Z-frame marker and the related detection algorithm. It offers a fast, simple, independent and accurate automated instrument targeting for iMRI. For future work, we plan to conduct phantom targeting tests in combination with robotic alignment systems.
Severity of corrosion under insulation (CUI) to structures and strategies to detect it
Authors: Eltai Elsadig O. , Musharavati Farayi , Mahdi El-sadig
Published: September 2019

This review paper considers the research conducted in the past 30 years in the field of corrosion under insulation (CUI). CUI is a significant challenge in many industries for reasons of high cost and risk because it proceeds undetected under insulation. CUI is an unavoidable problem which may potentially cause personnel injury or even fatalities. Presently, CUI counts for as much as 40 to 60% of pipeline-repairing cost. The use of coating under the insulation has been shown very efficient in the mitigation of CUI. Moisture and ion penetration, particularly chlorides, through the insulation and coating may produce stress corrosion cracking of austenitic stainless steels. The process of applying insulating materials on metal surfaces and the precautions that need to be taken are explained. Beside visual inspection, techniques such as neutron backscatter, capacitive imaging and pulsed eddy current can be used to detect the presence of CUI. The strength and limitations of the available commercial detection techniques are evaluated. A comprehensive list of industrial standards dealing with CUI is provided.
Clinical evidence of the effect of bisphosphonates on pregnancy and the infant
Authors: Machairiotis Nikolaos , Ntali Georgia , Kouroutou Paraskevi , Michala Lina
Published: September 2019

Bisphosphonates (BPs) are potent inhibitors of osteoclast mediated bone resorption. These drugs are widely used in the management of osteoporosis and other diseases, characterized by high bone turnover. The effect of BPs on gestation and lactation, when they are used as therapeutic agents in premenopausal women, is yet unknown. We conducted a detailed literature review and identified the cases of BPs use in young women, as well as, the effects of this therapy on the gestation and the embryo. The published data, regarding the use of BPs in premenopausal women and their effects on the pregnancy outcome, are limited. However, we could identify the outcomes of 40 pregnant women, who had received BPs prior to or during pregnancy, that have been documented in the literature. All women had valid indications to receive BPs for serious bone metabolism conditions. We could not identify any prospective trials, which focus on pregnancy outcomes following after the in-utero exposure to BPs. In total, no serious adverse effects were reported. Problems related to the offspring, such as hypocalcemia and a tendency for low body weight (LBW), were self-resolving. In addition, no serious adverse outcomes were reported for women having completed pregnancy. Nevertheless, follow-up was limited for both outcomes suggesting the necessity of national and international registries.