Volume 5, Issue 1 - Proceedings of the 2019 Annual Meeting of the German Society of Biomedical Engineering (25–26 September 2019, Frankfurt am Main)

This work targets the development of a neighborhood-based Collaborative Filtering therapy recommender system for clinical decision support. The proposed algorithm estimates outcome of pharmaceutical therapy options in order to derive recommendations. Two approaches, namely a Relief-based algorithm and a metric learning approach are investigated. Both adapt similarity functions to the underlying data in order to determine the neighborhood incorporated into the filtering process. The implemented approaches are evaluated regarding the accuracy of the outcome estimations. The metric learning approach can outperform the Relief-based algorithms. It is, however, inferior regarding explainability of the generated recommendations.

Endovascular catheters are necessary for state-ofthe- art treatments of life-threatening and time-critical diseases like strokes and heart attacks. Navigating them through the vascular tree is a highly challenging task. We present our preliminary results for the autonomous control of a guidewire through a vessel phantom with the help of Deep Reinforcement Learning. We trained Deep-Q-Network (DQN) and Deep Deterministic Policy Gradient (DDPG) agents on a simulated vessel phantom and evaluated the training performance. We also investigated the effect of the two enhancements Hindsight Experience Replay (HER) and Human Demonstration (HD) on the training speed of our agents. The results show that the agents are capable of learning to navigate a guidewire from a random start point in the vessel phantom to a random goal. This is achieved with an average success rate of 86.5% for DQN and 89.6% for DDPG. The use of HER and HD significantly increases the training speed. The results are promising and future research should address more complex vessel phantoms and the use of a combination of guidewire and catheter.

Better handling of neurological or neurodegenerative disorders such as Parkinson’s Disease (PD) is only possible with an early identification of relevant symptoms. Although the entire disease can’t be treated but the effects of the disease can be delayed with proper care and treatment. Due to this fact, early identification of symptoms for the PD plays a key role. Recent studies state that gait abnormalities are clearly evident while performing dual cognitive tasks by people suffering with PD. Researches also proved that the early identification of the abnormal gaits leads to the identification of PD in advance. Novel technologies provide many options for the identification and analysis of human gait. These technologies can be broadly classified as wearable and non-wearable technologies. As PD is more prominent in elderly people, wearable sensors may hinder the natural persons movement and is considered out of scope of this paper. Non-wearable technologies especially Image Processing (IP) approaches captures data of the person’s gait through optic sensors Existing IP approaches which perform gait analysis is restricted with the parameters such as angle of view, background and occlusions due to objects or due to own body movements. Till date there exists no researcher in terms of analyzing gait through 3D pose estimation. As deep leaning has proven efficient in 2D pose estimation, we propose an 3D pose estimation along with proper dataset. This paper outlines the advantages and disadvantages of the state-of-the-art methods in application of gait analysis for early PD identification. Furthermore, the importance of extracting the gait parameters from 3D pose estimation using deep learning is outlined.

This paper examines the question of how strongly the spectral properties of the EEG during microsleep differ between individuals. For this purpose, 3859 microsleep examples were compared with 4044 counterexamples in which drivers were very drowsy but were able to perform the driving task. Two types of signal features were compared: logarithmic power spectral densities and entropy measures of wavelets coefficient series. Discriminant analyses were performed with the following machine learning methods: support-vector machines, gradient boosting, learning vector quantization. To the best of our knowledge, this is the first time that results of the leave-one-subject-out cross-validation (LOSO CV) for the detection of microsleep are presented. Error rates lower than 5.0 % resulted in 17 subjects and lower than 13 % in another 11 subjects. In 3 individuals, EEG features could not be explained by the pool of EEG features of all other individuals; for them, detection errors were 15.1 %, 17.1 %, and 27.0 %. In comparison, cross validation by means of repeated random subsampling, in which individuality is not considered, yielded mean error rates of 5.0 ± 0.5 %. A subsequent inspection of raw EEG data showed that in two individuals a bad signal quality due to poor electrode attachment could be the cause and in one individual a very unusual behavior, a high and long-lasting eyelid activity which interfered the recorded EEG in all channels.

The electrical activity of the diaphragm (EAdi) is a novel monitoring parameter for patients under assisted ventilation and is used for assessing the patient’s neural respiratory drive. It is recorded by an array of electrodes placed inside the esophagus at the level of the diaphragm. A noninvasive alternative is the measurement of the electromyogram by means of skin surface electrodes (sEMG). The respiratory sEMG signal, however, is subject to electrocardiographic interference and crosstalk from other muscles and may also pick up a different part of the muscular activity. In this work, we propose to use a deep neural network to predict the electrical activity of the diaphragm as measured by a nasogastric catheter from sEMG measurements. We use a ResNet based architecture and train the network to directly regress the EAdi as a supervised learning task - we further investigate a heatmap based regression approach. The proposed methods are evaluated on a clinical dataset consisting of 77 recordings from mechanically ventilated patients. For the direct regression task, the network’s predictions reach a Pearson correlation coefficient (PCC) of 0.818 with EAdi on the hold-out set. The heatmap regression increases the PCC to 0.830 while at the same time achieving a lower mean absolute error, indicating a superior performance. From our results we conclude that sEMG measurements may be used to predict the internal activity of the diaphragm as measured invasively using a nasogastric catheter.

The location of a puncture needle’s tip and the resistance of tissue against puncture are crucial information for clinicians during a percutaneous procedure. The tip location and needle alignment can be observed by image guidance. Tactile information caused by tissue resistance to rupture, allow clinicians the perception of structural changes during puncture. Nevertheless, this sense is individual and subjective. To improve percutaneous procedures, the implementation of transducers to enhance or complement the senses offer objective feedback to the user. Known approaches are e.g. based on integrated force sensors. However, this is connected to higher device costs, sterilization and certification issues. A recent publication shows the implementation of an audio transducer clipped at the proximal end of the needle. This sensor is capable of acquiring emitted sounds of the distal tiptissue interaction that are transmitted over the needle structure. The interpretation of the measured audio signals is highly depended on the transmission over the needle, the tissue and, the penetration depth. To evaluate the influence of these parameters, this work implements a simplified experimental setup in a controlled environment with a minimum of noise and without micro tremors induced by clinician’s hands. A steel rod simulating a needle is inserted into pork meat of different thickness. A controlled impact covering the needle’s tip mimics tissue contact. The resulting signals are recorded and analyzed for better understanding of the system.

In this paper, we present an approach for getting an initial pose to use in a 2D/3D registration process for computer-assisted spine surgery. This is an iterative process that requires an initial pose close to the actual final pose. When using a proper initial pose, we get registrations within two millimeters of accuracy. Consequently, we developed a fully connected neural network (FCNN), which predicts the pose of a specific 2D image within an acceptable range. Therefore, we can use this result as the initial pose for the registration process. However, the inability of the FCNN for learning spatial attributes, and the decrease of the resolution of the images before inserting them in the FCNN, make the variance of the prediction large enough to make some of the predictions entirely out of the acceptable range. Additionally, new researches in deep learning field have shown that convolutional neural networks (CNNs) offer high advantages when the inputs of the net are images. We consider that using CNNs can help to improve our results, generalizing the system for a greater variety of inputs, and facilitating the integration with our current workflow. Then we present an outline for a CNN for our application, and some further steps we need to complete to achieve this implementation.

The application of artificial intelligence (AI) in the areas of health, care and social participation offers great opportunities but also involves great challenges. Extensive regulatory, ethical and data-security related requirements exist for data recording, storage and processing of respective personalized and patient-related data. “Artificial Intelligence as a Service” (AIaaS) is pushed for consumer applications by global players, which implies data storage on external database server. However, the available solutions do not meet the requirements. Moreover, small and medium-sized enterprises (SMEs) in the field of healthcare fear the loss of data sovereignty and information outflow. In this paper, we propose a secure and resource-efficient approach by embedding AI directly close to the sensor in combination with secure and distributed data processing on local server or certified “Trusted Data Center”. For this purpose, we have developed the Artificial Intelligence for Embedded Systems (AIfES) platform-independent machine learning library in C programming language. It contains a fully configurable deep artificial neural network with feedforward structure. The library can be run directly on a microcontroller and even allows to train the neural network. Possible healthcare applications include direct (pre-) processing of sensor data, sensor calibration, pattern recognition and classification.

Stroke volume (SV) and cardiac output (CO) estimations with non-invasive approaches like thoracic electrical bioimpedance (TEB) measurement become state of the art in clinical practice. Despite the advantages like low costs, low risk of infection and relatively easy application, there are also disadvantages like the sensitivity to movement artifacts and, electrode displacement mistakes. The bioimpedance signal acquired with a tetrapolar measurement has a relatively weak signal strength compared with another common recorded signal, e.g., the electrocardiogram (ECG). For reconstruction and filtering of the dZ/dt signal, different approaches exist like ensemble averaging (EA), scaled fourier linear combiner (SFLC), wavelet denoising and adaptive filter. We propose an artificial neural network with long short-term memory (LSTM) layer for signal reconstruction during ergometry. The LSTM network performs well compared with other algorithms, e.g., with better amplitude (C point) reconstruction. The SV estimation with the LSTM network was at least comparable or even better than the estimation based on SFLC.

We introduce a wearable-based recognition system for the classification of natural hand gestures during dynamic activities with surgical instruments. An armbandbased circular setup of eight EMG-sensors was used to superficially measure the muscle activation signals over the broadest cross-section of the lower arm. Instrument-specific surface EMG (sEMG) data acquisition was performed for 5 distinct instruments. In a first proof-of-concept study, EMG data were analyzed for unique signal courses and features, and in a subsequent classification, both decision tree (DTR) and shallow artificial neural network (ANN) classifiers were trained. For DTR, an ensemble bagging approach reached precision and recall rates of 0.847 and 0.854, respectively. The ANN network architecture was configured to mimic the ensemble-like structure of the DTR and achieved 0.952 and 0.953 precision and recall rates, respectively. In a subsequent multi-user study, classification achieved 70 % precision. Main errors potentially arise for instruments with similar gripping style and performed actions, interindividual variations in the acquisition procedure as well as muscle tone and activation magnitude. Compared to hand-mounted sensor systems, the lower arm setup does not alter the haptic experience or the instrument gripping, which is critical, especially in an intraoperative environment. Currently, drawbacks of the fixed consumer product setup are the limited data sampling rate and the denial of frequency features into the processing pipeline.

Orthognathic surgery is used to treat misaligned jaws in adults by repositioning them. Intervention planning has to take into account different clinical, anatomical, functional, and aesthetic parameters to determine the optimal position. Current planning systems usually present 3D surface models obtained from a CT or Cone-Beam scan of the patient. The surgeon then interactively positions the upper and lower jaw. Thus, the surgeon can manually optimize anatomical aspects but has to consider functional and aesthetic effects simultaneously, which may be error-prone. We are developing a computer-assisted planning system which generates an optimized position for both jaws based on different analyses (cephalometric, plaster model, photostat) of the head, using a gradient descent algorithm. For this purpose, landmarks are interactively identified on a 3D surface representation. The system is developed as a plugin for MITK utilizing a knowledge base realized in the sematic web standard RDFS, which is queried with SPARQL requests. In a preliminary evaluation with five different cases we compare the automatically generated planning proposal with the planning results of a maxillofacial expert (ground truth). Good general agreement is observed, although more research for the identification and development of 3D cephalometric analyses is needed.

The circadian rhythm that drives the human sleepwake cycle manifests itself in the variation of the core body temperature (CBT). Measuring CBT continuously, however, is intricate. Heart rate and its variability also varies notably over the course of the day, but is more accessible to measure. We present first results from a study that investigates the biorhythmic relationship between the circadian rhythm of CBT and measures of heart rate variability (HRV). Twelve subjects participated in a 50-hour experiment that was segmented into one hundred 30-minute blocks. In each block, subjects attempted to sleep for ten minutes. CBT and the ECG were continuously recorded. To date, intervals between successive heart beats (RR intervals) were determined for three subjects. From RR intervals of each attempted-sleep episode, power spectral densities (PSD) were estimated with the Lomb-Scargle periodogram and averaged into 0.02-Hz wide bands. The periodogram of each RR-frequency-band time series was estimated and compared against the periodogram of CBT, which, as expected, shows a dominant maximum at a period length of 24 hours. Mutual information, an entropy-based measure of interdependence, was used for the comparison. The highest coherence towards CBT was found for the RR-PSD between 0.24 and 0.34 Hz. This RR-PSD range usually includes the respiratory rate, which may indicate that heart rate is more closely linked to respiration at certain times of the day than at others.

In dysphagia the ability of elevating the larynx and hyoid is usually impaired. Electromyography (EMG) and Bioimpedance (BI) measurements at the neck can be used to trigger functional electrical stimulation (FES) of swallowing related muscles. The height and speed of larynx elevation can be assessed by evaluating the BI during a swallow. For the triggering of an supporting FES and for biofeedback online detection of swallow onsets is required. Patients can practice by a gamified biofeedback to swallow harder, swallow in a timely manner or to maintain the larynx elevation for a longer time period (Mendelson maneuver). The success of the stimulation and biofeedback therapy as well as the acceptance by the patient strongly depends on the precise detection of swallow onsets. We have introduced a classification algorithm based on a random forest classifier to trigger FES in phase with voluntary swallowing based on EMG and BI. Although the classification is successful in healthy subjects, difficulties appear in the utilization on some patients. The reason for this can be found in a strongly varying residual swallow activity. Usually the activity of EMG and change in BI are smaller in patients compared to healthy subjects. Thus an adaption procedure is needed, that can be easily applied. In this paper we introduce an algorithm that is capable to find an optimal classifier for a patient in terms of sensitivity. The adaption algorithm uses a small number of recorded swallow onsets of a patient at the beginning of a therapy session to evaluate different classifiers and to pick the most suitable for the treatment. The set of random forest classifiers has been trained with data from healthy subjects by step wise shifting the class weights of swallows and non-swallows, yielding classifiers with different sensitivities. The evaluation is done using data from 41 patients. It showed that the sensitivity of the classification can be increased by 4 to 6 % in average compared to fixed classifiers, but up to 66 % for individual patients. Finally, we studied the effect this adaptive classifier in triggered stimulation therapy in a single dysphagia patient. Swallowing performance was measurements during one week of therapy consisting of eleven therapy session. An improvement of 40 and 63 % in larynx elevation and speed could be observed, respectively.

We present the concept of a novel epiretinal prosthesis, consisting of a foil-based, miniaturized electronics with wireless optical energy and signal transmission and integrated electrostimulation. The aim is achieving a wideangle projection to create a large visual field. The implant having a diameter of 14 mm consists of a mosaic-like array of thinned silicon-based photodiodes combined with a polyimide foil. This thin implant, realized on a flexible foil for the first time, adapts to the curvature of the eye. Thin-film stimulation electrodes on the foil are electrically connected to the photodiodes. The influence of the electrode geometry on the electrical current density at the location of electrostimulation is investigated by computer simulations. First experiments towards realization of via holes in a 10 μm thick polyimide layer were successful and led to vias with inclined sidewalls and rounded openings. This shape is advantageous concerning uninterrupted conductor paths leading from the photodiodes to the stimulation electrodes.

Endoprostheses such as hip replacements are subject to wear. Lubrication of the joint interface plays a key role in the wear process, but the mechanisms of lubrication is challenging to understand. The main issue is the three-body abrasion which leads to a shorter life cycle. In order to improve the life cycle, the surfaces of the articulating components can be modified, for example by pulsed femtosecond-laser microstructuring. By microstructuring of the implant surface, the viscosity of the synovial fluid between the joint can be increased due to the non-Newtonian properties of the synovia. This leads to better lubrication and therefore lower particle abrasion. The objective of this study was to evaluate the impact of different microstructures on the viscosity of a joint fluid substitute. Various microstructures were investigated in a modified rheometer setup featuring a decreased gap size. As a test fluid, a synovial fluid substitute was used. The results show that an increase in the viscosity of the synovial fluid substitute can be achieved by microstructuring. An increase of viscosity of up to 20 % compared to the unstructured reference was observed with ring-structures with a diameter of 100 μm and a depth of 20 μm.

Due to the broad spectrum of individual functionalities, current hospital information systems in most cases do not offer quick information access or proper assistance in information assessment. This results in extensive use of raw value representations and the need to process and evaluate those cognitively through the physician. This can result in an error-prone and ineffective process, especially in complex and chronic treatment scenarios. With an example scenario of laboratory value assessment in head and neck oncology, we have evaluated the requirements for extensive support of case interpretation through the conduction of a Delphi study including five medical experts with different levels of expertise. Based on the results, we propose a solution with integrated HL7 FHIR compliant clinical decision-support functionality through a set of integrated rules from relevant clinical practice guidelines. Furthermore, we introduce the implementation of a dedicated application that allows for the definition of custom laboratory value evaluation rules to enable automated and patientindividual value interpretation.

In clinical patient monitoring scenarios, the detection of hemorrhage is still a major problem. Traditional vital signs like heart rate and blood pressure are insensitive to blood loss due to compensatory mechanisms in the body that can sustain these parameters until shortly before cardiovascular collapse. These compensatory mechanisms during blood loss are primarily driven by the autonomic nervous system. Heart rate variability analysis is a viable tool in the quantitative analysis of the autonomic nervous system and shows promising results in the context of hypovolemia detection. In order to investigate if HRV parameters suitably reflect a mild to moderate blood volume reduction, we conducted a lower body negative pressure test study with 30 volunteering participants thereby simulating progressive central hypovolemia. Here, HRV parameters from the time domain (mean HR, SDNN, RMSSD, rSDRM, pNN50), the frequency domain (VLF, LF, HF, LF/HF), non-linear HRV parameters (SD1, SD2, SD1/SD2, SampEn, ApEn) and the respiratory rate (RR) were collected. The changes of the evaluated parameters as a consequence of the reduced blood volume were statistically evaluated. A statistically significant deviation from their baseline values could be found for RMSSD, rSDRM, pNN50, HF, LF/HF, SD1 and SD1/SD2 at a chamber pressures starting at −30 mmHg. Therefore, we support the proposition that heart rate variability analysis can help in detecting otherwise occult hypovolemia.

Chronic kidney disease (CKD) affects 13% of the worldwide population and end stage patients often receive haemodialysis treatment to control the electrolyte concentrations. The cardiovascular death rate increases by 10% - 30% in dialysis patients than in general population. To analyse possible links between electrolyte concentration variation and cardiovascular diseases, a continuous non-invasive monitoring tool enabling the estimation of potassium and calcium concentration from features of the ECG is desired. Although the ECG was shown capable of being used for this purpose, the method still needs improvement. In this study, we examine the influence of lead reduction techniques on the estimation results of serum calcium and potassium concentrations.We used simulated 12 lead ECG signals obtained using an adapted Himeno et al. model. Aiming at a precise estimation of the electrolyte concentrations, we compared the estimation based on standard ECG leads with the estimation using linearly transformed fusion signals. The transformed signals were extracted from two lead reduction techniques: principle component analysis (PCA) and maximum amplitude transformation (Max- Amp). Five features describing the electrolyte changes were calculated from the signals. To reconstruct the ionic concentrations, we applied a first and a third order polynomial regression connecting the calculated features and concentration values. Furthermore, we added 30 dB white Gaussian noise to the ECGs to imitate clinically measured signals. For the noisefree case, the smallest estimation error was achieved with a specific single lead from the standard 12 lead ECG. For example, for a first order polynomial regression, the error was 0.0003±0.0767 mmol/l (mean±standard deviation) for potassium and -0.0036±0.1710 mmol/l for calcium (Wilson lead V1). For the noisy case, the PCA signal showed the best estimation performance with an error of -0.003±0.2005 mmol/l for potassium and -0.0002±0.2040 mmol/l for calcium (both first order fit). Our results show that PCA as ECG lead reduction technique is more robust against noise than MaxAmp and standard ECG leads for ionic concentration reconstruction.

Maintaining a prescribed peripheral oxygen saturation (SpO 2 ) target during routine care of neonates is challenging and inspired fraction of oxygen (FiO 2 ) titration practices differ among caregivers and centers. Algorithms for automatic feedback control of SpO 2 are being developed and tested, that would adapt to the changing neonatal organism and better maintain the required SpO 2 target range. While clinical data is necessary to validate differences in the titration strategies, a continuous physiological model of oxygenation in neonates would facilitate baseline testing of different approaches, manual or automated. The objective of our study was to enhance a mathematical model of oxygenation of the neonate and to compare the performance of the model with available clinical data. We have implemented the diffusion resistance into the model as well as a variable oxyhemoglobin dissociation relationship and the bias between arterial and peripheral oxygen saturation. Values of model parameters were scaled to fit preterm infant scenarios. The comparison of the clinical data and computer simulations suggest that the model can reliably simulate episodes of oxygen desaturation and describe the relation between ventilation, FiO 2 and SpO 2 . It appears that the model may be an effective tool to test manual and automatic FiO 2 titration strategies.

The formation of a thrombus is associated with dramatic consequences for the patient, such as increased risks of neurologic events and myocardial infarction or even death. A pathologically altered blood flow is associated with these complications. Consequently, a consistent fluid-mechanical analysis of implants, such as coronary stents, must be carried out. Computational fluid dynamics (CFD) is an important in silico tool for the analysis of different stent designs. Using three different generic stent designs (closed-cell, open-cell and helical), CFD could be performed with the OpenFOAM software package. The stents were implemented in a vascular model having a fully developed Hagen-Poiseuille velocity profile (u mean = 0.6 m/s) as inlet condition. In combination with the dynamic viscosity of the Newtonian test fluid of 6.04·10 -5 m 2 /s, Reynolds numbers up to 460 were achieved. Spatially high-resolved velocity fields from measurements in the magnetic resonance tomograph (magnetic resonance velocimetry, MRV) were available for validation. The velocity field was compared in selected cross sections and longitudinal sections. The difference of the main flow proximal and distal to the stent models were below 6 %. In addition, a similar flow topology could be quantified using the Q-criterion. Due to the very good agreement of the numerical results with the MRV-measurements, the numerical method has been applied to further analysis of stent designs regarding to time average wall shear stress (TAWSS) distribution on the luminal vessel surface (surface area with TAWSS < 0.4 Pa was related to overall vessel surface) under pulsatile conditions. Although all stent designs have the same square cross-section, a large influence of the stent design on WSS distribution could be observed (closedcell vs. helical = -50.2 %; open-cell vs. helical = -38.5 %). By using validated CFD it was possible to quantify the hemodynamic benefit of helical stent design in terms of thrombosis potential.

Reepithelialization is the single requirement to define a wound as healed when the barrier function of the skin is restored. An existing reepithelialization mathematical model (RM) simulates wound healing in vitro. This work performs a parameter sensitivity analysis on an existing RM to see how robust the model is for changing wound healing rates for application to chronic wounds (inhibition) and wound healing therapies (activation). The existing RM balances the optimal distance between cells and basal membrane segments (BMs) according to the calculation of intercellular pressure and adhesion force. The RM mimics cell behavior and their interaction by passive migration, which is the displacement of cells from its initial position. First, this work reproduces the RM. The initial case recreates the interaction of a cell with its surrounding cells, while the second case recreates the interaction of the cell with its nearest BMs. These two cases were implemented in MATLAB to estimate optimal distance, intercellular pressure, an adhesive force between cells and the BMs. The analysis computes movement vectors and new positions of each cell at different time steps. Parameter sensitivity analysis was then conducted on the adhesion coefficient, where the original value in the RM was unknown. The results obtained at the assumed original parameter values are similar to the existing RM. As a result of the parameter sensitivity analysis, increasing the adhesion coefficient increases cell movement. High basal adhesion causes passive movement of cells, which in the simulation results is seen as a cellular movement towards wound closure. The existing RM is robust to changing adhesion coefficient values which change the rate of the advancing reepithelialization front. Future work includes fitting adhesion coefficient parameter values to an in vitro wounded tissue visualized by live dyes in treatment therapy experiments.

Current dipoles are well established models in the localization of neuronal activity to electroencephalography (EEG) data. In physical phantoms, current dipoles can be used as signal sources. Current dipoles are often powered by constant current sources connected via twisted pair wires mostly consisting of copper. The poles are typically formed by platinum wires. These wires as well as the dipole housing might disturb the electric potential distributions in physical phantom measurements. We aimed to quantify this distortion by comparing simulation setups with and without the wires and the housing. The electric potential distributions were simulated using finite element method (FEM). We chose a homogenous volume conductor surrounding the dipoles, which was 100 times larger than the size of the dipoles. We calculated the difference of the electric potential at the surface of the volume conductor between the simulations with and without the connecting wires and the housing. Comparing simulations neglecting all connecting wires and the housing rod to simulations considering them, the electric potential at the surface of the volume conductor differed on average by 2.85 %. Both platinum and twisted pair copper wires had a smaller effect on the electric potentials with a maximum average change of 6.38 ppm. Consequently, source localization of measurements in physical head phantoms should consider these rods in the forward model.

Spinal cord stimulation (SCS) is the most commonly used technique of neurostimulation. It involves the stimulation of the spinal cord and is therefore used to treat chronic pain. The existing esophageal catheters are used for temperature monitoring during an electrophysiology study with ablation and transesophageal echocardiography. The aim of the study was to model the spine and new esophageal electrodes for the transesophageal electrical pacing of the spinal cord, and to integrate them in the Offenburg heart rhythm model for the static and dynamic simulation of transesophageal neurostimulation. The modeling and simulation were both performed with the electromagnetic and thermal simulation software CST (Computer Simulation Technology, Darmstadt). Two new esophageal catheters were modelled as well as a thoracic spine based on the dimensions of a human skeleton. The simulation of directed transesophageal neurostimulation is performed using the esophageal balloon catheter with an electric pacing potential of 5 V and a trapezoidal signal. A potential of 4.33 V can be measured directly at the electrode, 3.71 V in the myocardium at a depth of 2 mm, 2.68 V in the thoracic vertebra at a depth of 10 mm, 2.1 V in the thoracic vertebra at a depth of 50 mm and 2.09 V in the spinal cord at a depth of 70 mm. The relation between the voltage delivered to the electrodes and the voltage applied to the spinal cord is linear. Virtual heart rhythm and catheter models as well as the simulation of electrical pacing fields and electrical sensing fields allow the static and dynamic simulation of directed transesophageal electrical pacing of the spinal cord. The 3D simulation of the electrical sensing and pacing fields may be used to optimize transesophageal neurostimulation.

In vitro, hydrogel-based ECMs for functionalizing surfaces of various material have played an essential role in mimicking native tissue matrix. Polydimethylsiloxane (PDMS) is widely used to build microfluidic or organ-on-chip devices compatible with cells due to its easy handling in cast replication. Despite such advantages, the limitation of PDMS is its hydrophobic surface property. To improve wettability of PDMS-based devices, alginate, a naturally derived polysaccharide, was covalently bound to the PDMS surface. This alginate then crosslinked further hydrogel onto the PDMS surface in desired layer thickness. Hydrogel-modified PDMS was used for coating a topography chip system and in vitro investigation of cell growth on the surfaces. Moreover, such hydrophilic hydrogel-coated PDMS is utilized in a microfluidic device to prevent unspecific absorption of organic solutions. Hence, in both exemplary studies, PDMS surface properties were modified leading to improved devices.

The aim of this study was to determine whether non-invasive heart rate variability (HRV) recordings can be used to monitor training exercises and to estimate athletic performance. Thus far, condition and performance have been evaluated with lactate test procedures and spirometry. Several tests were conducted to determine the relationship of data from lactate test samplings, spirometry and HRV recordings. Four groups of professional athletes in different disciplines such as ball sports (n=15), martial arts (n=17), endurance sports (n=8) and hobby athletes (n=6) underwent a standardized treadmill or bicycle ergometer step test while increasing load rates, e.g. 2 km/h or 20-50 Watt every 3.5 minutes, synchronized with standardized series of lactate test sampling, spirometry and ECG recording. An inclusion criterion for all athlete groups was a minimum training frequency of an hour, five days a week focusing on continuous performance improvement. Evidence shows that offline analysis of ECG data allows conclusions on actual individual athletic performance without the need for complex instrumentation and laboratory environment. The total power parameter of the HRV reaches a plateau phase in all tested subjects and this plateau phase reaches zero near the 2 mmol threshold of lactate concentration in all subjects recorded on a bicycle ergometer. Nine out of ten subjects measured on the bicycle ergometer had negatively correlating data of lactate concentration and total power of HRV (α < 0.05). Lactate measurements using treadmills require resting periods for blood sampling. As the HRV increases instantly in these resting periods, the use of bicycle ergometers, where no testing breaks are needed, is recommended for further research.

Quantifying the atrial conduction velocity (CV) reveals important information for targeting critical arrhythmia sites that initiate and sustain abnormal electrical pathways, e.g. during atrial flutter. The knowledge about the local CV distribution on the atrial surface thus enhances clinical catheter ablation procedures by localizing pathological propagation paths to be eliminated during the intervention. Several algorithms have been proposed for estimating the CV. All of them are solely based on the local activation times calculated from electroanatomical mapping data. They deliver false values for the CV if applied to regions near scars or wave collisions. We propose an extension to all approaches by including a distinct preprocessing step. Thereby, we first identify scars and wave front collisions and provide this information for the CV estimation algorithm. In addition, we provide reliable CV values even in the presence of noise. We compared the performance of the Triangulation, the Polynomial Fit and the Radial Basis Functions approach with and without the inclusion of the aforementioned preprocessing step. The evaluation was based on different activation patterns simulated on a 2D synthetic triangular mesh with different levels of noise added. The results of this study demonstrate that the accuracy of the estimated CV does improve when knowledge about the depolarization pattern is included. Over all investigated test cases, the reduction of the mean velocity error quantified to at least 25 mm/s for the Radial Basis Functions, 14 mm/s for the Polynomial Fit and 14 mm/s for the Triangulation approach compared to their respective implementations without the preprocessing step. Given the present results, this novel approach can contribute to a more accurate and reliable CV estimation in a clinical setting and thus improve the success of radio-frequency ablation to treat cardiac arrhythmias.

Imaging photoplethysmography allows to capture spatio-temporal patterns related to the perfusion. One such approach is based on the analysis of the time delay between pulse waves at different locations by so-called phase maps. There are different ways to establish such maps. However, neither a comparison between existing methods has been published nor has the impact of different stimuli been sufficiently examined until today. In this work, we compare three previously published approaches for the generation of phase maps and investigate the impact of two physiological stimuli on such maps. Our results show pairwise correlation coefficients between the different approaches of phase map generation from r = 0.65 to r = 0.82, indicating substantial differences between maps. The different maps reflect our physiological expectation in varying degrees. Particularly for a weaker (distant) stimulation refinements are needed to reveal characteristic changes.

Epilepsy affects about 50 million people worldwide of which one third is refractory to medication. An automated and reliable system that warns of impending seizures would greatly improve patient’s quality of life by overcoming the uncertainty and helplessness due to the unpredicted events. Here we present new seizure prediction results including a performance comparison of different methods. The analysis is based on a new set of intracranial EEG data that has been recorded in our working group during presurgical evaluation. We applied two different methods for seizure prediction and evaluated their performance pseudoprospectively. The comparison of this evaluation with common statistical evaluation reveals possible reasons for overly optimistic estimations of the performance of seizure forecasting systems.

Automated classification of waveforms is an important method of data processing used in various fields of science, such as neuroscience, biomedical engineering, etc. This work shows the possibility of sorting special waveforms i.e. spikes recorded with multichannel electrode arrays by using principles of correlation and data-driven reference. A new method to estimate the number of k-means clusters by using a Monte Carlo method is introduced. To demonstrate the performance of the algorithm, generated signals were used, which are created to mimic multichannel recording of the extra-cellular neuronal signals.

The consortium RESPONSE is a cooperation between partners from science and industry within the BMBF-Program “Twenty20 - Partnership for Innovation”, 2014-2021. RESPONSE gives its partners opportunities to put medical device innovations into practice more efficiently. In order to accelerate innovation processes, joint efforts are being made along the entire translation chain. RESPONSE is focusing on the development of novel concepts of implantable medical devices for cardiovascular, ophthalmologic and ENT application. Platform technology approaches are being used to extend the range of device applications. See also: www.response.uni-rostock.de

Mimicking the structural properties of natural tissue was aimed to be achieved by combining complementary mechanical properties of materials showing high tensile strength with those of high elasticity. By using two polymers with different properties, the advantages of both can be combined to access innovative materials for biomedical applications. Dual co-electrospinning was established to generate biocompatible nonwoven fibre composites with fused properties from polyamide (PA6) and polyurethane based silicone elastomers (PU-co-Si), respectively. By electrospinning both compounds simultaneously, significant advantages, such as combining different fibre thicknesses and mechanical properties, are accessible. Furthermore, the effect on the fibres via an optional post-processing step in the shape of different thermal treatments was investigated. Initial results concerning surface morphology, biocompatibility and tensile properties of the obtained electrospun nonwovens are very auspicious. Thus, the suitability of two complementary polymer classes for tissue biomimicry through a synthetic approach was shown, offering the opportunity of novel implant materials for permanent replacement of biological tissue.

Although the development of the transcatheter aortic valve (TAV) has saved many lives of inoperable patients and has a very good clinical outcome, concerns about valve thrombosis are increasing. Due to the potential risk of late clinically relevant events, the US Food and Drug Administration (FDA) suggests a careful systematic investigation of thrombosis and reduced leaflet motion related to hemodynamic changes induced by TAV implantation. Furthermore, recently published position papers of the ISO working group address numerical and experimental flow field assessment of TAV. In particular, pathologically high shear rates and a reduced washout of the sinuses may increase the risk of valve thrombosis and should therefore be investigated. By means of fluid-structure interaction (FSI) as a powerful in silico tool, the transient flow field in an aortic valve was analyzed. A linear elastic behavior was assumed for leaflet material properties (Young modulus: 10 MPa, Poisson ratio: 0.46 and leaflet material density: 1000 kg/m 3 ) and blood was specified as a homogeneous, Newtonian and incompressible fluid (fluid density: 1060 kg/m 3 and a dynamic viscosity: 0.0035 Pa s). In this numerical study we present a Eulerian approach, which is based on transport equation of the residence time (RT) as a passively transported scalar. It can be clearly seen that the RT is significantly higher in the sinus referred to the main flow. At time step t = 0.25 s, the average residence time in the main flow is RT avg ≈ 0.05 s, whereas RT ≈ 0.25 s in the sinus. In particular, RT is a valuable hemodynamic metric to quantify the washout of the sinus in order to evaluate the thrombogenic potential of TAV devices. Further studies will concentrate on particle image velocimetry measurements for validation purposes. In particular the velocity in the sinus and therefore the washout is one important hemodynamic key feature that has to be improved for future TAV designs.

A new internship for the module human factors engineering of the study course biomedical engineering was developed on the concept of learning by researching combining the transfer of knowledge with gathering new and publishable findings. Students pass the research cycle, investigating whether perfusionists strain can be reduced by utilizing data glasses. Corresponding to the concept of cooperative learning, students (n = 40) are divided into teams of five, giving each member a predefined expert role. Each expert is responsible either for physiological measurements, the perfusionists workspace, planning of usability tests, data glasses applications or team leading. Following the research cycle, milestones are set at which the teams present partial results to the entire group. Initially, students immerse in the field of research by reviewing literature. They prepare and present research hypotheses and select one for their investigation. Proximately, each team develops and introduces their research design. Teams organize themselves with planning test days and inviting subjects (n ≥ 10 each team). Finally, results are presented in group and collated by each team in a scientific paper. Every team reviews a scientific paper from another team and returns it before they are send in for grading. Evaluation shows higher workloads for students, but also relevant and interesting input. Two groups publish their papers in scientific journals.

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.

The laryngeal adductor reflex (LAR) is an important protective function of the larynx to prevent aspiration and potentially fatal aspiration pneumonia by rapidly closing the glottis. Recently, a novel method for targeted stimulation and evaluation of the LAR has been proposed to enable non-invasive and reproducible LAR performance grading and to extend the understanding of this reflexive mechanism. The method relies on the laryngoscopically controlled application of accelerated water droplets in association with a high-speed camera system for LAR stimulation site and reflex onset latency identification. Prototype laryngoscopes destined for this method require validation prior to extensive clinical trials. Furthermore, demonstrations using a realistic phantom could increase patient compliance in future clinical settings. For these purposes, a model of the human larynx including vocal fold actuation for LAR simulation was developed in this work. The combination of image processing based on a custom algorithm and individual motorization of each vocal fold enables spatio-temporal droplet impact detection and controlled vocal fold adduction. To simulate different LAR pathologies, the current implementation allows to individually adjust the reflex onset latency of the ipsi- and contralateral vocal fold with respect to the automatically detected impact location of the droplet as well as the maximum adduction angle of each vocal fold. An experimental study of the temporal offset between desired and observed LAR onset latency due to image processing was performed for three average droplet masses based on highspeed recordings of the phantom. Median offsets of 100, 120 and 128 ms were found (n=16). This offset most likely has a multifactorial cause (image processing delay, inertia of the mechanical components, droplet motion). The observed offset increased with increasing droplet mass, as fluid oscillations after impact may have been detected as motion. In future work, alternative methods for droplet impact detection could be explored and the observed offset could be used for compensation of this undesirable delay.

Nurses suffer from musculoskeletal strains because of frequent patient mobilizations. Therefore, mobile patient hoists were developed. However, patient hoists are rarely used. A possible reason is a low user acceptance due to poor usability of available products. To increase the user acceptance in health facilities and thus the frequency of use, a comparative usability assessment was conducted. The goal is to support health facilities in future purchasing decisions. 12 hoists were tested by 40 nurses in three everyday scenarios. Every nurse tested three hoists in randomized order. In total, each hoist was tested ten times. The success rate was used to measure the effectiveness. To identify poorly designed components, success rates were clustered into categories, which describe different hoist parts. User acceptance was quantified in the range of 0 to 100 using a standardized questionnaire. The success rate over all hoists was high and ranges from 88 % to 95 % (M = 92 %, SD = 2 %). However, serious use errors occurred in 24 % of the scenarios. The slingbars of the hoists showed the lowest effectiveness (M = 82 %, SD = 6 %). The user acceptance of the hoists ranges from 49 to 86 (M = 68, SD = 10). Besides structural problems like limited space or product availability, design deficits are a possible reason, why hoists are not used. All in all, the study identifies ergonomically better-designed hoists. Based on the results, health facilities can take usability aspects into account when making purchasing decisions.

Most kinematic structures in robot architectures for medical tasks are not optimal. Further, the workspace and payloads are often oversized which results in high product prices that are not suitable for a clinical technology transfer. To investigate optimal kinematic structures and configurations, we have developed an adaptive simulation framework with an associated workflow for requirement analyses, modelling and simulation of specific robot kinematics. The framework is used to build simple and cost effective medical robot designs and was evaluated in a tool manipulation task where medical instruments had to be positioned precisely and oriented on the patient's body. The model quality is measured based on the maximum workspace coverage according to a configurable scoring metric. The metric generalizes among different human body shapes that are based on anthropometric data from UMTRI Human Shape. This dexterity measure is used to analyze different kinematic structures in simulations using the open source simulation tool V-REP. Therefor we developed simulation and visualization procedures for medical tasks based on a patchwork of size-variant anatomical target regions that can be configured and selectively activated in a motion planning controller. In our evaluations we compared the dexterity scores of a commercial lightweight robot arm with 7 joints to optimized kinematic structures with 6, 7 and 8 joints. Compared to the commercial hardware, we achieved improvements of 59% when using an optimized 6- dimensional robot arm, 64% with the 7-dimensional arm and 96% with an 8-dimensional robot arm. Our results show that simpler robot designs can outperform the typically used commercial robot arms in medical applications where the maximum workspace coverage is essential. Our framework provides the basis for a fully automatic optimization tool of the robot parameters that can be applied to a large variety of problems.

The integration of surgical robotics into the operating room requires reliable and flexible communication with other medical devices. The IEEE 11073 SDC standard can provide the necessary requirements to deploy robotics for the application of focused ultrasound in radiation therapy. The aim of this work was to implement and evaluate an SDC compliant connection between two collaborative robots. For this purpose, the KUKA LBR iiwa 7 R800 was adapted and the connectivity modelled and then tested successfully with 42 transmittable properties. Latency measurements were conducted to evaluate the network stability, resulting in a median round trip time of 10.13 ms.

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.

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.

Magnetic microspheres (MMS) used for magnetic drug targeting consist of magnetic nanoparticles (MNP) and a pharmaceutical agent embedded in a polymeric matrix material. The application of MNP for drug targeting enables guiding the MMS to a target area, imaging the position of the MMS with magnetic particle imaging, and finally inducing drug release. As latter takes place by degradation of the MMS or diffusion through the matrix, an increase in temperature, e.g. through magnetic hyperthermia, leads to an accelerated drug release. Here, MMS consisting of poly(lactic-coglycolic) acid (PLGA) with different monomer ratios were prepared by an oil-in-water emulsion evaporation method. The model drug Camptothecin (CPT) and magnetic multicore nanoparticles (MCNP) with a high specific heating rate were embedded into the microspheres. We obtained MMS in the preferred size range of 1 to 2 μm with a concentration of MCNP of 16wt%, a drug load of about 0.5wt% and an excellent heating performance of 161 W/g MMS . Investigations of the drug release behaviour showed an accelerated drug release when increasing the temperature from 20 °C to 37 °C or 43 °C by using a water bath. In addition, an increase in drug release of about 50% through magnetic heating of the MMS up to 44 °C compared to 37 °C was observed. By this, a magnetic hyperthermia induced CPT release from PLGA MMS is demonstrated for the very first time.

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.

Cell-free based approaches are introduced as a promising treatment method for articular cartilage. The success of this method requires cell colonisation from resident tissue into cell-free implants. The objective of our study is to promote the cell colonisation into cell-free collagen I based implants by mechanical stimulation. Therefore, a new in vitro cellular model consisting chondrocyte-seeded matrix and cell-free implants was developed in a polydimethylsiloxan (PDMS) mold. These constructs were cultured under dynamic and static culture conditions. For the dynamic culture, we have developed an in-house bioreactor system where both the load and the deformation applied to the specimen are recorded. Cyclic compression, with a strain of 5% and frequency of 0.1 Hz, was applied to constructs without any break. At the end of three days of dynamic and static cultivation, the cell-free implants were seperated from cell-seeded matrix and cultured in a petri dish three days long. Afterwards, they were analysed using fluoresence dyes. The microscopic assessment indicated that there was a cell migration into the cell-free implants which were cultured dynamically.

Cerebrovascular diseases such as stenosis, atherosclerosis or distention of the carotid artery are accountable for about 1 million death per year across Europe. Diagnostic tools like ultrasound imaging, angiography or magnetic resonance-based imaging require specific hardware and highly depend on the experience of the examining clinician. In contrast auscultation with a stethoscope can be used to screen for carotid bruits - audible vascular sounds associated with turbulent blood flow - a method called phonoangiography. A reliable auscultation setup is prerequisite to ensure high signal quality, adequate processing and the objective evaluation of this audible signal. We propose a computer assisted auscultation system for the acquisition of vascular sounds of the carotid. The system comprises of an auscultation device, a smartphone-based control application and cloud-based signal analysis and storage. It is designed to facilitate the objective assessment, screening and monitoring of long-term changes in the vessel condition based on auscultation of the carotid artery.

Venous blood circulation can be restricted due to various conditions commonly indicating a related medical condition. However, current non-invasive methods for determining venous blood flow are limited to be either very inaccurate or expensive. Alternatively, a method to measure sap flow non-invasively in trees is through thermal mass measurement principles. This paper investigates applying the thermal mass flow measurement principle to determine venous blood flow. A simplified finite element model (FEM) and simulation are created to determine the operating behavior and expected response of a thermal mass flow meter with venous blood flow under the skin. An initial prototype of a thermal mass venous blood flow meter is designed using a Peltier-element and RTD thermistors. Initial tests were done on N = 8 subjects identifying the presence of blood flow and, testing the devices basic functionality and performance. The simplified FEM model of venous blood flow proved the thermal mass blood flow device is feasible, and determined the initial characteristics of the first prototype. The initial prototype proved to be functional detecting rises in temperature downstream of +1.4 K (0.8 - 1.8 inter- quartile range) when the blood flow was released (t = 90 s after release), compared to when blood was not flowing. The initial prototype proved to be able to detect the presence of blood flow in all subjects. However, further work is required to increase the differences in temperature values or gradient measured for a change in flow rate so the actual flow rate can be determined.

In this work, an assistant system is presented for the automatic assessment of falling and belaying in sport climbing. Both climber and belayer are equipped with inertial measurement unit (IMU) sensors. Forces as well as movements in the form of multi-dimensional accelerations on the legs and torso are captured. It can be shown that forces can be estimated by means of IMU sensors, thus eliminating a complex force measurement unit in the safety chain. Furthermore, the data can be used to assess both falling and belaying by automatic segmentation and evaluation algorithms. The sensor data should later be evaluated automatically in order to objectively measure faulty behavior by climber or belayer (for example wrong jump-off behavior, too hard protection, etc.). The overall goal is to provide quantified feedback in fall training for injury and accident prevention.

For medical research, approximately 115 million animals are needed every year. Rodents are used to test possible applications and procedures for the diagnosis of anatomical and physiological diseases. However, working with living animals increases the complexity of an experiment. Accurate experimental planning is essential in order to fulfill the 3R rules (replace, reduce and refine). Especially in tracer-based imaging modalities, such as magnetic particle imaging (MPI), where only nanoparticles give a positive contrast, the anatomical structure of the rodent is not visible without co-registration with another imaging modality. This leads to problems in the experimental planning, as parameters, such as field of view, rodent position and tracer concentration, have to be determined without visual feedback. In this work, a 3D CAD rat model is presented, which can be used to improve the experiment planning and thus reduce the number of animals required. It was determined using an anatomy atlas and 3D printed with stereolithography. The resulting model contains the most important organs and vessels as hollow cavities. By filling these with appropriate tracer materials, the phantom can be used in different imaging modalities such as MPI, magnetic resonance imaging (MRI) or computed tomography (CT). In a first MPI measurement, the phantom was filled with superparamagnetic nanoparticles. Finally, a successful visualization of all organs and vessels of the phantom was possible. This enables the planning of the experiment and the optimization of experimental parameters for a region of interest, where certain organs in a living animal are localized.

Detailed knowledge about the three-dimensional morphology of the human cochlea and its intra-cochlear bony and soft-tissue structures is essential for development of new cochlear implant electrode carriers. A manual cross-sectional preparation and imaging technique, hereinafter referred to as “microgrinding”, uses human temporal bone samples embedded in epoxy resin. This process was automated to shorten the time needed for preparation and to increase reproducibility. In this study, reconstruction accuracy of the automated microgrinding technique was determined. Four assemblies of LEGO® bricks were used as artificial samples to analyze the resulting reconstruction accuracy of the whole procedure including embedding, preparation and image registration. The outer surfaces of the samples were measured using a portable coordinate measuring machine by manually choosing points on each surface. After embedding the samples in epoxy resin, following the protocol for human temporal bone samples, preparation using the automated microgrinding was performed with a slice thickness of 50μm. Pixel-spacing within an image was 11.5μm/px. The samples were identified within the dataset using threshold segmentation. Subsequently, points were manually chosen on each surface of the segmented samples. Planes, angles between planes and distances between corners were calculated for the physical and the digital samples. Deviation of the digitally derived measures compared to the physically derived ones describe the reconstruction accuracy of the automated microgrinding process. Parallel planes had a deviation of 0.5° ± 0.5° (range: 0 - 2.9°). Orthogonal planes, whose line of intersection is parallel to the direction of milled abrasion, had a deviation of 0.8 ° ± 0.5 ° (range: 0 - 2.1°), whereas such orthogonal planes whose line of intersection is parallel to the documented sample surface had a deviation of 0.4° ± 0.3 ° (range: 0 - 1.7 °). Distances between corners had an absolute deviation of 0.1 mm ± 0.1mm (range: 0 - 0.6mm), which corresponds to a relative deviation of 1% ± 1% (range: 0 - 6.5%). This study shows a highly accurate sample preparation using an automated microgrinding technique as an essential prerequisite for three-dimensional morphological imaging.

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.

Electrical Impedance Tomography (EIT), an imaging technique which operates non-invasively and without radiation exposure, provides information about ventilation- and cardiac-synchronous (pulsatile) changes in the lung. It is well known, that perfusion within the thorax is influenced by lung volume or intrathoracic pressure. In this observational study, it shall be investigated if this phenomenon can be monitored by EIT. Therefore, the impact of the amount of air within the lung on the pulsatile EIT signal was evaluated by carrying out EIT measurements with a spontaneously breathing lung healthy subject holding the breath at three different inspiratory and three various expiratory volume levels during normal tidal breathing. For EIT data analysis, a region of interest was defined by including lung tissue and excluding the heart region. The EIT data revealed, that the shape and the amplitude of the pulsatile EIT signal (evaluated per heartbeat) during the phases of breath holding were dependent on the enclosed lung volume. For lung volumes > 4 L, the amplitude of the pulsatile EIT signal increased with rising inspiratory level and the shape remained almost unchanged. For lung volumes < 4 L, a change in shape was visible but the amplitude remained more or less the same with decreasing expiratory level. Since the results of this observational study show that the pulsatile EIT signal is influenced by the lung volume, it might be used in future to draw conclusions of cardiacpulmonary interactions or intrathoracic pressure states, benefitting the treatment of intensive care patients.

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.

Millions of people around the world have lost their upper limbs mainly due to accidents and wars. Recently in the Middle East, the demand for prosthetic limbs has increased dramatically due to ongoing wars in the region. Commercially available prosthetic limbs are expensive while the most economical method available for controlling prosthetic limbs is the Electromyography (EMG). Researchers on EMG-controlled prosthetic limbs are facing several challenges, which include efficiency problems in terms of functionality especially in prosthetic hands. A major issue that needs to be solved is the fact that currently available low-cost EMG-controlled prosthetic hands cannot enable the user to grasp various types of objects in various shapes, and cannot provide the efficient use of the object by deciding the necessary hand gesture. In this paper, a computer vision-based mechanism is proposed with the purpose of detecting and recognizing objects and applying optimal hand gesture through visual feedback. The objects are classified into groups and the optimal hand gesture to grasp and use the targeted object that is most efficient for the user is implemented. A simulation model of the human hand kinematics is developed for simulation tests to reveal the efficacy of the proposed method. 80 different types of objects are detected, recognized, and classified for simulation tests, which can be realized by using two electrodes supplying the input to perform the action. Simulation results reveal the performance of proposed EMG-controlled prosthetic hand in maintaining optimal hand gestures in computer environment. Results are promising to help disabled people handle and use objects more efficiently without higher costs.

Glioblastoma, an aggressive malign tumor of the brain, is one of the most shattering diagnoses due to its very poor prognosis and limited treatment options. These options mainly consist of surgical or radiation therapeutic removal of as much tumor mass as possible, which unfortunately is almost always incomplete. Even worse, chemotherapy is of little use, as the special setup of the brain′s vessels severely limits the transit into the parenchyma of elsewhere efficient cytostatica. This Blood-Brain-Barrier (BBB) is for quite some time the target of sophisticated and nano-particle based transport mechanisms, however it is reported, that a boost of permeability for most of the brain can be achieved based on moderate temperature increase. One means to locally and reversibly increase the brain′s temperature and thus potentially opening the BBB may be achieved by illuminating the skull with infrared laser light, thus causing punctual heating and heat diffusion into the cortex. In extension of the common laser light guiding by glass fibres, we use a micro-positioned simple optics to focus a 1470 nm laser beam of approximately 500 µm in diameter on the skull. The apparent opening of the BBB is evidenced by the localized spread of Evans Blue injected into the tail vein of said rat, binding to Albumin (64,6 kDa) in the body. This marker molecule is usually blocked from passing through the intact BBB, but under IR illumination for half a minute, it appeared in post mortem visible blobs. Temperature profiles and potential tissue damage are now under investigation by high speed thermal camera and post mortem histology.

Primary open angle glaucoma represents an eye disease that usually is associated with an increased intraocular pressure (IOP). Implants for micro-invasive glaucoma surgery (MIGS) are gaining importance as a promising option for IOP lowering. Currently available devices are implanted into the eye ab interno based on a clear corneal incision and drain aqueous humour into the schlemm’s canal, suprachoroidal or subconjunctival space. Fibrosis is known as a major limitation for long term success and often leads to the necessity of an additional medication or a surgical re-intervention. The current work focusses on the development of an antifibrotic drug-eluting coating for a minimally invasive implantable glaucoma microstent. Tubular microstent base bodies manufactured from a polycarbonate based silicone elastomer were spray-coated with a chloroform based mixture of the same polymer and the antifibrotic drug pirfenidone (PFD, P2116, Merck KGaA, Germany) in a polymer/drug ratio of 85/15% (w/w). Coating mass of 89 μg according to a drug loading of 1.96 μg mm-2 was aspired. Coating mass was measured using an ultramicrobalance (XP6U, Mettler-Toledo International, Inc., Switzerland). Glaucoma microstent prototypes with a drugeluting coating mass of (84 ± 19) μg (n = 12) were manufactured. Characterization by means of scanning electron microscopy (Quattro S, Thermo Fisher Scientific, FEI Deutschland GmbH, Germany) yielded a reproducible smooth surface of the coating. High performance liquid chromatography (KNAUER Wissenschaftliche Geräte GmbH, Germany) was used for analysis of drug release behaviour in 0.9% NaCl solution at 37°C. The in vitro PFDrelease is characterized by an initial burst phase of approximately 6 h followed by a more retarded release phase. The entire drug was released within 36 h (n = 3). Sterilization processing has a minor impact on drug release kinetics. Appropriate drug stability after sterilization could be proven. Future studies will focus on the antifibrotic properties of drug-eluting glaucoma microstents in animal studies.

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.

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.

Digital light microscopy techniques are among the most widely used methods in cell biology and medical research. Despite that, the automated classification of objects such as cells or specific parts of tissues in images is difficult. We present an approach to classify confluent cell layers in microscopy images by learned deep correlation features using deep neural networks. These deep correlation features are generated through the use of gram-based correlation features and are input to a neural network for learning the correlation between them. In this work we wanted to prove if a representation of cell data based on this is suitable for its classification as has been done for artworks with respect to their artistic period. The method generates images that contain recognizable characteristics of a specific cell type, for example, the average size and the ordered pattern.

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).

The visualization of heart rhythm disturbance and atrial fibrillation therapy allows the optimization of new cardiac catheter ablations. With the simulation software CST (Computer Simulation Technology, Darmstadt) electromagnetic and thermal simulations can be carried out to analyze and optimize different heart rhythm disturbance and cardiac catheters for pulmonary vein isolation. Another form of visualization is provided by haptic, three-dimensional print models. These models can be produced using an additive manufacturing method, such as a 3d printer. The aim of the study was to produce a 3d print of the Offenburg heart rhythm model with a representation of an atrial fibrillation ablation procedure to improve the visualization of simulation of cardiac catheter ablation. The basis of 3d printing was the Offenburg heart rhythm model and the associated simulation of cryoablation of the pulmonary vein. The thermal simulation shows the pulmonary vein isolation of the left inferior pulmonary vein with the cryoballoon catheter Arctic Front Advance TM from Medtronic. After running through the simulation, the thermal propagation during the procedure was shown in the form of different colors. The three-dimensional print models were constructed on the base of the described simulation in a CAD program. Four different 3d printers are available for this purpose in a rapid prototyping laboratory at the University of Applied Science Offenburg. Two different printing processes were used and a final print model with additional representation of the esophagus and internal esophagus catheter was also prepared for printing. With the help of the thermal simulation results and the subsequent evaluation, it was possible to draw a conclusion about the propagation of the cold emanating from the catheter in the myocardium and the surrounding tissue. It was measured that just 3 mm from the balloon surface into the myocardium the temperature dropped to 25 °C. The simulation model was printed using two 3d printing methods. Both methods, as well as the different printing materials offer different advantages and disadvantages. All relevant parts, especially the balloon catheter and the conduction, are realistically represented. Only the thermal propagation in the form of different colors is not shown on this model. Three-dimensional heart rhythm models as well as virtual simulations allow very clear visualization of complex cardiac rhythm therapy and atrial fibrillation treatment methods. The printed models can be used for optimization and demonstration of cryoballoon catheter ablation in patients with atrial fibrillation.

We propose a one-step person detector for topview omnidirectional indoor scenes based on convolutional neural networks (CNNs). While state of the art person detectors reach competitive results on perspective images, missing CNN architectures as well as training data that follows the distortion of omnidirectional images makes current approaches not applicable to our data. The method predicts bounding boxes of multiple persons directly in omnidirectional images without perspective transformation, which reduces overhead of pre- and post-processing and enables realtime performance. The basic idea is to utilize transfer learning to fine-tune CNNs trained on perspective images with data augmentation techniques for detection in omnidirectional images. We fine-tune two variants of Single Shot MultiBox detectors (SSDs). The first one uses Mobilenet v1 FPN as feature extractor (moSSD). The second one uses ResNet50 v1 FPN (resSSD). Both models are pre-trained on Microsoft Common Objects in Context (COCO) dataset. We fine-tune both models on PASCAL VOC07 and VOC12 datasets, specifically on class person. Random 90-degree rotation and random vertical flipping are used for data augmentation in addition to the methods proposed by original SSD. We reach an average precision (AP) of 67.3%with moSSD and 74.9%with resSSD on the evaluation dataset. To enhance the fine-tuning process, we add a subset of HDA Person dataset and a subset of PIROPO database and reduce the number of perspective images to PASCAL VOC07. The AP rises to 83.2% for moSSD and 86.3% for resSSD, respectively. The average inference speed is 28 ms per image for moSSD and 38 ms per image for resSSD using Nvidia Quadro P6000. Our method is applicable to other CNN-based object detectors and can potentially generalize for detecting other objects in omnidirectional images.

4D ultrasound (4D US) is gaining relevance as a tracking method in radiation therapy (RT) with modern matrix array probes offering new possibilities for real-time target detection. However, for clinical implementation of USguided RT, image quality, volumetric framerate and artifacts caused by the probe’s presence during planning and / or setup computed tomography (CT) must be quantified. We compared three diagnostic 4D US systems with matrix array probes using a commercial wire phantom to measure spatial resolution as well as a calibration and a torso phantom to assess different image quality metrics. CT artifacts were quantified in the torso phantom by calculating the total variation and percentage of affected voxels between a reference CT scan and CT scans with probes in place. We found that state-of-the-art 4D US systems with small probes can fit inside the CT bore and cause fewer metal artifacts than larger probes. US image quality varies between systems and is task-dependent. Volume sizes and framerates are much higher than the commercial guidance solution for US-guided RT, warranting further investigation regarding clinical performance for image guidance.

Digital Light Processing (DLP) enables high precision 3D-printing of photopolymers and holds promising potential for patient-specific implant solutions. On the material side, Poly(ethylene glycol) diacrylate (PEGDA) has emerged as an interesting material for use in biomedical applications. For adequate photopolymerization, a photoinitiator and a light absorber are necessary, using welldefined concentrations. This study shows preliminary results of DLP 3D-printing of different PEGDA hydrogel compositions with varying water content (90; 70; 50; 30; 10; 0 % w/w) as well as varying concentrations of a photoinitiator and a light absorber. Printing performance and accuracy are investigated by printing rectangular test samples as well as an anatomically customised tubular frontal sinus implant prototype. For basic mechanical characterisation, the hardness of the printed hydrogels is investigated using a Shore A durometer. The results show a decrease in printing accuracy and hardness with an increasing water content of the composition. There is a need to use a light absorber to reach high printing accuracy. This leads to a need for increasing photoinitiator concentration and prolonged light exposure to achieve proper printing performance.

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.

This work presents a new system concept for the prevention, diagnosis and interactive treatment of neck pain. It comprises two measurement units worn at the head and the torso, a smartphone/tablet and a medical assistance software. The system aims to provide mobile measurement of full neck movement including rotatory and translatory movements under a patients everyday life circumstances. Multiple features including biofeedback and therapy exercises are intended to be individually configurable according to the specific medical indications of the patient. In addition to the system concept the current implementation state comprising the two measurement units and a visualization app running on a tablet is presented.

Stethoscope auscultation is a diagnostic method widely used by medical professionals. With the introduction of digital stethoscopes, auscultation sound analysis has been objectified, which led to an increased interest in the field. Until today, however, no standard to assess the acoustical properties of stethoscopes is available. Some approaches use phantoms mimicking the properties of human soft tissue. In most cases, however, the properties of the phantoms have not been analyzed with respect to environmental variables. In our work, we propose a stethoscope characterization system for the frequency range between 50 Hz and 2.5 kHz with a small financial footprint. We analyzed its frequency behavior over temperature, time and position on the phantom and derived quantitative recommendations for environmental variables. Finally, the frequency response of a commercial digital stethoscope was characterized at different pressure levels. We conclude that the presented system is capable to stably and reproducibly assess the transfer function of digital stethoscopes. We hope that future stethoscope designs will be characterized with respect to their acoustical properties.

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.

Recently, we could demonstrate positive effects of microfluidic cultivation conditions on maturation of cardiomyocytes derived from human induced pluripotent stem cells (iPS-CMs) in a 2D model. However, 3D cell culture models are much closer to physiological conditions. Combined with microfluidics, 3D systems should resemble the in-vivo conditions even better than standard 2D cultivation. For 3D models, two main technical challenges arise, the tissue integration and sufficient nutrient supply for the cells. This work focuses on concepts for the tissue integration based on a modular approach and different manufacturing technologies as well as using an oxygenator in the microfluidic device to provide sufficient oxygen supply for the cells.

Optical image processing is part of many applications used for brain surgeries. Microscope camera, or patient movement, like brain-movement through the pulse or a change in the liquor, can cause the image processing to fail. One option to compensate movement is feature detection and spatial allocation. This allocation is based on image features. The frame wise matched features are used to calculate the transformation matrix. The goal of this project was to evaluate different feature detectors based on spatial density and temporal robustness to reveal the most appropriate feature. The feature detectors included corner-, and blob-detectors and were applied on nine videos. These videos were taken during brain surgery with surgical microscopes and include the RGB channels. The evaluation showed that each detector detected up to 10 features for nine frames. The feature detector KAZE resulted in being the best feature detector in both density and robustness.

Pressure ulcers (decubiti) are one of the most frequent side effects in the palliative care setting. Terminally ill and dying people have multiple comorbidities resulting in a high risk to develop pressure ulcers. These skin lesions are caused by pressure, friction and shearing forces in combination with several risk factors (e.g. moisture, tissue condition). People of all ages with reduced activity can suffer from decubitus ulcers. In palliative care, the treatment of symptoms to ensure the highest possible quality of life is of primary importance. Ethical controversies and difficult decision-making often lead to uncertainties and burdens for caregivers, patients and relatives. In the DekuProSys project, a decubitus prophylaxis system for inpatient and outpatient palliative care of people of all ages is being developed. The system will assist caregivers in patient care in multiple ways. It will capture and report risk factors for decubitus, assist at decision making and documentation. Furthermore, it will provide care information and instruction if needed. Aiming for an innovative and useful solution, the project follows a user-centered and interdisciplinary approach.

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.

Inference from medical image data using machine learning still suffers from the disregard of label uncertainty. Usually, medical images are labeled by multiple experts. However, the uncertainty of this training data, assessible as the unity of opinions of observers, is neglected as training is commonly performed on binary decision labels. In this work, we present a novel method to incorporate this label uncertainty into the learning problem using weighted Support Vector Machines (wSVM). The idea is to assign an uncertainty score to each data point. The score is between 0 and 1 and is calculated based on the unity of opinions of all observers, where u = 1 if all observers have the same opinion and u = 0 if the observers opinions are exactly 50/50, with linear interpolation in between. This score is integrated in the Support Vector Machine (SVM) optimization as a weighting of errors made for the corresponding data point. For evaluation, we asked 15 observers to label 48 2D ultrasound images of aortic roots addressing whether the images show a healthy or a pathologically dilated anatomy, where the ground truth was known. As the observers were not trained experts, a high diversity of opinions was present in the data set. We performed image classification using both approaches, i.e. classical SVM and wSVM with integrated uncertainty weighting, utilizing 10-fold Cross Validation, respectively (linear kernel, C = 7). By incorporating the observer uncertainty, the classification accuracy could be improved by 3.1 percentage points (SVM: 83.5%, wSVM: 86.6%). This indicates that integrating information on the observers’ unity of opinions increases the generalization performance of the classifier and that uncertainty weighted wSVM could present a promising method for machine learning in the medical domain.

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.

Ex vivo lung perfusion (EVLP) is a preservation method for donor lungs, which keep lungs viable in a physiological environment outside of a body for a short period of time. EVLP is established clinically for lung transplantation. Experimental applications for EVLP are e.g. lung cancer research or medical device development and testing. For preservation, a lung is ventilated artificially in an organ chamber and perfused antegrade through the pulmonary artery. Here we introduce a thermoregulation system for an experimental EVLP system to be used for translational research approaches as well as for training medical staff. To implement physiological culture conditions that are a prerequisite for lung preservation and tissue homeostasis, a thermoregulation is needed to rewarm the explanted lung tissue (storage temperature 4°C). Technically, the EVLP system must be thermally insulated, so loss of caloric is avoided. For monitoring, temperature sensors are integrated within the lung, in the organ chamber and in the afferent perfusate tube, whereby the measured values determine the thermoregulation. Initial tests using thermal packs (cooled to 4-6°C) placed on a heating mat, as a part of the perfusion circuit, showed that the perfusate temperature falls to 34°C, but restores after approximately 60 minutes (36.5°C), whereby the thermal pack is warmed. With this setup longer perfusion times should be obtained rather than without thermoregulation due to normothermic perfusion of the lung.

The design of Smart Biomedical Devices will be a defining element of future research in the context of intelligent medical devices for the Internet of Medical Things (IoMT). A prerequisite for serving the disposable market is the use of cost-effective electronic components and the highest reliability of the developed products in terms of biocompatibility and bioprotection. In the study, resistors, capacitors, and light-emitting diodes, different in their materials and construction forms, were examined. The selected types represented electronic components as they are commonly installed on electronic system from the segment of low-cost standard components. These were subjected to steam sterilization with up to 50 cycles, gamma sterilization, and a CCK-8 assay to test in vitro cytotoxicity. Functional failure could not be determined for any component. Gamma sterilization did not result in significant changes in resistance values, but in capacitors with barium titanate as dielectric. Non-cytotoxic electronic components could be identified. The results show that certain electronic standard components are suitable for disposable Smart Biomedical Devices.

Immobilizing a single growth factor such as rhBMP-2 on Implant materials can significantly increase the integration of implants into bone in animals. Paradoxically the effective osteoinductive dose of rhBMP-2 in humans is ca. 100-1000-fold higher than in animals and may induce serious side effects in spine fusion surgery. In physiological bone healing at least 10 separate growth and differentiation factors are sequentially involved in the first two healing phases leading to a callus and/or woven bone. It is therefore hypothesized that a significant dose reduction for rhBMP-2 applications in humans may be achieved by a combination of rhBMP-2 with other growth factors in a biomimetically oriented manner. Some aspects involved in multimodal bioactive hybrid carriers with spatio-temporal release kinetics and a new phenomenon ("protein interference") are presented.

The direct detection of the spatial distribution of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a tracer for Magnetic Particle Imaging (MPI) enables threedimensional functional images with high spatial and temporal resolution. The commercially available tracers have not been developed primarily for MPI. Therefore, they do not sufficiently contribute to the desired image quality. Hence, optimizing the SPIONs during the production process is of interest. A peculiarity of the here presented synthesis method - the alkaline coprecipitation - is that this process takes place under ultrasonic control. The use of ultrasound creates extraordinary reaction conditions through sonochemical phenomena, such as formation, growth and implosive collapse of cavitation bubbles within a liquid. In addition, the ultrasonic waves and the oscillation of the medium improve the mixing process and thus ensure the homogenization during the synthesis. The objective of this study is the variation of ultrasonic frequencies and the type of used dextran as coating material, to provide SPIONs with better performance for MPI and more suitable properties for in vivo application. The focus of the optimization is to increase the magnetite core size while simultaneously reducing the hydrodynamic size. The experiments have shown that both, the ultrasound frequency and the molecular weight of used dextran, influence the properties of the SPIONs.

Insertion of a cochlear implant (CI) into the scala tympani evokes electrode insertion trauma that can result in mechanical damage of the lateral and medial wall and causes ingrowth of fibrous tissue on the implant surface. In consequence, it is of great clinical interest to modify the silicone surface of CI electrodes in order to inhibit and minimize the overgrowth by connective tissue. In this case, the covalent coupling of bifunctional polymers on common CI silicone surfaces is a versatile method to influence the implant cell interaction, but is still a challenge due to the chemically unreactive properties of silicone. We present a sophisticated method to apply a biodegradable polymer coating, such as polylactide or polyhydroxybutyrate, on silicone surfaces to generate a drug delivery system using a covalently bound intermediate layer. The adhesive coatings were applied via spincoating processes with different adherence to the intermediate layer. Changes in surface morphology were investigated by comparison of pure silicone and coated silicone. Specific polymer bands of the infrared spectra were detected by IR spectroscopy. Results indicate a complete coating with polylactide or polyhydroxybutyrate. The presented method is a versatile tool for the coating of silicone CI electrodes with degradable polymer layers.

Plasma enhanced chemical vapor deposition is a promising process for the generation of tailor-made polymer coatings on medical devices in order to improve their implant/ host interaction. The ultra-thin coatings can fulfil a variety of purposes, depending on the monomers used, the process conditions and the location of the coated implants in the human body. In addition, even complex geometries can be coated easily and without the application of solvents. Particularly hydrophilic and hydrophobic plasma polymer coatings can improve biocompatibility, especially in blood contact. Furthermore, the selection of the monomers used enables the generation of specific functional groups for further surface immobilization of drugs, such as proteins, by chemical crosslinking. The release of toxic residues from polymeric implants, such as monomers, additives or degraded components, can also be avoided. The aim of our investigation was the generation of plasma polymer films, their characterization and application as coatings for biodegradable metallic biomaterials in order to retard the degradation process. Metallic biomaterials, in various forms are frequently used in orthopaedics, dentistry, cardiovascular and neurosurgical equipment, because of their tensile strength, fracture toughness, fatigue strength and electrical conductivity. Plasma polymerization was performed using the monomers hexamethyldisiloxane and allylamine. The resulting plasma polymers were analysed in an accelerated degradation test. Both plasma polymers appear to be promising, while polyHMDSO appears to degrade over time and polyallylamine indicates to be stable.

The technology of pharmaceutical drug delivery systems (DDS) as an individual and adjustable tool for drug administration has been intensively developed in the last years. Additive manufacturing (AM) techniques, such as stereolithography, are a promising approach towards DDS scaffold manufacturing. Stereolithography, by using layerby- photo-polymerisation, creates DDS scaffolds with highly controlled 3D geometry. Combined with inkjet printing it allows a very precise positioning of the drug depot in the basic scaffold and therefore also a better control of the drug release. Furthermore, this hybrid AM technique also allows for the creation of a multi-drug DDS with a several drug depots localized in desired positions within the scaffold. Determination of the scaffold and drug depot material properties is one of the initial steps for such novel DDS development. Basic characteristics, such as stiffness, elasticity or glass transition temperature (T g ), are important for designing and adapting the material for biomedical application. The photosensitive poly(ethylene glycol) diacrylate (PEGDA) can be easily formed into a desired biocompatible scaffold geometry via stereolithography. In this study we have focused on the evaluation of PEGDA (Mn=700 g/mol) as a pure and copolymer system in combination with other acrylates (butanediol diacrylate, pentaerythritol triacrylate) as possible materials for DDS using this novel hybrid AM technique. Irgacure 2959, a biocompatible photoinitiator (PI), was used as a radical starter for photopolymerisation. Samples varying in PI and coacrylate concentration were prepared by conventional photopolymerisation. Physico-chemical analyses of the samples were performed and several parameters, such as stiffness, elongation at break and glass transition temperatures, were determined.

Drug Delivery Systems (DDS) are frequently operating in a surrounding liquid environment, such as blood in the case of drug-eluting stents or perilymph in the case of cochlear implants. However, there is also a demand for systems with sustained drug release in predominantly dry environments, mostly consisting of ambient air. Examples are the treatment of diseases located in the middle ear or the paranasal sinuses. On the one hand, due to the lack of transportation media, the functionality of a polymer/drug combination for delayed release would be limited in such environments. On the other hand, these environments are generally equipped with mucus membranes. Hence, a somewhat humid surrounding is ensured. In this study, a concept of a hydrogel equipped DDS for drug delivery through the round window membrane is presented, addressing two objectives. First objective is to ensure the drug transport by serving as a diffusion channel. For instance the route to the drug target destination, the round window membrane, can be provided by a hydrogel. The second objective is to ensure the adhesion to the membrane. Two promising approaches are presented in this study: The photo induced immobilisation of PEGDA700, as well as the immobilisation of chitosan on poly(l-lactid) (PLLA). For both approaches PLLA specimen had to be modified with oxygen plasma followed by activation for crosslinking with subsequent immobilisation of the hydrogel. With these methods a layer thickness of at least 5 μm was achieved. All steps were characterized with contact angle measurements. After the immobilization of the hydrogel, the swelling factor, as well as the layer thickness was examined.

The generation of electrospun nonwovens from polyimide (PI) is challenging as the fibers are prone to distinct delamination. In consequence, the resulting nonwoven material has particularly low structural integrity and loose fibre interlocking, demanding for a follow-up treatment, such as high temperature thermal treatment. In this work, a facile method for a post-processed treatment of PI nonwoven is presented in order to obtain a mechanically stable material while maintaining the characteristics of the electrospun nonwoven. The procedure was performed using a solution of EDA in methanol at 37 °C and ambient pressure to achieve a modified fiber interaction. Overall, the developed protocol opens new possibilities in the processing of PI into delamination-free nonwovens. Potential adverse effects of a high temperature thermal treatment are being avoided, and new applications in the field of medical devices may become accessible.

Resveratrol is a member of stilbenoids with promising anti-atherosclerotic properties. This hallmark makes it an extremely interesting candidate for local drug delivery to damaged tissue adjacent to the implant in order to reduce implant-related complications. For the regulatory approval drug-eluting medical devices have to be thoroughly tested for safety, efficacy and interactions with the surrounding tissue, including tests for sensitization among others. Studies for sensitization help to estimate the risk for an allergic reaction upon prolonged exposure to a chemical compound. Due to increased social and regulatory demand for replacement of animal experiments by in vitro approaches a number of reliable predictive non-animal tests have been developed. Here, we assessed the skin sensitization potential of resveratrol by the direct peptide reactivity assay (DPRA), one of the first non-animal tests adopted by the OECD.

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.

The automation of instruments and tools (e.g. bone drill) or robotic devices (e.g. needle positioning robot for prostate surgery) for use in interventional MRI (iMRI) is still challenging due to a lack of accurate, affordable and completely metal-free actuators and motors. Inspired by biological muscles, a bionic equivalent known as the fluid muscle actuator (which can be operated pneumatically or hydraulically) is well-known in the mechanical engineering industry. Fluid muscle actuators have multiple beneficial characteristics: they are simple, self-returning, low-friction and can produce relatively high actuation forces at low diameters and pressures. We present two novel designs for metal-free, pneumatic stepper motors for potential application in iMRI. Our stepper motors are powered by simple pneumatic muscles, which are assembled from low-cost off-the-shelf components. Besides, the components of the stepper motor demonstrators were 3Dprinted using a stereolithographic additive manufacturing process (SLA printing). We evaluate the effect of pneumatic muscle length on contractile force and length. Our results demonstrated the functional feasibility of the pneumatic muscle-powered and fully MRI-compatible stepper motor designs. In a next step, we will optimize the motor´s design, characterize their performance and reliability, and use the stepper motors to power a micropositioning device in iMRI-phantom tests.

Vibration measurement and signal analysis methods are common to evaluate the functionality and characteristics of technical components in different industrial and scientific areas. Modal analysis for example is a standard method to characterize the dynamic behavior of a structure and enables the development of validated bone models. The state of the art of analyzing bone structures does not include the modal damping, although it has a significant influence on the dynamic characteristics. Within the presented investigations, the modal analyses have been performed contactless with respect to excitation and response acquisition, which implies that there are no influences of shakers or sensor couplings. Therefore, an automatic impulse hammer and a 3D Scanning Laser Doppler Vibrometer were used for excitation and response detection. Various supports of the test specimens, surface pretreatments, excitation points and excitation impulses were examined to optimize the measurement setup and process. Experimental modal analysis data were analyzed by curve fitting methods to determine the modal parameters. To evaluate different structures and effects of damping, 3D printed artificial bones and animal in vitro bones were used to perform the measurements. To produce the cortical layer of the artificial bone models, volume models were generated based on medical image data and printed by polyamide-based selective laser sintering. The cancellous bone was represented by different foam fillings for the artificial bones. Thereby, the variation of the porosity was achieved by using different mixing ratios of polyurethane foam and hardener. Furthermore, the modal damping parameters were determined from the measurement of animal bones. The measurement time was optimized during the practical implementation of the parameter determination to minimize the influence of drying and decomposition processes on the measurement results.

The lumbo-pelvic complex is a highly complex structural system. The current investigation aims to identify the kinematics between interacting bone segments under different loading conditions. A specimen of the lumbo-pelvic complex was obtained from a human body donor and tested in a self-developed test rig. The experimental setup was designed to imitate extension, flexion, right and left lateral bending and axial rotation to the left and to the right, respectively. The vertebra L3 was firmly embedded and load was introduced via hip joints. Using a digital image correlation (DIC) system, the 3D motions of 15 markers at different landmarks were measured for each loadcase under cyclic loading. For each loadcase, the kinematics were analyzed in terms of three-dimensional relative movements between L3 and the sacrum. The usefulness of the experimental technique was demonstrated. It may serve for further biomechanical investigations of relative motion of sacroiliac and vertebral joints and deformation of bony structures.

Theoretical and experimental investigations were carried out for development of human lens implants made from hydrogel material. The material properties were measured and implemented in a Finite element model. Though the material is still too stiff for accommodative lenses, the theoretical and experimental foundations for the implant development were established.

As an alternative to optical flow cytometry, magnetic flow cytometry has emerged in recent years for single cell analysis with sheath-less flow conditions. Instead of measuring scattered light, magnetic fields of magneticallylabeled cells are recorded and analyzed. To determine microfluidic opportunities to manipulate cell trajectories for in-situ cell focusing we use mechanical guiding structures and magnetophoretic forces. A 3D-microfluidic particle simulation has been implemented that revealed parameters ensuring the crucial balance between hydrodynamic drag and magnetophoretic forces. Experimental measurements verified the 3D particle tracking simulation.

This work investigates the performance of eventsynchronous noise cancelling algorithms to separate ECG artifacts from thoracic EMG recordings. In focus are the precise detection of heart beats, the exact time alignment of the QRS segments and the construction of a template QRS signal. Among the utilized methods is a modified structural intensity (SI) approach based on the observation of extrema in low pass filtered versions of the second derivative as a detector. An adoption of this approach is also used to obtain the exact time alignment of QRS segments. Artificial test signals are constructed based on addition of ECG and sEMG with different magnitudes. We show that approaches based on the observation of extrema in different scales yield superior results.

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.

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.

The access to the abdomen and the creation of a pneumoperitoneum is an initial and particularly critical step of minimally invasive laparoscopic procedures. Insertion instruments such as the Veress needle need to be introduced blindly into the abdominal cavity, which is associated with inadvertent visceral and vascular injuries. To ensure safe positioning of the instrument, information about the entry path advancement of the tip through the abdominal wall is needed. The main objective of this work is to demonstrate the capability to acquire information about intracorporeal tissuetool interactions of the Veress needle tip, utilizing acoustic emissions recorded at the extracorporeal end of the needle. In an experimental setup, a Veress needle was inserted in a multitissue- layer phantom with a defined insertion speed. Acoustic emissions were recorded with a MEMS microphone attached to the extracorporeal end of the needle. In addition, the counteraction forces during insertion of the needle were measured and a video of the experiment was recorded as reference. With this setup, an audio database of characteristical insertion events was generated. For the classification of characteristic audio events and detection of tissue-layer crossing, features were calculated in the time and frequency domain. Subsequently, a feature dimensionality reduction was performed. The distribution clustering of the audio database in the three-dimensional feature subspace allows a distinction between certain characteristic audio events. The preliminary results show the capability of this acoustic emission based method to detect events related to the insertion of a Veress needle, such as tissue-layer crossing.

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.

This paper describes the advantages and disadvantages of inertial sensors and stationary camera-based measuring methods for the application of detecting head and shoulder angles. For this purpose three inertial sensor modules from Shimmer Sensing and a Kinect 2 camera system are used. The recorded data of both systems are converted into a comparable form. Based on an evaluation of the recorded measurement data, the inertial sensor and the camera-based methods are compared with regard to their suitability for detecting movements in the head and shoulder area.

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.

Electrocardiogram (ECG) is a widely used tool for the early diagnosis and evaluation of cardiac disorders. The ECG signal is usually distorted during recording by different types of noise which may lead to incorrect diagnosis. Therefore, clear ECG signals are required to support good cardiac disorder diagnosing. In this paper, an efficient ECG denoising method using combined discrete wavelet with Savitzky-Golay (S-G) filter is proposed. The performance of S-G filter is studied in terms of polynomial degree and frame size, i.e. signal section. In addition, the performance of denoising wavelet is studied in term of mother wavelet type and wavelet order. The advantage of S-G filter is combined with discrete wavelet denoising method to get better denoising performance. The performance of denoising ECG are evaluated using signal to noise ratio (SNR) and percentage root mean square difference (PRD). For this we used simulated and gaussian white noise surrogated ECG signals. Our results show that combined S-G and wavelet filter denoising is noticeable better than the respective individual procedures. In addition, we found that the selection of frame size, order of the S-G filter and the wavelet type and order should be done carefully in order to get optimal results. It also holds true for the new filter that the optimal choice of filter parameters is a compromise between noise reduction and distortion.

Chronic kidney disease (CKD) is a global health problem that affects around 11 to 13% of the world’s population and more than 18% of European citizens. Characteristic syndromes of CKD during all stages of the disease are proteinuria and ongoing glomerular dysfunction caused by cellular damages at the glomerular filtration barrier. While some rare cases of the disease are correlated to genetic depositions the majority of cases are caused by diabetes, glomerulosclerosis, high blood pressure and glomerulonephritis. Thus, recapitulating the interplay of high blood pressure and changes at the glomerular filtration barrier in vitro seems an adequate way to mimic CKD. Here we present a microphysiological system of the glomerular filter that is capable to simulate high blood pressure at the glomerular filtration barrier in vitro. It consists of a closed loop microfluidic circuit with an integrated pneumatically driven heart like micro pump that constantly circulates the cell culture media at the blood site of the glomerular barrier. The ThinCert™ insert could be reversibly integrated into a holder system that ensures the correct position of the insert within the microfluidic circuit. By using different modulations of the integrated pneumatic micro pump different physiological and pathophysiological conditions e.g. hypertonic stress, like in CKD, could be applied. The influence of hypertonic conditions on the filtration above the barrier was studied by changes of TEER values and measurement of the flux of fluorescent labelled albumin through the cellular barrier.

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 (Ac 4 GalNAz). Toxicity and viability assays after 24 h and 72 h incubation revealed high biocompatibility of Ac 4 GalNAz 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, Ac 4 GalNAz in combination with ASCs was confirmed to achieve an azidemodified ECM as a multifunctional biomaterial for further applications.

Thermographic imaging is a known technology to detect temperature differences. For medical applications, the patterns of heat distribution are used for diagnosis. It is already tested to visualize blood supply, inflammatory processes, and superficial or more extensive tumors, e.g. in the breast tissue. This method was promoted for breast screening purposes and as a substitute for mammography for mid aged women, but the results were not convincing for younger women, where tissue density is higher, tumor growth is often connected to local temperature increase and radiation-based mammography is not an option. Infrared (IR) thermography can support tumor screening. The screening should allow the early detection of small lesions even in the depth. Therefor we evaluated the feasibility of dynamic cooling in combination with IR imaging in a phantom study. A temperature-controllable gel phantom including a heating plate, a depth-adjustable heat source mimicking a tumor, and three sensors for temperature monitoring was built up. A raspberry pi device serves as a control unit to create a stable temperature balance comparable to a human breast. For the experiments, the tumor was placed in various depth. After cooling, the thermal recovery phase of the phantom was imaged using an IR camera and a webcam. A pixel-wise analysis of the IR data detects a higher gradient of temperature change in the tumor region. The experiments demonstrated the feasibility of tumor detection based on dynamic cooling and IR imaging.

In this work, a methodology for the classification of breathing patterns in order to prevent sudden infant death (SID) incidents is presented. The basic idea is to classify breathing patterns which might lead to SID prior to an incident. A thorax sensor is proposed, which is able to simulate breathing patterns given by certain parameters. A sensor combination of conductive strain fabric and an inertial measurement unit is used for data acquisition. The data is then classified using a neural network.

Online recognition of surgical phases is essential to develop systems able to effectively conceive the workflow and provide relevant information to surgical staff during surgical procedures. These systems, known as context-aware system (CAS), are designed to assist surgeons, improve scheduling efficiency of operating rooms (ORs) and surgical team and promote a comprehensive perception and awareness of the OR. State-of-the-art studies for recognizing surgical phases have made use of data from different sources such as videos or binary usage signals from surgical tools. In this work, we propose a deep learning pipeline, namely a convolutional neural network (CNN) and a nonlinear autoregressive network with exogenous inputs (NARX), designed to predict surgical phases from laparoscopic videos. A convolutional neural network (CNN) is used to perform the tool classification task by automatically learning visual features from laparoscopic videos. The output of the CNN, which represents binary usage signals of surgical tools, is provided to a NARX neural network that performs a multistep-ahead predictions of surgical phases. Surgical phase prediction performance of the proposed pipeline was evaluated on a dataset of 80 cholecystectomy videos (Cholec80 dataset). Results show that the NARX model provides a good modelling of the temporal dependencies between surgical phases. However, more input signals are needed to improve the recognition accuracy.

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.

Cochlea Implant (CI) planning is usually based on preoperative obtained CT or MRI data, visualising risk structures in the petrosal bone. In the past years, Digital Volume Tomography (DVT) with an increased spatial resolution and reduced radiation has become more important in the clinical routine for otology. In this work we propose an extension of our interactive “wizard”-guided approach for the interactive segmentation of the middle and inner ear structures for the use with DVT data. Different filter pipelines enable the user to interactive segment the acoustic canal, ossicles, tympanic cavity, facial nerve, chorda tympani, round window, cochlea and semicircular canals. The approach has been evaluated on six pre-operative acquired DVT datasets by an ENT expert. Results imply that the proposed method can handle DVT well and can potentially be used for interactive OR planning.

Magnetomotive Ultrasound is an imaging technique that is capable to detect tissue, which is perfused by magnetic nanoparticles. However, this modality is restricted to qualitative imaging only. Therefore, we present an extended Magnetomotive Ultrasound algorithm, which allows the quantitative determination of the spatial distribution of magnetic nanoparticle density in tissue. The algorithm is based on an iterative adjustment of simulated data to measurements. Experiments with tissue-mimicking phantoms reveal that the presented method leads to the spatial particle concentration in the correct order of magnitude.

In-vitro wound area measurement tracks the rate of wound healing. This project develops and validates an automatic image analysis system to calculate wound area from digital images of an in-vitro 3D tissue model wounded with a biopsy punch. The algorithms were evaluated for repeatability, reliability, and reproducibility, and validated against a known area. Repeatability was checked through repeated measurements under repeated conditions. Reproducibility was evaluated using a Bland Altman plot and paired t-test. Reliability was validated using an image of a known pixel area as a control. The validated image analysis system then calculated wound area from the digital camera and microscope images obtained from an in vitro photo biomodulation treatment experiment. A total of 48 wounded tissues were grouped into red and blue light treatment groups and untreated controls. All daily images were fed into the image analysis system to calculate wound area. The wound area (normalized by day 0) is plotted along the 2-week treatment experiment period to observe wound area in time. The normalised wound area plotted across treatment days show no change in wound area during the treatment period. Future work will adapt the imaging system for visualizing the reepithelialisation cell front marked by live dyes.

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.

Optical tracking systems, such as the Moiré Phase Tracking system (MPT), can be used to correct motion prospectively especially during magnetic resonance imaging (MRI, MR) in neurologic application. For that an MRI safe camera is mounted in the MRI bore to detect motion by tracking a specific MPT marker, which is rigidly attached on the subject’s head. To enable prospective updates of the imaging volume´s position and orientation, and therefore to correct motion from the subject, the motion information captured from the camera need to be transformed from the camera into the MR coordinate system. The process of finding the transformation between both coordinate systems is called cross calibration and is essential for the overall motion correction performance. For the procedure of the cross calibration, an MR visible phantom with an attached MPT-marker is measured simultaneously with MRI and the MPT camera in multiple specific alignment positions. To reduce cross calibration errors, it is essential to move the phantom precisely into specified alignment positions. Due to the long and narrow bore design of ultra-high field systems (tunnel length > 3 m), the phantom can not be moved simply from a person leaning inside the scanner bore. Thus, to rotate it after each measurement step, either a technician must work inside the tunnel during the complete period of the cross calibration or the table must be moved in and out of the bore multiple times. To improve this currently established cross calibration procedure, we have developed an MRI safe phantom rotation system, which can be controlled remotely and precisely from outside the MRI bore. Even for ultra-high field imaging, the rotation system is fully MRI compatible. Initial tests were performed at a 7T whole-body MRI system and have proven the benefit of our rotation system.

The key purpose of assistance robots is to help people coping with work-related or everyday tasks. To ensure an intuitive and effective support by an assistance robot, its expectation conform behavior is essential. In particular, when using assistance robots in geriatrics to assist elderly patients, special attention to the human-robot interaction should be paid. In order to help elderly patients maintain their independence and abilities as much as possible, the robot should only intervene when its support is needed. Therefore, the continuous estimation of the patient’s need for interaction is of particular importance. For enabling suitable models to estimate this need, we elaborate the use of Bayesian Networks. The analysis of our results seems promising, yielding a robust and practical approach.

Nowadays, cell-based assays are an elementary tool for diagnostics, animal-free substance testing and basic research. Depending on the application, the spectrum ranges from simple static cell cultures in microtiter plates to dynamic co-cultures in complex micro physiological systems (organ-on-a-chip). Depending on the complexity of the assay, numerous working steps have to be performed and the data from different analysis systems have to be processed, combined and documented. A universal platform has been developed for the automated handling of cell-based assays, which combines a laboratory information management system (LIMS) with a laboratory execution system (LES), a universal laboratory automation platform and established laboratory equipment. The LIMS handles the administration of all laboratory-relevant information, the planning, control and monitoring of laboratory processes, as well as the direct and qualified processing of raw data. Using a kidney-on-achip system as an example, the realization of complex cellbased assays for the animal-free characterization of the toxicity of different antibiotics will be demonstrated. In the kidney-on-a-chip system the artificial proximal tubular barrier was formed by seeding human immortalized proximal tubule cells (RPTEC) and human blood outgrowth endothelial cells (BOEC) on ThinCert™ membranes. Transepithelial electrical resistance (TEER) was measured daily to evaluate the barrier function of the cellular layers. Fluid handling and TEER measurements were performed using a laboratory automation platform that communicates directly with the LIMS. The LES supports laboratory assistants in executing the manual handling steps of the experiments.

Insertion studies in artificial cochlea models (aCM) are used for the analysis of insertion characteristics of different cochlear implant electrode carrier (EC) designs by measuring insertion forces. These forces are summed forces due to the measuring position which is directly underneath the aCM. The current hypothesis is that they include dynamic friction forces during the insertion process and the forces needed to bend an initially straight EC into the curved form of the aCM. For the purposes of the present study, straight EC substitutes with a constant diameter of 0.7 mm and 20.5 mm intracochlear length were fabricated out of silicone in two versions with different stiffness by varying the number of embedded wires. The EC substitutes were inserted into three different models made of polytetrafluoroethylene (PTFE), each model showing only one constant radius. Three different insertion speeds were used (0.11 / 0.4 / 1.6 mm/s) with an automated insertion test bench. For each parameter combination (curvature, speed, stiffness) twelve insertions were conducted. Measurements included six full insertions and six paused insertions. Paused insertions include a ten second paused time interval without further insertion movement each five millimetres. Measurements showed that dynamic and static components of the measured summed forces can be identified. Dynamic force components increase with increased insertion speeds and also with increased stiffness of the EC substitutes. Both force components decrease with larger radius of the PTFE model. After the insertion, the EC substitutes showed a curved shape, which indicates a plastic deformation of the embedded wires due to the insertion into the curved models. The results can be used for further research on an analytical model to predict the insertions forces of a specific combination of selected parameters as insertion speed and type of EC, combined with given factors such as cochlear geometry.

The bend and free recovery (BFR) test according to ASTM F2082 is a standard method to determine the transition temperatures of Nitinol shape memory alloys (SMAs). Unfortunately, this standard method is limited to SMA wires which are straight in its trained shape. Thus, the standard BFR test is not suitable for thermomechanical characterization of curved Nitinol SMA wires which should serve as actuators in cochlear implants in future. We developed a modified BFR measurement setup to determine the active austenite finish (AF) temperature of these very thin wires (Ø100 μm). The active AF temperature specifies the completion of the shape recovery upon heating. A parametric study of the measurement setup was carried out to investigate the influence of the heating rate on the observed active AF temperature and to verify the repeatability of the measurement setup. First, the curved wire was straightened in a cold water bath before inserting it into a water bath that is gradually heated from 5 °C to 45 °C. The shape change of the previously straightened wire was then recorded throughout the experiment using a digital microscope. Five different heating rates were employed: 0.25 K/min, 0.33 K/min, 0.5 K/min, 1 K/min as well as an unregulated maximum heating rate achievable of approximately 1.5 K/min. Furthermore, an investigation on the test-retest reliability was performed with three wires by repeating the experiment ten times with each wire. The results of this study revealed no influence of the heating rate on the thermomechanical response of the wires. Based on data from this study, a regulated heating rate of 1 K/min is suggested for future investigations, as this reduces the duration of the measurement from four hours to less than an hour. The values obtained from each wire through the test-retest reliability investigation showed a standard deviation of 1.9 K, 1.1 K and 2.1 K respectively. Our developed measurement setup demonstrates appropriate repeatability of the measurements.

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.

Polyurethane-bases block copolymers (TPCUs) are block-copolymers with systematically varied soft and hard segments. They have been suggested to serve as material for chondral implants in joint regeneration. Such applications may require the adhesion of chondrocytes to the implant surface, facilitating cell growth while keeping their phenotype. Thus, aims of this work were (i) to modify the surface of soft biostable polyurethane-based model implants (TPCU and TSiPCU) with high-molecular weight hyaluronic acid (HA) using an optimized multistep strategy of immobilization, and (ii) to evaluate bioactivity of the modified TPCUs in vitro. Our results show no cytotoxic potential of the TPCUs. HAbioactive molecules (Mw =700kDa) were immobilized onto the polyurethane surface via polyethylenimine (PEI) spacers, and modifications were confirmed by several characterization methods. Tests with porcine chondrocytes indicated the potential of the TPCU-HA for inducing enhanced cell proliferation.

Occluders made of the shape memory alloy Nitinol are commonly used to close Atrial Septal Defects (ASD). Until now, standard parameters are missing defining the mechanical properties of these implants. In this study, we developed a special measuring setup for the determination of the mechanical properties of customly available occluders (i.e. Occlutech Figulla® Flex II 29ASD12 and AGA AMPLATZER™ 9-ASD-012).

The implantation of an occluder in the left atrial appendage (LAA) is an emerging therapy for the treatment of patients suffering from atrial fibrillation and with a contraindication to oral anticoagulation. The LAA occluder (LAAO) provides a reduction of the potential risk of strokes by thromboembolism. Currently, only a few CE-approved devices are available on the market and the number of clinical trials is comparatively low. Furthermore, there is currently no standardized test method available for testing functionality of the occluder, especially for testing safe anchorage and permeability. Therefore, the aim of this study is to establish an in vitro test method to prove anchorage mechanism and permeability regarding thromboembolism of the LAAO under physiological conditions. A standardized technical and fully parameterized silicone model of a LAA, based on studies of different morphologies and sizes, was developed. The LAA model was mounted onto the left atrial chamber of a commercial pulse duplicator system to simulate physiological hemodynamic conditions. The test was performed using the Watchman device (Boston Scientific, USA; size: 31 mm). The inner implantation diameter of the LAA model was designed according to a target compression of 10% for the Watchman device in the implanted configuration. Furthermore, thrombus-like particles (n=150, d=1,7±0,05 mm) were added to represent the flushing of thrombi out of the LAA after device implantation. Within several cycles it was confirmed that no particles were washed out of the LAA model with the implanted occluder leading to a full protection against thromboembolism. It could also be shown that the occluder is firmly anchored in the LAA. Pressure measurements with sensors in the left atrium and in the LAA distal to the occluder could also show that the occluder has no influence on the pressure conditions in the LAA.

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.

The analysis of device drug content typically is carried out by means of chromatographic methods such as high performance liquid chromatography (HPLC) or liquid chromatography-mass spectrometry (LCMS). These approved methods are particularly fast, cost-efficient and ubiquitous in chemical-analytical laboratories. However, these quantitative methods necessitate the drug being eluted, which represents a destructive process. A novel alternative to these well-established methods [1, 2] is the Raman spectroscopy, which is fast and cost-efficient, as well [3]. Additionally, it offers the advantage of nondestructive analysis without the need for a special sample preparation. Within the current investigation we applied Raman spectroscopy for the qualitative and quantitative analysis of dexamethasone (DMS), a glucocorticoid, incorporated in a silicone matrix. The investigation was conducted in a rectangular area on the sample surface. The required number of measuring points (spectra) was determined. Calibration was performed with samples containing different amounts of DMS. The evaluation of Raman spectra is based on the analysis of the peak areas of the bands at 795 rel. cm -1 (silicone) and 1,663 rel. cm -1 (DMS). Remarkably, next to a precise overview of DMS distribution, an exact and reproducible quantification of incorporated DMS could be obtained.

The implantation of transcatheter aortic valve prostheses (TAVP) for therapy of aortic valve stenosis shows more and more clinically non-inferiority results compared to surgical valve replacement in intermediate and low risk patients. Commonly clinically used TAVP are manufactured from chemically fixed xenograft leaflet material, e.g. bovine or porcine pericardium. While the clinical use of TAVP currently extends, challenges concerning valve durability and leaflet calcification have to be addressed. In this regard, artificial leaflet materials represent a promising option for a next generation of TAVP. As a first step for the development of TAVP from polymeric nonwoven, the aim of this study was to determine the influence of leaflet geometry on hydrodynamic performance of TAVP prototypes. Based on a parametric model of the valve leaflets, we varied the curvature of the belly line forming the leaflet coaptation area from an initial, quite concave, leaflet geometry with a value of 0.5° to an almost straight geometry for the leaflets with a value 0.15°. Manufacturing of TAVP prototypes was conducted by means of electrospinning technique with a polycarbonate based silicone elastomer. Hydrodynamic characterization according to ISO 5840-3 standards was performed using a pulse duplicator system with a heart rate of 70 BPM, systolic duration of 35%, mean aortic pressure of 100 mmHg and a stroke volume of 96 ml. Cardiac output as well as mean transaortic pressure gradient, closing volume, leakage volume and regurgitation were measured to compare the different leaflet geometries. To summarize, the curvature of the leaflets’ belly has a crucial impact on TAVP hydrodynamics under physiological test conditions. In particular, the opening and closing behavior is strongly influenced by a steeper curvature leading to larger closing volumes and higher regurgitant fractions. Further studies are planned to identify an optimum with respect to leaflet material selection, leaflet geometry and hydrodynamic properties of TAVP.

Chronic venous insufficiency (CVI) is a common disease characterized by impaired venous drainage leading to congestion in the lower limbs. Currently, there are no artificial or biological venous valve prostheses commercially available. Previous minimally invasive design concepts failed to achieve sufficient long term results in animal or in vitro studies. The aim was to implement structural numerical simulation of clinically relevant loading cases for minimally invasive implantable venous valve prostheses. A bicuspid valve design was chosen as it showed superior results compared to tricuspid valves in previous studies. The selfexpanding support structure was developed by using diamond-shaped elements. Using finite-element analysis (FEA), various loading cases, including expansion and crimping of the stent structure and the release into a venous vessel, were simulated. A hyperelastic constitutive law for the vascular model was generated from uniaxial tensile test data of unfixated human vein walls. This study also compared numerical and experimental results regarding compliance and tensile tests to validate the vein material model. The calculated performance concerning expansion and crimping, as well as the release of the stent into a venous vessel, demonstrated the suitability of the stent design for minimally invasive application.

Implants that feature a drug delivery system loaded with antifibrotic active drugs provide a promising approach to address postoperative complications caused by fibrosis. This study is intended to clarify whether Actinomycin D has an impact specifically on components of the extracellular matrix (ECM) and its formation in human primary fibroblasts of the Tenon capsule (hTF). Furthermore, the suitability of this agent in poly(N-vinylpyrrolidone)- poly(methylmethacrylate)(PVP-co-PMMA) as a drug delivery model is evaluated in drug incorporation and release studies. RT-qPCR revealed a significant downregulation of the fibrotic marker genes ACTA2, COL1A1 and FN1 in cells stimulated with TGF- β1 and additionally treated with Actinomycin D. However, these findings could only be confirmed on α- SMA protein level. collagen I and Fibronectin synthesis stayed unaffected. The diffusion based incorporation of Actinomycin D into the polymer model proved to be very effective. The release of the agent was retarded with a slightly prolonged kinetic. These findings make Actinomycin D a promising antifibrotic agent in ophthalmic implant surgery.

At present, a main focus in the field of stent technologies is on the development of biodegradable polymeric stents. Due to inferior material characteristics of polymers compared to permanent metals stents require thicker stents struts to accomplish adequate mechanical properties. Therefore, a thermo-mechanical treatment of polymeric stents was tested, which showed a positive effect on mechanical stent characteristics.

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.

Fluid mechanical characterization of artificial heart valve prostheses requires reliable measurement of temperature, flow and pressure at normal heart rate. In vitro fatigue test procedures of artificial heart valve prostheses can take several months with up to 400 million cycles to assess valve performance and durability under simulated cardiac conditions at increased pulse frequency. In both cases, a minimum of user interventions for recalibration are required. In these tests, pressure data are collected for hydrodynamic heart valve characterization and for closed-loop control of pressure loading. In our study, the improvement of commercial heart valve testing systems (Vivitro Pulse Duplicator, Vivitro Labs Inc. and VDT-3600i, BDC Laboratories) is considered by substituting the built-in disposable pressure sensors (lifetime: one week) by longterm stable sensors. The selected highly accurate sensors (86A, TE Connectivity Corp.) provide amplified, linearized, calibrated and temperature compensated analog output signals. Their stainless steel construction allows for high media compatibility with corrosive liquids. Due to different sensitivity characteristics, these sensors are not fully compatible to the testing devices. To overcome this limitation, application-specific emulator interfaces were developed to connect the new sensors to the data acquisition part of the validated valve testing systems. To stay consistent with manufacturer’s device and software specification, we utilized fast analog signal conditioning, including scaling, offset calibration, out of range alarm and status indication. Compared to the originally equipped pressure sensors, emulator parameters, such as pressure range, precision, resolution and accuracy remained unchanged or even improved. For system verification the response characteristic, long-term stability and dynamic properties were examined in comparative studies

In recent years, a progressive interest in the implementation of wireless access to cardiovascular implants has been established. This manifests in new devices, such as arterial pressure sensors, or additional functionalities added to established implants like stents. However, common stent designs, possessing highly optimized mechanical properties, often consist of cylindrically arranged struts with connections in-between which can be considered as short-circuited inductive coils. As a consequence, the small inductance raises the resonance frequency, which may decrease the in vivo performance of the wireless connection between the stent and the external readout device. Thus, new designs were developed to overcome this limitation, for example by avoiding the short-circuit due to a helical arrangement of the struts. Within this work we compare the performance of a common stent design and a helical design by means of numerical simulations. We are using two designs which only differ in the arrangement of the struts. The electromagnetic and mechanical properties are investigated using a finitedifference time-domain algorithm and finite element method, respectively. We will show that a common stent design exhibits resonance frequencies in the gigahertz regime, much higher than the frequencies of comparable helical designs. Furthermore, we compare the mechanical performance of the two designs and reveal individual distinctions in the radial stiffness, bending stiffness, and the von Mises stress.

Mitral regurgitation (MR) occurs with a prevalence of approximately 10 % in patients aged 75 years or older and therefore is one of the most frequent indications for heart valve surgery. During the last decade surgical mitral valve repair (MVR) procedures emerged as the gold standard for the treatment of clinically relevant MR. However, for surgically inoperable or high-risk patients transcatheter-based MVR devices present a valuable treatment option. Within the current study, we developed an experimental setup to investigate the hydrodynamic performance of transcatheterbased MVR devices in vitro. The bicuspid mitral valve (MV) model employed in the experimental setup features a D-shaped MV annulus with d 1 = 26.30 mm, d 2 = 30.05 mm and chordae tendineae with a length of l 1 = 25 mm attached to two papillary muscle structures. Pressure gradient - volumetric flow rate (Δp-Q) relations were investigated for steady state backward flow with transvalvular pressure gradients ranging from 0.75 mmHg ≤ Δp ≤ 103.13 mmHg. Deionized water at 37 °C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m 3 was used. A test-chamber consisting of a press-fit MV holder and cylindrical in- and outflow tracts were developed. Different designs for the exchangeable press-fit MV holder were manufactured using additive manufacturing technologies providing an optimal fitting for variable MV sizes and pathologies. In- and outflow tracts featuring a diameter of d = 50 mm and a height of h = 60 mm were made from transparent polymethylmethacrylate to allow for easy optical access during measurements. The experimentally investigated Δp-Q relation yields a quadratic correlation for the open MV and a linear correlation for the closed MV. A transvalvular closing pressure of (4.94 ± 0.04) mmHg was measured for the MV model.

Along with increasing enthusiasm for sports comes an increase of sport related injuries. One of the most common injuries in the human knee is the tear of the anterior cruciate ligament (ACL). The selection of a graft fixation device is an important factor that determines the outcome of an anterior cruciate ligament reconstruction. Before the healing process is completed, the graft is dependent on tibial and femoral fixation devices to maintain normal ACL graft tension. Among various devices, the use of an adjustable loop suspensory fixation device (ALD) in soft-tissue graft reconstruction attracts current interest. An advantage of the ALD is the ability to draw the graft to the depth of the bone tunnel to achieve adequate graft tension while minimizing the empty space in the tunnel. In this study a comprehensive controlled laboratory investigation is performed to examine the biomechanical properties of commonly used cortical fixation devices, with the aim of implementing a standard testing procedure for adjustable loop devices. The procedure consists of three test series, a loop shortening test and two different stability test series (singe device and tendon device test). Those test series are used to compare the performance of a new ALD from Arthrex (Naples, USA) with five competitor devices already on the market. In order to obtain representative results eight samples of each device are tested. In comparison to the previously performed studies, a complete unloading is applied in the stability tests, which allows for a detailed examination of the ALDs locking mechanisms in dynamically loaded test situations. Furthermore, the performed loop shortening tests reveal important aspects, such as the shortening accuracy and settling effects of the loops, that are not found in previous studies. Therefore, the used test protocol can be recommended for further testing.

In developing countries airborne micro-organisms are one of the most common causes of surgical wound infection. In the operating room low-turbulence displacementflow has been shown to reduce the influence of airborne bacteria. However, due to complexity and cost, current systems are not accessible to all potential users. In this paper a low-cost ventilation system is presented that provides lowturbulence displacement-flow over a surgical operating environment. A stand-alone, simple to assemble, mobile airflow system was developed using the principle of speed compensation for laminar airflow. From visual inspection and measurements, the system was seen to generate a continuous downwards displacement of air over the protected area around the situs. The entire system can be assembled quickly with minimal standard tools, making it very suitable for mobile use, such as in disaster areas. Future work is required to achieve the vertical dimension of a laminar flow field required by the DIN 1946-4. Overall, the low-cost and simple system could provide many potential users access to the technology and thus improving hygiene conditions in their operating environment.

In this work, a low-priced smart fabric forcesensing glove is developed which is able to measure the total amount and direction of the force a person applies on a patient in a physiotherapeutic context. A device like this would be beneficial for the education of physiotherapists, to measure the progress of a patient and to evaluate the treatment. The proposed device uses a new sensor, which is based on a piezoresistive fabric. This fabric changes its electrical resistance according to the applied stress. The characterization of this sensor revealed that the change in resistance of the sensor is dependent of the amount of force, the loaded area, the total time the sensor is loaded and hysteresis. To compensate these behaviours, an additional sensor based on the same smart fabric was developed which measures the loaded area of the first sensor. By combining these two sensors, it is possible to calculate the applied force. The results show the feasibility to build a measurement system out of smart fabric material that can measure the applied force. Furthermore, the prototype shows promising results in determining the applied force in amount and direction.

Minimally invasive surgery in some cases suffers from a limited view because certain areas are obscured by others. In this paper, a system is described, which can be used in minimally invasive procedures as an addition to a standard endoscope to improve the range of view. Through FEM simulation a magnetic circuit was designed to position the camera head. Subsequently, a camera positioning system was set up that includes an extracorporeal and an intracorporeal unit. The first controls the intracorporeal system. The latter has a camera inclination angle of up to 65° and an additional vertically downward viewing angle when aligned in parallel (inclination angle 0°). The panning angle is 360°. The camera system was evaluated in lab and cadaver trials. It has been found that the size of the intracorporeal system (16 × 10 × 150 mm) represents a major problem. Future work will focus of the reduction of the system’s size, the improvement of the camera image quality, and design changes considering mechanical stability.

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.

The purpose of this work was to develop and investigate a radiofrequency (RF) coil to perform image studies on small animals using the 7T magnetic resonance imaging (MRI) system, installed in the imaging platform in the autopsy room (Portuguese acronym PISA), at the University of Sao Paulo, Brazil, which is the unique 7T MRI scanner installed in South America. Due to a high demand to create new specific coils for this 7T system, it is necessary to carefully assess the distribution of electromagnetic (EM) fields generated by the coils and evaluate the patient/object safety during MRI procedures. To achieve this goal 3D numerical methods were used to design and analyse a 8-rungs transmit/receive linearly driven birdcage coil for small animals. Calculated magnetic field (B 1 ) distributions generated by the coil were crosschecked with measured results, indicating good confidence in the simulated results. Electric field results were post-processed and predictions of local specific absorption rate (SAR) values were achieved for a spherical phantom filled with muscle-like tissue, indicating that the sample would not suffer any unsafe deposition of energy. Post mortem abdomen images obtained from a rat presented good image quality and no artifacts related to field non-homogeneity were observed.

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.

Stroke is the third-most cause of death in developed countries. A new promising treatment method in case of an ischemic stroke is selective intracarotid blood cooling combined with mechanical artery recanalization. However, the control of the treatment requires invasive or MRI-assisted measurement of cerebral temperature. An auspicious alternative is the use of computational modeling. In this work, we extended an existing 1D hemodynamics model including the characteristics of the anterior, middle and posterior cerebral artery. Furthermore, seven ipsilateral anastomoses were additionally integrated for each hemisphere. A potential stenosis was placed into the M1 segment of the middle cerebral artery, due to the highest risk of occlusion there. The extended model was evaluated for various degrees of collateralization (“poor”, “partial” and “good”) and degrees of stenosis (0%, 50%, 75% and 99.9%). Moreover, cerebral autoregulation was considered in the model. The higher the degree of collateralization and the degree of stenosis, the higher was the blood flow through the collaterals. Hence, a patient with a good collateralization could compensate a higher degree of occlusion and potentially has a better outcome after an ischemic stroke. For a 99.9% stenosis, an increased summed mean blood flow through the collaterals of +97.7% was predicted in case of good collateralization. Consequently, the blood supply via the terminal branches of the middle cerebral artery could be compensated up to 44.4% to the physiological blood flow. In combination with a temperature model, our model of the cerebral collateral circulation can be used for tailored temperature prediction for patients to be treated with selective therapeutic hypothermia.

Phantoms mimicking special physiological processes of the human body are essential for evaluating prototypes of medical devices. Especially for thermometric MRI measurements, the temperature distribution in the brain needs to be simulated. Since this parameter is dependent on the tissue perfusion, a new hydrogel by MAGDASSIS et al. was evaluated in this work for building models with hollow artery structures. This hydrogel can be polymerized through UV-light due to the nanoparticles contained in it. Additionally, thermal parameters were measured and compared to human brain tissue. The indirect manufacturing of hydrogel phantoms showed good qualitative results for vessels with a diameter > 3 mm. In this process a 3D printed wax core was inserted in the hydrogel and the structure was then UV cured after molding. After curing the core was dissolved in an isopropanol bath. The thermal properties, obtained by the transient planesource- method, showed similar values compared to that of human brain tissue mentioned in literature. Further limitations in the manufacturing process needs to be overcome to use the indirect manufacture approach for smaller vessels of the brain.

This paper discusses the influence of different design parameters of stents by mathematical flow simulations and flow measurements using micro-particle image velocimetry (micro-PIV). A stent strut may cause recirculation areas, which are considered to be the source of thrombosis and the process of in-stent restenosis. The simulations showed that a reduced strut height and a chamfering of the struts reduce these recirculation zones. The numerically determined results were compared with experimental investigations. For this purpose metallic stent structures were transferred into transparent channel systems made of PDMS. The experimental investigations confirm the results of numerical simulations.

The future of personalized diagnostics commences on the single cell level. Even high-end technologies like Next Generation Sequencing can be improved if applied on pure single cell populations (e.g., tumor cells without contaminating stromal cells) or on a single cell level (DNA/RNA sequencing). The vast majority of these technologies need individual and preferably undistorted cells for the analytical process. Thus, decisive prerequisite for high-end analytics is to remove cells from their tissue matrix as gently as possible. This can be accomplished by an enzyme-free, fast and reproducible approach of generating pure and individual single cells from tissue samples. In this study we demonstrate the utility of a semi-automated Tissue Grinder that is compatible with standard 50 ml centrifuge tubes and standard cell strainer for mechanically, nonenzymatic and parallel processing of tissue samples. We show that without enzymatic treatment viable single-cell yields match or exceed reference enzymatic methods, while reducing processing time by at least 80%.

The advantages of automatic control of the fraction of inspired oxygen in neonates have been documented in recently published clinical trials. Many control algorithms are available, but their comparison is missing in the literature. A mathematical model of neonatal oxygen transport could be a useful tool to compare and enhance both automatic control algorithms and manual control of fraction of inspired oxygen. Besides other components, the model of neonatal oxygen transport must include a module linking arterial (SaO 2 ) and peripheral (SpO 2 ) oxygen saturation. The pulse oximeter module must reflect issues of SpO 2 measurement typical for clinical practice, such as overestimation of SpO 2 over SaO 2 documented by several studies, or inaccurate pulse oximeter readings due to high noise. The aim of this study was to describe both the bias between SaO 2 and SpO 2 and the noise, characteristic for continuous SpO 2 recording, for a computer model of oxygenation of a premature infant. The SpO 2 -SaO 2 bias, derived from available clinical data, describes a typical deviation of the SpO 2 measurement as a function of the true SaO 2 value in three different SaO 2 intervals. The SpO 2 measurement noise was considered as a random process that affects biased SpO 2 values at each time point with statistical properties estimated from SpO 2 continuous recordings of 5 stable newborns. The results of the study will help to adjust a computer model of neonatal oxygenation to the real situations observed in the clinical practice.

Although osteosynthesis plates rarely break, such cases still occur. Since the construction of these plates is mainly focussing on the best fit for anatomical structures, they may not provide optimal mechanical stability. It should be considered whether they might be changed in terms of e.g. hole size and number. Finite element analysis can help to estimate whether the plates will withstand loads or break. However, these analyses can be very time-consuming. To counteract this problem, a new software solution (ANSYS Discovery Live) has been established for estimation of stresses in real time. In this study the accuracy of the new software was compared to a conventional finite element analysis software solution to investigate whether this software solution provides appropriate accuracy to be used for medical applications.

In order to test medical devices, industry increasingly uses simulators closely reassembling the behaviour of physiological systems. In the context of respiratory therapy, most available simulators are designed based on a ventilated volume. This highly adjustable volume allowing for fast dynamical changes often leads to very costintensive test devices, particularly when incorporating realistic spontaneous breathing. Therefore, in this article we introduce a novel concept for a low-cost lung simulator, capable of mimicking the ventilation behaviour of the human lung at the Y-piece of a mechanical ventilator. The proposed design does not require any enclosed spaces to hold inhaled air nor expensive precise linear actuators adjusting its volume. Instead, the setup is designed based on the design of a mechanical ventilator, connecting the system with one port to the ventilator and then dividing the hose into two independent branches. Each branch has an integrated radial fan and a proportional valve, controlling the inspiratory and expiratory flow, individually. The mass flow and pressure are measured at the systems inlet port, representing the condition at patient airway. In contrast to existing setups, the proposed design is not limited by the physical properties of a volume such as fixed maximum size, allowing the simulation of various types of patients and conditions. Numerical simulations to evaluate this system design showed the ability to generate a realistic spontaneous breathing pattern. With a first experimental setup it was possible to prove the feasibility of this approach, by generating common flow curves during spontaneous breathing. Building on this design, the approach could eventually lead to a more accessible method for testing.

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 “.

Obstructive sleep apnea (OSA) is a common sleep disorder caused by the collapse of the upper airway during sleep due to a shift of soft tissues. To optimise the treatment, one needs a better understanding of the patient-specific causes of OSA. As a first step, a flexible tube with a stenosis was manufactured, representing a simple model of the pharynx geometry. The phantom has been used to carry out magnetic resonance imaging (MRI) flow sensitive measurements, to investigate the flow conditions that lead to the collapse. This contribution is concerned with the comparison and analysis of the flow and phantom deformation using varying boundary conditions, such as the Reynolds number and transmural pressure.

While the current generation of devices for minimally invasive treatment of severe symptomatic aortic valve stenosis is based on xenogenic leaflet-material, artificial polymeric leaflet-structures represent a promising approach for future improvement of heart valve performance. For enhanced long-term success of polymeric leafletstructures, limitations regarding calcification and durability have to be addressed. The objective of the presented study was the development of a constitutive law representing the material properties of artificial polymeric leaflet-structures of transcatheter heart valve prostheses in numerical simulation to assess the in silico leaflet-performance. Mechanical characterization of cast films and nonwoven specimens of a polycarbonate based silicone elastomer were conducted by means of uniaxial tension and planar shear testing, respectively. For validation purposes, experimental data were compared with the results of finite-element analysis (FEA) using different hyperelastic models. Strain energy function for third-order ogden hyperelastic model achieved the best fit of the non-linear stress-strain behavior of the isotropic polymeric material with the experimental data. It was chosen for further FEA of valve leaflet-performance under physiological pressurization to analyze the suitability of various manufacturing processes for polymeric leafletstructures. Therefore a specific leaflet-design with a wall thickness of 400 μm was used. As a result of FEA, time dependent leaflet-deformation, leaflet coaptation surface area (CSA) and leaflet opening area (LOA) of cast and nonwoven leaflet-structures were calculated. While LOA was comparable for cast and nonwoven leaflet-structures, obtained leaflet-dynamics in a cardiac cycle under physiological pressurization demonstrated crucial influence of the manufacturing process. For nonwoven leafletstructures, an enhanced CSA could be demonstrated in comparison to cast structures. FEA using a validated hyperelastic constitutive law represents a useful tool for in silico performance evaluation of polymeric leaflet-structures under physiological loading and proves the suitability of the polymeric artificial leaflet-material for percutaneous heart valve prostheses.

Magnetic nanoparticles are highly promising for the usage in various biomedical applications including magnetic particle imaging (MPI), cancer hyperthermia treatment or as drug carriers. The present study aims at assessing in vitro biocompatibility of two commercially available magnetic iron oxide nanoparticle formulations: dextran-based magnetic nanoparticle synomag-D and bionized nanoferrite BNF-starch. Biological performance of both nanoparticle formulations were studied in human endothelial cells by analyzing cell viability and nanoparticle internalization in order to judge their suitability as theranostics.

For imaging of the vascular structure, angiography is state of the art. This can be done by contrast enhanced XRay, CT or MR imaging. But these modalities typically only show the blood flow and do not allow a depiction of the vasculature itself. To provide information about the vessel walls and plaques narrowing the blood flow, catheter based intra vascular ultrasound or vascular optical coherence tomography can be used. Optical endoscopic imaging is rarely used in vascular diagnosis. But endoscopic imaging can depict superficial inflammations or defects of the intima vessel layer and the real anatomical shape of the inner vasculature e.g. at bifurcations or aneurysms. Since OCT and endoscopic imaging both need a flushing to remove the blood for a short time, a combination of both modalities seems viable. For combining the two modalities, various background studies were performed including the selection of a feasible fibre endoscope, light source and camera system. A new pull-back and flushing device was designed and created for realizing the synchronous image acquisition using the two modalities. For calibration of the system and definition of the pullback and imaging parameters, first tests on artificial phantoms were performed. Then vascular and tissue models were imaged in a combined pullback mode after using the flush for complete blood removal. Endoscopic images were acquired in a video mode. The analysis of the images was done subjectively. As expected, the OCT provided structural information of the wall. The endoscopic images in combination with pullback appear blurry in video mode. The flushing liquid hinders the automatic focusing of the camera. Thus, smaller details could not be identified but bifurcations were visible. Even though the results were not good as expected, the study showed the potential of a bimodal system and addressed the issues faced in the initial implementation.

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.

An approach to improve chemotherapy, while minimizing side effects, is a local drug release close to the tumorous tissue. For this purpose, the active drug component is often bound to nanoparticles employed as drug carriers. In the present study, we investigate sonosensitive, biocompatible poly-(L)-lactic acid (PLA) nanoparticles, which shall be used as drug carriers. For drug release, High Intensity Focused Ultrasound (HIFU) will be employed to introduce inertial cavitation, which separates the active drug component from the drug carrier. The cavitation effect generates an acoustic noise signal, which characterizes the cavitation activity and is expected to serve simultaneously as an indicator for the release of the active drug component. Depending on the ultrasound frequency, different acoustic levels of the inertial cavitation activity were measured. Investigations using a setup for passive cavitation detection (PCD) deliver quantitative results regarding the frequency dependence of the cavitation activity level of nanoparticles and reference media.

Magnetic Drug Targeting (MDT) is a cancer treatment technique that enables a local chemotherapy. In MDT, chemotherapeutic drugs are bound to magnetic nanoparticles and are accumulated in the tumor area by means of an external magnetic field. Unfortunately, a single magnet can only generate a pulling magnetic force. However, in some applications a pushing force on the nanoparticles could be advantageous. One way to realize pushing forces is to exploit the acoustic radiation force based on the nonlinearity of sound propagation in fluid media generated by a high intensity focused ultrasonic transducer. In this context, we built a test setup was built to investigate the utility of High Intensity Focused Ultrasound (HIFU) to generate a pushing force on the magnetic nanoparticles. The results show that the acoustic radiation force can be employed for particle guidance to achieve concentration differences similar to those obtained by using an electromagnet.

In this research computer tomography (CT) iterative reconstruction (IR) algorithms are investigated, specifically the impact of their statistical and model-based strength on image quality in low-dose lung screening CT protocols in comparison to filtered back projection (FBP). It has been probed whether statistical, model-based IR in conjunction with low-dose, and ultra-low-dose protocols are suitable for lungcancer screening. To this end, artificial lung nodules shaped as spheres and spicules made from material with calibrated Hounsfield units (HU) were attached on marked positions in the lung structure of an anthropomorphic phantom. Nodule positions were selected by distinguished radiologists. The phantom with nodules was scanned on a CT Scanner using standard high contrast (SHC), low-dose (LD) and ultra low-dose (ULD) protocol. For reconstruction FBP and the IR algorithm ADMIRE at three different strength levels were used. Volume CT dose index (CTDIvol) and dose-length product were recorded. Radiologists assessed subjective image quality using a six-point Likert scale by reading all image series in terms detectability of lung nodules. As a measurable objective image quality parameter signal-to-noise ratios (SNR) were investigated. The CTDIvol decreases by more than 70% for all protocols and nodules compared to diagnostic reference value for chest CT (p<0.00001). The evaluation of image quality parameters, i.e. SNR, indicates that LD and ULD protocols in conjunction with IR assert high quality lung-nodule detection. The results reveal that IR algorithm with moderate to high strength is an indispensable alternative to FBP in low-dose scanning, thus, potentially suitable for lung-tumour screening.

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.

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.

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.

Due to globalization and the quick development of technology, each government aims to ensure the safety and performance of products brought to their markets to protect its population. The peoples’ health state is of great significance and influenced easily by the quality of medical products. Therefore governments enact laws, directives and regulations to assure that quality. Nevertheless, these regulations can impede innovation and create trade barriers which result in an adverse effect on national economies. Where in some states no regulatory system is installed, others have highly sophisticated registration requirements that must be met. These diversities result in a challenge especially for small and medium sized companies, whose resources are often limited. [1] Manufacturers must control these diverse regulatory requirements by analyzing each market. Therefore an efficient procedure of registration should be defined that streamlines different registration requirements and ensures regulatory compliance. Next to regulatory authorities describing these requirements also harmonization groups play an important role in the design of the global regulatory landscape. Therefore also the most important harmonization groups and their current activities were investigated. The analysis showed that the impact of harmonization groups can be identified easily since new defined or updated regulatory requirements are oriented on their guideline. Still the harmonization of regulatory requirements in the medical device sector is not sufficiently enhanced. Thus the confrontation with each national regulatory system is inevitable.

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, CO 2 cools 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.

In Medical Training Therapy (MTT), the precise execution of the training exercises is of decisive importance for the success of the therapy. Currently, a therapist has to treat up to 15 patients simultaneously on an outpatient basis. We propose, an assistance system, can evaluate both quantity and quality of the movement performed using a target-oriented model and give recommendations for action directly to the patient by means of feedback. An avatar in traffic light colours signals in which body region an error has occurred. The individualisation of the underlying three-dimensional avatar increases the willingness of the patients to participate in the exercises without the supervision of therapist. The monitored error frequency was decreased by 50% by the assistance system.