Volume 4, Issue 1

Different complex physiological functions might be restored by means of distributed active implants. Wireless communication between the implants, on the one hand, and an external control unit, on the other hand, is necessary to synchronize electrical stimulation of neural and muscular tissue. Seventeen project partners from industries, universities, healthcare providers and research organizations closely cooperate in the framework of the BMBF Innovation Cluster “Interactive Implants (INTAKT)”. The goal of this cluster is to develop and evaluate networks of distributed implants. Challenges of the project include complex interaction between humans and technology, wireless power supply, long-term stability of implants as well as secure and safe signal transmission [1].

Tinnitus is a phantom sound perceived only by the affected person. Although the causes for tinnitus may be very diverse (e.g. hearing loss, cardiovascular diseases, diabetes, Meniere’s disease, otosclerosis), they all lead to pathological activation of the auditory pathway. Cochlear implants are electronic inner ear prostheses used to restore the hearing abilities of hard of hearing people. It has been noticed that the cochlear implants not only enable hearing but also reduce tinnitus that usually accompanies deafness and hearing loss. One of the likely mechanisms behind the latter phenomena is thought to be the unknown properties of electrical stimulus. This project was designed as a proof of concept for a device, which would be sending the tinnitus-suppressing electrical signal. To achieve this, the project was split into a preclinical part using experimental animals (guinea pigs) and a clinical trial part with tinnitus patients. In the preclinical part, together with Inomed Medizintechnik GmbH, we are testing the physical design and biocompatibility of anti-tinnitus implant. In the clinical part of the project, we use an electrical stimulation in the ear canal, through the eardrum (tinnitus patients), or via cochlear implant in a sample of cochlear implant patients (pre- and post-implantation). We ask the patients to mark the loudness of their tinnitus on a visual scale from 1 to 10 before, during and after routine electrical stimulation and quality of the tinnitus The results obtained during our preclinical and clinical testing as well as future plans will be presented and discussed.

Gastrointestinal (GI) motility disorders are frequent and clinically significant conditions with impairment of patient’s quality of life. Examples range from upper GI symptoms such as dysphagia and gastroparesis to lower GI manifestations, namely chronic-intestinal pseudo obstruction, diarrhea and constipation. Furthermore, postoperative motility disorders are common. Currently, available pharmacological or dietetic treatment options are limited. Since GI motility is based on myoelectric activity, electrical stimulation (ES) is a promising alternative. Numerous studies have demonstrated suitable pacing strategies and parameters in different GI segments. However, results of multilocular ES are rare. We report the first experimental study to evaluate ES of five GI parts in a porcine model. Multi-channel electromyography (EMG) recordings of gastrointestinal baseline and poststimulatory electrical activity were realized together with video-based marker tracking (VBMT). ES provoked visible GI contractions and appeared to modulate frequencies of slow waves and spikes. Further investigations are needed for analysis of locoregional and cross-organ effects of ES on the GI tract.

The use of intelligent implants and prostheses offers significant advances for optimizing medical treatment methods and is combined with an increasing technological modification of human body. This raises many exciting questions concerning law, ethics and social implications: Does the use of these techniques stay in line with our legal system and if yes, can the technical use be limited by governmental restrictions under certain conditions? Have moral values to be incorporated into technical artifacts? If machines are recreated from human beings, do they have to be provided with a legal subjectivity? Medical devices must be compatible with a high level of protection of health and safety. Therefore challenges, which are consequences of the indeterminate behaviour and the autonomous learning abilities of artificial intelligence, have to be faced. For avoidance of any hazards for legally protected rights medical product manufacturers have to assume legal duties, which affect construction, instruction and product development. For medical professionals there are also liabilities of maintenance measures and technical control that have to be accomplished. Associated with the use of intelligent medical devices is the processing of personal data on health. Health data have a high potential for misuse and discrimination and therefore they’re in need of special protection, particularly with regard to the development of “Big Data”, “Ubiquitous computing”, “Internet of Things” and constantly increasing cybercrime. If damages are suffered from the use of intelligent medical devices, difficulties in determining infringing acts, causality and culpability occur, especially because of the missing view into the technical progress of decision-making. It has to be explored, if the current liability law is able to assign responsibility adequately, otherwise there has to be found an appropriate concept for liability.

In the past, different training scenarios have been developed and implemented on robotic research platforms, but no systematic analysis and comparison have been done so far. This paper deals with the comparison of an isokinematic (motion with constant velocity) and an isotonic (motion against constant weight) training algorithm. Both algorithms are designed for a robotic research platform consisting of a 3D force plate and a high payload industrial robot, which allows leg extension training with arbitrary six-dimensional motion trajectories. In the isokinematic as well as the isotonic training algorithm, individual paths are defined i n C artesian s pace by sufficient s upport p oses. I n t he i sotonic t raining s cenario, the trajectory is adapted to the measured force as the robot should only move along the trajectory as long as the force applied by the user exceeds a minimum threshold. In the isotonic training scenario however, the robot’s acceleration is a function of the force applied by the user. To validate these findings, a simulative experiment with a simple linear trajectory is performed. For this purpose, the same force path is applied in both training scenarios. The results illustrate that the algorithms differ in the force dependent trajectory adaption.

The continuous positive airway pressure (CPAP) therapy is the gold standard to treat the obstructive sleep apnoea syndrome. This continuous pressure splints the upper respiratory tracts and prevents a collapse of the pharynx. If not being treated a collapse of the upper respiratory tracts reduces the blood oxygen concentration and increases the CO2 concentration leading to repeated sleep disruptions. Many CPAP-devices cannot maintain the reference pressure, which can lead to an uncomfortable perception for the patient. To reduce the pressure deviation in the mask we want to apply the Iterative Learning Control (ILC) method, because the breathing of the patient is a repetitive process - and at night the breathing patterns are even and recurring from breath to breath.

The segmentation and registration of structures are gaining importance due to the increasing demand of automated image enhancement and understanding. Especially in medicine and life science, assistance systems could have a large impact on diagnosis, treatment and quality control. Dye driven procedures, such as fluorescence imaging with Indocyanine green (ICG), are nowadays indispensable because they enhance contrast, reveal structures and deliver the operator with important information. The contact free ICG angiography is providing the surgeon spatial and temporal information on blood flow within a vessel. The processing of those information is done manually or semi automated but is very helpful for the surgeon. Extending the degree of automatism, the amount of information processed and even augment or transfer it into another domain could deliver the operator useful support and improve surgical work flow. Using, analyzing and transferring those information from ICG-IR domain into the RGB domain is the focus of this project. We are introducing a vessel registration method in the RGB domain driven by the spatial fluorescence behavior of the vessel in the ICG-IR domain. The method includes Superpixel based segmentation of the vessel in the ICG-IR domain, the spatial gradient based transfer and registration in the RGB domain and the continuous segmentation of the vessel in a RGB video. This paper show a proof of concept of the method. The results show an successful inter domain information transfer and registration of the vessel. Further tracking of the vessel over all frames is possible. Nevertheless limitations are revealed and discussed.

The success of aneurysm surgery depends on complete clipping of the aneurysmal sacculation without compromising quality of cerebral perfusion of vessels concerned. An established intraoperative method to visualize cerebral blood flow i n a pparent v essels i s fl uorescence vi deo angiography based on indocyanine green (ICG). However, major disadvantages of indocyanine green video angiography (ICG VA) are the need of a specialized imaging system, potential drug side effects as well as the limited number of repetitions due to long decay time of ICG in blood circulation. In particular the last drawback prevents brain parenchymal perfusion monitoring with ICG VA. The application of time-resolved thermography as a fast, contactless, noninvasive, marker-free and harmless imaging tool became a promising approach for perfusion imaging and thus offers several advantages compared to ICG. Measurements of deep structures in heat traps for identification of i nternal patterns, e ssential f or e .g. s uccess monitoring of aneurysm clipping, are still unsolved challenges of thermography. This work reveals as a proof of concept that the combination of thermography and an intravenous cold saline bolus injection as a contrast agent is capable to detect arterial and parenchymal perfusion located in the surgical cavity during aneurysm surgery in comparison to state-of-the-art ICG VA. The investigations provide evidence that thermography has the capability to perform intraoperative imaging of cerebral perfusion at an advanced stage in surgery for vessels and parenchyma located both cortically and in the surgical cavity.

In extracorporeal blood circulation intensive care treatments, the occurrence of gas within the circulation is one known major hazard. This gas volume can cause severe harm to the patient like infarctions. Consequently, within risk assessment for these treatments gas bubbles are usually addressed by either constructive or signal based approaches. All signal-based approaches do have in common that they need a sufficient amount of data to be parameterized. These data can only be acquired in animal trials or laboratory experiments, as they could result in harm to patients. Hence, we designed a mock loop, which is automatically able to create annotated data of gas bubbles injected into an extracorporeal circulation. We were able to run this setup with a periodicity of 15 seconds, which results in 240 annotated measurements per hour. For the evaluation, we created 1095 bubbles of varying sizes (0.3 to 0.5 ml). The elaborated setup enables us to produce a great amount of annotated data, which is shown to be comparable to manually generated data in a convenient and fully automated manner.

Minimally invasive procedures are more and more becoming the standard treatment for many surgical procedures such as the treatment of cerebral aneurysms. In an endovascular procedure the aneurysm is filled with flexible platinum coils leading to embolization and blocking the blood flow in the aneurysm. This established treatment needs high skills and experience on the surgeon. In order to practice and plan a specific procedure or test a new device, a realistic simulation environment is needed. Modern 3D printing technology allows the fabrication of patient specific models incorporating the exact geometry of the pathological anatomy. This article describes the development of a low-cost physiological simulation system for the training of the endovascular treatment of aneurysms. In order to practice the procedure in a realistic scenario, a 3D printed model of the aneurysm is embedded in a fluidic simulation s ystem. In addition to the patient-specific anatomy of the aneurysm a pulsatile water flow is generated, which emulates the influence of blood flow on the behaviour of catheters and coils during deployment. The system consist of a controllable pump circuit generating a pulsatile flow which can be regulated automatically and additionally controlled externally by the user. For a suitable representation, a display which graphically represents the sensor data and settings is employed. The components were compactly integrated in a small case allowing for easy deployment in training workshops. The simulation setup was successfully tested in prospective patient specific treatment planning and workshops for students.

Due to its advantages like minimal trauma and a low risk of infections, the minimally invasive surgery (MIS) has become the standard operation technique for many surgical procedures. During this type of intervention, one of the main tasks from a technical point of view is the control of the pressure in the operation area in order to give the surgeon sufficient space to perform his actions. Because no invasive measurements are available, an extended Kalman filter incorporating the peristaltic behavior of the used medical device was developed to estimate the pressure in the operation area. This contribution focuses on the observer design while a separately designed PI controller using loop shaping was employed for validation. The proposed observer-based control structure was tested with a simulator deploying the principle of physical equivalence.

The achievement of a low priming volume of the components in an extracorporeal perfusion system for neonatal and pediatric patients is an open research question. This paper presents a concept of a pump-oxygenator in which an oxygenator and a pulsatile blood pump are combined in one housing. For operation of the pump-oxygenator, a special actuating system for the pump process was designed. It consists of a piston pump which is directly coupled with a voice coil actuator (VCA). A servo positioning system was developed to assure the piston motion according to predefined reference trajectories. First experimental results indicate the feasibility of driving this blood pump with a VCA. In an in-vitro study, the pump produced mean flow rates of 60-900 mL/min with stroke frequencies in the range of 60-240 beats per minute.

The routine clinical use of diagnostic ultrasound (US) has spread considerably worldwide in recent decades. This is due in large part to the availability of US probes that enable a wide range of clinical applications as well as provide performance benefits arising from technological improvements. This paper describes the current commercially available US probe types, lists some of their clinical applications and briefly explains the technologies that are responsible for recent enhancements in image quality and ergonomics. Our intention is to summarize information that will allow healthcare professionals to select the appropriate probe for the intended use and the desired performance-price ratio.

An in silico investigation of modelled Extracorporeal Life Support (ECLS) via a femoral arterial cannula revealed the existence of both a defined separation zone between the opposing flows (ECLS, native flow) and different ranges dependent on flow distribution. The interaction between pulsating native circulation and constant ECLS flow is dynamic. A transient simulation model was developed to investigate the dynamic influence on this fluid mechanical interaction. The in silico model is based on a CT-generated 3D model derived from a life-sized silicon aorta. A geometric standard cannula (16Fr) is inserted femoral. Inlet boundary conditions such as the temporal flow profile of a subject from the left ventricle (native circulation) and the flow from the femoral cannula are varied such that during transient simulations the summed flow (total perfusion) is 5.5 l/min. The outlet pressure boundary conditions at the branching arteries are selected such as to model the downstream vascular system. Transient simulations revealed the dynamic effects of different flow fractions (Heart - ECLS) on the flow. Stationary simulations show a separation zone between the two flows, the position of which respectively the ECLSrange, oscillates dependent of the native circulation. Furthermore, it was noted that a raised pulse was impedimental to ECLS. This can be partly compensated by increasing the length of cannula inserted. At the same time the ECLS supply for the brain can improve at the cost of performance post-bifurcation. Increasing the ECLS fraction to above 50% flow led to retrograde flow combined with blood suction from the femoral artery. The EMPAC project model has been further developed to include investigation of the dynamic effects of blood flow. This has made it possible for the first time to analyse in detail and evaluate the temporal effects of both opposing flows streams. A subsequent investigation explains whether aortic elasticity plays a significant role.

In Germany in 2016 17,085 patients received TAVI operations and 9,579 had conventional aortic valve surgery. The ‘Heart Team’ uses established scoring systems (EuroSCORE, STS, German AV Score) to evaluate operation risks and which technique to use. However, such risk grading fails to consider patient morphology and possible long-term behavior of the replacement valve chosen. Therefore, preoperative simulation of the dynamic loading on the valve leaflets after TAVR provides information vital for the selection of the appropriate aortic valve therapy - interventional versus conventional. Individual aorta used in this study was captured by MRI. Segmentation and data processing were done with Mimic In-novation Suite. The available biological aortic valves prostheses were reverse engineered to create a 3D CAD model. Simulations combined bi-directional fluid structure interaction (FSI) with a first order Ogden model of the hyperelastic behavior of aortic leaflets from bovine pericardium. Movements induced by flow and the resultant tension on the biological leaflets were computed with developed simulation model. Stress analyses of the leaflets showed behavior attributable to their particular structure. Both valves showed two stress peaks within the initial 0.3 s. Maximum stress occurred, however, at other time points. Furthermore, the initial increase in stress showed a delayed onset. The patterns of movement were also significantly different. So, at opening of the valve, the freely perfused area of the valve, the freedom of leaflet movement and symmetry at closure were different in the two valves. Simulated movement of valve leaflets corresponds well with reality. The estimated stresses clearly lie below thresholds published in the literature for bovine pericardium. It is planned to further develop the current workflow to increase stability and optimize processing time, with the intention of providing the ‘Heart Team’ with a tool for incorporating individual anatomy when selecting the aortic valves.

In orthopedic hand surgeries C-arms are the standard imaging modalities for procedure and tool guidance. However, the currently used systems have a large footprint and high weight, which can lead to workspace restrictions and difficult positioning of the device at the desired imaging position. The aim of this paper is to present a prototype of a new, flexible, lightweight and small footprint X-ray system, which is capable to create 2D projection images from different orientations. The new design includes a miniaturized Xray tube covered in a custom-made case mounted on a flexible holding arm attached to the standard OR table rail. With that, fast positioning and fixation for the subsequent image acquisition is achieved. A flat panel detector is placed in an adjustable metal sheet construction below the table. For safety aspects an overlay of the X-ray cone beam with an integrated light source visualizes the irradiation area. The acquired images are visualized on a 2-in-1 netbook. A foot pedal initiates the imaging process. A prototype of the free movable miniaturized X-ray system FlexScan was build. Workspace restriction, usability and general imaging needs were simulated and tested. FlexScan has the potential to improve X-ray guided interventions on extremities especially for small private surgery centers. It fulfills the general imaging needs and is capable of producing 2D projection images from different orientations within a small and lightweight setup.

Robotic surgeries are still limited with respect to the surgeon’s natural senses. The tactile sense is exceptional important in conventional clinical procedures. To identify critical structures inside the tissue, palpation is a commonly used technique in conventional open surgeries. The underlying organ or pathological structures conditions (healthy, abnormally hard or soft) can for example be localized and assessed through this process. Palpation needs a tactile sense; however, that is commonly not available or limited in robotic surgeries. The palpation need was already addressed by several research groups that integrated complex sensor-feedback-systems into prototype surgical instruments for robotic systems. We propose a new technique to acquire data of the tissue tool interaction of the surgical instruments. The structure borne transmission path is used to measure acoustic emission (AE) at the outpatient (proximal) end of the instruments with the help of different sensors attached to the surface of the surgical tool. Initial tests were performed using a microphone in combination with a stethoscope. This setup showed promising results and a more integrated prototype was subsequently designed. A piezoelectric charge accelerometer was used as vibration sensor and compared to a MEMS microphone. A signal acquisition system was developed to acquire signals from both sensors in parallel. The sensors were then attached onto the shaft of a daVinci Prograsp Forceps instrument. According to the surgery observation, a series of simulated experiments was conducted. The tip of the grasper was swiped manually over a human subject’s dorsal and palmar hand side, lateral side of neck and over the carotid artery. Additionally, contact with soft tissue and other instruments were evaluated since these are events of interest during surgery. Advanced signal processing techniques allowed the identification and characterization of significant events such as palpation dynamics, contact and pulsation. Signals acquired by the MEMS microphone showed the most promising results. This approach will now be used to build a prototype for further evaluation in a clinical setup. The paper presents the first results that show that this novel technique can provide valuable information about the tool-tissue interaction in robotic surgery that typically can only be obtained through advanced distal sensor systems or actual human touch.

Pre-operative planning of valve-sparing aortic root reconstruction relies on the automatic discrimination of healthy and pathologically dilated aortic roots. The basis of this classification are features extracted from 3D ultrasound images. In previously published approaches, handcrafted features showed a limited classification accuracy. However, feature learning is insufficient due to the small data sets available for this specific problem. In this work, we propose transfer learning to use deep learning on these small data sets. For this purpose, we used the convolutional layers of the pretrained deep neural network VGG16 as a feature extractor. To simplify the problem, we only took two prominent horizontal slices throgh the aortic root, the coaptation plane and the commissure plane, into account by stitching the features of both images together and training a Random Forest classifier on the resulting feature vectors. We evaluated this method on a data set of 48 images (24 healthy, 24 dilated) using 10-fold cross validation. Using the deep learned features we could reach a classification accuracy of 84 %, which clearly outperformed the handcrafted features (71 % accuracy). Even though the VGG16 network was trained on RGB photos and for different classification tasks, the learned features are still relevant for ultrasound image analysis of aortic root pathology identification. Hence, transfer learning makes deep learning possible even on very small ultrasound data sets.

At present transoral laryngeal interventions are mainly observed and controlled by an external two dimensional direct microscopic view. This modality provides an overall view on the surgery situs in a straight line of sight. For treatment planning and appropriate documentation, an endoscopic inspection is mandatory prior to surgery. Nowadays a detailed endoscopic work-up of laryngeal lesions can be performed by contact endoscopy in combination with structure enhancement like Narrow Band Imaging. High resolution and magnification of up to 150 times provide detailed visualization of vascular structures and pathological changes of the tissue surface. In these procedures it is difficult however to localize the evaluated areas on large scale scenes like the microscopic view used for surgery. To provide a fast and easy image matching an automated vessel pattern recognition and allocation is presented. Endoscopic images depicting representative vessel structures of the vocal folds are selected out of contact endoscopy video scenes. These images are pre-processed for background homogenization. A Frangi Vessel Segmentation filter and morphological operations are used to extract the vessel structure and match it to the microscopic image. Using this method 4 detailed contact endoscopy images could be allocated in different scenes of the microscope video. This method can be used to simplify treatment planning and to prepare image data for documentation.

The development of new medicines against virus infections like the Marburg virus disease requires an accurate knowledge of the respective pathogens. Conventionally, this process is very time expensive. In cooperation with the Virology of the Philipps-University in Marburg an automatic tracking algorithm for subviral particles in fluorescence image sequences was developed and programmed. To expand the benefit for the pharmaceutical researchers, also the trackevaluations need to be widely automated. In this work, a new parameterizing-method facing the fractal dimensions of spline interpolated subviral particle tracks is presented and tested with simulated and real data. The results reveal a good potential to classify tracks and, thus, types of subviral particles in infected cells.

Magnetic particle imaging (MPI) is a novel tomographic imaging modality which uses static and dynamic magnetic fields to measure the magnetic response generated by superparamagnetic iron oxide nanoparticles (SPIONs). For the characterization of the SPIONs magnetic particle spectroscopy (MPS) is used. In the current research, a low noise amplifier (LNA) suitable for MPI and MPS is presented. LNA plays a significant role in the receive chain of MPI and MPS by amplifying the signals from the nanoparticles while keeping the noise induced through its own circuitry minimal. The LNA is based on the summing configuration and fabricated on a printed circuit board (PCB). Moreover, the prototyped LNA is compared with a commercially available pre-amplifier. The input voltage noise of the prototyped LNA with a receiving coil of series resistance of 0.551 mΩ and an inductance of 130 μH is 561 pV/ √ Hz with a noise figure (NF) of 11.57 dB.

Medical device innovations may contribute to the reconstruction of biological functions, and thereby improve the quality of patients’ lives, as well as extend their life expectancy. The coordinated research project “RESPONSE - Partnership for Innovation in Implant Technology” (BMBF program Twenty20 - Partnership for Innovation, 2014 - 2021) is focusing on the development of novel concepts for implantable medical devices for cardiovascular, ophthalmologic and otorhinolaryngologic applications. The joint research efforts of academia and industry in the RESPONSE consortium address the challenges in implant design, biofunctionalization, process development and production. Particular attention is paid to the process of translation of medical device innovations, cost analysis, as well as health technology assessment.

Electrospinning is a method for producing fibrous polymer scaffolds that can be applied in drug delivery systems as well as for polymer-based implants. Biodegradable polymers for the purpose of cardiac tissue engineering are often applied as fibrous scaffolds for morphological mimikry of natural matrices but also drugeluting approaches are very promising. Hydrolytic degradation is one of the key parameters for successful application. The focus of our investigations is on monitoring accelerated in vitro degradation of electrospun nonwoven scaffolds. In the presented study degradation of poly(Llactide) is accelerated by alkaline hydrolysis. The process is characterized by weight loss, loss of molecular mass, surface morphology and thermal behavior of nonwoven samples, showing a fast degradation of the fibrous material within two weeks.

In-stent thrombosis is a major complication of stent implantations. Unlike pathological occurrences as in-stent restenosis for instance, thrombosis represents an acute event associated with high mortality rates. Experiments show that low wall shear stress promotes undirected endothelial cell coverage of the vessel wall and therefore increases the risk of thrombus formation. Stent design represents a crucial factor influencing the surface areas of low wall shear stress and thus the incidence of acute in-stent thrombosis. In this study, we present an optimization method for stent designs with minimized thrombosis risk. A generic stent design was developed, based on five different stent design parameters. Optimization was conducted based on computational fluid dynamics analysis and the gradient-free Nelder-Mead approach. For each optimization step, a numerical fluid simulation was performed in a vessel with a reference vessel diameter of 2.70 mm with stent-overexpansion ratio of 1.0:1.1. For each numerical fluid simulation a physiological Reynolds number of 250, resulting in a mean velocity of 0.331 m/s at the inlet and a laminar flow as well as stiff vessel walls were assumed. The impact of different stent designs was analyzed based on the wall shear stress distribution. As a basis for the comparison of different stent designs, a dimensionless thrombosis risk number was calculated from the area of low wall shear stress and the overall stented area. The first two optimization steps already provide a decrease of thrombosis risk of approximately 83%. In conclusion, computational fluid dynamic analyses and optimization methods usind the Nelder-Mead approach represent a useful tool for the development of hemodynamically optimized stent designs with minimized thrombosis risk.

The weakened heart is supported by a left ventricular assist device (LVAD) to supply the heart muscle with oxygenated blood. In case the heart muscle recovers during LVAD therapy, the patient has to be weaned from the device. To date, there is no adequate method to detect heart muscle recovery in LVAD therapy. In order to establish a novel method based on the measurement of electric conductivity, this study presents a silicone model of a ventricle mock-up to simulate the electrical properties of cardiac muscle tissue. Previously, it has been shown that the electrical properties of myocardial tissue change during ischemia, so that these changes are a possible estimate for measuring the condition of myocardial tissue. To this purpose, this study presents a casting process for a ventricle model and describes the materials used to imitate the electrical properties of the heart muscle to obtain conductive material. Initial results showed that the higher the carbon concentration in the silicone, the higher the conductivity of the silicone samples. The measurements were performed at different frequencies and the samples were analyzed for homogenization.

The human heart is an organ of high complexity and hence, very challenging to simulate. To calculate the force developed by the human heart and therefore the tension of the muscle fibers, accurate models are necessary. The force generated by the cardiac muscle has physiologically imposed limits and depends on various characteristics such as the length, strain and the contraction velocity of the cardiomyocytes. Another characteristic is the activation time of each cardiomyocyte, which is a wave and not a static value for all cardiomyocytes. To simulate a physiologically correct excitation, the functionality of the cardiac simulation framework CardioMechanics was extended to incorporate inhomogeneous activation times. The functionality was then used to evaluate the effects of local activation times with two different tension models. The active stress generated by the cardiomyocytes was calculated by (i) an explicit function and (ii) an ode-based model. The results of the simulations showed that the maximum pressure in the left ventricle dropped by 2.3% for the DoubleHill model and by 5.3% for the Lumens model. In the right ventricle the simulations showed similar results. The maximum pressure in both the left and the right atrium increased using both models. Given that the simulation of the inhomogeneously activated cardiomyocytes increases the simulation time when used with the more precise Lumens model, the small drop in maximum pressure seems to be negligible in favor of a simpler simulation model.

To estimate the severity of airway abnormalities in cystic fibrosis (CF) Brody et al. developed a computed tomography (CT) scoring system. Each pulmonary lobe is analyzed separately considering various morphological defects. A study from Zhao et al. demonstrates that this CTbased score correlates with regional airway obstruction (RAO) measured by the real-time imaging method Electrical Impedance Tomography (EIT). Zhao et al. performed EIT measurements at the 5 th intercostal space (ICS) and median RAO, including both lungs, was correlated with the associated score. In the present feasibility study, it was investigated if RAO determined by EIT within the left and right lung respectively at the 3 rd and 5th ICS corresponds with the scores of the left and right lobes. EIT measurements and CT-based scoring were carried out on two CF patients. RAO was identified by ratios of impedance values associated to the maximal forced expiratory flow at 25% and 75% of the forced vital capacity. Mean RAO of each lung within both thorax sections was compared with the lobar scores. Airway abnormalities within upper lobes are assigned to RAO measured within the 3rd ICS, whereas abnormalities of the right middle lobe, both lower lobes and the lingula are mainly represented by EIT images of the 5 th ICS. Results show that differences in the CT-based score between the left and right lung concur with differences in EIT derived RAO. The regional information provided by EIT might be used for a more targeted therapy of CF-related lung diseases.

Gold-standards for biosignal acquisition require body-spanning sensor positioning which is contradictory to the high integration of modern wearable medical monitors. In applications where obtrusiveness can decrease accuracy, as in sleep monitoring, compact sensor configurations are not only a matter of convenience. To acquire respiratory signals, most systems rely on nasal cannula pressure sensors or inductance plethysmography. Another well-established method is the impedance pneumography, where we aim to contribute to the field of short distance electrode configurations. Evaluating distances down to 8 cm we report linear correlations above 0.85 with respect to a pneumotachometer reference. We estimate the respiratory rate with an error below 0.2 bpm. Inspiratory and expiratory phase detection is possible with an error below 2.5 %. Using a first order polynomial model we estimated the respiratory flow with a relative error of down to 19 % at 8 cm. We conclude that short distance impedance pneumography is feasible and rough flow and volume estimates are possible using linear models. Further research regarding shorter distances and calibration is of great interest.

In this work, Bioimpedance Spectroscopy (BIS) is used to study fluids and cell solutions. A n ew fourelectrode- terminal (4T) chamber using 3D printing and stainless steel corrosion resistant V4A was designed to measure the impedance of live cell solutions at the frequency range 0.1Hz- 1MHz. At f < 1kHz the double layer (DL) that builds at electrode’s surface raises the impedance substantially preventing the observation of the real impedance of the cells. The new 4T design circumvents the DL, is more robust and cheap, and allows for the repeatability of the results. Experiments were performed in vitro with two cell lines, L929 (mouse fibroblasts) and HaCaT (human keratinocytes). Results show that it is possible to distinguish between the two cell types by means of its BIS measurements in the new setup. Also, a low-frequency dispersion (α-dispersion) was observed in HaCaT cells solution, but not in L929. Furthermore, a potentiostat circuit model was developed in LTSpice to simulate the hardware setup and two different circuit models were used to fit cell’s data.

The open, cross-vendor interoperability of medical devices is an enabling technology for the implementation of context-aware biomedical systems in daily clinical routine. The surgical working environment is both a valuable field of application and a particular challenge. A design of context-aware medical technologies that shows intelligent behaviour and ensures safe operation is demanding; thus implementations are yet limited to prototypes and specific surgical use cases. Many open research questions need to be addressed to empower context-aware medical systems to be a relief and not a burden for the clinical user.

Light is an important factor for regulation of circadian, endocrine and metabolic processes in the human body. Through this light has a positive effect on cognition, on the stabilization of circadian rhythms and for general wellbeing. These effects are described as non-visual effects of light. Many dynamic lighting systems are already in use in workplaces and living spaces, aiming to address visual and also non-visual effects. In Europe and US the term “Human Centric Lighting” or abbreviated "HCL” was introduced, as a scientifically agreed concept on how to plan non-visual effects of artificial light in synergy with natural light. Older people, especially with neurological and psychological diseases can especially benefit from this lighting concept. However, in order to achieve the desired non-visual effects, certain conditions should be fulfilled. In Germany the DIN SPEC 67600 is a guideline for the design of biologically effective illumination, with examples for senior- and nursing homes. A goal of this evaluation was to check whether the recommendations of the specification DIN SPEC 67600 in three nursing homes were met and another goal was if effectiveness of the lighting on residents and nursing staff can be determined. Photometric measurements were taken and subjective perceived non-visual effects of light were surveyed using a questionnaire. Results: Although none of the three facilities met all the criteria of the DIN SPEC 67600 guidelines, non-visual lighting effects on residents and nursing staff could be detected. The results also indicate that careful attention should be paid on maintenance of HCL systems. The correct use of HCL solutions in homes for the elderly has opportunities to improve health status if the system is properly designed and maintained. Therefore next to the existing (non-visual) metrics and HCL design guidelines, guidelines for maintaining and regular inspections should be established.

We describe a holistic AAL concept for senior residences that is based on a large-area sensor floor. This system provides general home-automation functions such as light control, intrusion alarm and energy saving. However, advanced homecare features such as activity monitoring, fall detection and the discovery of changes in daily routines assist the resident and support the carer. After explaining the components and general working principle of the system, we describe how these applications are realized in practice. The focus lays on the unobtrusiveness, flexibility and multifunctionality of the solution.

Aiming at devices for bioelectronic medicine, this paper proposes a die embedding process for the fabrication of flexible smart implants. By combining thinned bare dies with a polymeric encapsulation, completely flexible implants can be designed. The dies are encapsulated using a flip-chip process and a backfilling with silicone rubber. A completely even surface without detectable edge between the chip and the surrounding polymer substrate is achieved by gluing the chips face-down onto a polyimide-covered substrate. The backside is coated with silicone rubber and a second carrier substrate is attached. Removing the first substrate subsequent to curing of the silicone leads to chips located under a continuous polyimide layer, enabling the use of microtechnology for further processing steps. A custom-made test chip is proposed that enables the evaluation of the mechanical and chemical stability of the system.

The presented investigation was designed to assess the biomechanical behavior of a 3D biomimicking self-expanding stent with respect to general technical parameters added by first clinical tests. The test sample was a Veryan Medical Biomimics 3D with 6.0 mm expanded diameter and 80 mm length. The profile of the delivery catheter with mounted stent, the strut thickness, the bending stiffness, the axial stiffness for tension and compression and the length change during expansion were measured. The bending stiffness was 2.73 Nmm², axial stiffness at tension 7.77 N/mm and at compression 97.61 N/mm. The stent shortened during expansion by 11.54 %. Radial force at 5 mm diameter was 2.54 N. Clinical experience provided no stent fractures after 24 months. Duplexsonography showed stent patency without any binary restenosis or intimal hyperplasia.

Three-dimensional (3D) printing has become a popular technique in many areas. One emerging field is the use of 3D printing for the development of 3D drug delivery systems (DDS) and drug-loaded medical devices. This article describes a novel concept for the fabrication of timecontrolled drug delivery systems based on stereolithography combined with inkjet printing. An inkjet printhead and an UV-LED light source have been integrated into an existing stereolithography system. Inkjet printing is used to selectively incorporate active pharmaceutical ingredients (API) during a stereolithographic 3D printing process. In an initial experimental study, poly (ethylene glycol) diacrylate (PEGDA) was used as polymer whereas 2-Hydroxy-4´-(2- hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) and Lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) were used as photoinitiators. Basic structures could be manufactured successfully by the new hybrid 3D printing system.

For the treatment of deafness or severe hearing loss cochlear implants (CI) are used to stimulate the auditory nerve of the inner ear. In order to produce an electrode array which is both atraumatic and reaches a perimodiolar final position a design featuring shape memory effect was proposed. A Nitinol wire with a diameter of 100 μm was integrated in a state of the art lateral wall electrode array. The wire serves as an actuator after it has been ‘trained’ to adopt the spiral shape of an average human cochlea. Three small diameter platinum-iridium wires (each 20 μm) were crimped to the Nitinol wire in order to produce thermal energy. An insertion test was pursued using a human temporal bone specimen. The prototype electrode array was cooled down by means of immersion in ice water and freeze spray to enable sufficient straightening. Thereafter, insertion into the cochlea through the round window as performed. Insertion was feasible but difficult as premature curling of the electrode occurred during the movement towards the inner ear while passing the middle ear cavity. Therefore, the insertion had to be performed faster than usual. The shape memory actuator was subsequently activated with 450mA current at 5V for 3 seconds. After insertion the specimen was embedded in epoxy resin, microgrinded and all histological slices were assessed for trauma. Perimodiolar position was achieved. No insertion trauma was observed and there were no indications of thermal damage caused by the electrical heating. To the best of our knowledge, this is the first histological evaluation of the insertion trauma caused by an electrically activated shape memory electrode array. These promising results support further research on shape memory CI electrode arrays.

Venous ulcers of the lower limbs are one clinical manifestation of chronic venous insufficiency. Currently, there is no venous valve prosthesis available. This study presents novel venous valve prostheses made of threedimensional electrospun fibrous nonwoven leaflets. The aim of this study was to prove the feasibility of the manufacturing process as well as to investigate design features of the venous valve prostheses from a hemodynamic point of view. An adapted pulse duplicator system (ViVitrolabs, Victoria, BC, CA) was used for characterization of the hydrodynamic performance. For eight different venous valve prototypes flow rate, effective orifice area and regurgitation fraction was investigated in vitro. In particular, tricusp valve designs showed an up to 40% higher effective orifice area as well as 15% higher maximum flowrate compared to bicusp valve designs. However, the regurgitation fraction of the bicusp valve designs is up to 86% lower compared to tricusp valve. Additionally, the hemodynamic performance of the tricuspid valves showed a high sensitivity regarding the leaflet length. Bicuspid valves are less sensitive to changes of design parameters, more sufficient and therefore highly reliable.

Many patients in radiotherapy carry active implantable medical devices (AIMDs) such as pacemakers or cardioverter defibrillators (ICDs). The influence of the ionizing radiation can lead to failures in the device function. This study presents a tissue-equivalent test environment to investigate the influence of ionizing radiation on AIMDs. The in-vitro test environment is designed to simulate a human torso. Structures such as the heart, lungs, ribs, spinal column and soft tissue are replicated from tissue-equivalent materials to allow realistic treatment planning and to simulate the effect of ionizing radiation on active implants. CT measurements and Monte-Carlo validations have shown that Polytetrafluorethylen (bone), carrageenan (heart), Styrodur (lung) and Biresin ® G27 (soft tissue) fulfill all requirements for suitable tissue surrogates. A plug-in unit integrated in the test environment has been designed specifically to allow the placement AIMDs in the phantom at typical positions for implant placement in humans. The dosimetry validation showed that the test environment is applicable in the full treatment planning process.

Due to the increasing number and the complexity of devices in the operation room (OR), which are caused by the diversity and variety of proprietary interface designs, the probability for use errors increases. In order to ensure a safe intraoperative workflow in the OR, integrated OR systems with central work stations have been developed. For this, there also exist concepts for handhelds, which offer touchbased graphical user interfaces (GUI). However, those come along with various limitations, e.g. possibility for one-handed interaction, which is influenced i.a. by the size, the design and the working task. Within our investigations, requirements for an enhanced concept have been gathered by taking into account corresponding standards regarding ergonomics, riskmanagement and usability-engineering. According to DIN EN 60601-2-46, machinery directive 2006/42 EG and guideline VDI/VDE 3850, the stipulated user interface has been designed in order to preselect functions on the touchscreen and their subsequent activation by physical buttons. Furthermore, the accessibility of areas of interest has been considered on the touchscreen, to avoid the re-gripping of the handheld. As a first step, the OR-table control for a tablet has been realized with Microsoft Blend, using a 22’ touch monitor. The usability study has been conducted in accordance with DIN EN ISO 9241-11 and IEC 62366. A group of ten surgeons and OR nurses underwent multiple tasks in the framework of a usability test, comparing the developed concept with a common keypad handheld. The study showed comparable results concerning the usability criteria effectiveness and efficiency. However, the concept clearly outperforms the handheld regarding user satisfaction, in particular due to the higher learnability and the easy transfer of daily-used GUI skills. The current approach motivates to develop a functional model of a touch-based handheld for OR-tables as well as with further integrated OR devices and to conduct additional usability studies.

Paramedics perform physically demanding tasks during patient transport in daily routine and therefore suffer more often from musculoskeletal ailments, mainly low back pain, than any other profession. We hypothesise, that current transport aids do not offer sufficient support when it comes to obstacles and stairs during patient transport. Therefore we conducted an Ovako Working Posture Analysing System (OWAS) field study to capture postural workloads during patient transport and connected the results to a survey among paramedics about occurring obstacles. The results of the OWAS analysis showed strenuous working conditions during barrier-free transport with classical transport aids, like stretcher and stretcher chair, but enormous postural workloads when barriers occurred. Our survey revealed, that stairs occurred in 38 %, and at least one barrier, like narrow passages, curbs, etc., in 48.1 % of all deployments (n=405), we can quantitatively link postural workloads with occurring obstacles. In conclusion, there is a high demand for ergonomic improvements of current transport aids and a high potential of active assist devices to reduce harmful loads on paramedics.

Robotic assistance in clinical interventions provides high precision and performance. However, the acceptance of such systems is still very low. The idea of collaborative robotics promises practical solutions for this problem. To further promote these ideas in the medical domain, novel concepts for user interactions are needed. This work presents a preliminary study on the recognition accuracy of touch gesture interaction with a KUKA LBR iiwa robotic arm. A recognition application utilising a set of 4 different touch gestures was implemented and evaluated by eight participants. The overall recognition accuracy of the system is 89.8%.

Our work focuses on enhancing the illumination optics of a rigid medical endoscope using optomechanical simulation. We aim on improving the efficiency of the illumination optics to provide more light in the surgeon’s field of view (FOV) and therefore better image quality. We conducted an extensive market analysis and measured several rigid endoscopes and their external light sources in the lighting technology laboratory. Surprisingly, all endoscopes showed a degree of efficiency below 20 %. Our optimization approach is based first on a photometric and colorimetric analysis carried out with an integrating sphere and a goniophotometer. Secondly, the results obtained are implemented in a 3Doptomechanical simulation model developed with the raytracing software LightTools (Synopsis©). In the simulation model both the geometrical components as well as the critical interfaces are examined considering light coupling at boundary surfaces and light transfer within the illumination optics. Moreover, the optimization takes into account spectral power distribution (SPD) and angular light distribution (ALD) of the light provided from the fiberoptic cable connected to an external light source as well as additional interfering factors like gluing, dispersive absorption and total reflection at critical angles.

Computer applications in medicine are very important. However, there are differences in quality of such software, which periodically led to discussions about safety, regulation, and registration of software applications. Today, the admission procedure of medical products is highly regulated, and this applies also for mobile medical apps. The clinical evaluation is one important aspect of the admission procedure, especially due to the latest regulatory changes of the guideline MedDev 2.7/1 revision 4. The requirements have increased, and uncertainty grows in medical app development companies. The aim of this paper was the development of a process orientated guide, that gives an overview of the needed steps of a clinical evaluation of mobile medical apps and that could help to give a rough estimation about the necessary effort. The guide was developed, based on the relevant literature and legal texts. The clinical evaluation can be conducted in five substeps: “Planning and Scoping”, “Literature Research”, “Literature Assessment”, “Clinical Data Analysis” and “Reporting”. Prospectively, this guide will be evaluated by developers and adjusted, as soon as Medical Device Regulation is legally binding.

The purpose of this work was to evaluate the decontamination potential of the Potok system both in an experimental setting in a research Operating Room (OR) with standalone Air Decontamination Units (Potok 150-M-01) and in a clinical setting in a real operating theatre in Moscow. Our experiments showed an impact of the Potok units on the bacterial contamination of the room air according to the Swedish SIS-TS 39:2015 standard. For the initial measurements in our research OR in Weiden this could be shown by a decrease of the bacterial burden at all three different measurement points (OR table, instrumentation tray, periphery). Also the subsequently done measurements in the Moscow hospital verified this decontaminating effectivity of the Potok system. In this case the initial background contamination of the operating theatre was higher than in the research OR in Germany. This bacterial burden could be effectively decreased by the use of the installed Potok based ventilation system.

The porosity of surgical meshes makes them flexible for large elastic deformation and establishes the healing conditions of good tissue in growth. The biomechanic modeling of orthotropic and compressible materials requires new materials models and simulstaneoaus fit of deformation in the load direction as well as trannsversely to to load. This nonlinear modeling can be achieved by an optical deformation measurement. At the same time the full field deformation measurement allows the dermination of the change of porosity with deformation. Also the socalled effective porosity, which has been defined to asses the tisssue interatcion with the mesh implants, can be determined from the global deformation of the surgical meshes.

For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses have more recently become the lifesaving solution for elderly patients with high operational risk and thus, are often implanted in patients with challenging aortic root configuration. A correct prosthesis deployment and stent adaption to the target region is essential to ensure optimal leaflet performance and long-term prosthesis function. The objective of this study was the development of a suitable in silico setup for structural numerical simulation of a transcatheter aortic valve (TAV) in different cases of clinical relevance. A transcatheter valve prosthesis comprising an unpressurized trileaflet heart valve and an adapted stent configuration was designed. An aortic root (AR) model was developed, based on microcomputed tomography of a native healthy specimen. Using the finite-element analysis (FEA), various loading cases including prosthesis biomechanics with valve opening and closing under physiological pressure ratios throughout a cardiac cycle, prosthesis crimping as well as crimping and release into the developed AR model were simulated. Hyperelastic constitutive law for polymeric leaflet material and superelasticity of shape memory alloys for the self-expanding Nitinol stent structure were implemented into the FEA setup. Calculated performance of the valve including the stent structure demonstrated enhanced leaflet opening and closing as a result of stent deformation and redirected loading. Crimping and subsequent release into the AR model as well as the stent adaption to the target region after expansion proved the suitability of the TAV design for percutaneous application. FEA represented a useful tool for numerical simulation of an entire minimally invasive heart valve prosthesis in relevant clinical scenarios.

Cavitation is a major fracture mechanism in extracorporeal shock wave lithotripsy (ESWL). However, it can cause tissue trauma and its effects on kidney stones and surrounding tissue are not fully understood. Therefore experimental setups enabling systematic parameter studies are crucial. We developed and evaluated a testing rig comprising three measuring methods in order to examine this mechanism. Our initial evaluation of this setup based on standard components showed promising results. Primary cavitation was displayed by high-speed photography 195 μs after the shock front had passed the focal zone. The effect of different pulse repetition rates (30, 60, 90, 120 SW/min) on the extension of the cavitation area was determined. The lifetime of secondary cavitation was analysed by B-mode ultrasound imaging. In a post processing progress the images showing bubbles were compared to a reference picture for both types of cavitation and the number of pixels that changed colour was counted. Furthermore stone comminution at different pulse repetition rates (30, 60, 90, 120 SW/min) was investigated by fixed-dose fragmentation. We observed an inverse correlation of cavitation and fragmentation. As the pulse repetition rate increases, the area of primary cavitation grows whereas the fragmentation efficiency decreases. B-mode imaging showed that secondary cavitation bubbles persisted between the shocks and can serve as nuclei. The higher the pulse repetition rate is, the more of these nuclei remain and thus facilitate formation of primary cavitation. The experimental setup provides reproducible results regarding the development of primary and secondary cavitation on the one hand and the fragmentation of phantom stones on the other hand. Therefore it can be utilized to further investigate the effect of different boundary conditions and shock wave parameters on cavitation and stone comminution. The impact of different focal sound fields is subject of ongoing research.

The assessment of hydrodynamic performance of transcatheter aortic valve prostheses in vitro is essential for the develosepment and approval of novel devices. Therefore, this study aims to investigate the correlation of target implantation depth and paravalvular regurgitation in a controlled in vitro test situation. We designed a test setup with retrograde steady flow conditions measuring paravalvular regurgitation as a function of increasing pressure on the closed valve ranging from 0 mmHg to 200 mmHg. Our future aim is to benchmark different valve prosthesis designs and describe the correlation between target implantation depth, paravalvular regurgitation and prosthesis design aspects. The current study describes the developed test setup, validation experiments as well as first results for a selfexpanding valve prosthesis. The highest regurgitation was measured at an implantation depth of 2 mm. In fact, regurgitation increases from 26.1 ± 8.2 ml/min at 0 mmHg to 1,490.7 ± 182.7 ml/min at 160 mmHg. The slightest regurgitation, however, was measured for an implantation depth of 6 mm ranging from 2.2 ± 0.6 ml/min at 0 mmHg to 605.8 ± 18.9 ml/min at 200 mmHg.

Stroke is one of the most frequent diseases among the elderly and often leads to an ongoing failure of functions in the central nervous system. Due to the plasticity of the brain affected may regain lost motor function by repetitive training. Robotic devices can be an approach to accelerate the rehabilitation process by maximizing patients’ training intensity. End-effector based robotic systems are particularly suitable for this purpose and often an advantage over exoskeletons since the proximal part of the upper limb remains under the control of the patient. Furthermore, the integration of the assistas- needed principle (AAN) into these devices enables individualized, adaptable robotic support to patients during therapy. In this study an end-effector based robotic rehabilitation device based on the Robot Operating System (ROS) framework is introduced. The system allows patients to perform 3- dimensional movements without a therapist’s assistance. With regard to the AAN, focus was based on impedance control and an additional real-time adaption of the impedance control parameters by using a feedback loop. 10 healthy subjects took part in this study to evaluate the overall concept with regard to usability and quality of the supported movement. Hence, the three most promising adaption models of AAN (without adaption, adaption according to position and time, adaption according to velocity) under three different levels of movement support (0%, 50%, 100%) were investigated by administering a self-designed questionnaire and the robot kinematics. The results showed no significant differences between the three different adaption models of AAN. However, the subjective assessment of the movements was in keeping with robot kinematics and the control approaches as well as the overall system have experienced remarkable support.

This research aimed to study the efficacy of a novel implant for osteoarthritic knees. This implant is designed to eliminate excessive loads through the knee and to provide suitable conditions for possible tibiofemoral cartilage regeneration. The implant was designed for the medial side of the knee joint. Finite Element Analysis (FEA) was performed for an extended knee position of the knee joint. Contact pressure distributions on the medial and lateral compartments were investigated as well as stress distributions throughout the implant’s plates. Results with and without the implant were compared, and it was seen that the contact pressures on the surface of the distal femur were reduced by more than 90% after the introduction of the implant.

Implant design in total knee arthroplasty is a key factor for the recovery of function and mobility of the joint. However, there is a lack of knowledge on the complex relationship between design features and the biomechanical situation. The posterior inclination of the tibial plateau (tibial slope) has a known functional impact on knee joint kinematics. In the native knee it shows high inter-individual differences, which is inadequately considered in total knee arthroplasty. We investigated the effects of the separate and combined variation of the medial and lateral tibial slope on knee joint kinematics in an in vitro setup. Therefore, the medial and lateral inserts of a knee implant were parameterised and the initial slope was gradually varied to +4°, +2° (posterior) and -2°, -4° (anterior). The variations were manufactured by using polymer based rapid prototyping. The effects on semi-active tibiofemoral and patellofemoral kinematics were studied and quantified in terms of the Root Mean Square Error and Pearson’s Correlation coefficient. The overall largest effect was observed on tibiofemoral internal-external rotation by the variation of the lateral insert. The anterior-posterior translation was predominantly effected by the combined variation. Nevertheless, the lateral variation showed greater influence than medial. In contrast, changes in patellofemoral kinematics were small. Our findings suggest that in total knee arthroplasty the lateral tibial slope has a larger functional effect than the medial tibial slope. Thus, functional design optimization should focus on the lateral insert.

Bacterial biofilm formation on surfaces is still a critical challenge regarding the application of implants. Generally, in order to avoid this, an additional systemic administration of antibiotics is given, which can lead to side effects, such as the reduction of the intestinal flora. Continuous treatment may lead to antibiotics resistance. Within this study we investigated the local drug delivery of N-acetyl-L-cysteine (NAC) from a Poly-L-lactide (PLLA) coating, an ished biodegradable polymer and a polyetherurethane (PEU) coating, a promising representative non-degradable polymer for cardiovascular applications as alternative to the administration of antibiotics. The incorporation of NAC influenced the surface properties of PEU in contrast to that of PLLA. The in vitro NAC release is almost completed after 24 h for PEU. For PLLA only small amounts of incorporated NAC, depending on the NAC loading, is released after a short time. Both systems are rather useful as local NAC delivery system directly after implantation.

Polyelectrolyte multi-layer (PEM) coatings are prepared by alternative deposition of single polyelectrolyte monolayers on charged surfaces using the Layer-by-Layer (LbL) dip coating procedure. These are nanometre scaled coatings which allow fulfilling of different technical or biological requirements. The build-up process is based on selfassembly and self-organization of polycations and polyanions on different substrates including complex geometrical structures and even closed volumes, forming homogeneous layer without defects. Depending on the proper selection of the applied polyelectrolytes, coatings with different stabilities can be prepared. Some of the coatings are stable and cannot be removed from the surface. Others are degradable and can be used as systems for controlled local drug delivery. Here we summarise the results of our experience in preparation of PEM coatings with different functionalities. PEM coatings can be used as controllable delivery system for siRNA polyplexes. They can be used to control the adhesion of different cell types on the surfaces and support e.g. the endothelialisation process on cardio-vascular medical devices as e.g. stents or reduce the immunological response of the tissue after implantation. We summarise results from physical characterisation of the coatings (e.g. film thickness, roughness, electrical charge and hydrophilicity) combined with in-vitro biological studies on adhesion of HUVEC cells.

Polycarbonate urethane and polyether urethane nonwovens as promising representatives of novel polymer heart valve materials were analysed regarding the susceptibility to calcification in comparison to porcine pericardium and polyamide 6. The applied method represents an accelerated calcification out of a metastable solution in short time with significant precipitates on the reference material. As our results show, urethane based nonwoven structures exhibit considerably lower susceptibility to calcification compared to pericardium as widely established material for leaflet design.

Glaucoma is the second most common cause of blindness. An increased intraocular pressure is the only treatable symptom of glaucoma. Because patients often exhibit a poor therapy adherence, a drug depot consisting of ELA-NCO and hyaluronic acid with timolol was developed to ensure sustained drug release. This drug depot is formed by in situ polymerisation after injection into the subconjunctival space. To test the in vivo drug release of timolol in serum and aqueous humour, a liquid chromatography mass spectrometry (LCMS) method was developed and tested using spike- and recovery experiments, and on in vivo samples after topical application. Samples of serum and aqueous humour were taken from New Zealand White rabbits. For topical application, a commercially available formulation of timolol was used. This study presents results concerning the recovery of timolol from spiked samples. Serum and aqueous humour samples were spiked with timolol maleate to a final concentration of 50 ng/mL. Subsequently, the samples were extracted and analysed by LCMS. External calibration of the developed method showed high linearity. Recovery experiments showed no loss of timolol. Hence, the extraction method is robust and able to recover the whole amount of timolol from aqueous humour and serum.

Antimicrobial coatings are typically tested for their activity and effectiveness based on an artificial procedure, the standard JIS Z 2801 (or ISO 22196). The test samples are contaminated with a predetermined concentration of bacteria and covered with a sterile film. Due to the artificial structure of this process, however, there is always the question of the validity in the practical application of these surfaces and how comparable this germ-reducing effect is to currently common disinfection measures. Therefore, we developed a more realistic test procedure in our laboratory. The test samples are inoculated and incubated at standard room conditions. To compare the antimicrobial activity to standard cleaning procedures also disinfection and wipe controls were performed. The results show that the antimicrobial test patterns we use have a strong efficacy. This could be shown reproducibly both with the standard method JIS Z 2801 as well as with our new test procedure.

Inkjet printing has become essential for pharmaceutical research as well as biomedical applications. It is a promising tool to meet future challenges in patientindividual designed pharmaceuticals and implants. In this context, the main areas of use are high-throughput screening (HTS), drug-loaded microparticles, drug formulation and oral dose development, 3D-printing/bioprinting as well as coating of implants. This study deals with the latter. In view of promising applications for localized coating and functionalization of implant surfaces this work shows preliminary results on inkjet printing of the polymer poly(2- ethyl-2-oxazoline) (PetOx), a protein repellent polymer (PRP). To deposit single droplets with small volumes (~500 pl) of aqueous PetOx solution (50 g/l), printing parameters were determined for the piezo-driven drop-ondemand inkjet printhead NanoTip J, operating in a Nanoplotter 2.1 (both from GeSiM mbH, Germany). Different printing strategies are demonstrated by varying droplet spacing and drying time while printing on hydrophilic glass substrate. Printing and stacking of almost uniform polymer lines (width ~ 200 μm) is demonstrated.

In this study, characteristic features of a new regenerative 3D collagen matrix with an orientated open pore structure are studied in-vitro and in-vivo. The noncrosslinked porcine-based resorbable collagen-elastin matrix is designed to provide support during coverage procedures of localized gingival recessions and for local soft tissue augmentation around teeth and implants and is designed to provide an off-the-shelf alternative to autogenous soft tissue grafts. The in-vitro studies show that the mechanical properties (e.g. suture retention, volume recovery after cyclic compression) and the observed active cell migration into the open porous structure of the matrix fulfil essential design requirements. The in-vivo pig animal study shows that the matrix is well integrated into the surrounding tissue and replaced by newly formed autogenous soft tissue without a significant loss in tissue volume. First clinical case series are being performed to further analyse the new 3D matrix in clinical settings.

The purpose of this work was to evaluate the decontamination potential of the Potok system both in an experimental setting in a research Operating Room (OR) with standalone Air Decontamination Units (Potok 150-M-01) and in a clinical setting in a real operating theatre in Moscow. Our experiments showed an impact of the Potok units on the bacterial contamination of the room air according to the Swedish SIS-TS 39:2015 standard. For the initial measurements in our research OR in Weiden this could be shown by a decrease of the bacterial burden at all three different measurement points (OR table, instrumentation tray, periphery). Also the subsequently done measurements in the Moscow hospital verified this decontaminating effectivity of the Potok system. In this case the initial background contamination of the operating theatre was higher than in the research OR in Germany. This bacterial burden could be effectively decreased by the use of the installed Potok based ventilation system.

The human heart is an organ of high complexity and hence, very challenging to simulate. To calculate the force developed by the human heart and therefore the tension of the muscle fibers, accurate models are necessary. The force generated by the cardiac muscle has physiologically imposed limits and depends on various characteristics such as the length, strain and the contraction velocity of the cardiomyocytes. Another characteristic is the activation time of each cardiomyocyte, which is a wave and not a static value for all cardiomyocytes. To simulate a physiologically correct excitation, the functionality of the cardiac simulation framework CardioMechanics was extended to incorporate inhomogeneous activation times. The functionality was then used to evaluate the effects of local activation times with two different tension models. The active stress generated by the cardiomyocytes was calculated by (i) an explicit function and (ii) an ode-based model. The results of the simulations showed that the maximum pressure in the left ventricle dropped by 2.3% for the DoubleHill model and by 5.3% for the Lumens model. In the right ventricle the simulations showed similar results. The maximum pressure in both the left and the right atrium increased using both models. Given that the simulation of the inhomogeneously activated cardiomyocytes increases the simulation time when used with the more precise Lumens model, the small drop in maximum pressure seems to be negligible in favor of a simpler simulation model

Patients suffering from end stage of chronic kidney disease (CKD) often undergo haemodialysis to normalize the electrolyte concentrations. Moreover, cardiovascular disease (CVD) is the main cause of death in CKD patients. To study the connection between CKD and CVD, we investigated the effects of an electrolyte variation on cardiac signals (action potential and ECG) using a computational model. In a first step, simulations with the Himeno et al. ventricular cell model were performed on cellular level with different extracellular sodium ([Na + ] o ), calcium ([Ca 2+ ] o ) and potassium ([K + ] o ) concentrations as occurs in CKD patients. [Ca 2+ ]o and [K + ] o changes caused variations in different features describing the morphology of the AP. Changes due to a [Na + ] o variation were not as prominent. Simulations with [Ca 2+ ] o variations were also carried out on ventricular ECG level and a 12-lead ECG was computed. Thus, a multiscale simulator from ion channel to ECG reproducing the calcium-dependent inactivation of ICaL was achieved. The results on cellular and ventricular level agree with results from literature. Moreover, we suggest novel features representing electrolyte changes that have not been described in literature. These results could be helpful for further studies aiming at the estimation of ionic concentrations based on ECG recordings.

Mechanical ventilation is a primary therapy for patients with respiratory failure. However, incorrect ventilator settings can cause lung damage. Optimising ventilation while minimising risk is complex in practice. A common lung protective strategy is to titrate positive end-expiratory pressure (PEEP) to the point of minimum elastance. This process can result in additional available lung volume due to alveolar recruitment but comes with the risk of subjecting the lungs to excessive pressure and lung damage. Predictive elastance models can mitigate this risk by estimating airway pressure at a higher PEEP level. Due to the increased risk of barotrauma during inspiration, many models exclude expiration data. However, this section of the breath can include useful information about lung mechanics. This research investigates the impact that including expiration data into the fitting of a validated predictive elastance model will have on its ability to predict peak inspiratory pressure. Results showed that expiration data did not improve the efficacy of the model in this case with an increase in error (median (%)) of predicting peak inspiratory pressure through an increase in PEEP of 8 cmH 2 O from 6% to 16%.

An established therapy for aortic valve stenosis and insufficiency is the transcatheter aortic valve replacement. By means of numerical simulation the valve dynamics can be investigated to improve the valve prostheses performance. This study examines the influence of the hemodynamic properties on the valve dynamics utilizing fluidstructure interaction (FSI) compared with results of finiteelement analysis (FEA). FEA and FSI were conducted using a previously published aortic valve model combined with a new developed model of the aortic root. Boundary conditions for a physiological pressurization were based on measurements of ventricular and aortic pressure from in vitro hydrodynamic studies of a commercially available heart valve prosthesis using a pulse duplicator system. A linear elastic behavior was assumed for leaflet material properties and blood was specified as a homogeneous, Newtonian incompressible fluid. The type of fluid domain discretization can be described with an arbitrary Lagrangian-Eulerian formulation. Comparison of significant points of time and the leaflet opening area were used to investigate the valve opening behavior of both analyses. Numerical results show that total valve opening modelled by FEA is faster compared to FSI by a factor of 5. In conclusion the inertia of the fluid, which surrounds the valve leaflets, has an important influence on leaflet deformation. Therefore, fluid dynamics should not be neglected in numerical analysis of heart valve prostheses.

Quantitative native T1 Mapping of the myocardium without the application of contrast agents can be used to detect fibrosis in the left ventricle. Spatial resolution of standard native T1 mapping is limited by cardiac motion and hence is not sufficient to resolve small myocardial structures, such as the right ventricle and the atria. Here, we present a novel MR approach which provides cardiac motion information and native T1 maps from the same data. Motion information is utilized to optimize data selection for T1 mapping and a model-based iterative reconstruction scheme ensures high-resolution T1 maps for the entire heart. Feasibility of the approach was demonstrated in three healthy volunteers. In the T1 maps, the myocardium of all four chambers can be visualized and T1 values of the left atrium and right chambers were comparable to left ventricular T1 values.

Microscopy enables fast and effective diagnostics. However, its functionality is not accessible to everyone. Smartphone-based low-cost microscopes could be a powerful tool for diagnostics and educational purposes. Current smartphone-based microscopy approaches struggle with high cost, poor image quality and/or insufficient smartphone compatibility. In this paper, a very feasible and effective lowcost microscope is presented which addresses these issues. To minimize cost, a monolithic foldable structure is designed for production by injection molding. The design has a high order of functional integration, minimizing the number of components, while still enabling a micrometer focusing accuracy.

Superparamagnetic iron oxide nanoparticles, so called SPIONs, are used as tracers in medical imaging, e. g. for magnetic particle imaging (MPI) or magnetic resonance imaging (MRI). Since the half-life time of the SPIONs in the bloodstream is quite short because they are quickly absorbed by the reticuloendothelial system (RES), the particles are introduced into human red blood cells (RBCs) to increase their half-life time in the blood circulation. The hypotonic swelling procedure is used to incorporate the particles into the RBCs. Before the SPIONs are introduced into the RBCs, they are fluorescent labelled. To evaluate the result transmission electron microscopy, magnetic particle spectroscopy and fluorescence microscopy are used. Fluorescein isothiocyanate and rose Bengal were chosen as fluorescent dyes because their biocompatibility is guaranteed. The results suggest that the method hypotonic swelling can be used to successfully introduce the nanoparticles into RBCs and that the magnetic properties of the particles which are necessary for imaging are not influenced.

In Hyperspectral imaging (HSI) applications in medicine a uniform illumination is used and the illuminated surface is recorded with a camera with spectral resolution. Unlike in tissue reflectance spectroscopy with fixed light source - detector distances, in HSI the contribution of the influence of different tissue layers to the absorption signal is poorly understood. In this work a Monte-Carlo simulation is implemented which simulates the specific HSI illumination and detector geometry. A four-layer tissue model with variable blood volume fraction and oxygen saturation is used. With 5 % blood volume fraction and 75 % oxygen saturation, SaO2, of surrounding tissue, saturation changes in 1 mm and 2 mm deep layers lead to a change in remission of up to 3 % and up to 1 % respectively. Changes in deeper layers are hardly detectable. Further simulations will be focused on different tissue models as the depth resolution is expected to vary with tissue parameters like blood volume fraction.

The integration of dies is a possibility to reduce the number of conducting tracks within electrical active implants. For passive microelectrode arrays the number of conducting tracks limits the number of electrodes. By embedding an array of small dies (250 μm edge length) employed to amplify and multiplex the signals of 25 electrodes each into a flexible foil we create a flexible active microelectrode array with more than 1000 electrodes. A fabrication process was developed containing a transfer process for the dies as well as an embedding procedure. Here a non-functional Dummy-System is presented as a demonstrator proving the feasibility of the proposed microelectrode array.

Emergency medical service (EMS) is an essential part of health care with the main task to transport and monitor patients. However, this duty often becomes a challenge due to obstacles - especially stairs - on the way. Associated lifting and carrying of patients regularly imposes high loads in unergonomic working postures on paramedics, leading to the highest work induced injury rates among all industries also due to a deficient usability of existing transport aids. Therefore our goal is the development of a stair climbing mechanism for a novel mechatronic transport aid characterized by high mobility and a small footprint, whereby particular attention has to be paid to application specific requirements. This paper presents the general approach accompanied by results of a functional model from an initial concept study. Acceleration and jerk measurements showed promising results, while most predefined velocities on the model test parkour rise could be reached.

Louis Lapicque introduced the hyperbolic stimulation law with the key parameters “rheobase” and “chronaxie” that were obtained with rectangular current pulses. With rectangular pulses rheobase cannot be measured. It was found recently that hyperbolic stimulation rules are also valid for non-rectangular pulses and that their rheobase or chronaxie values are identical with that of their rectangular counterparts. Threshold measuring with exponential pulses allow for determining rheobase directly and chronaxie by calculation with only two measurements. The measuring procedure is described in detail.

In surgery, the possibilities of fully automatic assistance are limited. A valuable automated assistance can be implemented by realizing context-aware behaviour of control consoles in integrated operating rooms (ORs). We developed an intraoperative pipeline for surgical context interpretation and an integrated console. Based on that, we propose a method for the context-aware ranking of configuration profiles, which facilitate the handling of devices during endoscopic interventions. The method is evaluated with twenty-four simulated endoscopic ear-nosethroat (ENT) workflows. The results indicate that a continuous automatic ranking based on the surgical situation, can significantly reduce manual user interaction while the surgeon’s control is preserved.

Low-dose CT has received increasing attention in the recent years and is considered a promising method to reduce the risk of cancer in patients. However, the reduction of the dosage leads to quantum noise in the raw data, which is carried on in the reconstructed images. Two different multilayer convolutional neural network (CNN) architectures for the denoising of CT images are investigated. ResFCN is based on a fully-convolutional network that consists of three blocks of 5 × 5 convolutions filters and a ResUNet that is trained with 10 convolutional blocks that are arranged in a multi-scale fashion. Both architectures feature a residual connection of the input image to ease learning. Training images are based on realistic simulations by using the XCAT phantom. The ResUNet approach shows the most promising results with a peak signal to noise ratio of 44.00 compared to ResFCN with 41.79.

Dental caries is one of the most widespread diseases and the early and non-invasive detection of carious lesions remains an ongoing topic in biomedical research. In contrast, optical coherence tomography (OCT) is an emerging, non-invasive imaging technique for near-surface structures, that has already proved its capability for manifold biomedical applications and can be extended by several modalities such as polarization sensitivity. We have recently shown that polarization sensitive OCT combined with an algorithm for depolarization imaging, visualizing the degree of polarization uniformity (DOPU), is a promising tool for the detection and assessment of carious lesions. In this paper, we evaluate different visualization approaches based on both the intensity and DOPU data with cross-sectional and en-face representations and discuss limitations and the potential of the proposed method for the assessment of dental lesions on the example of a molar tooth with a brown spot.

Endoscopic optical coherence tomography is a non-invasive and contactless imaging technique based on white light interferometry. It enables high-resolution three-dimensional imaging of scattering tissue up to a depth of about 2 mm. In addition, Doppler-OCT can detect sub-resolution movements. These features can be used to examine the tympanic membrane, the surrounding tissue and nearby areas of the tympanic cavity. For this purpose, we present an endoscopic OCT system, which provides access to the tympanic membrane. The design of the endoscope is based on a gradientindex (GRIN) lens system. This allows a broad field of view and a large working distance. An additional VIS beam path allows visual imaging and orientation inside the auditory canal. Therefore, illumination fibers are attached a round the GRIN-system. The resulting endoscope has a length of 55 mm and a diameter of 3.5 mm. By attaching an earphone and a probe microphone, the oscillation of the tympanic membrane can be measured under acoustic stimulation. With the endoscopic OCT system, we provide an examination tool for the diagnosis of a broad number of diseases like conductive hearing loss.

Wound area is a primary outcome measure in wound healing studies. This method comparison study evaluates differences of wound area measurements of a newly developed image analysis method based on wound edge contour to an existing method based on contrast tolerance. Digital images of 64 wounds were taken immediately after wounding matured in vitro 3D organotypic tissues with a biopsy punch. Wound area measurements were calculated using each image analysis method and then normalized. The method comparison study evaluates the difference of each paired measurements for all 64 wound areas. Measurement differences are demonstrated and evaluated in normalized data boxplots, scatter plots with a line of equality, data histogram and Normal probability plots, and a Bland-Altman plot of paired measure difference against mean. The measured wound areas using the tolerance method have large variability in comparison to the contour method measures. The tolerance method measures often underestimate and overestimate what is assumed to be an approximately repeatable initial wound size. Skewness in comparison plots are due to the ‘fat tails’ introduced by the variability of measurements of the tolerance method. In contrast, the contour method results in larger wound area measurements on average at a statistically significant level of difference. The relatively less variable range of contour method measurements suggest this method has more potential to agree with the ‘true’ wound area. Future work to improve the method are proposed for application of image analysis methods to distinguish true wound area and measurement error in time for wound healing treatment-control experiments.

It is widely known that tendon tissues are subjected to repeated cyclic mechanical load which influences cellular processes. The involvement of principles of mechanics in tissue engineering contributes to the investigations of the connection between mechanical and biological parameters in cellular processes and as well as to the development of new approaches for specific treatment methods. The healing process of injured tendons includes tenocyte migration which occurs from intact regions of tendon into the wound site. The aim of the present study is to investigate and enhance the migration characteristics of tenocytes under uniaxial mechanical stretching using an in-house tensile bioreactor system. Uniaxial mechanical stretching is applied to tenocyte-seeded silicone as well as collagen membranes, which possess different material properties. Tenocyte-seeded silicone membranes were investigated under three different loading conditions, including unstimulated (control), 3% and 5% strain, at frequency of 0.5 Hz. Tenocyte-seeded collagen membranes were investigated using three different frequencies, including unstimulated (control), 0.1 Hz and 0.5 Hz at strain of 4%. The main finding in this study is that uniaxially mechanical stretching at 3% strain enhances the cell migration more than 5% strain on silicone membranes.

For package testing of active implants internal humidity measurements are performed. Thereby, the water absorbency of the measurement components can affect the measurement result, leading to an erroneously prolonged predicted lifetime. Here, the influence of internal components is discussed using an exemplary setup. It is described how to model and consider the components’ absorbencies for lifetime estimation and how beneficial they are during implant operation.

Model-based perfusion reconstruction (MBPR) by using a weighting sum of basis functions, is used to describe the dynamic contrast agent distribution by superposition of incorporated prior knowledge. It handles temporal under-sampling in measurements acquired with a slowly rotating X-ray-based imaging system, in our case a C-arm based computed tomography (CT). However, here challenging issue arises that the computing complexity increases proportional to the number of prior knowledge elements. Thus, the aim of this study is to analyze clinical data and elaborate basis functions, that maps various patients with a small orthonormal basis set (ONB). This work is based on five reconstructed clinical perfusion CT data sets. For each patient, regions of interest were manually figured out in order to enhance the content. Therefore, bones and catheters have to be removed out of the data, to prevent a falsification of the curves by them. The principal component analysis (PCA) to compress the relevant information of perfusion and create an ONB was used. In order to achieve an ONB which also optimal maps unknown patients, the cross validation method was used, i.e. the datasets of four patients were utilized for the estimation of the ONB, while the remaining patient was used for evaluation. Finally, the ONB gets evaluated by the mean-absolute-percentage-error (MAPE) of MBPR. A compact ONB with three basis functions that maps all five patients without a significant d eviation o f t he approximated curves and the original ones is obtained. Especially, regions with high blood supply can be reconstructed very accurately and a reduction of noise is qualitatively visible in the image. An optimum ONB for the MBPR requires that the curves can be modeled as exactly as possible with a few basis elements. The use of only a few elements also leads to short computing times. In this work a good approximation of the curves with three basis elements is received. This results in an improved MBPR that in turn can lead to a higher precision of stroke diagnostics and treatments by using C-Arm CT.

Optical coherence tomography (OCT) is a noninvasive medical imaging modality, which provides highresolution transectional images of biological tissue. However, its potential is limited due to a relatively small field of view. To overcome this drawback, we describe a scheme for fully automated stitching of multiple 3D OCT volumes for panoramic imaging. The voxel displacements between two adjacent images are calculated by extending the Lucas-Kanade optical flow a lgorithm to dense volumetric images. A RANSAC robust estimator is used to obtain rigid transformations out of the resulting flow v ectors. T he i mages a re t ransformed into the same coordinate frame and overlapping areas are blended. The accuracy of the proposed stitching scheme is evaluated on two datasets of 7 and 4 OCT volumes, respectively. By placing the specimens on a high-accuracy motorized translational stage, ground truth transformations are available. This results in a mean translational error between two adjacent volumes of 16.6 ± 0.8 μm (2.8 ± 0.13 voxels). To the author’s knowledge, this is the first reported stitching of multiple 3D OCT volumes by using dense voxel information in the registration process. The achieved results are sufficient for providing high accuracy OCT panoramic images. Combined with a recently available high-speed 4D OCT, our method enables interactive stitching of hand-guided acquisitions.

Computed tomography (CT) scans are frequently used intraoperatively, for example to control the positioning of implants during intervention. Often, to provide the required information, a full field of view is unnecessary. I nstead, the region-of-interest (ROI) imaging can be performed, allowing for substantial reduction in the applied X-ray dose. However, ROI imaging leads to data inconsistencies, caused by the truncation of the projections. This lack of information severely impairs the quality of the reconstructed images. This study presents a proof-of-concept for a new approach that combines the incomplete CT data with ultrasound data and time of flight measurements in order to restore some of the lacking information. The routine is evaluated in a simulation study using the original Shepp-Logan phantom in ROI cases with different degrees of truncation. Image quality is assessed by means of normalized root mean square error. The proposed method significantly reduces truncation artifacts in the reconstructions and achieves considerable radiation exposure reductions.

After a liver tumor intervention the medical doctor has to compare both pre and postoperative CT acquisitions to ensure that all carcinogenic cells are destroyed. A correct assessment of the intervention is of vital importance, since it will reduce the probability of tumor recurrence. Some methods have been proposed to support the medical doctors during the assessment process, however, all of them focus on secondary tumors. In this paper a tool is presented that enables the outcome validation for both primary and secondary tumors. Therefore, a multiphase registration (preoperative arterial and portal phases) followed by a registration between the pre and postoperative CT images is carried out. The first registration is in charge of the primary tumors that are only visible in the arterial phase. The secondary tumors will be incorporated in the second registration step. Finally, the part of the tumor that was not covered by the necrosis is quantified and visualized. The method has been tested in 9 patients, with an average registration error of 1.41 mm.

The motility of the gastrointestinal tract is crucial for digestive activity and dysfunction can lead to severe disease pattern. A method for analysing the motility is needed when treatment approaches shall be evaluated. Therefore markers attached to different locations on the stomach and the bowel of pigs are video tracked in this research study. The markers are designed to provide a high contrast and have an adhesive side for fixation. Above the operation field a video camera has been placed to film the markers during the procedure. To analyse the video data a special algorithm has been implemented. The algorithm requires a registration process at the beginning of each recording which allows the parallel tracking of multiple markers. After the registration the algorithm tracks the position of the marker frame by frame. Each frame is converted into a greyscale picture by adding specified colour values of each pixel. This allows emphasizing certain colours. The centre of the marker is determined by computing the horizontal and vertical centre of the marker starting at the corresponding marker position of the previous frame. After completion the data is stored as coordinates and a video with the marker position displayed for further processing. For advanced analysis the data can be synchronized with electromyography signals, for example. The marked videos show a promising tracking of the markers. However, if the algorithm loses track of a marker during a recording, it is unlikely to relocate it due to the successive processing of the frames. Nevertheless this method provides a simple and easy to use solution for movement detection of the gastrointestinal tract.

Image segmentation plays an increasingly important role in image processing. It allows for various applications including the analysis of an image for automatic image understanding and the integration of complementary data. During vascular surgeries, the blood flow in the vessels has to be checked constantly, which could be facilitated by a segmentation of the affected vessels. The segmentation of medical images is still done manually, which depends on the surgeon’s experience and is time-consuming. As a result, there is a growing need for automatic image segmentation methods. We propose an unsupervised method to detect the regions of no interest (RONI) in intraoperative images with low depth-of-field (DOF). The proposed method is divided into three steps. First, a color segmentation using a clustering algorithm is performed. In a second step, we assume that the regions of interest (ROI) are in focus whereas the RONI are unfocused. This allows us to segment the image using an edge-based focus measure. Finally, we combine the focused edges with the color RONI to determine the final segmentation result. When tested on different intraoperative images of aneurysm clipping surgeries, the algorithm is able to segment most of the RONI not belonging to the pulsating vessel of interest. Surgical instruments like the metallic clips can also be excluded. Although the image data for the validation of the proposed method is limited to one intraoperative video, a proof of concept is demonstrated.

In the noninvasive determination of the hemoglobin concentration a main challenge is the "optical path". With sensors - fixed on human skin - the optical path cannot be exactly determined, as it is defined as the layer thickness in the Lambert Beer principle. The layer thickness is significantly involved in the optical interactions in the tissue. To circumvent this problem self-learning algorithms were evaluated which provide the hemoglobin concentration from reflection and transmission data without knowledge of the layer thickness. First various regression models were trained based on an high rate data set. To evaluate the six most promising models, a prediction dataset was measured in a prospective randomized and blinded study to guarantee integrity of the results. For both data sets, the transmission and reflection of diluted heparinized erythrocyte concentrate was determined with a double integrating sphere setup (laser diodes with 780 to 1310 nm). The evaluated hemoglobin concentrations ranged from 4 to 16 g/dl at a constant oxygen saturation above 97 %. Optical flow through cuvettes (1, 2, 3 mm) simulated different layer thicknesses of the blood. The evaluation of the predictions yielded that the layer thickness independent prediction of the hemoglobin concentration is feasible with the selected approaches. The mean absolute error (MAE) of the best regression model (GPRM - Matern 5/2) is 0.79 g/dl. In the clinically relevant tHb range of less than 8 g/dl the MAE was as low as 0.52 g/dl.

Mechanical ventilation requires optimal parameter setting for every single patient. For instance sufficient positive end-expiratory pressure (PEEP) may ensure oxygenation and prevent overdistension of lungs or alveolar collapse. To find optimal PEEP, transpulmonary pressure (airway pressure minus pleural pressure) guides as an indicator for both, chest wall mechanics and lung characteristic. Since measurement of pleural pressure is impractical in clinical routine, esophageal pressure can be used to estimate pleural pressure and may help to assure protective mechanical ventilation. We developed a PESO (derived from PESO = esophageal pressure) measurement system, which provides a compact stand-alone device to measure the esophageal pressure during mechanical ventilation of patients. In addition to the esophageal pressure, air way pressure is also measured to provide the synchronized data independent of the ventilator manufacturer. The device works with two commercial pressure transducers, whose signals are conditioned and digitized with an Arduino Nano microcontroller, which samples data with 62 kHz and transmits averaged data with 100 Hz to a mobile tablet PC, which acts as process, display and record unit. The compact system provides a working time of 5 hours. Therefore, the system supports the progress for mechanical ventilation research. This paper describes technical details as well as functionality.

The development of a drug against pathogens of hemorrhagic fever, like the Marburg virus, is a great challenge. Therefore, accurate knowledge of the properties of subviral particles in the host cell must be obtained. The base for subviral particle analysis is a special fluorescence microscopy technique. In order to automate and visualize the subviral particles’ motion patterns, previously a tracking algorithm was developed. In this article a new algorithm to parameterize and visualize the achieved particle tracks is introduced. A good potential for a fast data recognition is shown, with constantly respecting a high usability for pharmaceutical researchers. This algorithm was tested on both simulated and real data and provides reproducible results.

For further development and optimization of novel uncooled magnetoelectric (ME) sensors, a better understanding of spectral power distribution and signal strength of nerve signals is of high interest. For obtaining information on these signal properties, Superconducting Quantum Interference Device (SQUID) measurements were performed at the Physikalisch-Technische Bundesanstalt (PTB) in Berlin. Signal amplitudes were subject-dependent and ranged from 17 fT to 60 fT in a frequency range from 100 Hz to 1 kHz. The required SQUID averaging time was in the range of minutes, while for current ME sensors significantly longer averaging times are expected to be necessary.

It has been shown that the formation of calcium phosphate crystals can be detected in patient blood using a polymer microchip manufactured by ultrasonic processing. Ultrasonic processing is recently evolving for the fabrication of low-cost microfluidic devices from thermoplastic polymers. The formation of calcium phosphate crystals can be measured in the blood serum of a patient both optically from a change in turbidity or in electrical resistance.

Being able to non-obtrusively and continuously monitor arterial blood pressure is of great interest, particularly in the context of wearable sensors. A common limitation is the need for dedicated hardware, which is either obtrusive or expensive. In our current work, we investigate unimodal pulse waves from three handily accessible heterogeneous sources: photoplethysmography, bioimpedance and pulse applanation tonometry. We derive and evaluate multiple parameters regarding their correlation to reference blood pressure curves. These parameters stem from features of the warping paths resulting from dynamic and derivative dynamic time warping. The warping is performed between adjacent pulses or to a reference waveform. Spearman Rho coefficients of up to 0.98 and averaging 0.77 at highly significant p-values are recorded for single parameters. We record mean absolute deviation values of 0.08 across subjects. The results indicate there are negligible lags between reference and parameter curves. The sign of the correlation coefficients is consistent only for a small subset of parameters; the underlying cause could not yet be identified. We conclude that the warping path approach seems a promising way to go, yet still needs refinement. In particular, developing a time and amplitude warping method is paramount. Since warping quantizes all the morphological changes in the pulse wave without fiducial point detection, it could become a powerful tool for future investigations.

Autoregressive models (AR) are fundamental for analysis, representation, and prediction of signals. AR modelling uses the premise that past signal values influence current ones. This influence is causal and is modelled as a linear superposition, because a weighted addition of past values is used. The calculation of the required linear superposition parameters or weights can be done by the classical Yule-Walker approach or by least squares procedures. Here we show how to use singular value decomposition (SVD) for generalized linear autoregression (GLAR), i.e. using SVD to compute the weights of a linear combination of functions of given signal values and to check or optimize the GLAR model. The GLAR approach opens the possibility to take directly into account non-linear influences from past to current signal values. T he potential of this approach for analysis and representation is presented and demonstrated for simulated signals, i.e. pure and noisy sequences of non-linear recursions, and biomedical signals.

Cardiovascular diseases are the leading cause of death worldwide. Early detection of abnormal vascular morphologies like aneurysms in the abdominal (abdominal aortic aneurysm, AAA) or thoracic aorta (thoracic aortic aneurysm, TAA) are essential to prevent fatal events. The aim of this study is the development of a patient-specific simulation model to obtain statistical information about ab- /normal pressure-flow conditions to improve the basic understanding and methods for the early detection of diseases. For this purpose, the numerical cardiovascular modeling tool SISCA was used, to generate a series of simulations by Monte- Carlo parameter variation. The considered variational scenario was built upon a control group of normal patients, deriving two pathological conditions for AAA and TAA with different severity and location. Therefore, the nominal diameters were enlarged between 200 % and 500 %, while the length of the aneurysms were modified within a range of 30 and 90 mm. Within each statistical set the convergence was tested by the bootstrap method ensuring that within a set of 3500 runs a 2 % deviation error of the mean value of the blood pressure was obtained compared to a set of 10000 runs.The parameter variation method allows the generation of disease specific data in the context of physiological/clinical findings and consequently the disease specific quantification of signal uncertainties and variances.

Cardiac arrhythmias such as atrial fibrillation occur frequently in industrialized countries. Radiofrequency ablation (RFA) is a standard treatment if drug therapy fails. This minimally invasive surgery aims at stabilizing the heart rhythm on a permanent basis. However, the procedure commonly needs to be repeated because of the high recurrence rate of arrhythmias. Non-transmural lesions as well as gaps within linear lesions are among the main problems during the RFA. The assessment of lesion formation is not adequate in state of the art procedures. Therefore, the aim of this study is to investigate the short-term reversibility of lesions using human electrograms recorded by a high-density mapping system during an electrophysiological study (EPS). A predefined measurement protocol was executed during the EPS in order to create three ablation points in the left atrium. Subsequently, after preprocessing the recorded signals, electrogram (EGM) paths were formed along the endocardial surface of the atrium. By analyzing changes of peak to peak amplitudes of unipolar EGMs before and after ablation, it was possible to distinguish lesion area and healthy myocardium. The peak to peak amplitudes of the EGMs decreased by 40-61% after 30 seconds of ablation. Furthermore, we analyzed the morphological changes of EGMs surrounding the lesion. High-density mapping data showed that not only the tissue, which had direct contact with the catheter tip during the RFA, but also the surrounding tissue was affected. This was demonstrated by low peak to peak amplitudes in large areas with a width of 14 mm around the center of the ablation lesion. After right pulmonary vein isolation, high-density mapping was repeated on the previous lesions. The outer region of RFA-treated tissue appears to recover as opposed to the central core of the ablation point. This observation suggests that the meaningfulness of an immediate remap after ablation during an EPS may lead the physician to false conclusions

Motion capture systems or MoCap systems are used for game development and in the field of sports for the assessment and digitalization of human movement. Furthermore, MoCap systems are also used in the medical and therapeutic field for the analysis of human movement patterns. As examples gait analysis or examination of the musculoskeletal system and its function should be mentioned. Most application relate to a specific person and their movement or to the comparison of movements of different people. Within the scope of this paper an averaged motion sequence is supposed to be generated from MoCap data in order to be able to use it in the field of biomechanical modeling and simulation. For the averaging of individual movement sequences of different persons a Hidden Markov Model (HMM) based approach is presented.

For several decades, researchers are aiming for the detection of precursors of epileptic seizures. A system that is able to issue a warning about an impending seizure could dramatically improve the quality of life of affected patients. In this work, we apply multivariate autoregressive (MVAR) modeling to intracranial electroencephalography (iEEG) recordings of patients with therapy resistant epilepsy. As compared to our previous investigations, we studied the optimal model order of the autoregressive process as a feature for seizure prediction. In a statistical evaluation, we obtain significant results for 17 out of 20 patients.

Unintended injuring of anatomical structures during endocrine neck operations can have severe consequences for patient. Especially the nerves and the parathyroid gland can be hard to identify visually. Therefore, intraoperative methods are needed to support the surgeon in this task. Hyperspectral imaging (HSI) is a new approach in the medical area which combines a camera with a spectrometer. It showed promising results for the discrimination of tissue. In this work, HSI-data of seven patients were acquired during thyroid and parathyroid operations. The mean absorbance spectra of both glands showed differences in the range between 600 and 700 nm and at 760 and 960 nm. This means that thyroid and parathyroid have different oxygenation states and different contents of deoxygenated hemoglobin and water. From these observations, it is possible to define spectral signatures to characterize both glands. We showed on one patient how spectral signatures can be used in classification algorithms to automatically identify the thyroid and parathyroid from other structures.

Hearing restoration using a cochlear implant requires a surgical access to the inner ear. In order to enhance patient safety, reduce trauma, and shorten the patient’s time under anaesthesia current research focusses on minimally invasive cochlear implantation surgery by drilling only a single bore hole. This demands a highly accurate surgical assistance device to guide the drill along a predetermined trajectory planned in patient’s image data. In this study a recently developed surgical targeting system was evaluated for the first time in a human cadaver trial. After screwing a reference frame on a temporal bone specimen and imaging of both, a trajectory through the facial recess was planned in order to reach the middle ear. Based on this plan a patient specific surgical template including a linear guide for the surgical drill was composed utilizing bone cement. After the hardening of the bone cement the surgical template was mounted on top of the reference frame. The drilling could be performed as previously planned without harming facial nerve and chorda tympani. The deviation of the actual drill hole to the planned trajectory was 0.17 mm at the level of the facial recess. The minimal distance of the drill hole to the facial nerve was 0.59 mm. This proof-of-concept study demonstrates the feasibility of performing the access to the middle ear in a minimally invasive manner using the mouldable surgical targeting system. The presented process allows the patient specific individualization of a drill guide under sterile conditions. This might facilitate its integration into clinical routine.

Laparoscopic videos are a very important source of information which is inherently available in minimally invasive surgeries. Detecting surgical tools based on that videos have gained increasing interest due to its importance in developing a context-aware system. Such system can provide guidance assistance to the surgical team and optimise the processes inside the operating room. Convolutional neural network is a robust method to learn discriminative visual features and classify objects. As it expects a uniform distribution of data over classes, it fails to identify classes which are under-presented in the training data. In this work, loss-sensitive learning approach and resampling techniques were applied to counter the negative effects of imbalanced laparoscopic data on training the CNN model. The obtained results showed improvement in the classification performance especially for detecting surgical tools which are shortly used in the procedure.

Surgical robots have been introduced in the field of Computer Assisted Surgery (CAS) to assist the surgeon by providing an accurate link between the computer-based plan and the exact (a) positioning or (b) dynamic path control of an instrument on the operating site respectively. Whereas initial systems mostly have been based on an active supervisory control scheme of industrial robots with large universal workspaces, later on specialized miniaturized kinematics have been proposed, with restricted workspaces adapted to specific applications in order to ease handling and provide inherent safety properties. However, this specialization resulted in even narrower fields of application, low quantities and higher costs. Modularization seems to be a key factor to combine the benefits of both approaches. In this paper two modular robotic solutions, validated in the context of their purpose, are analysed regarding their modular design. Based on this, the potential of modularity for instrument guiding tasks in surgery is discussed.

Surgical workflow analysis in laparoscopic surgeries has been studied widely during last years because of its various applications. For example, optimising the schedule of operating rooms (OR) and developing a context-aware system that supports surgical team during the intervention. Surgical phase recognition has been applied to various kinds of laparoscopic procedures, mainly of type cholecystectomy. Sigmoid resection procedures are considered more complex than cholecystectomy, and they have not been extensively studied. Therefore, the focus of this work is to study phase recognition in sigmoid resection. In this paper, a convolutional neural network (CNN) architecture and Hidden Markov Model (HMM) were evaluated for performing phase recognition in sigmoid resection videos. The CNN is an extension of a pretrained model, and it was fine-tuned to perform the recognition. To consider the temporal aspect of the phase sequences, confidences obtained by the CNN were then provided into a HMM to release final classification. Experimental results show a low performance of the proposed method to recognise surgical phases in such complex procedures. Therefore, the dataset used for the evaluation was also reviewed, and statistics of each phase were generated.

The purpose of this study is to develop a method to discriminate spectral signatures in wound tissue. We have collected a training set of the intensity of the remitted light for different types of wound tissue from different patients using a TIVITA™ tissue camera. We used a neural network technique (self-organizing map) to group areas with the same spectral properties together. The results of this work indicates that neural network models are capable of finding clusters of closely related hyperspectral signatures in wound tissue, and thus can be used as a powerful tool to reach the anticipated classification. Moreover, we used a least square method to fit literature spectra (i.e. oxygenated haemoglobin (O 2 Hb), deoxygenated haemoglobin (HHb), water and fat) to the learned spectral classes. This procedure enables us to label each spectral class with the corresponding absorbance properties for the different absorbance of interest (i.e. O 2 Hb, HHb, water and fat). The calculated parameters of a testing set were consistent with the expected behaviour and show a good agreement with the results of a second algorithm which is used in the TIVITA™ tissue camera.

In tissue engineering and regenerative medicine mesenchymal stem cells (MSC) are widely used to replace and restore the function of dysfunctional or missing tissue. Recent studies have shown significant enhancements of the in vivo healing process following dentofacial bone augmentation procedures employing stem cell-loaded xenografts. We conducted experimental and numerical investigations in perfusion flow bioreactor-xenograft-systems to identify flow conditions as well as bioreactor design features that allow for homogeneous MSC-distribution in Geistlich Bio- Oss Block xenografts. Pressure gradient - velocity characteristics and flow distributions were investigated experimentally and numerically for two bioreactor designs at steady-state flow conditions with Reynolds numbers (Re) ranging from 0.01 ≤ Re ≤ 0.32. Distilled water at 20°C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m3 was used. The geometry of the xenograft utilized in three-dimensional computational fluid dynamics (CFD) simulation was obtained by means of micro-computed tomography (μCT) at an isotropic spatial resolution of 9.5 μm. The permeability values calculated from the experimental data are in good accordance with the numerical results. The investigations showed that the increase of the inflow- and outflow-area diameter, as well as the decrease of the volumetric flow rate, result in a decreasing heterogeneity of the flow distribution within the xenograft. The calculated wall shear stress rates in the three-dimensional (3D) scaffold range from 1∙10 -12 Pa ≤ τ ≤ 0.2 Pa. Experimentally validated CFD simulations introduced in this study provide an applicable tool to assess optimal flow conditions for homogeneous MSC distribution in bioreactor-xenograft-systems.

Motion tracking of thorax kinematics can be used to determine respiration. However, determining a minimal sensor configuration from 64 candidate sensor locations is associated with high computational costs. Hence, a hierarchical optimization method was proposed to determine the optimal combination of sensors. The hierarchical method was assessed by its ability to quickly determine the sensor combination that will yield optimal modelled tidal volume compared to body plethysmograph measurements. This method was able to find the optimal sensor combinations, in approximately 2% of the estimated time required by an exhaustive search.

Wearable sensor systems are of increasing interest in clinical gait analysis. However, little information about gait dynamics of patients under free living conditions is available, due to the challenges of integrating such systems unobtrusively into a patient’s everyday live. To address this limitation, new, fully integrated low power sensor insoles are proposed, to target applications particularly in home-monitoring scenarios. The insoles combine inertial as well as pressure sensors and feature wireless synchronization to acquire biomechanical data of both feet with a mean timing offset of 15.0 μs. The proposed system was evaluated on 15 patients with mild to severe gait disorders against the GAITRite ® system as reference. Gait events based on the insoles’ pressure sensors were manually extracted to calculate temporal gait features such as double support time and double support. Compared to the reference system a mean error of 0.06 s ± 0.06 s and 3.89 % ± 2.61 % was achieved, respectively. The proposed insoles proved their ability to acquire synchronized gait parameters and address the requirements for home-monitoring scenarios, pushing the boundaries of clinical gait analysis.

With the advances of IMU-based human motion tracking, joint angle tracking in an home environment has become a realistic goal. Achieving it, could enable novel applications in rehabilitation and sports medicine. However, in existing systems the process of aligning the mounted sensors with the body coordinate system is either not robust enough or to complicated for fully unsupervised usage. In this publication the performance of a promising existing algorithm is evaluated with a range of different calibration motions. Further, an extension to this implementation is proposed, aiming to improve its stability when only non-ideal calibration data is available. It could be validated that the modification of the algorithm can increase the stability and reduce the dependency of the calibration on specific calibration motions. Based on these results, we recommend the proposed extension of the algorithm as a drop-in replacement for the existing implementation.

Electric field of biventricular (BV) pacing, left ventricular (LV) electrode position and electrical interventricular desynchronization are important parameters for successful cardiac resynchronization therapy (CRT) in patients with heart failure, sinus rhythm and reduced LV ejection fraction. The aim of the study was to evaluate electric pacing field of transesophageal left atrial (LA) pacing and BV pacing with 3D heart rhythm simulation. Bipolar right atrial (RA), right ventricular (RV), LV electrodes and multipolar hemispherical esophageal LA electrodes were modeled with CST (Computer Simulation Technology, Darmstadt). Electric pacing field were simulated with bipolar RA and RV pacing with Solid S (Biotronik) electrode, bipolar LV pacing with Attain 4194 (Medtronic) electrode and bipolar LA pacing with TO8 (Osypka) esophageal electrode. 3D heart rhythm model with esophagus allowed electric pacing field simulation of 4-chamber pacing with bipolar intracardiac RA, RV, LV pacing and bipolar transesophageal LA pacing. The pacing amplitudes were 3V RA pacing amplitude, 50V LA pacing amplitude, 1.5V RV pacing amplitude and 3V LV pacing amplitude with 0.5ms pacing pulse duration. The atrioventricular delay between RA pacing and BV pacing was 140ms atrioventricular pacing delay and simultaneous RV and LV pacing. Electric pacing fields were simulated during the different pacing modes AAI, VVI, DDD and DDD0V. The intracardiac far-field pacing potentials were evaluated with intracardiac electrodes and a distance of 1mm from the electrodes with RA electrode 1.104V, RV electrode 0.703V and LV electrode 1.32V. The transesophageal far-field pacing potential was evaluated with transesophageal electrode and a distance of 10mm from the elelctrode with LA electrode 6.076V. Heart rhythm model simulation with esophagus allows evaluation of electric pacing fields in AAI, VVI, DDD, DDD0V and DDD0D pacing modes. Electric pacing field of RA, RV and LV pacing in combination with LA pacing may additional useful pacing mode in CRT non-responders.

For the investigation of reaction moments of wrist joint with external fixator, a test device was developed that allows a well-defined investigation of the joint loads during hand flexion movements. The reaction moments are considered as a measure for the joint loads due to the constraint forces, which occur with differences of the rotation axis of the fixator device from the physiological rotation axis of the wrist joint. The developed test device allows a dynamic momentum load application into the wrist by a servohydraulic testing machine. This testing device converts the force to a moment by a constant lever arm and allows thereby the measurement of the reaction moments by the force load cell of the testing machine. Measurements on cadaveric wrist joints with external fixator can be thereby performed under reproducible conditions. The cadaveric wrist joints can be integrally casted into bone cement and thereby clamped to the testing device. Preliminary experiments with artificial bones showed that forces within the measuring range of the load cell of the testing machine can be measured. The design of the test device is presented. Hence, the requirements for measurements of the reaction moments with wrists with external fixator for distal radius fractures under dynamic loads are created.

We present an approach for segmenting individual cells and lamellipodia in epithelial cell clusters using fully convolutional neural networks. The method will set the basis for measuring cell cluster dynamics and expansion to improve the investigation of collective cell migration phenomena. The fully learning-based front-end avoids classical feature engineering, yet the network architecture needs to be designed carefully. Our network predicts how likely each pixel belongs to one of the classes and, thus, is able to segment the image. Besides characterizing segmentation performance, we discuss how the network will be further employed.

Surface topographies are often discussed as an important parameter influencing basic cell behavior. Whereas most in-vitro studies deal with microstructures with sharp edges, smooth, curved microscale topographies might be more relevant concerning in-vivo situations. Addressing the lack of highly defined surfaces with varying curvature, we present a topography chip system with 3D curved features of varying spacing, curvature radii as well as varying overall dimensions of curved surfaces. The CurvChip is produced by low-cost photolithography with thermal reflow, subsequent (repetitive) PDMS molding and hot embossing. The platform facilitates the systematic invitro investigation of the impact of substrate curvature on cell types like epithelial, endothelial, smooth muscle cells, or stem cells. Such investigations will not only help to further understand the mechanism of curvature sensation but may also contribute to optimize cellmaterial interactions in the field of regenerative medicine.

Research in biomedical nanotechnology led already to a variety of applications of nanoparticles in diagnosis as well as in therapy. One of these medical applications is Magnetic Drug Targeting, a promising cancer treatment technique. The aim of this medical attendance is a local chemotherapeutic treatment of the cancerous tissue. For this purpose, chemotherapeutic drugs are bound to magnetic nanoparticles and accumulated in the tumor area by means of an external static magnetic field. Hereby, a well-defined particle concentration in the cancerous tissue requires monitoring of the particle accumulation. Therefore, we present an ultrasound imaging technique that is capable of detecting quantitatively the concentration of iron oxide nanoparticles in biological tissue. The evaluation is based on the variation of the speed of sound of an induced shear wave with respect to the particle concentration.

In a recently developed perfusion bioreactor, human nasal septum chondrocytes were seeded on decellularized porcine collagen scaffolds and cultivated for 6 weeks. Afterwards, the samples were stained with alcian blue and multiple histological microscope images were taken to assess the migration of the human cells and their redifferentiation. In this paper, we propose an image processing algorithm to objectively quantify the cultivation results. This algorithm performs a white balance, detects cell nuclei and their migration depth, and detects lacunae and their orientation. To evaluate performance, sensitivity and precision are calculated using manually labeled data over 50 images. The detection of cell nuclei has a reasonable precision (73%), but the level of sensitivity (42%) should be further improved. The proposed method demonstrates acceptable level of precision (83%) and sensitivity (86%) for the detection of lacunae.

In this study, PLLA-based sirolimus-eluting polymer scaffolds and permanent bare-metal stents (316L) were implanted interventionally into both common carotid arteries (CCA) of 6 female pigs via the left common iliac artery (8F-sheath). The pigs were administered dual antiplatelet drugs peroral starting 3 days before the procedure until the end of the study. Stented CCA segments were explanted after 12 weeks, and processed for quantitative histomorphometry, and estimation of vascular inflammation and injury scores. SIR/polymer scaffolds showed a decreased residual lumen area and higher restenosis after 12 weeks (4.45 ± 2.23 mm² and 61.68 ± 22.39%) as compared to the 316L reference stent (16.53 ± 1.23 mm² and 6.65 ± 1.30%). After 12 weeks, inflammation score and vascular injury score were higher in the SIR/polymer group (1.90 ± 1.15 and 1.26 ± 0.87) compared to the 316L group (0.57 ± 0.37 and 0.83 ± 0.34).

The quality of bioelectrical signals is essential for functional evaluation of cellular circuits. The electrical activity recorded from the cortical brain surface represents the average of many individual synaptic processes. By downsizing micro-electrode arrays, the spatial resolution of electrocortico-grams (ECoGs) can be increased. But, upon increasing electrode impedance, recorded noise from the electrode-tissue interface and the surroundings will become more prominent. Frequently, signal interpretation is improved by post-processing using filtering or pattern recognition. For a variety of applications, wavelet denoising has become an accepted tool. Here, we present how wavelet denoising affects the signal-to-noise ratio of ECoGs. The recording qualities from awake and anesthetized mice was artificially reduced by adding two noise models prior to filtering. Raw and filtered signals were compared by calculating the linear correlation coefficient.

Pulmonary vein isolation (PVI) is a common therapy in atrial fibrillation (AF). The cryoballoon was invented to isolate the pulmonary vein in one step and in a shorter time than a point-by-point radiofrequency (RF) ablation. The aim of the study was to model two cryoballoon catheters, one RF catheter and to integrate them into a heart rhythm model for the static and dynamic simulation of PVI by cryoablation and RF ablation in AF. The modeling and simulation were carried out using the electromagnetic and thermal simulation software CST (CST, Darmstadt). Two cryoballons and one RF ablation catheter were modeled based on the technical manuals of the manufacturers Medtronic and Osypka. The PVI especially the isolation of the left inferior pulmonary vein using a cryoballoon catheter was performed with a -50 °C heatsource and an exponential signal. The temperature at the balloon surface was -50 °C after 20 s ablation time, -24 °C from the balloon 0,5 mm in the myocardium, at a distance of 1 mm -3 °C, at 2 mm 18 °C and at a distance of 3mm 29 °C. PVI with RF energy was simulated with an applied power of 5 W at 420 kHz at the distal 8 mm ablation electrode. The temperature at the tip electrode was 110 °C after 15 s ablation time, 75 °C from the balloon at 0,5 mm in the myocardium, at a distance of 1 mm 58 °C, at 2 mm 45 °C and at a distance of 3 mm 38 °C. Virtual heart rhythm and catheter models as well as the simulation of the temperature allow the simulation of PVI in AF by cryo ablation and RF ablation. The 3D simulation of the temperature profile may be used to optimize RF and cryo ablation.

Due to the periodic contraction of the heart, a pulse-shaped course of the blood velocity is caused in the aortic system. The speed at which this pulse wave moves is called pulse wave velocity (PWV). Since it depends, among other parameters, on the elasticity of the vascular wall, it can be used clinically as an indicator of atherosclerotic changes and, above all, as a measure of the risk of stroke for hypertensive patients. PWV can be determined non-invasively if the blood flow in the aorta is measured via flow-sensitive MRI. Within the scope of this work, existing phase-contrast (PC) image analysis algorithms, resulting in the PWV, were embedded in a graphical user interface (GUI). These algorithms were only able to evaluate PC images which were acquired on a Philips tomograph. Therefore they have been extended for the analysis of PC images acquired on a Siemens tomograph.

Mechanical parameters of hard and soft tissues are explicit markers for quantitative tissue characterization. In this study, we present a biphasic 3D-FE-based method to determine the biomechanical properties of equine articular cartilage from creep indentation tests (F = 0.1 N, t = 1000 s). The FE-model computation was optimized by exploiting the axial symmetry and mesh resolution. Parameter identification was executed with the Levenberg-Marquardt-algorithm. Additionally, sensitivity analyses of the calculated biomechanical parameters were performed. Results show that the Young’s modulus has the largest influence and the Poisson’s ratio of ν ≤ 0.1 is rather insensitive. The R² of the fit results varies between 0.882 and 0.974. The determined values for the Young’s modulus were 0.806 ± 0.093 MPa, the Poisson’s ratio 0.03 ± 0.06 and the permeability 0.012 ± 0.002 mm4/Ns. Future work will deal with mathematical extensions of the biphasic 3D-FE-model.

The mechanical parameters of articular cartilage estimated from indentation tests depend on the constitutive model adopted to analyze the data. In this study, we present a 3D-FE-based method to determine the biomechanical properties of equine articular cartilage from stress relaxation indentation tests (ε = 6 %, t = 1000 s ) whereby articular cartilage is modeled as a biphasic material without (BM) and with tension-compression nonlinearity (BMTCN). The FEmodel computation was optimized by exploiting the axial symmetry and mesh resolution. Parameter identification was executed with the Levenberg-Marquardt-algorithm. The R² of the fit results varies between 0.695 and 0.930 for the BMmodel and between 0.877 and 0.958 for the BMTCN-model. The differences of the R² occur from the more exact description of the initial stress relaxation behaviour by the fiber modulus from the BMTCN-model. The fiber modulus defines the collagen matrix of cartilage. Furthermore, for both models the determined values of Young’s modulus and permeability were in the same order of magnitude.

Corneal collagen cross-linking (CXL) with riboflavin and UVA light is a therapeutic procedure to restore the mechanical stability of corneal tissue. The treatment method applies to pathological tissue changes, such as keratoconus. It induces the photochemical formation of new collagen cross-links. Although therapeutic effects are indisputable, the exact molecular process of CXL and how cross-links are formed is still unclear. In this work, Fouriertransform infrared (FT-IR) spectroscopy is used to investigate the cross-linking process. For that purpose, in-situ experiments with porcine corneas are carried out using attenuated total reflection (ATR) spectroscopy. Furthermore, IR micro-spectroscopic imaging in transmission mode is used to investigate thin tissue sections of the cornea and initial approaches for the distinction of cross-linked and untreated tissue by IR microspectroscopic imaging were performed. Multivariate methods are applied to access changes that occur as a result of CXL. It is shown that spectral changes after cross-linking are caused predominantly by an increase of methyl- and methylene groups as well as primary and secondary amines. In addition, a decrease of carbonyl groups could be observed.

Electrospun poly(L-lactide) (PLLA) nonwoven represent potential options for biodegradable medical implants. They can be manufactured with high reproducibility and do offer the potential for chemical modification to alter matrix properties. In our study, we investigate the mechanical, thermal and morphological properties of PLLA fiber matrices. Fibrous nonwovens were fabricated from polymer solution by needle electrospinning. The polymer solutions were loaded with Triton X-100 (TX- 100), formic acid and tetraethyl ammonium chloride (TEAC) with respect to polymer weight. Morphology of the PLLA nonwoven scaffolds was examined with SEM. We performed uniaxial tensile tests and differential scanning calorimetry (DSC). Different concentrations of the additives TEAC, formic acid and Triton X-100 lead to strong changes regarding mechanical and thermal properties of the electrospun PLLA fiber matrices. In comparison with mechanical properties of established biological tissue materials, the results indicate the suitability for medical applications.

An 18 years old male patient was diagnosed with genetically confirmed hereditary spastic paraplegia of type SPG11 - a rare disease of neurodegeneration. During normal clinical routine investigation, he presented with a moderate sinus bradycardia. The function of the cardiovascular system was investigated by recording electrocardiogram, impedance cardiogram and continuous blood pressure non-invasively. Cardiac function appeared normal in all modalities. Baroreflex sensitivity was strongly increased by a factor of 2.8. Results indicate that further to hyperactivity of deep tendon reflexes, also the responsiveness regarding control of heart rhythm by baroreceptors is significantly increased. This finding provides evidence for the impact of a neurological disorder onto the cardiovascular system and its autonomic control.

Conventional computed tomography (CT) systems are encapsulated in hardware and software. Integration of further imaging modalities and sensors which can acquire prior knowledge for dose saving image acquisition and reconstruction techniques are barely possible. Within the scope of our research project, an open interface and freely configurable CT system is now being developed. The integration of further modalities and sensors into this system is a main target. A subproject deals with a multi sensor patient table, which provides additional information through integrated sensors. In particular, force sensors are installed inside the patient table to determine the patient’s mass. This value can be used to specify the required tube voltage, so that a more precise setting can be made in comparison to today‘s clinical practice. Studys show that a more precise kVp estimation can significantly reduce patient dose. Sensors for the monitoring of respiration and pulse are also integrated into the setup of the patient table. On the one hand, these are designed to encourage the patients to minimize disturbing movements and on the other hand to generate trigger signals for the examination. In addition to the sensor concept of the table, a position control system for vertical and horizontal movement of the table is integrated. The position of the table can be adjusted using different input devices so that a fast and intuitive handling of the table movement can be achieved for standard diagnostic and CT guided interventional procedures. The communication between all sensors, actors and the CT ist realized via the Robot Operating System (ROS) framework.

To provide an effective and safe therapy for chronic Eustachian tube dysfunction (ETD), biodegradable stents should be developed to restore important functions, e.g. middle ear ventilation and drainage. After defining general requirements specifications, stent designs of cardiovascular polymeric stents were modified according to dimensions and conditions of the Eustachian tube. Finite element simulations demonstrated the crimping capacity of the developed stent design and the ability of expansion in the specific geometry of the target location. Subsequent in vitro tests of stent prototypes showed satisfying properties concerning crimpability, expansion behavior and elastic recoil to demonstrate general feasibility. Further developments and additional testing will advance the implementation of a new treatment option of ETD.

The choice of a cochlear implant electrode carrier for the individual patient is influenced by cochlear size, as this parameter has an impact on the risk of scala dislocations. Therefore, size and morphology should be represented in artificial cochlear models too, since these are generally used for insertion studies evaluating newly developed cochlear implant electrode carriers and insertion techniques, before human temporal bone studies are applied for. Within this study custom-made electrode carrier test samples were inserted into nine artificial cochlear models of different shape. To fabricate them, four human temporal bone samples have been processed by a serial cross-sectioning technique; the other four samples have been scanned with micro computed tomography. The cochlea was segmented on this data using rotating, midmodiolar slice planes, followed by the generation of a three-dimensional digital model, which finally was projected on a plane and 2D models were milled out of PTFE. The ratios of length to width of the cochlear basal turn of our samples were found to be within previously reported range. For comparative reasons a model used in previous studies was included in this study too. The maximal insertion forces per cochlear model followed a normal distribution. The insertion depth at initial insertion force increase is correlated to the length of cochlear basal turn. Using the here presented cochlear models with varying anatomical measures may help to increase the clinical relevance of insertion studies in artificial cochlear models.

Spirometry is the most commonly used pulmonary function test. The aim of this comparative study was to evaluate four commercially available spirometers with different measurement principles (turbine-, ultrasound-, differential pressure- and hot-wire anemometer). In particular, the measurement accuracy in breathing manoeuvres with low flow rates was investigated, which is highly relevant for paediatric use. Among the tested devices the hot-wire based spirometer showed the highest measurement accuracy at low flows whilst fully complying with the ATS/ERS standards.

Contemporary surgical microscope systems have excellent optical properties but some desirable features remain unavailable. The number of co-observers is currently restricted, by spatial and optical limitations, to only two. Moreover, ergonomics poses are a problem: Current microscope systems impede free movement and sometimes demand that surgeons take uncomfortable postures over long periods of time. To rectify these issues, some companies developed surgical microscope systems based on a streaming approach. These systems remove some of the limitations. Multi-observer positions, for example, are not independent from each other, for example. In order to overcome the aforementioned limitations, we are currently developing an approach for the next generation of surgical microscope: Namely the fully digital surgical microscope, where the current observation system is replaced with a camera array, allowing real-time 3D reconstruction of surgical scenes and, consequently, the rendering of almost unlimited views for multiple observers. These digital microscopes could make the perspective through the microscope unnecessary allowing the surgeon to move freely and work in more comfortable postures. The requirements on the camera array in such a system have to be determined. For this purpose, we propose of estimation the minimal number of cameras and their positions needed for the 3D reconstruction of microsurgical scenes. The method of estimation is based on the requirements for the 3D reconstruction. Within the MATLAB simulation environment, we have developed a 3D model of a microsurgical scene, used for the determination of the number of required cameras. In a next step a small, compact and costefficient system with few opto-mechanical components could be manufactured.

Electrophoretic deposition (EPD) is a material processing technology which uses direct current (DC) voltage to deposit thin layers on a metallic substrate. EPD is a promising coating technology for medical devices due to its advantages such as thin homogenous layers and a broad range of usable substrates. The objective of this paper is to demonstrate how EPD can be deployed successfully to apply an insulation layer on a stimulation electrode. The Mapping suction probe by inomed Medizintechnik GmbH, Germany, was coated in this investigation. The unique feature of this product is that it combines both a surgical vacuum and a stimulation probe and is used for brain tumour resection. As for the insulation layer, ethylene chlorotrifluoroethylene (ECTFE) was chosen because of its good dielectric and biocompatible properties. ECTFE particles (Halar®6514, Solvay Specialty Polymer, Italy) were mixed with a solvent (Novec™ 7100DL Engineered Fluid, 3M™) to form a suspension. The coating process was partly automatized to ensure good repeatability and reproducibility. For coating, the stimulation probe was immersed in the suspension so that the counter electrode, a stainless-steel net, surrounded it equidistantly. A heat treatment of the coated device in an oven (FED56, Binder, Germany) was required afterwards to melt the deposited polymer particles. After the heat treatment, a glossy black layer (layer thickness 42 μm) was observed on the substrate. A smooth and homogenous surface confirmed that the coating is suitable for surgical application. However, due to a high evaporation rate of the solvent, the ratio of particles and solvent changes and the coating process will have to be controlled in the future to achieve a stable process. Further advantages of EPD such as short processing time, straightforward process flow and scalability enables high production quantities which is attractive for industrial application. EPD might be a promising coating technology for medical devices in the future.

Many machine learning algorithms depend on the choice of an appropriate similarity or distance measure. Comparing such measures in different domains and on diversely structured data is common, but often performed in regards of an algorithm to cluster or classify the data. In this study, data assessed by experts is analyzed instead. The data is taken from the database of the Federal Institute for Drugs and Medical Devices (BfArM) and represents free text incident reports. The Average Silhouette Width, a cluster density measure, is used to compare the distance measures’ ability to discriminate the data according to the experts’ assessments. The Euclidean distance and four distance measures derived from the Jaccard similarity, the Simple Matching similarity, the Cosine similarity and the Yule similarity are compared on four subsets of this database. The results show, that a better data preprocessing is necessary, possibly due to boilerplate texts being used to write incident reports. These results will also provide the basis to compare improvements by different methods of data preprocessing in the future.

The presented three different balloon dilation devices for treating Eustachian tube dysfunction were compared regarding their geometries and designs. The balloon dilation behaviour was investigated by an in vitro test setup consisting of a test chamber with 37 °C water, a 2-axis laser scanner and a pressure controller. All balloons could be properly dilated up to the given nominal pressure (NP) or to rated burst pressure (RBP). The balloons reached their expected balloon diameter and length. The compliance data were 1.07 %/atm (TubaVent short), 1.16 %/atm (Acclarent Aera) and 1.28 %/atm (XprESS LoProfile). The measured profile and compliance data can be used for development of new devices for balloon dilation Eustachian tuboplasty.

A series of novel biomedical TPCUs with different percentages of hard segment and a silicone component in the soft segment were synthesized in a multi-stage one-pot method. The kinetic profiles of the urethane formation in TPCU-based copolymer systems were monitored by rheological, in line FTIR spectroscopic (React IR) and real-time calorimetric (RC1) methods. This process-analytically monitored multi step synthesis was successfully used to optimize the production of medical-grade TPCU elastomers on preparative scale (in lots of several kg) with controlled molecular structure and mechanical properties. Various surface and bulk analytical methods as well as systematic studies of the mechanic response of the elastomer end-products towards compression and tensile loading were used to estimate the bio-stability of the prepared TPCUs in vitro after 3 months. The tests suggested that high bio-stability of all polyurethane formulations using accelerating in vitro test can be attributed to the synthetic design as well as to the specific techniques used for specimen preparation, namely: (i) the annealing for reducing residual polymer surface stress and preventing IES, (ii) stabilization of the morphology by long-time storage of the specimens after processing bevor being immersed in the test liquids, (iii) purification by extraction to remove the shot chain oligomers which are the most susceptible to degradation. All mechanical tests were performed on cylindrical and circular disc specimens for modelling the thickness of the meniscus implants under application-relevant stress conditions.

For the development of new stent designs, the compliance of the surrounding biological tissue has to be considered. We expect to obtain parameters for simulation, stent dimensioning, and the forces acting on the stent after implantation. Starting point of the investigations is the commercially available Metricath system allowing cross-sectional lumen area measurements of arteries. Its working principle is based on the pressure-volume relationship using a balloon catheter, which is inflated to a specific pressure of about 250 mmHg and conforms to the shape and size of the lumen. However, for compliance charts multiple pressure levels and a larger pressure range are needed. To overcome this technical limitation, the Metricath balloon catheter is combined with a new inflation device, called pV-Monitor. The presented cross-sectional lumen area measurements in rigid tubes and compliance investigations of elastic tubes demonstrate the feasibility of the pV-Monitor system.

In biosignal processing, the importance of modeling and simulation to assist the development of methods, algorithms and systems is increasing. However, models and simulation environments may also be used in the later application, e.g. to enable physicians, therapists and nurses to provide assistance in treatment. Most of the time, however, the difficulty is to implement and apply the rather complex model data or to evaluate the output of the model. For this purpose, the paper presents a method that intelligibly prepares the input data of a biomechanical model for the end user using a game development environment

Intraoperative speech mapping is performed to preserve language function during tumour resections that involve eloquent cortical areas. For this technique the synchronization of the picture presentation to the patient with the electrical stimulation of the cortex is of major importance. During the operative routine images are manually presented by a psychologist or neurologist to the patient and have to be coordinated with the neurosurgeon stimulating the cortex by a neurostimulator, operated by an engineer. To increase the efficiency of this procedure and to minimize the time needed to localize functional cortical areas, images should appear automatically with electrical stimulation. To achieve this synchronization, the potential combination of an existing neurostimulator with commercially available software for image display was studied. A trigger signal was created to induce the presentation of a series of line drawings showing different objects. The software to control the neurostimulator and the software for image displaying were installed on two different computers. A cable was developed to transfer the trigger signal from the neurostimulator to the computer used for picture presentation. It was shown that it is possible to induce the image display via the neurostimulator using square-wave pulses of 5 V and a width of 10 ms. Thus, we present a system that enables the automated picture presentation synchronized to the electrical stimulation of cortical regions.

Cardiac contractility modulation (CCM) is a device-based therapy for the treatment of systolic left ventricular chronic heart failure. Unlike other devicebased therapies for heart failure, CCM delivers nonexcitatory pacing signals to the myocardium. This leads to an extension of the action potential and to an improved contractility of the heart. The modeling and simulation was done with the electromagnetic simulation software CST. Three CCM electrodes were inserted into the Offenburg heart rhythm model and subsequently simulated the electric field propagation in CCM therapy. In addition, simulations of CCM have been performed with electrodes from other device-based therapies, such as cardiac resynchronization therapy (CRT) and implantable cardioverter./.defibrillator (ICD) therapy. At the same distance to the simulation electrode, the electric field is slightly stronger in CCM therapy than in CCM therapy with additionally implanted CRT or ICD electrodes. In addition, there is a change in the electric field propagation at the electrodes of the CRT and the shock electrode of the ICD. By simulating several different therapy procedures on the heart, it is possible to check how they affect their behavior during normal operation. CCM heart rhythm model simulation allows the evaluation the individual electrical pacing and sensing field during CCM.

In this contribution we propose a feature-based method for motion estimation and correction in intraoperative thermal imaging during brain surgery. The motion is estimated from co-registered white-light images in order to perform a robust motion correction on the thermographic data. To ensure real-time performance of an intraoperative application, we optimise the processing time which essentially depends on the number of key points found by our algorithm. For this purpose we evaluate the effect of applying an non-maximum suppression (NMS) to improve the feature detection efficiency. Furthermore we propose an adaptive method to determine the size of the suppression area, resulting in a trade-off between accuracy and processing time.

Restoration loss based on interfacial adhesive defects and associated caries at the restoration margin are the main causes for invasive replacement of dental restorations. Assessment of the interfacial quality based on clinical inspection and radiographic examination is often difficult and not reliable. In this work, we present spectral domain optical coherence tomography (SDOCT) and polarization sensitive optical coherence tomography (PSOCT) for the evaluation of tooth-composite bond failure. Imaging of two composite restorations at the occlusal surface are presented using intensity-based images obtained by SDOCT and PSOCT based degree of polarization uniformity (DOPU). Both modalities revealed several defects beneath the surface such as inhomogeneous adhesive layers, marginal gaps and bubbles. In addition, DOPU representation showed an inhomogeneous structure within the composite material. OCT based imaging of dental restorations could add a valuable diagnostic tool for the evaluation of structural defects in clinical practice. The representation of polarization characteristics with the DOPU algorithm provides further information on the homogeneity of the restoration.

Prior to cochlear implantation, audiological tests are performed to determine candidacy in subjects with a hearing loss. This is usually done by measuring the acoustic auditory brainstem response (ABR). Unfortunately, for some subjects, a reproducible ABR recording cannot be obtained, even at high acoustic levels. Having a healthy stimulating auditory nerve is required for cochlear implantation in order to benefit from the electrical pulses that are generated by the implant and to improve speech comprehension. In some subjects, this prerequisite cannot be measured using routine audiological tests. In this study, the feasibility of recording electrically evoked auditory brainstem responses (eABR) using a stimulating transtympanic electrode, placed on the round window niche, together with MED-EL clinical system is investigated. The results show that it is possible to record reproducible eABR measurements using PromBERA. The response was also confirmed with intraoperative eABR measurements that were stimulated using the implanted CI electrode array. Similarities between the intraoperative measurements and the preoperative recorded waveforms were observed. In summary, the integrity and excitability of the auditory nerve can be objectively measured using the PromBERA in subjects where standard clinical testing procedures are unable to provide the information required.

For fabrication of polymeric implants and drug carriers volatile organic solvents, such as chloroform, are widely used. In order to remove solvents for patient safety several processes have to be carried out to avoid changes in the thermal characteristics of the polymers, as well as in the drug release profile and mechanical properties. We analyzed films of the polymer poly(ε−caprolactone) (PCL), a common commercial medical grade polymer which is widely used in implants and drug carriers. Considering the influence on the morphology and thermal properties we screened different post treatment processes. Acceptable chloroform contents according to recommendations of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) without changes in morphology and crystallinity were achieved via a simple annealing process for 24 h at 40°C and 40 mbar.

For minimising tissue reactions of implants hydrophilic silicone elastomers feature a high potential to be utilised as material for micro-implants in ophthalmologic pathology. To estimate the biocompatibility we quantified cell viability of human primary fibroblasts from scleral (hSF) and choroideal (hCF) origin in direct contact test and evaluated cell adhesion and cell morphology with Phalloidin- TRITC stained hSF and EA.hy926. Mechanical properties were analysed by means of uniaxial tensile testing. Direct contact testing revealed a good biocompatibility from 65 to 70% relative cell viability for hCF and moderate viabilities (46 to 63%) for hSF. EA.hy926 and also hSF exhibited typical cell morphology on the silicones. Improvement of cell adhesion was observed with increasing amount of hydrophilic component. Mechanical testing shows a minor decrease in elongation at break from 236% to 155% with increasing amount of hydrophilic component. These findings indicate that the investigated silicones may ensure a reliable integration of implants into the ocular tissues.

Chemical identification of particles increasingly gains importance concerning regulatory affairs of medical devices. Particle numbers of samples very easily add up to orders larger than 1.000. Therefore an automated particle measurement is absolutely worthwhile. As a method of chemical identification Raman spectroscopy combined with microscopy is commonly used. The challenge is to distinguish small particles in a range of a few microns on a surface from the background. Different specimen holder made of glass, polymer (e.g. polycarbonate) or metal are commonly used. After the choice of suitable background parameters such as magnification, optical resolution, focal plane and brightness have to be optimized. The used software for Raman microscopy offers the possibility to select particles for the subsequent measurement. Therefore the xand y-coordinates of particles have to be added to a list manually and separately. This so called point list can be processed automatically. However, this procedure is very laborious and requires a high degree of user interaction especially in case of large particle numbers. Furthermore the software offers the possibility to perform a so called area scan, where a defined surface of the the specimen will be spectroscopically analyzed. The measurements are performed in defined distances on a grid, e.g. every 10 micrometer in xand y-direction. The choice of this tool leads to a large number of measuring points associated with an unwanted long measuring time. By means of the freely accessible software ImageJ an alternative path was found to relate xand y-coordinates to every particle. These coordinates can be imported into the point list of the software for Raman microscopy. Afterwards a Raman spectrum for every particle can be measured without further high effort in time.

During labour, foetal monitoring enables clinicians to prevent potential adverse outcomes, whose surveillance procedure is commonly based on analysis of cardiotocographic (CTG) signals. Unfortunately, this procedure is difficult because it involves human interpretation of highly complex signals. In order to improve the CTG assessment, different approaches based on signal processing techniques have been proposed. However, most of them do not consider the progression of the foetal response over time. In this work, we propose to study such progression along the foetal heart rate (FHR) signal by using spectral analysis based on time-varying autoregressive modelling. The main idea is to investigate if a particular FHR signal episode in the time-domain reflects dynamical changes in the frequency-domain that can help to assess the foetal condition. Results show that each FHR deceleration leaves a particular time-varying frequency signature described by the spectral energy components which could help to distinguish between a normal and a pathological foetus.

Although current drug eluting stents show low risks of in-stent restenosis and stent thrombosis, the presence of a permanent foreign body inside the vessel represents a major limitation. In order to overcome this limitation, stents made of biodegradable polymeric materials are currently being developed. The present work describes an optimized fabrication process for tubular semi-finished products for manufacturing of stents made of poly-L-lactide (PLLA). The impact of the haul-off speed as a major parameter during extrusion processing on the cross-sectional area of tubular specimens was analyzed. It could be shown that the crosssection of the extrudate, in particular the tubing diameter and wall thickness, can be adjusted by varying haul-off speed. In a subsequent blow molding process the influence of the holding time on polymer cold crystallization was analyzed. Thermal properties of the polymeric material after processing were examined by differential scanning calorimetry (DSC). The results showed that there is almost no cold crystallization using a holding time of at least 20 minutes. The investigations showed that semi-finished products with variable geometry and improved mechanical properties can be produced with the described extrusion and blow molding process.

Computational Fluid Dynamics studies try to support physicians during therapy planning of intracranial aneurysms. However, multiple assumptions (e.g. rigid vessel walls) are required leading to a sparse acceptance of numerical approaches within the medical community. This study incorporates multiple fluid-structural simulations for an intracranial basilar artery bifurcation. Based on a patient-specific dataset, which was acquired using optical coherence tomography, minimum, mean, maximum, and diameter-dependent thicknesses were generated and compared w.r.t. hemodynamic and wall stress parameters. The comparison of different wall thickness models revealed a strong variability among the analyzed parameters depending on the corresponding assumption. Using the patient-specific configuration as a reference, constant thicknesses lead to differences of up to 100 % in the mean wall stresses. Even the diameter-dependent thickness results in deviations of 32 %, demonstrating the wide variability of computational predictions due to inaccurate assumptions. The findings of this study highlight the importance of geometry reconstruction including accurate wall thickness reproduction for fluid-structure simulations. Patient-specific wall thickness seems to be out of alternatives regarding the realistic prediction of wall stress distributions.

Sirolimus incorporated nonwoven polymer matrices were fabricated via electrospinning. Release kinetics considering different fiber diameters and layer thicknesses were investigated. In vitro drug release profiles were evaluated by measuring the drug concentration in an established drug release medium (0.9% saline solution with additives, not buffered) at predetermined time points. Furthermore, an NH 3 -plasma pretreatment was examined to ensure complete wetting from the beginning of the study. In comparison to thin drug-loaded PLLA spray coatings it was shown that the release of sirolimus is diffusion- and degradation-controlled regardless of the surface-to-volume ratio, though fiber diameters or a hydrophilization can affect its release kinetics.

Artificial limbs, equipped with miniaturized tactile sensors, can handle objects with more dexterousness. Next to detecting forces, the sensor devices are also able to measure temperature. With this additional information, the touched objects can be better characterized. As such sensors, active CMOS-based capacitive pressure sensors are used in this work. The Sensors are thinned to 20-30 μm target thickness to make them bendable. One challenge of such thin sensors is the strong dependence of the output signal upon bending. To compensate this dependency, two sensors were mounted back to back. This allows a numerical adjustment of the two characteristic sensor output signals to mechanical stress curves. After electrically contacting of the stacks with a 15 μm thin polyimide foil substrate, the bending dependence of the stacks was characterized with a four-point bending procedure. By this characterization the dependency of the pressure sensor output signal on the height of mechanical stress was determined. Both sensor output signals show an inverted behavior under the same mechanical stress which confirmed prior simulation results with the same setup. Based on this information, a numerical method for compensating the bending dependence was successfully proven.

The regaining elastic behavior of the artery after treatment with a bioresorbable scaffold is a measure for successful degradation. The investigation of the elastic properties of arteries is often performed using ultrasound based methods. The current study describes an in vitro test setup for the measurement of the elastic radial compliance of blood vessels with an automated laser scanning device. A porcine carotid artery was placed inside a phosphate buffered saline filled chamber and the outer diameter was measured during stepwise pressurization from 20 mmHg to 160 mmHg. Reference measurements were done with an ultrasound based method. The results show that the automated laser scanning device method provides similar values to the ultrasound measurements. Therefore, the automated laser scanning device method appears to be suitable to investigate radial compliance differences of a stented vessel segment during the degradation process of a bioresorbable scaffold in vitro. The high degree of automation allows for an effective investigation of a larger series of measurements.

Glaucoma represents the leading cause of irreversible blindness worldwide. Therapeutic approaches are based on the lowering of intraocular pressure (IOP). Micro-invasive glaucoma surgery (MIGS) offers perspectives for implant based IOP-reduction with reduced complication rates compared to conventional surgical approaches. Nevertheless, available devices suffer from complications like hypotony and fibrotic encapsulation. The current work focuses on the development of a minimally invasive implantable drugeluting microstent for the drainage of aqueous humour into suprachoroidal or subconjunctival space. Technical feasibility of a micro-scale resorbable nonwoven for the prevention of hypotony and of a drug-eluting coating for the prevention of fibrosis is assessed. Microstent base bodies with a length of 10 mm and an inner/outer diameter of 0.20 mm / 0.35 mm were manufactured. For the prevention of hypotony, resorbable nonwovens with an adequate flow resistance of 1.543 mmHg/μl min-1 were manufactured in the inflow area of microstents. A drug-eluting coating in the outflow area of microstents was developed based on the model drug fluorescein diacetate. Micro-invasive ab interno implantation of a microstent prototype into suprachoroidal space of a porcine eye post mortem was successfully performed, using an injector device. Future studies will focus on the development of an antifibrotic drug-eluting coating and further in vitro, ex vivo and in vivo testing of the devices.

Radiation therapy is a valuable option for treatment of skin cancer. In order to deliver the radiation dose to the superficial skin tumor, an X-ray source, electron beam radiation therapy or a radioisotope is applied. The effectiveness of these procedures is well established in the literature. Findings of some recent studies have indicated that beta particles can be of particular interest in suppressing skin tumor growth. Betaemitting radioisotopes are favorable because of the short penetration depth of their emitted particles. Beta radiation can induce significant damage in superficial skin tumor, and at the same time, result in enhanced protection of the underlying healthy tissues. In this study, we propose the design of a patch that can be used in beta radiation therapy of skin cancer patients. For that, we describe the components of this radioactive patch, as well as a proposal for the subsequent clinical application procedure. A scaffold was used as a substrate for embedding the desired beta-emitting radioisotope, and two layers of hydrogel to provide protection and shielding for the radioactively labelled scaffold. The proposed design could provide a universal platform for all beta-emitting radioisotopes. Depending on the depth of the tumor spread, a suitable beta emitter for that specific tumor can be selected and used. This is of particular and critical importance in cases where the tumor is located directly on top of the bone and for which the depth of penetration of radiation should be limited to only the tumor volume. The proposed design has the mechanical flexibility to adapt to curved body regions so as to allow the use in anatomically challenging areas of the body.

An ultrasonic-assisted bone instrument can be used for the dissection of bone in spinal surgery. During surgery, the tip of such a bone instrument can touch spinal dura mater. Especially during critical re-operations, high forces can be unintentionally applied on spinal dura mater. To prevent dural tears, the influence of application parameters on the tear force shall be analyzed. Collagen foil is used as a substitute material for spinal dura mater because of its similar mechanical properties and structure. Sponge cloth is placed below collagen foil to imitate cerebrospinal fluid and nerve tissue. A 3-axis CNC-machine is used to automate the movement of the bone instrument. In a full factorial experiment the influence of amplitude, shape of movement and velocity of movement on the tear force is analyzed. Amplitude has the strongest effect because of the increase in input energy. Velocity also has a significant influence, probably because of the strain rate increasing with velocity. Thus, a surgeon should mainly reduce the amplitude and furthermore the velocity of movement to generate higher safety in critical areas.

We report on investigations that illustrate the interaction between the specific immune system and a young avascular tumor growing due to a diffusive nutrient supply. We formulate a hybrid cellular automata-partial differential equation (CA-PDE) model which includes cell cycle dynamics and allows for tracking the spatial and temporal evolution of this elaborate biological system. We present results of two dimensional numerical simulations that, specifically in this work, include special cases of the spherical and papillary tumor growth, the infiltration of immune system cells into the tumor and the escape of tumor cells from the regime of the immune cells.

The 12-channel ECG is an important tool used for the diagnosis and treatment of various cardiac and other related diseases. The recording procedure requires the exact placement of 10 electrodes on the patients, because incorrect placement can lead to improper signals and, consequently, to false diagnoses. In addition, the placement of 10 electrodes is time consuming, often interferes with clinical processes, and is less patient-friendly. One possible solution could be the usage of a vector-based, 5-electrode, 12-lead monitoring ECG system (EASI). The aim of this work is to establish a quantitative comparison between the conventional 12-lead ECG and an EASI ECG by cross-correlating signals of the same type. For this purpose, we used a conventional 12-lead ECG device, Schwarzer Cardiotek GmbH; and an EASI device, Schwarzer Cardiotek GmbH. All instruments were made available by the company CRS medical GmbH. Both devices were simultaneously connected to an informed, healthy volunteer and signals were recorded under resting conditions. Crosscorrelation functions were calculated and analysed by using Matlab R2015a between the same original and filtered signal types, e.g. conventional and EASI lead I. Time lags between the recordings were compensated adequately. All signals, up to two conventional signals, were of high quality. We found a high degree of correlations between 10 of 12 leads (r > 0.9). However, the conventional recording system is more sensible to artifacts, muscle activities and noise, very likely due to its more complex electrode configuration and larger electrical sensing area. A visual inspection of the conventional and EASI time courses by an expert also indicated that EASI is useful in clinical practice. We compared a conventional 12-lead ECG with an EASI ECG by signal correlations. The results indicate that EASI is well suited for cardiologic routine: simplified electrode placement and reasonable signal quality. However, additional investigations are required, especially to test EASI for diagnostic purposes and with more sophisticated statistical methods.

Haptic feedback can be helpful for accurate needle insertion but is complicated by friction on the needle shaft. Concepts to directly measure the forces at the needle tip exist but cause additional cost and complexity. Moreover, haptic devices may show inaccuracies in recreating forces. We present a novel force feedback method that uses needle shaft forces and enhances haptic feedback of subsurfaces based on robotic ultrasound elastography. This approach allows to overcome accuracy limitations of haptic devices. We evaluate our method in a volunteer subject study using recordings from a robotic needle driver setup. We compare haptic feedback based on shaft and enhanced force for the detection of surfaces inside of gelatin phantoms. Using our method, the error of subsurface detection decreased from more than 16 to about 1.7 mm for the first subsurface. A second subsurface was solely detectable using our method with an error of only 1.4 mm. Insertion time decreased by more than 32%. The results indicate that our enhanced sensor is suitable to detect subsurfaces for untrained subjects using a haptic feedback device of limited accuracy.

Migraine attacks can be accompanied by many different symptoms, some of them appearing within 24 hours before the onset of the headache. In previous work, reduced habituation to an electrical pain stimulus at the head was observed in the pre-ictal phase within 24 hours before the headache attack. Based on these results, this work presents an application to track influence factors on migraine attacks and an Arduino-based control unit which replaces the traditional approach of manual electrical stimulation. The usability of both components of the project was evaluated in separate user studies. Results of the usability study show a good acceptance of the systems with a mean SUS score of 92.4. Additionally, they indicate that the developed control unit may substitute the current manual electrical stimulation. Overall, the designed system allows standardized repeatable measurements and is a first step towards the home-use of a device for establishing a new method for migraine prediction.

Standardized methods and measures are ubiquitous in biomedical engineering and a key factor for the successful development and certification of novel biomaterials, implants or other medical devices. Hence, the development of standardized measurement techniques, which can be applied to nearly every material and device is of crucial importance. Within the current work, we introduce a method to evaluate the water permeability according to ISO/FDIS 7198. The setup was designed to determine the volumetric flow through a test sample for a given hydraulic pressure. One key feature is the effortless replacement of the chamber containing the test sample. The measurement technique can thus be applied to a variety of materials and medical devices. To demonstrate the functionality of the setup we fabricated nanofiber membranes using the process of electrospinning. Nonwovens with comparable thickness and varying morphology were analyzed with regard to water permeability. In particular the different fiber diameters as well as the modified inter-fiber distances result in large deviations of the water permeability. Furthermore, there are hints for a rearrangement of the nanofibers due to the applied hydraulic pressure. The developed measurement technique provides a powerful tool for the standardized quantification of the water permeability and can be applied to a variety of biomaterials and medical devices.

The usage of synthetic scaffolds is a promising approach in development of implant materials. In this study we fabricated nanofibrous nonwovens of polyamide 6 (PA-6) by means of electrospinning and performed a systematic characterization with regard to the mechanical and biological performance of scaffold materials. Mechanical strength was assessed by uniaxial tensile testing and biological performance was evaluated by measuring cell viability and qualitative analysis of cellular morphology when human umbilical vein endothelial cells (EA.hy926) or human fibroblasts (HT-1080) were grown on polymeric substrates. While all polymeric materials exhibited an excellent biocompatibility with respect to cell viability, their surface topography promoted the adhesion of endothelial but not fibroblast cells. A better understanding of the physicochemical and morphological material properties with a selective impact on cell adhesion will help to further improve biocompatibility of nonwovens for biomedical applications.

Within this work we demonstrate different Anodic Oxidation processes to achieve a broad variety of nanostructures on titanium and the titanium alloy Ti6Al4V for the use as medical implant surfaces. The influence of electrolyte, reaction time and voltage on the nanostructure formation is described as well as the transfer to microstructured surfaces. As electrolytes we investigate sulfuric and hydrofluoric acids with different concentrations. The resulting nanostructures reach from nano porosities over amorphous sponge like structures to self-assembled hexagonal nanotubes.

The complexity of medical devices and its user interactions increases. A growing number of incident reports are assumed to be associated primarily with user errors. This development is tackled through current modifications in standards, such as ISO 13485:2016 and legislations, such as the Medical Device Regulation. Both intensify the focus on use errors significantly. The aim of this paper was the development of a process orientated approach integrating usability engineering into a consisting risk management based on a classic V-model. An appropriate procedure was worked out. For each development step, risk and usability activities were cumulated. Thus, the present paper might help medical device manufacturers to reflect their risk management and usability management processes to find synergies. Prospectively, a step-by-step guide for the integration of risk management and usability engineering based on this approach should be developed.

The aging of humans induces muscle weakness. Muscle weakness results the inability to climb stairs or stand up from a chair and thus, is one of the first steps towards elderly having a less autonomous and self-sufficient life. Therefore, an accessible active knee orthosis, which especially supports these movements would be of great assistance. Recent research projects have focused on feasibility, perfection of motion control and imitation of human movement. For active knee orthoses to be accessible it must be affordable. Hence, this paper systematically evaluates the current research projects around active knee orthosis and discuss the possibilities of implementing a lowcost active knee orthosis.

For known reasons, the European Parliament was forced not only to revise the old Medical Device Directive (MDD) and the Active Implantable Medical Devices Directive (AIMDD), but to replace it with the extensive MDR. With the implementation of the Medical Device Regulation (MDR) in May 2017, manufacturers of medical devices will face new challenges for their products in the future, which also have to be implemented in a timely manner. Particularly small and medium-sized enterprises (SMEs) are concerned about whether a timely adaptation to the MDR and their requirements can be implemented. The conversion is associated with a huge effort for all producers of medical devices and certainly, produkt launchers. The purpose of this paper is to get an overview of the most relevant and emerging requirements that manufacturers need to adapt to sell their medical devices in compliance with the MDR regulations. It also explains the extent to which changes and innovations in the MDR are discusses and problems for SMEs.

A software for automatic registration and differential visualization of pre- and postoperative surface scans for use in pediatric neurosurgery is developed and implemented. The core operations of the registration include an automatic head extraction, a rough registration by aligning the main axes, a depth map-based registration for robust determination and registration of feature points in the facial area, and a fine registration. A graphical user interface is implemented for the difference visualization and program control.

Prosthetic textile implants of different shapes, sizes and polymers are used to correct the apical prolapse after hysterectomy (removal of the uterus). The selection of the implant before or during minimally invasive surgery depends on the patient’s anatomical defect, intended function after reconstruction and most importantly the surgeon’s preference. Weakness or damage of the supporting tissues during childbirth, menopause or previous pelvic surgeries may put females in higher risk of prolapse. Numerical simulations of reconstructed pelvic floor with weakened tissues and organ supported by textile product models: DynaMesh ®- PRS soft, DynaMesh ®- PRP soft and DynaMesh ®- CESA from FEG Textiletechnik mbH, Germany are compared.

Following the VDMA guideline Industry 4.0 potential ways towards digitalization of production are illustrated using an example from dental technology. The special feature in medical engineering is the responsibility of the physician, particularly in the context of custom-made products. Data security, integrity, and traceability is mandatory in digital processes when responsibility is switching between parties, e.g. dental laboratory / practice. This article illustrates how those requirements can be met.

Current research activities focus on personalized, comfortable and safe products for systemic or local drug application in patients. Poly(ethylene glycol) diacrylate is in particular interest as a drug delivery material, as it shows appropriate biological properties such as hydrophilicity and low toxicity. Additionally, as an easily photopolymerizable compound it can be also utilized for the production of scaffolds with the use of different techniques such as stereolithography. Even though it is often used as a biomaterial or as a copolymer in many photopolymer systems for drug delivery, thermomechanical analysis and basic understanding are rare. Therefore, we investigated the tensile stress and the glass transition temperature of pure PEGDA and of its copolymers with 1,3-butanediol diacrylate or pentaerythritol triacrylate, as a function of the photoinitiator (PI) or acrylate concentration. Additionally, we demonstrated that the washing procedure decreases the tensile stress values. We showed, that by the means of composing PEGDA with these, it is possible to influence thermomechanical properties of the sample. Our outcomes have revealed, that there is no clear influence of the PI concentration on the thermomechanical properties. However there is an influence of the monomer concentration. Therefore, it should be possible to modify drug release profiles in future experiments.

The interest of this paper is the determination of the optical properties of oxygenated (saturation above 97 %) hemoglobin in clinical relevant concentrations (ranging from 5 to 15 g/dl), dependent on the layer thickness. Furthermore the generation of a high rate data set for training with machine learning approaches was intended. With a double integrating sphere setup (laser diodes from 780 to 1310 nm) - as a well referenced method - and flow through optical cuvettes ranging from 1 to 3 mm layer thickness, the transmission (𝑀 𝑇 ) and reflection (𝑀 𝑅 ) values of the samples were acquired. From those the layer thickness independent absorption (𝜇𝑎) and reduced scattering coefficients (𝜇𝑠’) were calculated by the means of the Inverse Adding Doubling (IAD) algorithm. For each sample the same coefficients should result correspondingly for all cuvette thicknesses in test. This relationship serves as an internal standard in the evaluation of the collected data sets. In parallel a spectrophotometer in the range from 690 to 1000 nm recorded transmission spectra for all samples as a second reference. First, the IAD algorithm provided optical coefficients (𝜇𝑎, 𝜇𝑠’) in all measurements, with few exceptions at low hemoglobin concentrations. The resulting coefficients match independently of the layer thickness. As a main second result, a high rate data set was generated which serves for further analysis - for example with machine learning approaches.

Within this work we demonstrate a UV-Lithography based method for the fabrication of microgrooves on titanium surfaces. The microgroove period, depth and profile form are easily controllable by process parameters. By controlled under-etching of a lithographically structured photo resist, different profile forms from nearly rectangular, over curvy/spiked to sinus-shaped forms with different amplitudes and sizes can be realized. The resulting microgrooves can be directly used as implant or implant abutment surfaces to enhance soft tissue integration or to create molds for cell/substrate interaction studies. Due to the lithographic process the whole method is highly controllable and reproducible.