Band 6, Heft 3 - Proceedings of the 2020 Annual Meeting of the German Society of Biomedical Engineering (29 September – 1 October 2020, Leipzig)

Healthcare in rural areas faces specific challenges, which make homecare of elderly people and cross-sectoral integrated care of chronically ill and multimorbid patients very complex and costly. Mobility and logistics are among other issues that need to be solved in this context. Therefore, it will be crucial to realize the potential of innovative solutions along the complete healthcare value chain, in order to deliver patient focused healthcare according to a value-based-healthcare-approach in the future. Against this background it is the objective of the project 5G4 Healthcare, which is funded by the Federal Ministry of Transport and Infrastructure, to establish a platform based on 5G technology, that enables the testing and the evaluation of digital applications in the context of rural healthcare. Consequently, the project 5G4 Healthcare aims at assessing the feasibility, opportunities and limitations of 5G regarding efficiency and effectiveness improvements in rural healthcare in order to derive recommendations and scalable solutions.

The Interoperability of medical devices and IT systems using various technologies in clinics and the preclinical area is still a research topic. The MOMENTUM project deals with the new 5G mobile technology and explores how they contribute to an improvement in emergency care. Different applications, as well as various technical and clinical aspects, including IT security, are considered. Integrated emergency care seems sensible, particularly for emergencies outside of metropolitan areas and for particularly critical cases.

Data from preclinical emergency care is often not available in an integrated, electronic way. Data flow between ambulances and trauma centers lacks a communication approach that allows for efficient aggregation, transmission and reuse. We present the results of the requirement analysis for 5G-supported emergency care scenarios. With the illustarted requirements and derived structural consequences, we conclude with a proposal that will allow us to provide mechanisms and technologies to enable integrated emergency communication for preclinical care using modern communication technologies.

The following work gives an overview of telemedical consultation in emergencies based on a research project. A telemedical centre located at a university hospital offers medical expertise for rural islands independent from place, time and urgency. Medical employees on the islands were relieved in matters of responsibilities and received medical support whenever it is necessary. Results from the projects mid-term evaluation compare the innovative concept with the conventional approach.

First aid of patients at the scene of an emergency requires an adequate flow of information. The publicly funded research project MOMENTUM aims at seamlessly connecting the point of care to the hospital. An unmanned aerial vehicle serving as a network relay may help in cases of limited or no mobile wireless connection, e.g. due to topographical circumstances. The aerial system may also provide situational awareness in cases of mass casualty incidents. For these two defined use-cases, safety and stability considerations are discussed, and required flight times and payloads are defined. The relay can be connected to the ground via a cable or wireless connection. It is concluded that the use-cases can be realized best when using a multicopter-either combined with a cable for independent flight times and reliable data communication or a wireless solution to mitigate the risk from the increased payload while limiting flight time. For the first option, the payload of the aircraft should be adjusted to ensure the power consumption in hover matches the power limitation of the cable.

Medical image processing comes along with object segmentation, which is one of the most important tasks in that field. Nevertheless, noise and intensity inhomogeneity in magnetic resonance images challenge the segmentation procedure. The level set method has been widely used in object detection. The flexible integration of energy terms affords the level set method to deal with variable difficulties. In this paper, we introduce a novel combined level set model that mainly cooperates with an edge detector and a local region intensity descriptor. The noise and intensity inhomogeneities are eliminated by the local region intensity descriptor. The edge detector helps the level set model to locate the object boundaries more precisely. The proposed model was validated on synthesized images and magnetic resonance images of in vivo wrist bones. Comparing with the ground truth, the proposed method reached a Dice similarity coefficient of > 0.99 on all image tests, while the compared segmentation approaches failed the segmentations. The presented combined level set model can be used for the object segmentation in magnetic resonance images.

Dipole radiofrequency (RF) elements have been successfully used to compose multi-channel RF coils for ultrahigh fields (UHF) magnetic resonance imaging (MRI). As magnetic components of RF fields (B 1 ) can be very inhomogeneous at UHF (B 0 ≥7T), dielectric pads with high dielectric constants were proposed to improve the B 1 efficiency and homogeneity [1]. Dielectric pads can be used as a passive B 1 shimmimg technique thanks to inducing a strong secondary magnetic field in their vicinity. The use of such dielectric pads affect not only the B 1 field but also the electric field. This in turn affects the specific absorption rate (SAR) and consequently the temperature distribution inside the patient’s body. To study these effects, a 29 cm-long transmission dipole RF coil element terminated by two meander was used for 7T MRI [2]. Using a cylindrical agarose-gel phantom, numerical and experimental results were analyzed with respect to homogeneity and amplitude of the magnetic and electric fields generated by the RF element in various configurations with and without dielectric pads. Calculated and measured B 1 results were cross-checked and found to be in good agreement. When using dielectric pads B 1 homogeneity and magnitude increase in regions where it was previously weak or insufficient. Calculations suggest that SAR distribution will change when using the pads.

For assessing clinically relevant structures in the neck area, especially the thyroid, it has been shown that 3D or tomographic ultrasound (3D US or tUS) is able to outperform standard 2D ultrasound [1] and computed tomography [2] for certain diagnostic procedures. However, when using a freehand and unassisted scanning method to acquire a 3D US volume data set in this area overlapping image slices, a variation of the probe angulation or differences in training might lead to unusable scanning results. Based on previous works [3] [4] we propose the design - with subsequent testing - of an assistive device that is able to aid physicians during the tUS scanning process on the neck. To validate the feasibility and efficacy we compared the image quality of both freehand and assisted scanning.

Electrical impedance tomography (EIT), a noninvasive and radiation-free imaging technique can be used in pulmonary function monitoring for determining regional ventilation distribution within the lung. Gold standard in pulmonary function monitoring is spirometry/body plethysmography, a method using forced breathing maneuvers to obtain global lung function parameters. However, this method is heavily dependent on the cooperation of the patients. Within this observational study, a method under normal breathing was tested with 5 healthy volunteers, which provides regional information about ventilation distribution. The occlusion method Rocc, a method for determining airway resistance, was used to create a short-term airway closure. Regional ventilation during the airway closure was examined with EIT. Simultaneously four different artificial airway resistances were used to simulate airway obstructions. Results show that EIT in combination with the ROcc method is suitable for the detection of regional differences in ventilation during airway closure for all four artificial airway resistances. Although the sum of relative impedances at the end of the shutter maneuver are smaller (nearly -0.100 AU) for the airway resistances Ø 12.5 mm, Ø 10.5 mm and Ø 9.5 mm than for the smallest one with Ø 30.0 mm (~ -0.070 AU), the changes in impedance from the start to the end of the shutter maneuver differs only slightly between the four artificial airway resistances. All impedance changes are in the range of 0.100 to 0.130 AU. The combination of EIT and the ROcc method provides not only global parameters such as airway resistance under normal breathing conditions, but also results of regional ventilation, which could enable the identification of areas affected by airway obstructions. However, the obtained results indicate that EIT might be a useful tool in the diagnosis and follow-up of obstructive lung diseases.

Purpose: To evaluate a novel structural-functional DCT-based EIT lung imaging method against the classical EIT reconstruction. Method: Taken retrospectively from a former study, EIT data was evaluated using both reconstruction methods. For different phases of ventilation, EIT images are analyzed with respect to the global inhomogeneity (GI) index for comparison. Results: A significant less variant GI index was observed in the DCTbased method, compared to the index from classical method. Conclusion: The DCT-based method generates more accurate lung contour yet decreasing the essential information in the image which affects the GI index. These preliminary results must be consolidated with more patient data in different breathing states.

In some applications such as 2D-3D registration, undistorted images are required to achieve optimal results. These types of images can be obtained from a distortion-free C-arm (flat-panel detector) or by undistorting the images given from a conventional C-arm (analogue image intensifier.) Undistorting images require a plate with fiducials connected to the C-arm detector. Detecting fiducials is affected by differences in the image contrast due to elements in the background. Therefore, the results vary from image to image and could require manual tuning of parameters. We propose a deep-learning approach for detecting undistortion-platefiducials in X-ray images to overcome the drawbacks previously stated. With an undistortion plate, we took 1120 XRays using a C-arm in different poses. Every X-ray is afterward cut into 60 sub-images. We used these sub-images for training a convolutional neural network (CNN). Comparing the CNN and a traditional image processing method based on the Hough Circle algorithm, we found that the detected fiducials using the traditional method give a similar fiducial positioning error. Nevertheless, the fiducial detection rate goes from 89.7% using the traditional method to 100% with the developed CNN. The results show that the detection rate and precision of our deep-learning approach guarantee the undistortion of conventional C-Arm images.

For the gastroscopic examination of the stomach, the restricted field of view related to the „keyhole“-perspective of the endoscope is known to be a visual limitation. Thus, a panoramic extension can enlarge the field of vision, supports the endoscopist during the examination, and ensures that all of the inner stomach walls are visually inspected. To compute such a panorama of the stomach, knowledge about the geometry of the underlying structure is required. Structure from motion an approach to reconstruct the necessary information about the 3D-structure from monocular image sequences as provided by a gastroscope. We examine and evaluate an existing deep neuronal network for stereo reconstruction, in order to approximate the geometry of stomach parts from a set of consecutive acquired image pairs from gastroscopic videos.

Optical coherence tomography (OCT) as imaging method is widely used in ophthalmology, oncology and cardiology. For intravascular imaging the OCT is used for pre-interventional as well as post-procedural assessments. Within the current study a test setup for ex vivo determination of the compliance of porcine coronary arteries via OCT is described. Diameter measurements based on OCT imaging were performed during consecutive pressurization of a porcine coronary artery from 40 to 200 mmHg in a physiological environment. The test results indicate that the radial compliance depends on the specific segment of the artery as well as the pressure range considered. The revealed compliance data can be used for numerical simulations of the vascular tissue as well as for optimization of in vitro test setups for pulsatile testing of vascular implants.

Intrathoracic ventilation related and pulsatile (perfusion) impedance changes can be measured by the noninvasive and radiation-free imaging method Electrical Impedance Tomography (EIT). Ventilation monitoring is still the key research area in EIT, whereby perfusion monitoring gain more and more in interest. However, there are still many unknown influencing factors concerning pulsatile impedance measurements which have to be investigated. Hence, in this observational case study the impact of prolonged apnea periods on pulsatile impedance changes was examined in a patient with suspected brain death undergoing several apnea tests. In addition, the correlation between changes in pulsatile impedance and certain blood gas parameters (carbon dioxide partial pressure, pCO 2 ; oxygen partial pressure, pO 2 ; pH; bicarbonate, HCO 3 -) were explored. Results show that the pulsatile impedance signal changes over time during apnea. An increase in the area under the curve (Mean AuC) and the maximum amplitude (Mean Max) of heart beat associated impedance signals was observed (Mean AuC: up to 65 %; Mean Max: up to 57 %). Furthermore, a positive correlation between the increase in impedance and pCO 2 and HCO 3 - was assessed (both: up to 0.99), whereas pO 2 and pH show a negative correlation (both: up to -0.99). These preliminary results indicate that pulsatile EIT monitoring may be applied to get additional information regarding cardio-pulmonary interactions sustaining diagnosis or treatment of lung diseases.

Cephalometric analysis is an important method in orthodontics for the diagnosis and treatment of patients. It is performed manually in clinical practice, therefore automation of this time consuming task would be of great assistance. In order to provide dentists with such tools, a robust and accurate identification of the necessary landmarks is required. However, poor image quality of lateral cephalograms like low contrast or noise make this task difficult. In this paper, an approach for automatic landmark localization is presented and used to find 19 landmarks in lateral cephalometric images. An initial predicting of the individual landmark locations is done by using a 2-D coupled shape model to utilize the spatial relation between landmarks and other anatomical structures. These predictions are refined with a Hough Forest to determine the final landmark location. The approach achieves competitive performance with a successful detection rate of 70.24% on 250 images for the clinically relevant 2mm accuracy range.

Electrical Impedance Tomography (EIT) is a clinically used tool for bed-side monitoring of ventilation. Previous work also showed a high potential for lung perfusion monitoring with indicator-enhanced EIT. However, many research questions have yet to be answered before it can be broadly applied in clinical everyday life. The goal of this work is to evaluate a new method to improve EIT perfusion measurements. Pulmonary hemodynamic transfer functions were estimated using regularized deconvolution with Tikhonov regularization to estimate spatial perfusion parameters. The final comparison between EIT images and PET scans showed a median correlation of 0.897 for the images which were reconstructed using the regularized deconvolution. In comparison the previously used maximum slope method led to a median correlation of 0.868.

In this paper, the impact of interference due to the geomagnetic field on a static magnetic localization setup for capsule endoscopy, which is suitable for a wearable application, was investigated. For this purpose, a study was carried out in which the average abdomen size of 15 subjects was evaluated. With the determined geometry values, a setup consisting of three elliptical sensor rings was modeled. Simulations were performed, where the magnetic flux density was evaluated at the sensors by using different-sized magnets. The measured values were compared with each other and the geomagnetic flux density. The results revealed that the measured values were for all evaluated magnet sizes of the order of the geomagnetic flux density, which is problematic since the calibration of sensors is no longer valid if the orientation of the wearable sensor array is changed. However, it is suggested that a differential measurement is suitable for the proposed system and could reduce static interference caused by the geomagnetic field.

Longitudinal and perpendicular changes in the blood vessels of the vocal fold have been related to the advancement from benign to malignant laryngeal cancer stages. The combination of Contact Endoscopy (CE) and Narrow Band Imaging (NBI) provides intraoperative realtime visualization of vascular pattern in Larynx. The evaluation of these vascular patterns in CE+NBI images is a subjective process leading to differentiation difficulty and subjectivity between benign and malignant lesions. The main objective of this work is to compare multi-observer classification versus automatic classification of laryngeal lesions. Six clinicians visually classified CE+NBI images into benign and malignant lesions. For the automatic classification of CE+NBI images, we used an algorithm based on characterizing the level of the vessel’s disorder. The results of the manual classification showed that there is no objective interpretation, leading to difficulties to visually distinguish between benign and malignant lesions. The results of the automatic classification of CE+NBI images on the other hand showed the capability of the algorithm to solve these issues. Based on the observed results we believe that, the automatic approach could be a valuable tool to assist clinicians to classifying laryngeal lesions.

Obstructions of the Fallopian tube represent one of the most common reasons for an unfulfilled desire to have children. Microstent technology opens up new therapeutic possibilities to restore the natural lumen of the Fallopian tube within a single treatment. Within the current work we developed a self-expandable biodegradable microstent for gynecological applications. Based on a novel microstent design, prototypes were manufactured from poly-L-lactide tubing by means of fs-laser cutting. Microstent prototypes were characterized morphologically by means of scanning electron microscopy and biaxial laser scanning. As manufactured, a microstents outside diameter of about 2.3 mm and a strut thickness / width of about 114 μm / 103 μm was measured. Mechanical characterization of microstents included bending as well as crimping and release behavior. After crimping to a minimum diameter of 0.8 mm and consecutive release, a microstent recovery to a diameter of 1.8 mm was found. Therefore, proof-of-concept for the self-expandable microstent could be successfully provided.

Modern technologies and methods such as computer simulation, so-called in silico methods, foster the development of medical devices. For accelerating the uptake of computer simulations and to increase credibility and reliability the U.S. Food and Drug Administration organized an inter-laboratory round robin study of a generic nozzle geometry. In preparation of own bench testing experiment using Particle Image Velocimetry, a custom made silicone nozzle was manufactured. By using in silico computational fluid dynamics method the influence of in vitro imperfections, such as inflow variations and geometrical deviations, on the flow field were evaluated. Based on literature the throat Reynolds number was varied Rethroat = 500 ± 50. It could be shown that the flow field errors resulted from variations of inlet conditions can be largely eliminated by normalizing if the Reynolds number is known. Furthermore, a symmetric imperfection of the silicone model within manufacturing tolerance does not affect the flow as much as an asymmetric failure such as an unintended curvature of the nozzle. In brief, we can conclude that geometrical imperfection of the reference experiment should be considered accordingly to in silico modelling. The question arises, if an asymmetric benchmark for biofluid analysis needs to be established. An eccentric nozzle benchmark could be a suitable case and will be further investigated.

Sustained local drug release and high local drug concentrations can be achieved by specially designed DDSs, which can be created for different applications. This results in therapeutic drug amounts at the site of action, simultaneously providing a very low drug amount in total. Bodily compartments that contain liquids may be used to transport the drugs from DDS into the tissue, such as the cochlea with the perilymph in the case of cochlea implants. However, predominantly dry environments, such as the middle ear, are lacking such a medium but may deliver enough moisture for the use of swellable DDS through the surrounding mucus membranes. Therefore, DDS with new functionalities are needed to ensure a sustained drug release. In this study, the release of dexamethasone out of a photopolymer system is presented. The system is built from UV-polymerized PEGDA followed by the incorporation of dexamethasone via swelling. The drug release is tested in vitro with isotonic NaCl solution for specified time periods, showing two phases: a swelling phase and a release phase. After the swelling phase the concentration of dexamethasone in the release medium was not controlled by diffusion, although sink conditions were ensured. In contrast, this system can be used to release the drug until equilibrium with a final medium concentration that is far below the solubility of dexamethasone. Hence, such DDS may be useful for dexamethasone delivery into the cochlea through the round window membrane by ensuring a constant concentration in the perilymph.

The consortium RESPONSE is a cooperation of partners from science and industry within the BMBFProgram “Twenty20 - Partnership for Innovation”, 2014- 2021. Current efforts are being made towards the transfer of new products, technologies and processes in the field of medical devices. Here, RESPONSE is focusing on novel concepts of implantable medical devices for cardiovascular, ophthalmologic and otolaryngologic application. Platform technology approaches, such as drug delivery systems for responsive functionalized implants or smart implant technologies, are being used to enable new applications.

The authors propose a glove with pressure sensitive fingertips and muscle tension detection of the thumb to aid in the physiotherapy of infants, children and adults according to Vojta. The therapy has to be carried out at home by the parents of children with cerebral palsy, or other movement disturbances up to 4 times per day. Often, parents struggle to carry out the practices because of insecurities regarding the therapy’s proper application. The presented glove is tailored towards the specific needs of Vojta therapy, e.g. flexibility and small sensor size, and can help parents gather objective data on their therapy application at home. It has been tested in multiple therapy sessions on adult probands and seems to be a suitable tool to support parents and therapists in training alike. Additionally, the results of the accompanied therapy sessions provide arguments against what the critics have often cited about the painfulness of the therapy.

Incisional hernia repair makes use of prosthetic meshes to re-establish a biomechanically stable abdominal wall. Mesh sizing and fixation have been found to be essential for the clinical outcome. Comparative CT images a) under rest versus b) under Valsalva maneuver (exhalation against closed airways) provide useful information for hernia characterization. However, this process incorporates several manual measurements, which led to observer variability. The present study suggests using an image registration approach of the CT data to reliably and reproducibly extract hernia quantities. The routine is implemented in the software framework MATLAB and works fully automatic. After CT data import, slice by slice undergo non-rigid B-spline grid registration. Local displacement and strain are extracted from the transformation field. The qualitative results correspond to the clinical observation. Maximum displacement of 3.5 cm and maximum strain of 25 % are calculated for one patient’s data set. Current approaches do not provide this type of information. Further research will focus on validation and possibilities to include this new kind of knowledge into the design process of prosthetic meshes.

Over the last decades, computational models have been applied in in-silico simulations of the heart biomechanics. These models depend on input parameters. In particular, four parameters are needed for the constitutive law of Guccione et al., a model describing the stress-strain relation of the heart tissue. In the literature, we could find a wide range of values for these parameters. In this work, we propose an optimization framework which identifies the parameters of a constitutive law. This framework is based on experimental measurements conducted by Klotz et al.. They provide an end-diastolic pressure-volume relationship. We applied the proposed framework on one heart model and identified the following elastic parameters to optimally match the Klotz curve: C=313 Pa, b f =17.8, b t =7.1and b ft =12A. In general, this approach allows to identify optimized parameters for a constitutive law, for a patient-specific heart geometry. The use of optimized parameters will lead to physiological simulation results of the heart biomechanics and is therefore an important step towards applying computational models in clinical practice.

Computer models of neonatal oxygenation could serve as a tool for a comprehensive comparison of closed-loop automated oxygen control systems. The behaviour of such models depends, besides the input data of the inspired fraction of oxygen and the premature infant's breath pattern, on internal parameters of the model. The aim of this study was to perform a sensitivity analysis of a computer model of neonatal oxygen transport to clarify the influence of its internal physiological parameters on the output signal of peripheral oxygen saturation (SpO 2 ). We performed a multi-parameter sensitivity analysis using Monte Carlo simulations for randomly generated values of eight internal parameters. The influence on the model output SpO 2 signal was evaluated using five characteristics of the output signal. The relations between the parameters and the output characteristics were displayed using scatter plots and analysed by linear correlation, standardized regression, and partial correlation. The main result of the study is that in our model the oxygen consumption in the tissue and the cardiac output have the greatest influence on the SpO 2 drop and minimal SpO 2 value during simulated desaturation. The rate of development of desaturation and its duration are most affected by the diffusion resistance of the alveolar-capillary membrane. The results of the sensitivity analysis will help to optimize the performance of the computer model of neonatal oxygen transport.

Programming in deep brain stimulation (DBS) is often a labour-intensive process. Although automatic closed-loop stimulation has recently been receiving considerable attention, it is still far from clinical settings. Testing in-loop stimulation in a clinical setting is extremely challenging due to manual programming and the lack of synchronisation between stimulation and monitoring devices. In this work, we present a simple rulebased expert system to test feedback-controlled DBS in a clinical setting. The new application operates in closed-loop with the physician as acting person and real-time feedback from an accelerometer. Patients with movement disorders such as in essential tremor announce an individually acceptable level of tremor as a boundary condition for control. As a proof-of-concept, the expert system provides continuous recommendations of stimulation parameters and guides the physician to increase or decrease DBS amplitude by capturing tremor acceleration power on the patients’ forearms. The introduced application considers the technical and practical aspects in a clinical setting. Data obtained from test subjects provide insight into tremor dynamics. We demonstrate the clinical applicability of the rule-based control system for future research focusing on tremor dynamics and inloop stimulation. Finally, a telemetry streaming system could provide the interface for the application of automatic tremor control without the physician as acting person.

Efficient numerical simulation of cardiac electrophysiology is crucial for studying the electrical properties of the heart tissue. The cardiac bidomain model is the most widely accepted representation of the electrical behaviour of the heart muscle. The bidomain model offers fast cardiac potential variation, which can lead to high computational cost due to the required large grid sizes and small time steps. In this paper, the complexity of the finite difference approximation of the bidomain equations is reduced with the model order reduction technique. Proper orthogonal decomposition, a projection-based algorithm, is used to efficiently approximate the original high fidelity cardiac bidomain model with a low-dimensional system of equations. The low-dimensional basis functions are computed first from the ‘snapshots,’ which contain the solutions of the full-order system for different temporal and spatial parameters. Galerkin projection of the original cardiac bidomain system onto the subspace of the reduced order basis functions reduces the size of the linear system. Numerical results confirm the efficiency of the proposed reduced order modeling technique, reducing the simulation time by a factor of 9.54, while maintaining an RMS error of 0.769 mV between the original full order solution and the reduced order POD solution.

INTRODUCTION: A torque-rotation model of the bone-screwing process has been proposed. Identification of model parameters using recorded data could potentially be used to determine the material properties of bone. These properties can then be used to recommend tightening torques to avoid over or under-tightening of bone screws. This paper improves an existing model to formulate it in terms of material properties and remove some assumptions. METHOD: The modelling methodology considers a critical torque, which is required to overcome friction and advance the screw into the bone. Below this torque the screw may rotate with elastic deformation of the bone tissue, and above this the screw moves relative to the bone, and the speed is governed by a speed-torque model of the operator’s hand. The model is formulated in terms of elastic modulus, ultimite tensile strength, and frictional coefficient of the bone and the geometry of the screw and hole. RESULTS: The model output shows the speed decreasing and torque increasing as the screw advances into the bone, due to increasing resistance. The general shape of the torque and speed follow the input effort. Compared with the existing model, this model removes the assumption of viscous friction, models the increase in friction as the screw advances into the bone, and is directly in terms of the bone material properties. CONCLUSION: The model presented makes significant improvements on the existing model. However it is intended for use in parameter identification, which was not evaluated here. Further simulation and experimental validation is required to establish the accuracy and fitness of this model for identifying bone material properties.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as in Parkinson's disease (PD) and essential tremor (ET). Adjusting the stimulation parameters, however, is a labour-intensive process and often requires several patient visits. Physicians prefer objective tools to improve (or maintain) the performance in DBS. Wearable motion sensors (WMS) are able to detect some manifestations of pathological signs, such as tremor in PD. However, the interpretation of sensor data is often highly technical and methods to visualise tremor data of patients undergoing DBS in a clinical setting are lacking. This work aims to visualise the dynamics of tremor responses to DBS parameter changes with WMS while patients performing clinical hand movements. To this end, we attended DBS programming sessions of two patients with the aim to visualise certain aspects of the clinical examination. PD tremor and ET were effectively quantified by acceleration amplitude and frequency. Tremor dynamics were analysed and visualised based on setpoints, movement transitions and stability aspects. These methods have not yet been employed and examples demonstrate how tremor dynamics can be visualised with simple analysis techniques. We therefore provide a base for future research work on visualisation tools in order to assist clinicians who frequently encounter patients for DBS therapy. This could lead to benefits in terms of enhanced evaluation of treatment efficacy in the future.

Computer-aided medical systems, e.g. in the fields of medical robotics or image-based assistance, are continuously investigated to overcome human limitations concerning perception, memory or dexterity. A common requirement of such systems is the availability of a digital model describing the patient’s position and morphology during a procedure. Operational complexity and technical limitations of established 3D imaging methods leave clinical settings in need of a method for the fast acquisition of a three-dimensional body surface representation. For this purpose, we propose an unsupervised and efficient body registration pipeline based on the markerless elastic registration and completion of single-view stereo range images of the body surface with statistical parametric body shape templates. Initial results show a promising representative quality of the models generated through the registration process with submillimetric fitting accuracy and realistic surface morphology, indicating the general feasibility of our approach as an instant body registration method for automated medical and biometric applications.

High intensity focused ultrasound is used as a surgical tool to treat completely non-invasively several diseases. Examples of clinical applications are uterine fibroids, prostate cancer, thyroid nodules, and varicose veins. Precise targeting is key for improving the treatment outcome. A method for an automated, robot-assisted tracking system was developed and evaluated. A wireless ultrasound scanner was used to acquire images of the target, in this case, a blood vessel. The active contour approach by Chan and Vese was used to segment and track while moving the scanner along the target structure with a collaborative robotic arm. The performance was assessed using a custom made Agar phantom. The mean tracking error, which is defined as the remaining distance of the lesion to the images’ centre line, was 0.27 mm ± 0.18 mm.

Access to systems for robot-assisted surgery is limited due to high costs. To enable widespread use, numerous issues have to be addressed to improve and/or simplify their components. Current systems commonly use universal linkage-based input devices, and only a few applicationoriented and specialized designs are used. A versatile virtual reality controller is proposed as an alternative input device for the control of a seven degree of freedom articulated robotic arm. The real-time capabilities of the setup, replicating a system for robot-assisted teleoperated surgery, are investigated to assess suitability. Image-based assessment showed a considerable system latency of 81.7 ± 27.7 ms. However, due to its versatility, the virtual reality controller is a promising alternative to current input devices for research around medical telemanipulation systems.

Wearable medical devices offer a great opportunity to monitor human vital signs to improve healthcare. The use of printing technologies is a promising approach to fabricate the wearables. An encapsulation must be applied to achieve longterm stability and reliability of the printed wearables. In this paper, we discuss the encapsulation requirements of printed wearable medical devices. Different encapsulation approaches are illustrated by means of various examples. Thereby, the focus lies upon solution-processed encapsulation, including the compatible materials and printing technologies.

Within the human blood immune cells assume specific functions to modulate and control the human immune response. Consequently, they are used for the diagnosis and treatment of autoimmune and hematologic diseases. Traceless Affinity Cell Selection Technology (Fab-TACS® technology) is a new method for selective isolation of specific immune cells from blood samples. Currently, the technology is used in a 60 mL syringe-like cartridge, which is operated by a control unit (Fabian®). Nevertheless, diagnostic applications require the reduction of the sample volume to several microliters. Therefore, we developed a cartridge for the purification of small blood volumes with the aid of suitable scaling and simulation methods. By implementing a multi domain physical systems model of the established cartridge we could simulate the separation process. Based on that a microfluidic cartridge was designed and several prototypes were manufactured. To operate the microfluidic cartridge a setup and software for fluidic control were created. Afterwards the prototype cartridge and the microfluidic control were used to isolate lymphocytes from a buffy coat. By flow cytometric analysis we could show that it is possible to isolate lymphocytes with a purity that is comparable to the established 60 mL syringe-like cartridge.

Monitoring brain activity at home using electroencephalography (EEG) is an increasing trend for both medical and non-medical applications. Gel-based electrodes are not suitable due to the gel application requiring extensive preparation and cleaning support for the patient or user. Dry electrodes can be applied without prior preparation by the patient or user. We investigate and compare two dry electrode headbands for EEG acquisition: a novel hybrid dual-textile headband comprising multipin and multiwave electrodes and a neoprene-based headband comprising hydrogel and spidershaped electrodes. We compare the headbands and electrodes in terms of electrode-skin impedance, comfort, electrode offset potential and EEG signal quality. We did not observe considerable differences in the power spectral density of EEG recordings. However, the hydrogel electrodes showed considerably increased impedances and offset potentials, limiting their compatibility with many EEG amplifiers. The hydrogel and spider-shaped electrodes required increased adduction, resulting in a lower wearing comfort throughout the application time compared to the novel headband comprising multipin and multiwave electrodes.

The paper presents an experimental study where the distinctness of grey and white matter of an in situ postmortem porcine brain by impedance measurements is investigated. Experimental conditions that would allow to conduct the same experiment on in vivo human brain tissue are replicated.

The development of drugs against pathogens that cause hemorrhagic fever, such as Marburg and Ebola virus, requires researchers to gather much information about the virus. The accelerating of the research process is of great interest; therefore a new algorithm was developed to analyze intracellular processes. The algorithm will classify the motion characteristics of subviral particles in fluorescence microscopic image sequences of Ebola or Marburg virusinfected cells. The classification is based on the calculation of mean squared displacement. The results look promising to distinguish different particle tracks in active and passive transport. The paper ends with a discussion.

In the sector of biomedical engineering and implant technology, high-precision geometry is often decisive for successful end product functionalization. Especially in the production of tubular polymer semi-finished products, e.g. for stent fabrication, it is important to assure the desired parameters, such as inner and outer diameter and wall thickness. Within the current study we analyzed semifinished products for manufacturing of polymeric stents using three different methods. Biodegradable poly-L-lactide (PLLA) tubes were examined by means of micro computed tomography, ultrasonic scanning and scanning electron microscopy. The final evaluation presents clear advantages of the ultrasonic measuring method for the measurement of outer and inner diameter and wall thickness.

In recent years, nanofiber based materials have emerged as especially interesting for several biomedical applications, regarding their high surface to volume ratio. Due to the superficial nano- and microstructuring and the different wettability compared to nonstructured surfaces, the water absorption is an important parameter with respect to the degradation stability, thermomechanic properties and drug release properties, depending on the type of polymer [1]. In this investigation, the water absorption of different non- and plasma modified biostable nanofiber nonwovens based on polyurethane, polyester and polyamide were analysed and compared. Also, the water absorption by specified water wetting, the contact angle and morphology changes were examined. The results show that the water uptake is highly dependent on the surface modification and the polymer composition itself and can therefore be partially changed.

Due to the raising number of TAVR implantations (transcatheter aortic valve replacement), tests for durability and prevention of associated diseases are becoming increasingly important. Not only the anatomy but also the positioning of the TAVR is decisive for its clinical performance. A misalignment in the circumferential direction can influence the flow in the sinus and thus inhibit the blood supply of the coronary arteries and influence the thrombosis potential. Therefore, the modification of the flow field is investigated in this study. For the characterization of the flow fields the measuring method of digital particle image velocimetry is used. A hydraulic circulation model is used to generate physiological flow and pressure conditions. Additionally, an aortic root model with Sinus Valsalvae, which represents the implantation environment, was developed. A prototype of a TAVR was implanted aligned to the commissure lines of the native valve leaflets on the one hand, and misaligned by 60 degree to the commissure of the native valves on the other hand. By determining the velocity vector fields, it could be shown that implantation of the TAVR with a commissureal misalignment influences the flow around the leaflets. A comparison of the flow fields shows that different recirculation areas occur. This is also indicated by a comparison of the mean velocities in the sinus and the observed shear rates. The influence of the altered flow field on the thrombosis and hemolysis potential should be investigated in future studies.

Endogenous electrical fields play an important role in various physiological and pathological events. Yet the effects of electrical cues on processes such as wound healing, tumor development or metastasis are still rarely investigated, though it is known that direct current electrical fields can alter cell migration or proliferation in vitro. Several 2D experimental models for studying cell responses to direct current electrical fields have been presented and characterized but suitable experimental models for electrotaxis studies in 3D are rare. Here we present a novel, easy-to-produce, multi-well-based galvanotactic-chamber for the use in 2D and 3D cell experiments for investigations on the influence of electrical fields on tumor cell migration and tumor spheroid growth. Our presented system allows the simultaneous application of electrical field to cells in four chambers, either cultured on the bottom of the culture-plate (2D) or embedded in hydrogel filled channels (3D). The set-up is also suitable for, live-cell-imaging. Validation tests show stable electrical fields and high cell viabilities inside the channel. Tumor spheroids of various diameters can be exposed to direct current electrical fields up to one week.

In this study, initial experiments are presented regarding the suitability of polyester based nonwoven composite materials for guided tissue regeneration based on degradation. The in vitro degradation of poly(lactic-coglycolic acid)/polydioxanone and polycaprolactone/ polydioxanone mats has been performed under accelerated condition in alkaline glycine buffer at 50 °C for 21 days. The degradation of the materials has been characterized regarding total mass loss and macroscopic morphological changes, as well as determination of the molecular weight degradation via GPC experiments.

The use of biomaterials in medicine is becoming increasingly important. One of the main concerns is the foreign body associated infection caused by direct microbial contamination or clinical infections. The bacterial biofilm formation on biomaterials depends on their surface properties. Therefore, several anti-adhesive surface modifications were developed. Nevertheless, the demand for antimicrobial agents that prevent bacterial colonisation is still largely unmet. The immobilization of active antimicrobial agents, such as antibacterial peptides or enzymes, offers a potential approach to achieve long-lasting effectiveness. In this investigation, the hydrolytic enzyme papain with its published antibacterial activity was covalently immobilized on the well-established biodegradable biomaterial poly-L-lactic acid (PLLA). For the characterization of the enzymes on the PLLA surfaces, the protein content and enzyme activity were determined. A biofilm assay was performed to test the effect of the papain-modified PLLA samples on the biofilm-forming bacterial strain Clostridioides difficile, one of the most frequently occurring human nosocomial pathogens. The investigated hydrolytic enzyme papain could be immobilized by coupling via the crosslinker EDC to the PLLA surface. Detection was performed by determination of the amount of protein and the reduced biofilm growth after 24 h and 72 h compared to the reference.

Hydrostatic high-pressure technology (HHD) devitalizes tissue quickly and gently, without negatively affecting the structural properties. HHD-treated tissues must be cleaned from devitalized cells. A partially automated, gentle, reproducible and timesaving rinsing test setup utilizing ultrasound is demonstrated in this study. The test setup is used to clean HHD-treated bone allografts of tissue residues and prevent microbiological contamination. A rinsing procedure is investigated. Residual DNA content determination is utilized to analyze cleaned bone allograft tissue for rinsing procedure evaluation.

Protein adsorption studies returned to the focus of medical therapeutics, when it was found that up to 2500 non-plasma proteins adsorbed to hip implants during arthroplastic surgery, challenging peri-implant healing models. Questions have re-emerged as to the implications of uncontrolled protein unfolding after adsorption. In past studies on the cooperativity of protein binding we discovered protein adsorption hysteresis, a thermodynamically irreversible process. The present precursory study comprises real-time kinetic (TIRF-Rheometry) and equilibrium ( 125 I-tracer ) studies on the hysteretic binding of fibrinogen and rhBMP-2 to titanium and glass surfaces via transient states. Thermodynamic constants (G On ), as well as kinetically derived (K' A ) and hysteresis derived (K' HA ) association constants in the range of 10 6 to 10 12 M -1 lead to a consistent picture.

The development and advancement of polymeric implant materials is a frequent focus in current research. The combination of polymeric materials with diverging properties provides a wide range of new materials with innovative characteristics. One technology for combining materials is to apply a coated layer onto a base material. In this work, a hyperelastic, synthetic base material was combined with a rigid biopolymer coating layer. A multilayered material with combined characteristics of both was built. In the field of processed polymers, the analysis of coating adhesion is not feasible using established methods. Therefore, a dynamic-mechanical method was investigated, which supplements the uniaxial tensile test and provides knowledge regarding mechanical resistance of the multilayered polymer structure. Furthermore, the method gets validated by SEM-imaging and evaluation of coating composition before and after testing under dynamic conditions.

Electrospinning is a popular method for creating nonwoven fiber materials for a wide variety of applications. In the field of biomaterials, electrospun materials are favoured because of a high surface-to-volume ratio which can be useful for drug loading and release, and because nanoscale fibers mimic native tissue structures, improving cell interactions. However limitations exist with regards to traditional solvent evaporation-based electrospinning techniques. A new area of research into reactive electrospinning is investigating methods of electrospinning that rely on in situ crosslinking rather than solvent evaporation to stabilize fibers. These techniques can potentially reduce the waste of excess solvents and make it easier to electrospin water soluble polymers. In this work, UV photocrosslinked PEGDA is evaluated as a material for reactive electrospinning. To facilitate the electrospinning process poly(ethylene glycol) diacrylate (PEGDA) is combined with polyvinyl alcohol (PVA). PEGDA/PVA solutions can be successfully electrospun under constant UV light exposure to initiate the crosslinking of the PEGDA. Reactive electrospun fibers appear more stable immediately after spinning and after washing with water, indicating successful photo crosslinking.

Individually tailored drug delivery systems (DDSs) are considered one of the most promising therapeutic tools for the creation of safe and effective treatments. DDSs as a novel approach should be beneficial in curing systemic as well as local ailments, where a high topical concentration of the drug and a reduction of side effects are desirable. It could also be favorable for patients requiring customized treatments, showing atypical profiles of drug metabolism. Development of particular drug delivery devices require the selection of a suitable scaffold material, which should exhibit proper mechanical and biological properties, but also enable adjustment of the drug release according to a specific need. Thus, it is extremely important to expand the knowledge concerning potential DDS components. Poly(ethylene glycol) diacrylate (PEGDA) according to its properties can be easily used as a DDS resin and shaped into a desired structure with the employment of techniques based on photopolymerization, including some novel 3D printing techniques. As a continuation of our previous works, in this paper drug release studies from conventionally prepared PEGDA scaffolds are presented. We have shown that in PEGDA materials, the release profile of the low molecular weight model drug acetylsalicylic acid can be altered by water content. PEGDA as a delivery material should be further investigated to specify its potential as a comonomer and a matrix for pharmaceutical agents.

To increase learning success in surgical training, physical simulators are supplemented by measurement technology to generate and record objective feedback and error detection. An opportunity to detect fractures following hip stem implantation early can be measurement of occurring strains on bone surface. These strains can be determined while using strain gauges, digital image correlation (DIC) or photoelasticity. In this research strain gauges and DIC were compared regarding their suitability as strain measurement tools for use in physical simulators. Therefore a testing method was described to replicate the implantation of a hip stem. Testing devices modelled on a realistic prosthesis were pressed into prepared porcine femora in a two-step procedure with a material testing machine. The local strains occurring on bone surface were determined using an optical measurement system for DIC and strain gauges. The initial fractures in the tested femora are located medial-anterior in most cases (73,6%). With increasing indentation depth of the test device, the strains on bone surface increase. Comparing the local strains determined by DIC and strain gauges consistencies in curves are noticeable. Maximal determined strains before fracturing amount to 0,69% with strain gauges and 0,75% with DIC. In the range of the fracture gap, strain gradients are determined by using DIC. However the detected surfaces are of low quality caused by gaps and motion artefacts. The results show strains on bone surfaces for early fracture detection are measurable with strain gauges and DIC. DIC is assessed as less suitable compared to strain gauges. Furthermore strain gauges have greater level of integration and economic efficiency, so they are preferred the use in surgical training simulators.

Methodologies to assess stem cell differentiation in the culturing state are needed for regenerative medicine and tissue engineering techniques. In recent years, convolutional neural networks (CNNs), a class of deep neural networks, have made impressive advancements in image-based classification, recognition and detection tasks. CNNs have been introduced as a non-invasive cell characterization method by learning features directly from image data of unlabeled cells. Furthermore, this approach serves as a rapid and inexpensive methodology with high performance compared to traditional techniques that require complex laboratory procedures including antibody staining and gene expression analysis. Here, we studied the potential of the CNNs approach to recognize stem cell differentiation based on cell morphology utilizing phasecontrast microscopy images.We have examined the differentiation potential of bone marrow mesenchymal stem cells (BMSCs) into tenocytes, with the treatment of bone morphogenetic protein-12 (BMP-12). After treatment, the phase-contrast images of cells were obtained directly from cell culture flasks to train CNN and the differentiated phenotype of stem cells was characterized by immunostaining. CNN was able to classify the cells into three groups including non-stem cells (chondrocytes), stem cells (BMSCs) and differentiated stem cells (tenocytes) based on their morphology with 92.2 % accuracy. The presented study revealed that CNN performed faster and non-invasive cell classification task compared to traditional methodologies.

In recent years, respiratory monitoring has gained attention due to the high prevalence and severe consequences of sleep apnea, post-anesthesia respiratory instability and respiratory diseases. Nevertheless, respiratory monitoring oftentimes relies on obtrusive masks and belts, which are unsuitable for wearable, long-term monitoring. Impedance pneumography (IP) is a bioimpedance method aiming to assess respiratory parameters unobtrusively. However, most IP configurations require far-spaced electrodes. Based on our recent work on wearable IP, we propose a dual-lead, wearable IP setup with 55 mm electrode spacing to estimate respiratory flow and rate (RR). Using our recently presented multimodal patch stethoscope as well as commercial systems, we conducted a study including 10 healthy subjects which were recorded in the supine, lateral and prone position. Using time-delay neural networks, we achieved RR estimation errors below 0.6 breaths per minute and flow correlations of 0.88 with relative errors of 25 % to a pneumotachometer reference. We conclude that dual-lead IP increases the performance of respiratory signal estimation compared to a single lead and recommend research in the area of subject position dependency and movement artefacts.

Selective laser melting (SLM) was used to manufacture smart programmed structures with customized properties made of biocompatible NiTi shape-memory alloy. A series of helixes was produced with systematically varied SLM process parameters Laser Exposure Time and Laser Power in order to specifically change the thermo-mechanical material properties of the 3D-structures. This innovation opens up the possibility to adjust the NiTi phase transformation temperature during the manufacturing process. This controllable property determines which of the two crystallographic phases martensite or austenite is present at a certain operating temperature and allows the mechanical properties to be adjusted: martensitic devices are soft and pseudo-plastic due to the shape-memory effect, whereas austenitic structures are pseudo-elastic. In a further step, the SLM process parameters were locally varied within 4Dprinted twin-helixes. As a result, the phases, respectively the mechanical properties of a single component were adjusted at different locations. The ratio of elastic to plastic deformation and the spring constant of the helix can be locally controlled. This allows, for example, the spatio-temporal programming of 3D-printed surgical instruments or implants that are stimuliresponsive.

Impairment of Eustachian tube function with nonsufficient ventilation of the middle ear is a main cause for chronic otitis media. To provide an effective and safe therapy, the innovative concept of Eustachian tube stenting was established. Biodegradable polymeric stents are developed to restore impaired tube function and dissolve after fulfilling their supportive purpose. To evaluate the applicability of the stents in the Eustachian tube, prototypes in conjunction with corresponding implantation instruments were tested in human cadaver studies. Radiopaque markers and a diaphanoscopic approach were tested as additional features to prove correct positioning of catheter and stent in the tube. In the current study biodegradable polymeric stents were implanted in the Eustachian tube of human cadavers without difficulty. Correct positioning of the stents in the tube was proved by diaphanoscopy during intervention and postoperative tomographic and histological analyses. Once designs are optimized on the basis of cadaver studies, preclinical safety and efficacy studies using animal models will be initiated.

Mitral regurgitation (MR) is the most prevalent valvulopathy in the USA and the second most prevalent valvulopathy in Europe. Despite excellent clinical results of surgical mitral valve repair (SMVR), transcatheter-based mitral valve repair (MVR) procedures emerged as a feasible treatment option for surgically inoperable or high-risk patients suffering from clinically relevant MR. The current study investigates the impact of device-induced coaptationwidth on the hydrodynamic performance of insufficient mitral valves (MV) during left ventricular (LV) systole. A non-calcified, pathological MV model (MVM) featuring a D-shaped MV annulus with an area of 7.6 cm2 and a flail gap in the A2-P2 region was employed in an experimental setup. Pressure gradient-volumetric flow rate (Δp-Q) relations were investigated for steady-state backward flow with transvalvular pressure gradients ranging from (0.75 ≤ Δp ≤ 177.36) mmHg. Glycerol-water mixture (36 % (v/v) glycerol in water) at 37 °C with a density of (1 098.2 ± 1.3) kg·m-3 and a dynamic viscosity of 3.5 mPa∙s was used as circulatory fluid. In order to determine the impact of the width of transcatheter MVR devices during LV-systole Δp-Q relations were investigated for three MVM-configurations: (i) MVM without MVR device, (ii) MVM with one MVR device and (iii) MVM with two MVR devices implanted in the A2-P2 region. The MVR devices were manufactured from steel sheets with a thickness of 0.2 mm and feature arm lengths of 9.0 mm and a width of 5.0 mm. The conducted investigations show that the implantation of MVR devices in the A2-P2 region prevents the manifestation of an A2-P2 flail gap and thereby effectively reduces the retrograde blood flow during the LV-systole by 13 % with one MVR device and 27 % with two MVR devices implanted. Thus, the application of two MVR devices with a combined device-induced width of 10 mm results in a better MR reduction than the implantation of one MVR device with a device-induced width of 5 mm.

Glaucoma represents a chronic eye disease that becomes increasingly prevalent worldwide. Therapies are commonly based on the reduction of intraocular pressure (IOP). Implant devices for micro-invasive glaucoma surgery (MIGS) represent a promising therapy option in refractory cases but suffer from limitations in long term efficacy or from dislocation associated complications. Our approach of an innovative drug-eluting glaucoma microstent for MIGS was presented previously. Within the current work we developed concepts and prototypes of a mechanism for the fixation of our glaucoma microstent in the region of the corneal limbus. A tripod and a haptics design of the fixation mechanism were developed and manufactured. Semifinished products were tested with regard to dimensional stability and mechanical properties according to the standard ANSI Z80.27-2014. Considering the mechanical properties of ocular target tissues, a gelatin based in vitro model for the measurement of microstent retention force was developed. Retention force testing of microstent prototypes in vitro resulted in a proof of concept for the fixation mechanism. Future studies will focus on the use of smaller fixation fibers, for example commercially available suture material, and on an overall miniaturization of the fixation mechanism enabling the use of our applicator device with a 22G x 1½” cannula.

Patients with hip arthrosis are increasing each year where total hip replacement is an effective solution when other non-invasive or surgical methods are no longer an effective solution. A pilot study of a new bone-preserving-biomimetic artificial femoral head cover was initiated. The purpose of the new implant is to be an alternative to the current hip arthroplasties. A special polyurethane (PU) femoral head cover was mechanically tested. Experiments were performed to investigate the implants mechanical behaviour and response to tensile load and study on the locking mechanism design concept of the prosthesis. The femoral head cover had a 45 mm outer diameter. Two suture techniques were selected to represent possible locking mechanisms. The experiment consisted of five cyclic loadings followed by a pull-to-failure test. The results show that each specimen has a consistency response and different suture technique results in a different outcome. This experiment intended to study the response of specimens as a whole part, not the material itself. Factors are influencing the outcome such as the femoral head cover positioning and suture rupture pattern. From this pilot study, some points need to be further considered. The information obtained in this experiment would influence further development achieving towards the goal of this alternative hip arthrosis treatment.

We propose three novel digital biomarkers for the longitudinal performance monitoring and movement evaluation of hemiparetic patients, e.g. after stroke. We devised convergence points (CP) for the bilateral walking analysis based on gait parameters, e.g. stride duration using regression- modelling to estimate similarity between body sides. The physical activity (PA) was devised to evaluate the energy expenditure of all extremities during training and free-living. The functional range of motion (fROM) is a digital biomarker to quantify the upper arm reaching ability, represented in 3D visualisations. In this work, we detail CP, PA, and fROM to derive rehabilitation insights for personalising therapies. We evaluated the proposed digital biomarkers in a clinical observation study with 11 patients after stroke during their rehabilitation including therapy and self-paced daily routines.

Respiratory diseases are a leading cause of death worldwide. The prevalence of sleep apnea, its cardiovascular consequences, postoperative respiratory instability and severe respiratory syndromes further highlight the importance of respiratory monitoring. Typical methods, however, rely on obtrusive nasal cannulas and belts. Impedance pneumography (IP) is a promising bioimpedance application which aims to estimate respiratory parameters from the thorax impedance. Currently, IP configurations require large inter-electrode distances, diminishing its applicability in a wearable context. We propose an IP configuration with 55 mm spacing using our recently presented sensor patch. In a study including 10 healthy subjects, respiratory rate (RR) and flow are estimated in the supine, lateral and prone position. Using time-delay neural network regression, RR errors below 1 bpm, flow correlations of 0.81 and relative flow errors of 38 % with respect to a pneumotachometer reference were achieved. We conclude that high accuracy RR estimation is possible in a 55 mm IP configuration. Respiratory flow can be roughly estimated. Further research combining several biosignals for a more robust, wearable flow estimation is recommended.

Demographic changes and increasing air pollution entail that monitoring of respiratory parameters is in the focus of research. In this study, two customary inertial measurement units (IMUs) are used to measure the breathing rate by using quaternions. One IMU was located ventral, and one was located dorsal on the thorax with a belt. The relative angle between the quaternion of each IMU was calculated and compared to the respiratory frequency obtained by a spirometer, which was used as a reference. A frequency analysis of both signals showed that the obtained respiratory rates vary slightly (less than 0.2/min) between the two systems. The introduced belt can analyse the respiratory rate and can be used for surveillance tasks in clinical settings.

Total lung capacity is usually measured by a body plethysmograph or helium dilution methods. In this study an alternative approach to obtain total lung capacity of spontaneous breathing subjects is introduced. The device utilises an optoelectronic plethysmograph and a small tube, which measures mouth pressure and allows total lung capacity to be obtained, which differs less than 0.4 L from the total lung capacity of the body plethysmograph. The method shows potential to be a less burdensome method to estimate total lung capacity determination than the body plethysmograph.

Bladder cancer is the sixth leading cancer cause worldwide. Non-muscle invasive tumors can be diagnosed and treated endoscopically. Based on biopsies alone, pathologists cannot determine the spatial organization of specimens, their relationship with each other, or their complete removal. To extend white light cystoscopy as the gold standard for bladder cancer detection, diagnosis and removal of small or flat lesions, new image-based technologies have been investigated. These include a stereo-cystoscope for improved orientation and navigation, computation of 2D and 3D panoramic images for extended visualization and documentation, as well as label-free fiber-based fluorescence-lifetime imaging (FLIM) and Raman-spectroscopy in combination with statistical data analysis. Combining all these technologies, cystoscopy can will be further enhanced to include new diagnostic possibilities.

Fiber optic Raman spectroscopy offers labelfree identification of cancer in the bladder under in vivo conditions. However, state-of-the-art Raman technology does not enable to scan the entire bladder wall. Our multidimensional approach within the project Uro-MDD combines panoramic 3D-image reconstruction of white light cystoscopy and fluorescence lifetime imaging to define regions of interest for Raman-assisted diagnostics. First Raman results are presented from human control and cancer bladder specimens that demonstrated how to obtain specific molecular information. Such Raman images can be used in a clinical setting to determine cancer margins and the resection status. Fiber probes are under development to translate the technique to in vivo screening.

We describe a metabolic imaging system based on simultaneous recording of lifetime images of NAD(P)H and FAD. The system uses one-photon excitation by ps diode lasers, scanning by galvanometer mirrors, confocal detection, and two parallel TCSPC FLIM recording channels. Two lasers, with wavelengths of 375nm and 410 nm, are multiplexed to alternatingly excite NAD(P)H and FAD. One FLIM channel detects in the emission band of NAD(P)H, the other in the emission band of FAD. For both channels, the data analysis delivers images of the amplitudes of the decay components, a1 and a2. We show that these are robust parameters to characterize the metabolic state of cells. FLIM results obtained from excised human-bladder tissue were in perfect agreement with histology.

We present a stereo-multispectral endoscopic prototype using a filter-wheel to guide the removal of cholesteatoma tissue in the middle ear. An image-based method is used that combines multispectral tissue classification for the detection of tissue to be removed and 3Dreconstruction to determine its metric dimensions. The multispectral illumination used for tissue classification ranges from λ = 400 nm to λ = 500 nm with step-size of 20 nm, which results in six different narrow-band illumination modes. For classical RGB imaging and metric calculations, a broadband illumination mode is applied before and after the narrow-band illumination. The spectral information is augmented into the broadband mode using an overlay technique. The combination of multispectral imaging with stereoscopic 3D-reconstruction results in new valuable visualization of intraoperative data. This allows to generate a 3D-model of the patients anatomy highlighting the identified malicious tissue and compare the anatomical dimensions with pre-operative CT data.

Discrimination of malignant and non-malignant cells of histopathologic specimens is a key step in cancer diagnostics. Hyperspectral Imaging (HSI) allows the acquisition of spectra in the visual and near-infrared range (500-1000nm). HSI can support the identification and classification of cancer cells using machine learning algorithms. In this work, we tested four classification methods on histopathological slides of esophageal adenocarcinoma. The best results were achieved with a Multi-Layer Perceptron. Sensitivity and F1-Score values of 90% were obtained.

Chronic non-healing wounds represent an increasing problem. In order to enable physicians and nurses to make evidence based decisions on wound treatment, the professional societies call for supporting tools to be offered to physicians. Oxygen supply, bacteria colonization and other parameters influence the healing process. So far, these parameters cannot be monitored in an objective and routinely manner. Existing methods like the microbiological analysis of wound swabs, mean a great deal of effort and partly a long delay. In this paper 42 fluorescence images from 42 patients with diabetic foot ulcer, recorded with a hyperspectral imaging system (TIVITA®), converted for fluorescence imaging, were analysed. Beside the fluorescence images, information about the bacterial colonization is available from microbiological analysis of wound swabs. After preprocessing, principal component analysis, PCA, is used for data analysis with a 405 nm excitation wavelength, the emission wavelength range 510 - 745 nm is used for analysis. After dividing the data into a training and a test dataset it could be shown, that bacteria are detectable in the wound area. A quantification in bacterial colonization counts (BCC) was not in the focus of the research in this study stage.

Transit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

Intraoperative neuromonitoring is without doubt important for all surgical interventions, where nerve structures are at risk. Mapping techniques for the identification of motor nerves and cortex are available. They rely on manual identification using an electrical stimulation probe. A landmark-based visualization of the results is currently not possible. To overcome these limitations, we are developing a system for automatic stimulation and display of functional tissue. Infrared neurostimulation (INS) was proposed to be a feasible alternative to electrical stimulation of nerves. It provides contactless and artifact-free activation of nerves. For our preclinical experiments we used an infrared diode laser system with a wavelength of 1470 nm. For automatic screening, we developed a scanning system and suitable scan-algorithms in order to provide optimal scanning parameters. Recording of compound muscle action potentials (CMAP) was performed with a differential amplifier and appropriate neurophysiologic software. Subunits of the system were combined via multiple interfaces. A control-software merges all relevant functions of the individual parts and parallel use. Marking of tissue was realized with a red pilot laser deflected by the same scanning system. With this work we could show, that a system for automatic laser deflection with parallel neurophysiologic recording and subsequent highlighting of irradiated tissue is possible. This system can serve as a tool for further systematic investigations in the field of INS.

For the visualisation of the intraocular space it is essential to illuminate the inside of the eye. One illumination approach is diaphanoscopy, in which the light of an extraocular source is transmitted through the tissue layers of the eyewall. The transmission properties of these tissues and their irradiation load depend on applied diaphanoscope contact pressure. However, excessive illumination can lead to irreversible photochemical and thermal damage to the retina. In diaphanoscopic illumination, the retina is particularly at risk due to its proximity to the light source. Therefore, the photochemical and thermal retinal hazards, resulting from direct transmitted light through the eyewall, are determined for different applied pressures of the diaphanoscope on the eye (15, 65 and 115 kPa). The study is performed on porcine eyes with different pigmentation. So, the difference in intraocular irradiance, photochemical and thermal hazards, as well as the maximal exposure time is also examined for different pigmentations. For less pigmented eyes the irradiance inside the eye, the photochemical and the thermal hazard are higher than for higher pigmented eyes. The values also become significantly higher for increasing applied pressure with the diaphanoscope but do not exceed given limits in the standard DIN EN ISO 15004-2: 2014.

Magnetic resonance image (MRI)-guidance for minimally invasive interventions instead of CT-guidance is a promising technique to reduce radiation exposure for both patients and clinicians. Technical challenges have to be managed in order to meet safety regulations while enabling inroom system control and communication. Using nonproprietary software and hardware, several gradations for a setup for interventional MRI were elaborated. Eventually, a quickly and easily installable setup was established for technical support during MRI-guided interventions in the PET/MRI suite at the Department of Nuclear Medicine at University Hospital Leipzig. It is adaptable for most MRI suites.

Aortic root aneurysm is treated by replacing the dilated root by a grafted prosthesis which mimics the native root morphology of the individual patient. The challenge in predicting the optimal prosthesis size rises from the highly patient-specific geometry as well as the absence of the original information on the healthy root. Therefore, the estimation is only possible based on the available pathological data. In this paper, we show that representation learning with Conditional Variational Autoencoders is capable of turning the distorted geometry of the aortic root into smoother shapes while the information on the individual anatomy is preserved. We evaluated this method using ultrasound images of the porcine aortic root alongside their labels. The observed results show highly realistic resemblance in shape and size to the ground truth images. Furthermore, the similarity index has noticeably improved compared to the pathological images. This provides a promising technique in planning individual aortic root replacement.

Endoscopy is an important modality in medical imaging. Thin flexible endoscopes are for example used to examine the upper airways, for gastroscopy procedures or lung inspection. With standard flexible endoscopes one can change the direction of view by bending the tip with the disadvantage of large space required due to the bending radius. With first experiences of a concept of a moveable camera head on the tip of rigid endoscopes, we now propose a novel design employing a swiveling camera for flexible endoscopes. This concept is based on the use of a shape memory wire used to control the movement of the camera, a flexible plastic flap joint for tight rotation and flexible printed circuits for the electronic connection. The prototype was realized in a first low cost setup using a 5,5 mm HD chip on the tip camera with LED light. The motion and imaging performance of the prototype allowed swiveling of the camera on the endoscope tip from straight view to 100° side view. The space needed in fully rotation was limited to 9mm with an overall diameter of the endoscope in straight view of only 5,6mm, but could even be further reduced in a more professional setup. The image quality is good, but close-up views appear blurry due to the fixed focus point of the low-cost camera. The presented steering concept of the camera is promising, as it could potentially improve imaging of narrow cavities using flexible endoscopes. Especially for “in office” examinations this principle could add value to diagnosis and patient comfort.

Heater Cooler Units (HCUs) are frequently used not only during heart surgery but also in ECMO therapy to regulate the blood temperature of patients. It is known from cardiac surgery that the water circuits of HCUs can be bacterially contaminated and under adverse conditions can lead to a nosocomial infection of the patient. The addition of chemical disinfectants to the water of HCUs is problematic. In addition, it is an increasingly significant cost factor due to the required material and personnel input. The aim of this research project is both the development of an automated device for disinfecting water in HCUs and proof of its effectiveness. The device is based on ozone, a substance with known antimicrobial properties. To prevent ozone from coming into contact with the HCU components, the water is irradiated with UV light (254nm). Two bypasses and ozone sensors guarantee a complete elimination of residual ozone. The effectiveness of the device was tested by series of experiments with the surrogate germ, Pseudomonas aeruginosa. The device allows a wide range of ozone concentrations and exposure times to be selected. In previous test series, it has been shown both that a reduction of the bacterial count to drinking water quality can be achieved with a treatment time of only one hour, and that self-cleaning can be carried out effectively before clinical use, and in standby mode. Attention must be paid to the water quality in HCUs as a potential source of infection, regardless of where they are used. The "proof of concept" showed an excellent disinfection effect with simultaneous elimination of excess ozone to drinking water levels. The number of indicator bacteria in the water tank of the dummy HCU was reduced by approx. 98% after only 30 minutes.

The risk of healthcare associated infections (HAI) is rising with the utilization of more complex medical devices. Cleaning and disinfecting measures of such devices are often insufficient leading to an increased microbiological contamination on these devices. Recent studies imply that antimicrobial coatings could present a solution for this topic. In this work a novel approach for the introduction of an antimicrobial technology into plastic granulate was tested. After 3-D printing the antimicrobial activity of the test samples was analysed. Our results show that the integration of an antimicrobial substance to ABS plastic is feasible only with sophisticated plastic processing technologies. Simple heating or mixing of the substance did not allow integration of the antimicrobial substance into the 3-D printed sample, but it was possible to integrate the antimicrobial ingredient into the raw material by compounding. The printed test samples showed strong antimicrobial activity in the standardized test procedures.

Antimicrobial surface coating of i.e. medical devices could contribute to infection prevention and reduction of hospital acquired infections (HAI). Recent studies showed a significant reduction in the microbial contamination of antimicrobial coated surfaces in clinical setups. Nevertheless, there are only few publications available that deal with the durability and stability of these coatings under routine clinical conditions. In this work different antimicrobial coating compositions were tested on different surfaces for their durability and remaining antimicrobial activity. Our results show that the durability and stability of a subsequent applied antimicrobial coating is strongly dependent on the chemical formulation of the coating and also the underlying surface condition. Whereas we could still detect remaining antimicrobial coating and activity on some samples after repeated abrasion testing, some other samples lost their coating and activity after only a few abrasion cycles. Interestingly the integrated antimicrobial substance in the 3-D printed samples showed strong antimicrobial activity even after rough treatment of the surfaces (brushing, scratching).

Microbiological burden of room-air in operating theatres is a known risk factor for surgical site infections. However, it is unclear how to best evaluate efficacy and efficiency under routine clinical conditions. Moreover, there still is a lack of data to assess the impact on infection rates. The aim of this study was to evaluate a temperature-controlled ventilation system (TcAF) under routine clinical conditions and assess its impact on infection rates. 10 clinical installations of the TcAF system Opragon (Avidicare AB, Sweden) were assessed during live surgeries according to the Swedish SIS TS 39: 2015 standard. Furthermore, a retrospective analysis of 1,000 consecutive cases of primary total joint arthroplasty (hip, knee) before and 1000 after installation of the TcAF system was performed. Endpoints for clinical outcome were length of stay and infection rates. Our results show that requirements of the Swedish standard were met or significantly exceeded by the TcAF system reliably and robustly ensuring "ultra-clean" air in the entire operating theatre and demonstrating the capability to reduce the risk of airborne microbial transmission under routine clinical conditions. The study shows positive impact on key clinical outcome parameters in line with previous research by Charnley and Lidwell.

Ventilation technology in German operating rooms is regulated by DIN 1946-4. Since the release of the latest version in 2018, a positioning analysis (worst-case scenario with the largest space requirement) for determining the required protected area in class 1a operating rooms is mandatory. The aim of this investigation was to use typical workflow scenarios to assess existing installations regarding the match of the required and the built size of the protected area. Positioning analyses were carried out together with the on-site staff for various clinical procedures in 2 hospitals to assess the built versus required protected areas. In all cases, the positioning analysis revealed that required protected areas need to be significantly larger than provided by the existing setup. The size of the protected area that is actually required can only be determined by individual positioning analysis. Most existing installations of low turbulence displacement flow systems (TAV) are likely to be too small. The larger protected areas actually require significantly larger rooms in order to maintain proper thermodynamics. Furthermore, significantly higher volumetric flow rates are required. Finally, the current mismatch between actual and necessary protected area would be a possible explanation for the controversial data situation regarding the infection preventive effects of TAV systems.

A closed-loop control software for the new mobile Berlin Heart EXCORR driving unit was optimized to balance usability, durability, pump wash out, blood stress and power consumption. The piston of the electro-pneumatic cylinder is moved on a pump-cannula-specific trajectory. A friction and a valve model are adapted online. Verification and real world data show constant flow, low power consumption and the adherence of all limits.

In this study a physiological closed-loop system for arterial CO 2 partial pressure control was designed and comprehensively tested using a set of models of the respiratory CO 2 gas exchange. The underlying preclinical data were collected from 12 pigs in presence of severe changes in hemodynamic and pulmonary condition. A minimally complex nonlinear state space model of CO 2 gas exchange was identified post hoc in different lung conditions. The control variable was measured noninvasively using the endtidal CO 2 partial pressure. For the simulation study the output signal of the controller was defined as the alveolar minute volume set value of an underlying adaptive lung protective ventilation mode. A linearisation of the two-compartment CO 2 gas exchange model was used for the design of a model predictive controller (MPC). It was augmented by a tube based controller suppressing prediction errors due to model uncertainties. The controller was subject to comparative testing in interaction with each of the CO 2 gas exchange models previously identified on the preclinical study data. The performance was evaluated for the system response towards the following five tests in comparison to a PID controller: recruitment maneuver, PEEP titration maneuver, stepwise change in the CO 2 production, breath-hold maneuver and a step in the reference signal. A root mean square error of 2.69 mmHg between arterial CO 2 partial pressure and the reference signal was achieved throughout the trial. The reference-variable response of the model predictive controller was superior regarding overshoot and settling time.

According to the European Medical Device Directive (MDR (EU) 2017/745), medical products of all risk classes are obliged to be labelled with Unique Device Identification Codes (UDI). In order to meet the requirements of the MDR, a novel method of identification for additively manufactured metallic products was developed at the Fraunhofer Institute for Machine Tools and Forming Technology (IWU). The method provides a product traceability within its production process and during the whole product lifespan, and also functions as a counterfeit protection. This paper shows the integration of a unique identification during an additive manufacturing process for a titanium part. The readout of the integrated identification was executed using ultrasonic and eddy current methods, as well as micro computed tomography. Obtained results are discussed in the paper.

Surgical tool recognition is a key task to analyze surgical workflow, in order to improve the efficiency and safety of laparoscopic surgeries. The laparoscopic videos are important sources to conduct this task, However, there are some challenges to analyze these videos. Focus on the imbalanced dataset problem, data augmentation method based on generate different synthetic datasets and evaluate their performance training on a convolutional neural network model are investigated in this research. The results show the effect on the model with different background patterns. A better performance was achieved when the model was trained by a structure background dataset. Further research will be needed to understand why the original background patterns support the correct classification. It is assumed that this is an overlearning effect, that will not hold if other procedures were included into the test set.

In this paper, a deep learning approach for classification of cough sound segments is presented. The architecture of the network is based on a pre-trained network and the spectrogram images of three recording channels have been extracted for the sake of training the network. The classification accuracy based on three recording channels is 92% for a binary classification model and the network converges fast. Two classification models based on binary and multi-class problems are proposed. Relevant classification parameters including the Receiver Operating Characteristic (ROC) curve are reported.

In case of cardiovascular implants classified as class III medical products there is a specific responsibility for manufacturers as well as regulatory authorities to follow international standards to guarantee for safety and efficacy. Fast developments of science and technology as well as novel clinical findings create permanent needs to match the standardization. Therefore, a set of international standards is analyzed with respect to their use for particular coronary drug-eluting stents and artificial heart valves. It was found that standards (ISO, ASTM) exist for general requirements on passive implants, but also specifically relate to arterial stents, stent grafts, bioresorbable and drug-eluting stents, as well as artificial heart valves. New work items address new methods for characterization of coating integrity, particulate matter and simulated use testing. European Medical Device Regulation (MDR) requires technical expertise and capacity at Notified Bodies supported by independent test laboratories. Generally, the interest in standardization from industry, test laboratories and authorities is high, but more input from medical experts would further improve the value of standardization and its relevance for safe and even more effective implants.

In case of cardiovascular implants classified as class III medical products there is a specific responsibility for manufacturers as well as regulatory authorities to follow international standards to guarantee for safety and efficacy. Fast developments of science and technology as well as novel clinical findings create permanent needs to match the standardization. Therefore, a set of international standards is analyzed with respect to their use for particular coronary drug-eluting stents and artificial heart valves. It was found that standards (ISO, ASTM) exist for general requirements on passive implants, but also specifically relate to arterial stents, stent grafts, bioresorbable and drug-eluting stents, as well as artificial heart valves. New work items address new methods for characterization of coating integrity, particulate matter and simulated use testing. European Medical Device Regulation (MDR) requires technical expertise and capacity at Notified Bodies supported by independent test laboratories. Generally, the interest in standardization from industry, test laboratories and authorities is high, but more input from medical experts would further improve the value of standardization and its relevance for safe and even more effective implants.

The European Parliament and the European Council on May 26, 2017 decided to introduce the new regulatory framework for medical devices. The transitional period of the so called Medical Device Regulation (EU 2017/745, MDR) should end on May 26, 2020. Currently the European Commission is working on a proposal to postpone the application for one year to relieve pressure from all stakeholders allowing them to fully focus on priorities related to the coronavirus crisis. From this date or most likely from May 26, 2021, manufacturers must present a CE-certificate according to the new MDR requirements not only for novel medical devices, but also for approved medical devices which are already on the market. The MDR will significantly complicate the process of bringing medical devices into market due to the increased requirements for the CE-certification process, particularly concerning increased documentation effort. This involves a risk for the translation of innovative products due to an overload of the overall system (manufacturers, Notified Bodies, experts) and might lead to shrinkage of the product range of existing products. Thankfully, adaption of transitional periods, special regulations, extensions of deadlines and most probably postponement of the MDR application date will ensure that there will be no gaps in medical supply that endanger patients. Establishing and keeping the relevant regulatory expertise up to date and devoting the necessary financial, time and human resources that is the biggest immediate challenge the medium-sized medical technology sector is facing in the near future. The current article, written about one month before the initially expected end of the first transition period on May 26, 2020, summarized the main aspects of the current state of MDR implementation with respect to regulatory novelties, the current legal basis in Germany, transition periods and changes in the requirements of CE-certification relevant technical documentation. Furthermore, challenges for existing and innovative medical devices were shortly discussed using a new stent based therapy of the proximal Fallopian tubal stenosis and transcatheter aortic valve implantation as two examples.

The geometric shape of our skull is very important, not only from an esthetic perspective, but also from medical viewpoint. However, the lack of designated medical experts and wrong positioning is leading to an increasing number of abnormal head shapes in newborns and infants. To make screening and therapy monitoring for these abnormal shapes easier, we develop a mobile application to automatically detect and quantify such shapes. By making use of modern machine learning technologies like deep learning and transfer learning, we have developed a convolutional neural network for semantic segmentation of bird’s-eye view images of child heads. Using this approach, we have been able to achieve a segmentation accuracy of approximately 99 %, while having sensitivity and specificity of above 98 %. Given these promising results, we will use this basis to calculate medical parameters to quantify the skull shape. In addition, we will integrate the proposed model into a mobile application for further validation and usage in a real-world scenario.

Cancer and normal tissues are visually different from each other, especially so in more advanced cancer stages. More important, they are not only visually contrasting, but if an electric field is applied to both tissue types and the frequency is varied in a wide range, it will be seen that the two tissue types in general have a spectral response divergent from each other and this has to do with the characteristics of cancer tissues in contrast to normal ones. In this work, Electrical Impedance Spectroscopy is applied to try to distinguish cancer from healthy tissues by means of their impedance spectrum using a four-electrode-terminal setup. The use of the fourterminal- setup setup is important to circumvent the impact of electrode polarization at frequencies below 1 kHz.

The indicator dilution method (IDM) is one approach to measure pulmonary perfusion using Electrical Impedance Tomography (EIT). To be able to calculate perfusion parameters and to increase robustnes, it is necessary to approximate and then to separate the components of the measured signals. The component referring to the passage of the injected bolus through the pixels can be modeled as a gamma variate function, its parameters are often determined using nonlinear optimization algorithms. In this paper, we introduce a linear approach that enables higher robustnes and faster computation, and compare the linear and nonlinear fitting approach on data of an animal study.

Magnetic actuation of medical devices is of great interest in improving minimally invasive surgery and enabling targeted drug delivery. With untethered, magnetically coated swimmers it is aimed at reaching regions of the body difficult to access with catheters. Such a swimmer was previously presented, which is suitable for the navigation by the magnetic fields of a magnetic particle imaging (MPI) scanner. The swimmer could be imaged with MPI as well, enabling the tomographic real-time tracking of the actuation process. In this work the steerability of the swimmer is further investigated in media of varying viscosities. For this, glycerol-water-mixtures of different mixing ratios were used. The velocities of the swimmer were measured for viscosities between those of pure glycerol and pure water. The experiments were performed with an MPI scanner at maximal magnetic field strength of the actuating fields. A viscosity range was found in which the swimmer is steerable by the fields of an MPI scanner, which leads to a prediction of the applicability of the swimmer in different body fluids.

GMLVQ (Generalized Matrix Relevance Learning Vector Quantization) is a method of machine learning with an adaptive metric. While training, the prototype vectors as well as the weight matrix of the metric are adapted simultaneously. The method is presented in more detail and compared with other machine learning methods employing a fixed metric. It was investigated how accurately the methods can assign the 6-channel EEG of 25 young drivers, who drove overnight in the simulation lab, to the two classes of mild and severe drowsiness. Results of cross-validation show that GMLVQ is at 81.7 ± 1.3 % mean classification accuracy. It is not as accurate as support-vector machines (SVM) and gradient boosting machines (GBM) and cannot exploit the potential of learning adaptive metrics in the case of EEG data. However, information is provided on the relevance of each signal feature from the weighting matrix.

The Medical Technology Advisory Committee of the VDI Society develops a guideline for the implementation of digital process chains for patient-specific medical devices. The underlying medical device constitutes the basis for each individualized medical device. It serves as the development framework for manufacturing.

Cognitive changes in general occur with normal aging. This may lead to the prevalence and effect of age associated diseases. The understanding and identification of these age-related cognitive impairments is an important aspect in elderly population. This leads in the simple case, supporting a functional independence of the elderly and in a complex case, an early identification of dementia in advance. One important change with normal aging is the decline in gait functionality. The decline in gait is more visible in the elderly with more cognitive impairment during dual cognitive tasks, multi-tasking exercises. For the classification of the healthy elderly from the elderly having cognitive impairments, the gait data of the elderly is acquired through Kinect V2. A waking trial of 5m long is used to collect the gait data. 3D based pose estimation using the depth data is performed. Gait parameters and gait cycles of the individual elderly are estimated. In this paper, Dynamic Time Warping (DTW) algorithm is used to compare the patterns of the gait cycles of the individual in different trails such as Regular Gait 1 (RG1), Regular Gait 2 (RG2), Counting Backward 1 (CB1), Counting Backward 3 (CB3), Fast Gait (FG) and Words with Special Letters (WSPL). The identified cross levels along with the estimated gait parameters are used for training the machine learning algorithm. Support Vector Machines (SVM) were used for the classification of the elderly persons with or without cognitive impairments. The experiment results proved that such a classification of cognitive impairment levels using 3D pose estimation and machine learning helps in future for the identification of dementia in advance.

Integrated operating rooms typically connect medical devices providing the clinical user a complete control over environment, device setting and digital management of intervention-related data. Consequently, the opportunity to analyse and present data from different perspectives and with different objectives has arisen. The available integrated ORs are so far designed as closed systems, thus connecting coexisting systems from different manufactures e.g. anaesthesia machines and surgical devices is demanding. The purpose of this project is to facilitate data collection from anaesthesiology, patient monitoring and surgical devices. The study is performed on laparoscopic procedures, and the data are going to be recorded at the Schwarzwald-Baar Klinikum (SBK) in Villingen-Schwenningen (Germany). Therefore, this part of the project focuses on the overall architecture for collecting data in the operating theatre at the SBK. In this work, (i) the system architecture (i.e. hardware components), (ii) software architecture and (iii) required protocols for synchronous recording of data in the OR are described. The proposed framework demonstrates that signal recording is possible with variety of devices at different sampling rates during surgical procedure.

Patients often report an effect after surgery of the anterior cruciate ligament which is called "giving way". This manifest itself by a drop of the knee or a felt instability. This phenomenon is difficult to measure and validate because it usually does not occur regularly and is not reproducible under laboratory conditions. The Knetex project takes up this point by trying to actively support the rehabilitation process with a bandage that can be worn in everyday life and is constructed as a smart textile using sensors and actuators. For this purpose, on the one hand it is attempted to actively record the phenomenon of the "giving way" by measuring knee angles etc. and by active user feedback. At the same time, the patient is specifically advised by means of actuators to correct incorrect posture or movement in order to make the rehabilitation process more effective and prevent further damage. Two 9-axis IMUs (inertial measurement units) form the basis of the system. These are used together with a textile strain sensor to calculate the knee angles. This paper gives an overview of the planned system, the initial experiments to measure the knee angles and the first results of the actuator study.

Acoustic or visual warning signals for workers in hazardous situations might fail under loud and/or lowvisibility work situations. A warning system should be developed that uses electrocutaneous stimulation through textile electrodes. Previous work investigated suitable stimulation parameters using TENS electrodes. The aim of this study was to compare TENS and textile cuff electrodes in terms of sensation thresholds, qualitative and spatial sensation. A study on 30 healthy volunteers (f=13, m=17) of mean age of 26.7 years was conducted applying bi-phasic rectangular current pulses to electrodes attached to the upper right arm. The study revealed that perception, attention and intolerance thresholds, qualitative and spatial perception are comparable indicating that future studies with the textile cuff electrodes can be generally based on the previous results with TENS electrodes.

In this paper, the classification models for Idiopathic Parkinson's syndrome (iPS) detection through timed-up-and-go test performed on iPS-patients are given. The models are based on the supervised learning. The data are extracted via Myo gesture armband worn on two hands. The corresponding models are based on extracted features from signal data and raw signal data respectively. The achieved accuracy from both models are 0.91 and 0.93 with reasonable specificity and sensitivity.

All aspects of daily life increasingly include digitization. So-called „smart home“ technologies, as well as „wearables“, are gaining attention from more and more dwellers. Therefore, sensor-based, individualized, AI-based services for improved post-intervention monitoring and therapy accompaniment will become feasible and possible if these systems offer a related context-awareness. This paper provides an approach on how to sense and interpret specific contexts with the help of wearables, smartwatches, smart home sensors, and emotion detection software.

In the upcoming years, the internet of things (IoT) will enrich daily life. The combination of artificial intelligence (AI) and highly interoperable systems will bring contextsensitive multi-domain services to reality. This paper describes a concept for an AI-based smart living platform with open- HAB, a smart home middleware, andWeb of Things (WoT) as key components of our approach. The platform concept considers different stakeholders, i.e. the housing industry, service providers, and tenants. These activities are part of the Fore- Sight project, an AI-driven, context-sensitive smart living platform.

In recent years, the demographic change in conjunction with a lack of professional caregivers led to retirement homes reaching capacity. The Alzheimer Disease International stated that over 50 million people suffered from dementia in 2019 worldwide and twice the amount will presumably be effected in 2030. The field of Ambient Assisted Living (AAL) tackles this problem by facilitating technical system-aided everyday life. AUXILIA is such an AAL system and does not only support elderly people with dementia in an early phase, but also monitors their activities to provide behaviour analysis results for care attendants, relatives and physicians. Moreover, the system is capable of recognizing emergency situations like human falls. Furthermore, sleep quality estimation is employed to be able to draw conclusions about the current behaviour of an affected person. This article presents the current development state of AUXILIA.

This paper discusses the influence of different designs of strut-connectors of stents by numerical flow simulations and flow examinations using micro particle image velocimetry (μPIV). Many studies have shown that there is a correlation between the hemodynamics after stent implantation and the cause of biological responses like thrombosis and the in-stent restenosis. Recirculation areas may occur through a stent, which are considered to be the cause of these clinical complications. In this study, three different coronary stent designs are investigated and the hemodynamic effects from the different designs is presented. The study focuses on the design of the strut-connectors that connect two struts. Numerical simulations were performed to evaluate various flow features like recirculation zones, velocity profiles and wall shear stress (WSS) patterns. To verify the numerical results μPIVmeasurements were performed. It could be shown that the alignment in the main stream of the connectors influences the size and number of recirculation zones.

The investigation of matching of endoprosthesis tibial components to the bone cross section is of interest for the manufacturer as well as for the surgeon. On the one hand, a systemic design of the prosthesis and the assortment is possible, on the other hand, a better matching implantation is enabled on the basis of experience of this study. CT sections were segmented manually using a CAD system and fitted by spline functions, then superseded with cross sections of the tibial component of a modified Hintermann H3 prosthesis. The principal moments of inertia, the direction of the principal axes and the area of the section were evaluated. Based on the relative differences of the principal moments of inertia, recommendations for application of the different prosthesis size and its selection with the surgery can be made.

The analysis of microscopic images from cell cultures plays an important role in the development of drugs. The segmentation of such images is a basic step to extract the viable information on which further evaluation steps are build. Classical image processing pipelines often fail under heterogeneous conditions. In the recent years deep neuronal networks gained attention due to their great potentials in image segmentation. One main pitfall of deep learning is often seen in the amount of labeled data required for training such models. Especially for 3D images the process to generate such data is tedious and time consuming and thus seen as a possible reason for the lack of establishment of deep learning models for 3D data. Efforts have been made to minimize the time needed to create labeled training data or to reduce the amount of labels needed for training. In this paper we present a new semisupervised training method for image segmentation of microscopic cell recordings based on an iterative approach utilizing unlabeled data during training. This method helps to further reduce the amount of labels required to effectively train deep learning models for image segmentation. By labeling less than one percent of the training data, a performance of 90% compared to a full annotation with 342 nuclei can be achieved.

Venepuncture is one of the most common invasive procedures performed worldwide, however, complications still occur. Currently, commercial single layer silicone phantoms used for venepuncture training do not accurately imitate the geometry and mechanical properties seen in the various patient groups. This paper presents the development of a realistic artificial venepuncture phantom. Three multilayered tissue phantoms are developed simulating venepuncture sites of paediatric, adult and geriatric patients. Silicone materials of different stiffnesses were selected to imitate the epidermis, dermis, subcutaneous fat, muscle and superficial veins. Singleaxis indentation tests were carried out on silicone samples and the multi-layered phantom inserts to characterize the material properties. The measured Young's moduli for the artificial dermis, fat and muscle show sufficient agreement with corresponding literature values. However, characterization of the complete phantom inserts showed stiffnesses four times larger than prior in-vivo studies. Future studies will work on developing a more comparable in-vivo study.

Photopolymerizing, high-resolution 3D printing methods such as Stereolithography (SLA) or Digital Light Processing (DLP) are very promising for the manufacturing of drug-incorporated, patient specific implants. However, a drug-load may be limited by adequately solubility of the active pharmaceutical ingredient (API) in the photopolymer. Furthermore, a drug-load may affect the mechanical properties of the material negatively. Here, we investigate the DLP 3D printing of drugincorporated photopolymers. Polyethylene glycol diacrylate (PEGDA, Mn = 700 g/mol) is used as matrix polymer and Dexamethasone (DEX) is used for drug-loading (10 g/L and 20 g/L). Compressive properties, drug release and drug stability of 3D printed test samples were analyzed. DEX was found to be sparingly soluble in the PEGDA-based photopolymer. Not all drug particles can be dissolved at a concentration of 20 g/L and a slurry-like suspension is formed. Drug-incorporated photopolymers of 10 g/L (solution) and 20 g/L (suspension) were processed successfully via DLP. The higher the drug-load, the lower the compressive strength. Mechanical properties can be improved via a post-curing in a UV light curing box. Drug-incorporated 3D printed test samples show burst-release of DEX. The post-curing process does not affect drug release. DEX degrades in 3D-printed test samples significantly (~ 30 %) over a several days time period.

The extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.

Impedance spectroscopy represents a basic operating principle for biomedical sensors, bioimpedance spectroscopy, electrochemical analyses and for characterization of functional biomaterials. For automated long-term investigations, an impedance analyzer for multi-channel testing of up to eight passive two-pole networks is presented in this paper. Its operating system is application-specific adapted to the required test functionalities and measuring ranges. Measurements are based on a commercially available integrated impedance converter circuit. Our current analyzer setup is capable of measuring impedance values from 50 kΩ up to 10 MΩ with automated range selection for most accurate results. The impedance under test is excited with a single frequency of 1 kHz. An impedance accuracy of 1.5 % was determined in reference measurements. The presented impedance analyzer is a low cost system ready for use particularly in long-term characterization of dielectric networks, such as material properties, with multiple samples.

Particulate evaluation is needed for the approval of cardiovascular devices. Air bubbles lead to higher particle counts when light obscuration method (LOM) is used. The aim of the study was to test a custom made bubble trap that removes air bubbles (2 - 100 μm) from a flow circuit prior to online particle counting. Artificially generated air bubbles were counted with an online particle counter with and without the bubble trap. Air bubbles were reduced by about 71 % to 91 % by using the bubble trap.

Fast scanning calorimetry (FSC) is an effective analytical tool to characterize the thermal properties of polymers. Heating rates up to 100 000 K/s allow studies at time scales inaccessible with conventional calorimeters, whose rates are typically less than about 0.5 K/s. Recent studies have successfully demonstrated methods for obtaining quantitative analysis of thermal properties of polymer samples using chip-based FSC. Therefore very small sample sizes, such as particles or nonwovens, can be characterized. In this study, we investigated the thermal properties of poly(L-lactide) PLLA with FSC compared to the results from standard DSC methods. PLLA specimens were fabricated via solution casting and needle electrospinning. The results suggest a significant influence of heating rates on the melting temperature of PLLA. The results show that different fabrication methods lead to changes in crystallinity and that FSC results are not completely comparable with standard DSC measurements.

Polyelectrolyte multilayer coatings (PEM) are prepared by alternative layer-by-layer deposition of cationic and anionic polyelectrolyte monolayers on charged surfaces. The thickness of the coatings ranges from nm to few μm. Their properties such as roughness, stiffness, surface charge and surface energy can be precisely tuned to fulfill different technical or biological requirements. The coating process is based on self-assembly of polyelectrolytes. Advantages of these coatings are their easy handling, no harsh chemistry and the possibility for coatings on complex geometries. The PEM coatings can be prepared from a variety of suitable polyelectrolytes. Their stability varies from very durable PEM coatings that are only soluble in strong solvents to quickly degradable, which may be applied as drug release system. One example of such a degradable PEM system is the one based on the polyelectrolyte pair Hyaluronan (HA) and Chitosan (CHI). These biopolymers originate from natural sources and show low toxicity towards human cells. However, HA/CHI multilayers shows only weak adhesiveness for human umbilical vein endothelial cells (HUVEC). In this article, we summarize our approaches to enhance the HA/CHI multilayer by incorporation of a non-polymer substance -graphene oxide- to improve the cell adhesion and keep such properties as low cytotoxicity and biodegradability. Different approaches for incorporation of graphene oxide were performed and the cellular adhesion was tested by metabolic assay.

Despite decades of research, fibrosis still remains a significant challenge for medicine in many different fields. Although there is a general model of fibrosis, the causes and characteristics of the various pathologies are as diverse as the variety of organs and tissues that can be affected by fibrosis. Moreover, fibrosis also impedes the long-term prospects of success in implantation surgery. One possibility to address this challenge is the development of biocompatible implants featuring drug delivery systems loaded with antifibrotic pharmaceuticals. Due to diverse regulatory mechanisms in organs, tissues and also cell types, these active substances must consequentially be designed for diverse specific applications. Compared to fibrosis in organs like lung or liver, these mechanisms were poorly addressed in ophthalmologic research, but it is known that transforming growth factor beta (TGF-β) plays a key role. This gene expression study revealed 30 genes being upregulated more than two fold in TGF-β1 treated human primary tenon fibroblasts (hTF). Furthermore, 15 genes were found to be downregulated more than two fold. Tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA) and inhibin beta (INHBE) were particular strongly regulated in TGF-β1 treated hTFs.

Biomaterials applied to replace or restore body functions are exposed to different mechanical forces and corrosion processes due to body fluids, which might result in the generation of corrosion products, wear debris and particles potentially leading to inflammation and inhibition or loss of function. This brief review will give a short overview about the processes of wear generation and corrosion, the occurrence of the respective wear products in different medical applications and their biological influences. Wear and corrosion are important factors that control and determine the long-term clinical performance of a biomaterial.

Fiber materials offer a high potential for improving the surface characteristics of medical implants. For quality assurance of nano- and microfiber structures the morphology is inspected by Scanning Electron Microscopy (SEM) as a standard method. Vast quantities of image data have to be evaluated. Usual practice for obtaining the fiber diameters is the manually setting of measurement points. The software DiameterJ which runs as plugin in ImageJ automatically computes fiber diameters. Here we investigated its capabilities and limitations by comparing the evaluation of selected sample SEM images of electrospun fibers. In this study the fibers of three examplary images specified by different contrast and fiber morphology were analyzed by using varied segmentation algorithms. The results are displayed in bar charts of frequency distribution. Additionally the computed fiber diameters were compared to manual measurements. Depending on various image properties the segmentation process works more or less reliable, and fault data of incomplete segmented fibers are computed. Often the results are eligible, but frequently DiameterJ generates data resembling to thin fibers, which are not present in the image. In some cases the peaks of fault data are much higher than peaks of real fibers. In consequence misinterpretation of data cannot be avoided. DiameterJ is a validated tool with the ability to generate reliable results. Future work on improving the segmentation algorithms can refine computed evaluation.

The expansion capacity and accessibility of the side branch is essential for the stenting of complex bifurcations. Since previous measurement methods only provide limited information based on geometrical data of stent cells, a new measurement approach was developed which considers the mechanical deformation capacity of the stent design. This approach provides essential information on the stent with regard to the application of bifurcation stenting. Four different commercially available coronary stents (nominal diameter 3.0 mm) were dilated and a central strut cell was over-expanded by means balloon catheters of increasing nominal diameter (2.0 to 5.0 mm). After balloon inflation, the remaining cell size was investigated for maximum cell diameter and strut fractures. Large expansion capacity without cell damage is taken as a measure of the accessibility of the side branch. In none of the expansion experiments the desired target size could be achieved, which is due to the elastic recoil of the stent cells. Deviations from the target diameter between 14-38% were determined. However, larger diameters also showed a constriction of the balloon, so that in some cases the target diameter could not be achieved at all. No strut fractures occurred even at maximum balloon diameter and pressure (5.0 mm noncompliant balloons). As a result the side branch accessibility differs depending on the individual stent designs. No particular risk for the stent was found by extensive overdilatation.

Thermoplastic polycarbonate urethane elastomers (TPCU) are potential implant materials for treating degenerative joint diseases thanks to their adjustable rubberlike properties, their toughness, and their durability. We developed a water-containing high-molecular-weight sulfated hyaluronic acid-coating to improve the interaction of TPCU with the synovial fluid. It is suggested that trapped synovial fluid can act as a lubricant that reduces the friction forces and thus provides an enhanced abrasion resistance of TPCU implants. Aims of this work were (i) the development of a coating method for novel soft TPCU with high-molecular sulfated hyaluronic acid to increase the biocompatibility and (ii) the in vitro validation of the functionalized TPCUs in cell culture experiments.

Pancreatic fluid collections (PFCs) are a common complication associated with pancreatic injury. Drainage of a PFC is usually indicated if a patient becomes symptomatic with complications such as bacterial superinfection, septicaemia, fistulas, biliary obstruction or gastric outlet obstruction. Endoscopic ultrasound guided drainage is a well-established minimally invasive procedure to insert stents into a fluid collection, most prominently plastic double pigtail stents (DPSs) and lumen-apposing metal stents (LAMS). Both, DPSs and LAMSs have advantages and disadvantages that need to be considered before treatment. However, the main factors leading to failure of currently available stent systems are the relatively short patency period and bacterial superinfection. In this study, we subjected two broadly used pancreatic stents, a DPS and a LAMS Hot AXIOS stent, which were retrieved from the same patient, to a systematic morphological analysis by scanning electron microscopy in order to identify factors related to stent topography and geometry and potentially involved in stent failure. Results of this work will provide essential information for future innovations regarding the stent design for drainage of PFCs.

To assess the hydrodynamic performance of transcatheter aortic valve prostheses (TAVP), in vitro test using pulse duplicators is required. Test conditions as well as minimum performance criteria are specified in ISO 5840- 3:2013 and ISO 5840-3:2019-draft. In the 2019 published draft, modifications regarding hydrodynamic testing are proposed. Among others, the geometrical configuration of the fixation has changed, with the intention to improve the anatomical representation as well as the comparability of results from different test laboratories. We analyzed the consequences of altered annulus fixations regarding native leaflets as well as a step in the proximal area of the protheses to prevent their migration. The analyses were conducted with regard to the degree of calcification of the annulus ring on hydrodynamic parameters. By using 3D stereolithography printing technology, molds for casting of silicone elastomer of annulus models with and without native leaflets were manufactured. A modular system enabled us to use the same annulus ring to model the degree of calcification as well as different step sizes. We performed in vitro hydrodynamic testing according to ISO 5840-3:2019-draft of a selfexpandable valve prototype with porcine pericardial leaflets by using a commercially available pulse duplicator system. As expected, regurgitation increases with increasing degree of calcification, whereby the use of a step has no influence on the backflow of fluid during diastole. The effective orifice area (EOA) of the valve showed a clear tendency with respect to radial protrusion of the step. The EOA decreased as the radial protrusion increased. We also present a suggestion to prevent migration without affecting the general test results, by using a novel step design. We also found that the novel annulus model with native leaflet drastically reduced the regurgitation.

The degradable polymer Polydioxanone (PDO) is used for medical implants since 1981. Manufacturers state a degradation timeframe of <180 days or an absorption duration of 182-238 days [1, 2]. Aim of this study was to find in vitro-conditions to degrade PDO films within four weeks. Therefore the degradation of PDO was performed in accelerated conditions in tempered alkaline glycine NaOH buffer. Molecular weight and mass loss were studied. PDO results were compared with poly lactic-co-glycolic acid P(LLA-co-GA).

Nanofiber nonwoven membranes produced by electrospinning provide the possibility to adjust mechanical material parameters as well as simultaneously the biologically relevant properties - a fundamental aspect in developing new implants and medical devices. Wettability and permeability are also of great importance, as they have a decisive influence on the release of drugs, cell attachment, degradability and finally the nutrient supply of the surrounding tissue. Within this work the wettability and permeability of several electrospun poly-L-lactide nonwovens, including different additives, were investigated and a correlation to membrane morphology was found. A potential modification of the permeability by the fluid viscosity was also investigated. The results form a fundamental building block in the development of permeable biodegradable implants and medical devices.

Electrospun fiber nonwoven materials of different polymer classes provide promising perspectives in almost all fields of application, including medical science. In this paper we present the fiber generation of selected biostable polymers (PBT, TPC-ET, PA 6.12 and PVDF) by direct electrospinning, as an extremely powerful tool for manufacturing of new superfiber implant materials. This initial study includes the variation of some relevant process parameters, such as polymer concentrations or electrode spacing. The influence on fiber morphology, tensile strength and biocompatibility is shown. The results presented indicate that the choice and combination of materials is crucial for the application on load-bearing implants, independent of the processing technology and thus of the fiber bonding, delamination or fiber strength.

Vascularization of bioprinted constructs to ensure sufficient nutrient supply still remains to be a significant task in the tissue engineering community. In order to mimic functional tissue, it is necessary to be able to print vessels in various size scales, which places particularly high demands on the 3D printing technology and materials. In this preliminary study, we focused on the production of small hollow structures for the application in small functional units of living tissue. To fabricate hollow structures, the freeform reversible embedding of suspended hydrogels (FRESH) - method was utilized (Hinton et al.). A sodium alginate solution (5 % w/v) was used as a bioink. The scaffolds were fabricated with the Allevi 1 (Allevi Inc., PA, USA), a pneumatic extrusion-based bioprinter and plotted into a gelatine slurry serving as fugitive support. For first cell experiments, the bioink was loaded with immortalized mouse HL1-cells. A proof of concept could be shown since we were able to reliably create vessel-like structures with an inside diameter of 1.2 to 1.6 mm, a length of up to 8 mm and a wall thickness of 0.4 to 0.6 mm. In this study, the geometric requirements to print hollow structures for small functional tissues could be achieved. To expand the field of applications the resolution of the printing process has to be further improved. Moreover, the cell density should be increased to reach physiological cell numbers and extended with endothelial cells.

Medical implants play a central role in modern medicine and both, naturally derived and synthetic materials have been explored as biomaterials for such devices. However, when implanted into living tissue, most materials initiate a host response. In addition, implants often cause bacterial infections leading to complications. Polyelectrolyte multilayer (PEM) coatings can be used for functionalization of medical implants improving the implant integration and reducing foreign body reactions. Some PEMs are also known to show antibacterial properties. We developed a PEM coating suggesting that it can decrease the risk of bacterial infections occurring after implantation while being highly biocompatible. We applied two different standard tests for evaluating the PEM’s antibacterial properties, the ISO norm (ISO 22196) and one ASTM norm (ASTM E2180) test. We found a reduction of bacterial growth on the PEM but to a different degree depending on the testing method. This result demonstrates the need for defining proper method to evaluate antibacterial properties of surface coatings.

Abdominal aortic aneurysm (AAA) is a common condition of increasing prevalence, particularly among older men. An AAA is defined as a permanent dilation of the abdominal aorta, with a diameter greater than 30 mm or a diameter greater than 50% of the aortic diameter at the level of the diaphragm. As the size of the aneurysm increases, so does the risk of rupture. Therefore, prophylactic repair with insertion of a prosthetic graft is offered. Since 1951 traditional open aneurysm repair (OAR) was reported and minimally invasive endovascular repair (EVAR) was first reported in 1986. Data from four randomized controlled trials (EVAR-1, DREAM, OVER, ACE) for abdominal aortic aneurysm, which enrolled almost 3000 patients, in a period from 1999 to 2008, were summarized. In addition, registry databases on the treatment of AAA of average 4000 patients per year, based from 2015 to 2018 of the German Institute for Vascular Medicine Healthcare Research of the German Society for Vascular Surgery and Vascular Medicine, were compared. The EVAR procedure for AAA showed a lower risk of perioperative mortality but was associated with a higher cardiovascular and aneurysm-related complication rate. In particular, patients aged 80 years or older benefited from EVAR since the 30-day mortality of patients receiving OAR was higher. In mid-term and long-term follow-up there were no differences in survival after endovascular and open aortic repair. Overall, it depends on the respective underlying disease and anatomy which of the two approaches is to be preferred. In conclusion, both treatment options can be considered as equal and can be offered to patients.

Application-specific integrated circuits (ASICs) embedded in polymers have been subject in implant manufacturing for the recent years. The increased functionality combined with good biocompatibility due to flexibility of thin implants makes them interesting for further studies. Thin-film ASICs can be used for the recording and processing of a high amount of biological signals, improving the performance of neural implants. Fabrication and analysis of gold and platinum thin-film connections are subject of this study, especially their capability as high frequency data transmission lines. Three layers of polyimide are used as flexible substrate and insulator of the traces. Various test structures were designed and fabricated, to investigate the resistance and reactance up to GHz frequencies, crosstalk and influence of vias between metallization layers. All conducting structures have a comparable design with a length of 50 mm and a metal thickness of 300 nm, while the line widths were varied. In this configuration gold and platinum thinfilm conductors are both suitable for high-frequency data transmission up to 100 MHz. This transmission frequency limit and impedances are unaffected by a wet environment and in accelerated aging tests. However, both metals show a high pass filter behavior, whose frequency behavior is mostly dependent by the self-inductance and resistance. A simplified ideal transmission model predicts the electrical behavior sufficiently and can be used to design the favored line impedance matching input impedances of the connected ASICs.

Biomechanical functionality of artificial hips strongly correlates with quality of life of patients after total hip arthroplasty. As the numbers of total hip arthroplasty are growing due to increasing life expectancy, biomechanical research is of utmost importance to improve the implants used and the operative procedures applied. Multibody simulation is used to predict forces and moments inside the human body. Generic scaling is usually performed to adapt the human models used in multibody simulation to individual patients. However, since the shape and size of the bones can vary considerably, this type of scaling often is not sufficient. In this work various CT datasets were used to quantify differences of individual femoral shapes, especially with regard to important biomechanical hip parameters, such as the CCD angle or the femoral offset. Our results prove that multibody simulations should be modeled more patientspecific to be able to calculate articular forces and moments more precisely, and thus, to improve surgical planning.

Artificial intelligence and neural networks are getting more and more relevant for several types of application. The field of prosthesis technology currently uses electromyography for controllable prosthesis. The precision of the control suffers from the use of EMG. More precise and more collected data with the help of EIT allows a much more precise analysis and control of the prosthesis. In this paper a neural network for gesture detection using EIT is developed and presented in a user-friendly way.

The morphology of the electrocardiogram (ECG) varies among different healthy subjects due to anatomical and structural reasons, such as for example the shape of the heart geometry or the position and size of surrounding organs in the torso. Knowledge about these ECG morphology changes could be used to parameterize electrophysiological simulations of the human heart. In this work, we detected the boundaries of ECG waveforms, i.e. the P-wave, the QRS-complex and the T-wave, in 12- lead ECGs from 918 healthy subjects in the Physionet Computing in Cardiology Challenge 2020 Database with the IBT openECG toolbox. Subsequently, we obtained the onset, the peak and the offset of each P-wave, QRS-complex and T-wave in the signal. In this way, the duration of the P-wave, the QRScomplex and the T-wave, the PQ-, RR- and the QT-interval as well as the amplitudes of the P-wave, the Q-, R- and Speak and the T-wave in each lead were extracted from the 918 healthy ECGs. Their statistical distributions and correlation between each other were assessed. The highest variabilities among the 918 healthy subject were found for the RR interval and the amplitudes of the QRScomplex. The highest correlation was observed for feature pairs that represent the same feature in different leads. Especially the R-peak amplitudes showed a strong correlation across different leads. The calculated feature distributions can be used to optimize the parameters of populations of cardiac electrophysiological models. In this way, realistic in-silico generated surface ECGs can be simulated in large scale and could be used as input data for machine learning algorithms for a classification of cardiovascular diseases.

Transcranial magnetic stimulation (TMS) is an established method to treat various neurological diseases, such as depression, Alzheimer’s disease, and tinnitus. New applications for TMS are closed loop neurofeedback (NF) scenarios, which require software control of the TMS system, instead of the currently used manual control. Hence, the MagCPP (https://github.com/MagCPP) toolbox was developed and is described in this work. The toolbox enables the external control of Magstim TMS devices via a C++ interface. Comparing MagCPP to two other toolboxes in a TMS application scenario with 40% power, we found that MagCPP works faster and has lower variability in repeated runs (MagCPP, Python, MATLAB [mean±std in seconds]: 1.19±0.00, 1.59±0.01, 1.44±0.02). An integration of MagCPP in a real-time data processing platform MNE-CPP with an optional GUI demonstrates its ability as part of a closed-loop NF-scenario. With its performing advantages over other toolboxes, MagCPP is a first step towards a complete closed loop NF scenario and offers possibilities for novel study designs.

The Institute of Virology at the Philipps-Universität Marburg is currently researching possible drugs to combat the Marburg virus. This involves classifying cell structures based on fluoroscopic microscopic image sequences. Conventionally, membranes of cells must be marked for better analysis, which is time consuming. In this work, an approach is presented to identify cell structures in images that are marked for subviral particles. It could be shown that there is a correlation between the distribution of subviral particles in an infected cell and the position of the cell’s structures. The segmentation is performed with a "Mask-R-CNN" algorithm, presented in this work. The model (a region-based convolutional neural network) is applied to enable a robust and fast recognition of cell structures. Furthermore, the network architecture is described. The proposed method is tested on data evaluated by experts. The results show a high potential and demonstrate that the method is suitable.

Heart rate variability (HRV) is a powerful measure to gain information on the activation of the central nervous system and is thus a strong indicator for the overall health and emotional state of a person. Currently, the gold standard for HRV analysis is the examination of R-peaks in electrocardiograms (ECG), which requires a placement of electrodes on the torso. This is often impracticable, especially for the use in daily routines or 24/7 measurements. Photoplethysmograms (PPG) are an alternative to ECG assessment and are easier to acquire, e.g. by using fitness trackers or smart watches. Nevertheless, PPG data is more susceptible to motion artifacts. Hence, goal of this work is to develop and evaluate an artificial neural network (ANN) approach to estimate the R-peak locations in complex PPG signals. Public data collections were used as benchmark to compare our ANN-based approach to state-of-the-art methods. Results show that ANNs can improve HRV estimation during motion. HRV estimations from baseline methods (decision-tree based and automatic multiscalebased peak detection) were compared with the best performing neural network (3L-GRU) using the TROIKA dataset with respect to reference parameters obtained from a manual selection of the peaks in ECG data. In most cases, the neural network based HRV estimation was closer to the reference HRV compared to baseline methods (lower μ and σ ) Also, σ is smaller for the best performing ANN approach across most HRV parameters. Inclusion of another PPG or acceleration channel did not affect HRV estimation. Although, the neural network learning approach outperforms conventional methods, the examined PPG-based HRV estimation has still accuracy limitations. Nonetheless, the proposed estimation approach opens up new directions for further improvement.

This study presents a novel method for estimating the signal quality of photoplethysmographic (PPG) signals. For this purpose a robust classifier is implemented and evaluated by using finger- and inear-PPG. A new procedure is proposed, which uses feature reduction to determine the Mahalanobis distance of the PPG-pulses to a statistical reference model and thus facilitates a robust heart rate extraction. The evaluation of the algorithm is based on a classical binary classification using a manually annotated gold standard. For the finger-PPG a sensitivity of 86 ± 15 % and a specificity of 94 ± 13 % was achieved. Additionally, a novel classification method which is based on a continuous signal quality index is used. Pulse rate estimation errors greater than 5 BPM can be detected with a sensitivity of 91 ± 13 % and a specificity of 91 ± 15 %. Also, a functional correlation between the signal quality index and the standard deviation of the pulse rate error is shown. The proposed classifier can be used for improving the heart rate extration in pulse rate variability analysis or in the area of mobile monitoring for battery saving.

This work focuses on investigating an optimal foetal heart rate (FHR) signal segment to be considered for automatic cardiotocographic (CTG) classification. The main idea is to evaluate a set of signal segments of different length and location based on their classification performance. For this purpose, we employ a feature extraction operation based on two signal processing techniques, such as the Improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise and time-varying autoregressive modelling. For each studied segment, the features are extracted and evaluated based on their performance in CTG classification. For the proposed evaluation, we make use of real CTG data extracted from the CTU-UHB database. Results show that the classification performance depends considerably on the selected FHR segment. Likewise, we have found that an optimal FHR segment for foetal welfare assessment during labour corresponds to a segment of 30 minutes long.

Clinical studies have shown that during standardized movements the Acoustic Emission (AE) from lesions in articular cartilage can be assessed. Specific lesions produce specific acoustic signals, therefore it is possible to evaluate the character of cartilage damage. Consequently it is possible to evaluate the condition of the joint cartilage in order to enhance therapy. Patients performed series of knee bends, first on a plane surface in order to assess the cartilage lesions. Then patients performed knee bends on boards simulating orthopaedic insoles by means of inner and outer edge elevations. Insoles aim at relieving the lesioned areas of cartilage from loads and strain. AEA monitoring reveals the effects of a shift of the zone of load transfer immediately and is an adequate tool for the diagnosis as well as the monitoring of therapeutic measures.

Microscopy enables fast and effective diagnostics. However, in resource-limited regions microscopy is not accessible to everyone. Smartphone-based low-cost microscopes could be a powerful tool for diagnostic and educational purposes. In this paper, the imaging quality of a smartphone-based microscope with four different optical parameters is presented and a systematic overview of the resulting diagnostic applications is given. With the chosen configuration, aiming for a reasonable trade-off, an average resolution of 1.23 μm and a field of view of 1.12 mm2 was achieved. This enables a wide range of diagnostic applications such as the diagnosis of Malaria and other parasitic diseases.

Nowadays, patients with metallic implants undergoing radiotherapy may suffer from inaccuracy in the treatment plan caused by the implant. To ensure a precise plan an accurate relation between Hounsfield values of the computer tomographic (CT) images and the electron density of the elements and material mixtures is indispensable. In order to extend the stoichiometric calibration approach known for tissues to the regime of metallic materials, the basic physical equations as well as approximations in the parametrization and fitting are carefully reviewed. CT images of a standard calibration phantom and pure metallic samples up to the atomic number Z = 29 were acquired for various energies. Hounsfield values were determined on an extended Hounsfield scale which allows the mapping of material having high atomic number Z. It is found that from basic physics an empirical factorization of the cross-sections into a function of Z and a function of photon energy E is not allowed over a wide range of Z. Specifically, the parameterization for tissue like materials cannot be prolonged to materials with high-Z. Thus, the calibration is subdivided into regions of materials and its accuracy is quantified in each region. It depends, among others, on the knowledge of the X-ray photon spectra, the segmentation of the material samples and the empirical parameterization of the linear-attenuation coefficient.

Microscopy is an essential tool in research and science. However, it is relatively resource consuming regarding cost, time of usage, and consumable supplies. Current low-cost approaches provide good imaging quality but struggle in terms of versatility or applicability to varying setups. In this paper, a Compact Microscope Module for versatile application in custom-made setups or research projects is presented. As a first application and proof of concept, the use of the module in a High-Throughput Microscope for screening of samples in microtiter plates is shown. The Compact Microscope Module allows for simple and resource-efficient microscopy in various applications while still enabling relatively good imaging qualities.

We investigate the suitability of statistical and model-based iterative reconstruction (IR) algorithm strengths and their influence on image quality and diagnostic performance in low-dose computer tomography (CT) protocols for lung-cancer screening procedures. We evaluate the inter- and intra-observer performance for the assessment of iterative CT reconstruction. Artificial lung foci shaped as spheres and spicules made from material with calibrated Hounsfield units were pressed within layered granules in lung lobes of an anthropomorphic phantom. Adaptively, a soft-tissue- and fat- extension ring were attached. The phantom with foci was scanned using standard high contrast, low-dose and ultra lowdose protocols. For reconstruction the IR algorithm ADMIRE at four different strength levels were used. Two ranking tests and Friedman statistics were performed. Fleiss k and modified Cohen’s k ney were used to quantify inter- and intra-observer performance. In conjunction with the standard lung kernel BL75 radiologists evaluated medium to high IR strength, with preference to S 4 , as suitable for lung foci detection. When varying reconstruction kernels the ranking became more random than with varying phantom diameter. The inter-observer reliability shows poor to slight agreement expressed by k<0 and k=0-0.20 . For the intra-observer reliability non- agreement with k ney =0-0.20and moderate agreement with k ney =0.60-0.79 for the first ranking test, and almost perfect agreement with k ney >0.90 for the second ranking test was observed. In conclusion, our validation suggests radiological preference of medium to high iteration strengths, especially S 4 , for lung foci detection. An investigation of the correlation between diagnostic experience and the subjective perception of IR reconstructed CT images still needs to be investigated.

Employing sonosensitive nanoparticles as carriers of active pharmaceutical ingredients emerges in ultrasonic Drug Delivery. Drug release can be initiated by focused ultrasound via the effect of inertial cavitation in certain target areas of particle loaded tissue. For stimulating inertial cavitation, a specific peak rarefaction pressure threshold must be exceeded. This pressure threshold has to be determined in order to estimate the risk of tissue damage during the drug release procedure. Therefore, this study provides a method to reliably verify the cavitation pressure threshold of sonosensitive and biocompatible nanoparticles.

Various medical procedures make use of magnetic nanoparticles, such as Magnetic Drug Targeting (MDT), which boosts the demand for imaging modalities that are capable of in vivo visualizing this kind of particles. Magnetomotive Ultrasound is an imaging technique that can detect tissue, which is perfused by magnetic nanoparticles. In this contribution, we investigate the suitability of Magnetomotive Ultrasound to serve as a monitoring system during MDT. With the conducted measurements, it was possible for the first time to observe in vivo the accumulation of iron-oxide nanoparticles during a Magnetic Drug Targeting cancer treatment applied to a small animal (rabbit).

Numerical simulations are increasingly often involved in developing new and improving existing medical therapies. While the models involved in those simulations are designed to resemble a specific phenomenon realistically, the results of the interplay of those models are often not sufficiently validated. We created a plugin for a cardiac simulation framework to validate the simulation results using clinical MRI data. The MRI data were used to create a static wholeheart mesh as well as slices from the left ventricular short axis, providing the motion over time. The static heart was a starting point for a simulation of the heart’s motion. From the simulation result, we created slices and compared them to the clinical MRI slices using two different metrics: the area of the slices and the point distances. The comparison showed global similarities in the deformation of simulated and clinical data, but also indicated points for potential improvements. Performing this comparison with more clinical data could lead to personalized modeling of elastomechanics of the heart.

This paper presents a simulation system (“patient model”) for intraoperative neuromonitoring (IONM) applied to mastoidectomy. IONM is an electrophysiological method for monitoring the integrity and localization of nerve tracts, which helps the surgeon to avoid injuries and damage to neural risk structures (e.g. facial nerve) during surgery. To use the IONM successfully, the surgeon needs appropriate training and experience. The presented simulation system provides training possibilities in a realistic, cost-efficient and reproducible way. In the simulation system, the position of the probe during training is determined by a magnetic tracking method. Depending on the distance to the virtual nerve, a synthetic electromyogram (EMG) signal is sent to a real neuromonitor. The trainee learns to interpret the output of the neuromonitor. The trainer can choose different training scenarios, such as localization of the nerve, milling or coagulating, using a web application.

A disturbed synchronization of the ventricular contraction can cause a highly developed systolic heart failure in affected patients with reduction of the left ventricular ejection fraction, which can often be explained by a diseased left bundle branch block (LBBB). If medication remains unresponsive, the concerned patients will be treated with a cardiac resynchronization therapy (CRT) system. The aim of this study was to integrate His-bundle pacing into the Offenburg heart rhythm model in order to visualize the electrical pacing field generated by His-Bundle-Pacing. Modelling and electrical field simulation activities were performed with the software CST (Computer Simulation Technology) from Dessault Systèms. CRT with biventricular pacing is to be achieved by an apical right ventricular electrode and an additional left ventricular electrode, which is floated into the coronary vein sinus. The non-responder rate of the CRT therapy is about one third of the CRT patients. His- Bundle-Pacing represents a physiological alternative to conventional cardiac pacing and cardiac resynchronization. An electrode implanted in the His-bundle emits a stronger electrical pacing field than the electrical pacing field of conventional cardiac pacemakers. The pacing of the Hisbundle was performed by the Medtronic Select Secure 3830 electrode with pacing voltage amplitudes of 3 V, 2 V and 1,5 V in combination with a pacing pulse duration of 1 ms. Compared to conventional pacemaker pacing, His-bundle pacing is capable of bridging LBBB conduction disorders in the left ventricle. The His-bundle pacing electrical field is able to spread via the physiological pathway in the right and left ventricles for CRT with a narrow QRS-complex in the surface ECG.

The short-range and sharp dose fall-off of beta particles in tissue make them an interesting option for use in the radiation therapy of superficial skin tumors. This can be used to protect bony or other sensitive structures located right beneath the tumor. In a previous study, we studied the feasibility of using 3D printing technology to create 2D radioactive models for the treatment of skin tumors. In the current study, the Monte Carlo method was used to simulate the transverse dose profile form 3D printed extruded line containing yttrium-90 (Y-90) particles. The time and activity required for treating a superficial skin tumor using these extruded lines were also calculated.

Proper treatment of prostate cancer is essential to increase the survival chance. In this sense, numerous studies show how important the communication between all stakeholders in the clinic is. This communication is difficult because of the lack of conventions while referring to the location where a biopsy for diagnosis was taken. This becomes even more challenging taking into account that experts of different fields work on the data and have different requirements. In this paper a web-based communication tool is proposed that incorporates a visualization of the prostate divided into 27 segments according to the PI-RADS protocol. The tool provides 2 working modes that consider the requirements of radiologist and pathologist while keeping it consistent. The tool comprises all relevant information given by pathologists and radiologists, such as, severity grades of the disease or tumor length. Everything is visualized using a colour code for better undestanding.

Automatic tendencies to approach addictionrelated stimuli have been linked to the development and maintenance of harmful drug use behavior. Recent studies have shown that these automatic approaches can be directly addressed and modified by cognitive bias modification (CBM). However, the training and treatment effects are rather small and compliance could be impaired by time-consuming, multiple laboratory training sessions. Here we present a mobile variant of the Approach-Avoidance Task (app-AAT), which is evaluated by a feasibility study. The app-AAT is designed to improve the efficiency of CBM training by allowing smokers to access the training at any time, and by offering the option to track consumed cigarettes. Our first run with eight participants showed that the app was rated very positively with 4.2 out of 5 points (engagement: 3.7, functionality: 4.5, aesthetics: 4.4) by using the german Mobile App Rating Scale (MARS-G).

In robot-assisted procedures, the surgeon controls the surgical instruments from a remote console, while visually monitoring the procedure through the endoscope. There is no haptic feedback available to the surgeon, which impedes the assessment of diseased tissue and the detection of hidden structures beneath the tissue, such as vessels. Only visual clues are available to the surgeon to control the force applied to the tissue by the instruments, which poses a risk for iatrogenic injuries. Additional information on haptic interactions of the employed instruments and the treated tissue that is provided to the surgeon during robotic surgery could compensate for this deficit. Acoustic emissions (AE) from the instrument/tissue interactions, transmitted by the instrument are a potential source of this information. AE can be recorded by audio sensors that do not have to be integrated into the instruments, but that can be modularly attached to the outside of the instruments shaft or enclosure. The location of the sensor on a robotic system is essential for the applicability of the concept in real situations. While the signal strength of the acoustic emissions decreases with distance from the point of interaction, an installation close to the patient would require sterilization measures. The aim of this work is to investigate whether it is feasible to install the audio sensor in non-sterile areas far away from the patient and still be able to receive useful AE signals. To determine whether signals can be recorded at different potential mounting locations, instrument/tissue interactions with different textures were simulated in an experimental setup. The results showed that meaningful and valuable AE can be recorded in the non-sterile area of a robotic surgical system despite the expected signal losses.

For the assessment of human reaction time, a test environment was developed. This system consists of an embedded device with organic light-emitting diode (OLED) displays with push buttons for the combined presentation of visual stimulation and registration of the haptic human reaction. The test leader can define the test sequence with the aid of a graphical user interface (GUI) on a personal computer (PC). The validation of the system was proved by measuring the latency times of the whole system, which are conditioned by the specific hard- and software constellation. Through the investigation of the display’s light radiation by a photodiode and the recorded current consumption, latency times and their variance were specified. In the fastest mode the system can reach an error limit of 60 μs.

Arterial blood pressure is one of the most important cardiovascular parameters. Yet, current-generation devices for continuous, noninvasive acquisition are few, expensive and bulky. Novel signal processing applied to easily acquired unimodal signals can alleviate this issue, reducing size, cost and expanding the use of such devices to ambulatory, everyday settings. The features of pulse waves acquired by photo- or impedance-plethysmography can be used to estimate the underlying blood pressure. We present a progressive dynamic time warping algorithm, which implicitly parametrizes the morphological changes in these waves. This warping method is universally applicable to most pulse wave shapes, as it is largely independent of fiducial point detection or explicit parametrization. The algorithm performance is validated in a feature selection and regression framework against a continuous, noninvasive Finapres NOVA monitor, regarding systolic, mean and diastolic pressures during a light physical strain test protocol on four clinically healthy subjects (age18- 33, one female). The obtained mean error is 2.13 mmHg, the mean absolute error is 5.4 mmHg and the standard deviation is 5.6 mmHg. These results improve on our previous work on dynamic time warping. Using single-sensor, peripherally acquired pulse waves, progressive dynamic time warping can thus improve the flexibility of noninvasive, continuous blood pressure estimation.

We introduce a novel method for electronic recording of cardiac signals from a single point at the skin in contrast to classical differential electrocardiography (ECG). Ultralownoise transistor devices with an adaptable, auto-stabilizing transimpedance amplifier are able to measure tiny skin potential modulations from a single contact electrode located at an individual’s wrist (single-point cardiography-SPC). Although SPC signals were highly prone to interspersed noise, they contained periodic patterns. In an electromagnetically shielded setting, we could clearly extract breathing and cardiac rhythms from the acquired SPC signals. As the reference, we measured ECG in parallel. Several signal-processing techniques like smoothening, correlation, decomposition and signal extraction showed that SPC signals contain breathing and periodic heart potential variations, which are time-correlated with ECG. In the future, we intent to use this novel technique to measure heart signals from patients in different health conditions.

Photodynamic therapy (PDT) is a potential option for treatment of cancer since it can be performed non- invasive for superficial cancers or minimal-invasive with low traumatization. But PDT is intrinsically inefficient due to the complex accumulation of the photosensitizing drug inside the tumor and the processes of heme syntheses to create the needed cell killing components. To optimize the outcome of PDT and increase acceptance as viable option it is necessary to predict the optimal time for the start of the treatment based on measurable precursors. A former cell study proposed a new filter fluorometer in a complex and sensitive setup. In this work we now designed and tested a simplified system that can be used in combination with standard endoscopic imaging systems. This system will be used as base to prove viability of this approach for a future clinical study.

Vascular endoscopic imaging is known for a long time but has never made its way into clinical routine. Reasons for that are the complexity, lack of low-cost portable systems, and the lack of suitable endoscopes providing high image quality with small dimensions. In addition, an interruption of the blood flow caused by the device and the opacity of blood are difficult to manage. In the past we have already developed ideas to overcome these difficulties and now we present a feasibility test of a thin diameter ureteroscope for observation of vascular procedures. The imaging system was tested in a phantom where side branches were explored, a stent was placed and a simulated aneurysm coiled.

Arthroscopic surgery is a technically challenging but common minimally invasive procedure with a long learning curve and a high incidence of iatrogenic damage. These damages can occur due to the lack of feedback and supplementary information regarding tissue-instrumentcontact during surgery. Deliberately performed interactions can be used however to obtain clinically relevant information, e.g. when a surgeon uses the tactile feedback to assess the condition of articular cartilage. Yet, the perception of such events is highly subjective. We propose a novel proximally attached sensing concept applied to arthroscopic surgery to allow an objective characterization and utilization of interactions. It is based on acoustic emissions which originate from tissue-instrument-contact, that propagate naturally via the instrument shaft and that can be obtained by a transducer setup outside of the body. The setup was tested on its ability to differentiate various conditions of articular cartilage. A femoral head with varying grades of osteoarthritic cartilage was tapped multiple times ex-vivo with a conventional Veress needle with a sound transducer attached at the outpatient end. A wavelet-based processing of the obtained signals and subsequent analysis of distribution of spectral energy showed the potential of tool-tissue-interactions to characterize different cartilage conditions. The proposed concept needs further evaluation with a dedicated design of the palpation tool and should be tested in realistic arthroscopic scenarios.

The effectiveness, efficiency, availability, agility, and equality of global healthcare systems are in question. The COVID-19 pandemic have further highlighted some of these issues and also shown that healthcare provision is in many parts of the world paternalistic, nimble, and often governed too extensively by revenue and profit motivations. The 4th industrial revolution - the machine learning age - with data gathering, analysis, optimisation, and delivery changes has not yet reached Healthcare / Health provision. We are still treating patients when they are sick rather then to use advanced sensors, data analytics, machine learning, genetic information, and other exponential technologies to prevent people from becoming patients or to help and support a clinicians decision. We are trying to optimise and improve traditional medicine (incremental innovation) rather than to use technologies to find new medical and clinical approaches (disruptive innovation). Education of future stakeholders from the clinical and from the technology side has not been updated to Health 4.0 demands and the needed 21st century skills. This paper presents a novel proposal for a university and innovation lab based interdisciplinary Master education of HealthTEC innovation designers.

Novel challenges and developments require adaptations on skill set, content, and associated education. A biomedical engineer will require a broad range of skills - which to a large extent are currently not taught - in the coming years to meet the development needs of future healthcare: intensive interdisciplinary team work, advanced communication skills, team management and coaching capabilities, advanced project management, learn how to learn, visionary and forward looking thinking, understanding of health economics, entrepreneurship and leadership. But above all empathy towards the clinical user and patients is needed as well as a basic understanding of the current and future clinical workflows that can globally vary. An innovation process for a healthcare related product or service will likely only create value through the consideration and implementation of several of these points. Even though techniques for the development of innovation and enhancing creativity in individuals are widely discussed, there are relatively few reports on the practice of mainstreaming creativity in an organizational setting. We report on the setup of our Graduate School “Technology Innovation in Therapy and Imaging (T²I²)” that has implemented a structured post graduate program and focuses on interdisciplinary and application-oriented innovation generation education. The educational process starts with the observation and identification of clinical needs and an in-depth understanding of the problem and subsequently covers all steps necessary to transfer prototypes into viable solutions and further into implementing valuable products.

Many medical interventions in therapy and diagnostics require needle insertion into tissue. Common complications such as increased pain and formation of haematoma are caused by wrong needle positioning. It has been shown that pain experience and needle positioning can be improved by a reduction of insertion force, which can be achieved by vibrating the needle axially. An experimental setup has been designed to investigate the influences of different combinations of vibration frequencies (10, 100, and 200 Hz) and vibration amplitudes (20, 100, and 500 μm) during needle insertion into thin sheets of polyethylene terephthalate (PET). A customary 20 W loudspeaker was used to generate the vibration. The results indicate a maximum reduction of 73 % in puncture force and up to a 100 % reduction in shaft friction force. However, the additional vibration force generated by the vibration movement has to be high enough to generate positive effects in terms of force reduction.

Paramedics face rising numbers of deployments every year. As obstacles like stairs occur often, paramedics must frequently manually carry patients and are thereby exposed to loads multitudes higher than recommended. This creates the need for patient transport aids (PTA), which can physically support paramedics in a wide variety of transport situations, without slowing down the transport. In this paper a workflow analysis for transport missions in an urban context and basic tasks for PTAs are presented. Subsequently, the high-level task modelling and human-centered risk analysis according to the HiFEM method are presented for the use case of a patient transport over stairs with a passive PTA, like a rescue chair, and an active PTA like the novel SEBARES prototype. The analysis shows that conventional PTA’s have a simple linear use process, however, impose excessive physical workloads, which cause risks like the paramedic or the PTA falling down the stairs. Contrary, active PTA’s reduce physical workloads, however, introduce additional concurrent steps, like identifying and correcting misalignments, which create further risks. In order to mitigate risks with active, stair climbing PTAs either new kinematic designs or intelligent assistance functions, like automatic stair detection, are necessary.

Paramedics face rising numbers of deployments every year. As obstacles like stairs occur often, paramedics must frequently manually carry patients and are thereby exposed to loads multitudes higher than recommended. This creates the need for patient transport aids (PTA), which can physically support paramedics in a wide variety of transport situations, without slowing down the transport. In this paper a workflow analysis for transport missions in an urban context and basic tasks for PTAs are presented. Subsequently, the high-level task modelling and human-centered risk analysis according to the HiFEM method are presented for the use case of a patient transport over stairs with a passive PTA, like a rescue chair, and an active PTA like the novel SEBARES prototype. The analysis shows that conventional PTA’s have a simple linear use process, however, impose excessive physical workloads, which cause risks like the paramedic or the PTA falling down the stairs. Contrary, active PTA’s reduce physical workloads, however, introduce additional concurrent steps, like identifying and correcting misalignments, which create further risks. In order to mitigate risks with active, stair climbing PTAs, either new kinematic designs or intelligent assistance functions, like automatic stair detection, are necessary.

This study evaluates the effect of ring-shaped microstructures on the rheological properties of a synovial fluid substitute. Two different materials that are frequently used in endoprostheses have been chosen in order to study the lubricating effect of femtosecond-laser microstructured implant surfaces by measuring the apparent dynamic viscosity of the lubrication fluid. The two different materials are the ceramic Al2O3 and the metal alloy CoCrMo. The results show that an increase in the viscosity of the synovia fluid substitute can be achieved by specific microstructuring. An increase of viscosity of up to 40% compared to an unstructured reference was observed with ring-shaped microstructures with a diameter of 100 μm, a texture area density of 2.5 % and an aspect ratio of 0.66. The measurements have also shown that the ceramic material resulted in slightly higher viscosity values, compared to the metal alloy which can explained by dimensional deviations of the microstructures caused by the laser microstructuring.

The Standard IEC 60601-2-2:2017 refers to neutral electrodes for high current without defining them. This paper suggests a practical distinction criterion between standard and high-current neutral electrodes and a test procedure.

Background. Digital technologies increasingly shape today’s world of work. This not only affects sectors such as knowledge work and the automotive industry, but also the care sector. On the one hand, many nurses today use technologies supporting some selected and rather peripheral nursing tasks (e.g., electronic documentation). However, on the other hand, more comprehensive and additionally proximal care-related task devices (e.g., diagnostics via telecare) seem to be used less often. From a psychological perspective, attitudes towards technology are an important antecedent of user behaviour. Therefore, in two studies we aimed to examine if nurses’ attitudes towards four digital technology fields (i.e., electronic documentation ED, ambient assisted living AAL, telecare application and robotics) are differing in relation to the type of task substitution, how technology appraisal and knowledge shape these attitudes, and how attitudes predict user behaviour. Method. We conducted two cross-sectional survey studies with German nurses (Study 1: N = 148, Study 2: N = 252) with well-established scales (i.e., general and work-related positive and negative attitudes towards technologies, ease of use, usability, knowledge, and technology use). Results. We found that it is important to consider positive and negative attitudes towards technology distinctively as intercorrelations were only moderately negative. As expected, we found in both studies that nurses reported stronger positive and less negative attitudes towards technologies assumed to be substituting more specific and peripheral (e.g., ED) than comprehensive and proximal care tasks (e.g., robotics). Moreover, we found that two types of technology appraisal (ease of use and usability) both positively correlated with positive attitudes towards all four technology fields, whereas patterns were more inconsistent and additionally influenced by technology knowledge when predicting negative attitudes. Although inconsistently across both studies and the considered technologies, in general, technology users reported more positive and less negative attitudes than non-users. Conclusion. If technology developers and nursing facility managers want to help nurses successfully adopting new technologies in their work routines, nurses’ technology appraisal and technology attitudes have to be considered already in the pre-development phase. Our study results show that nurses report different attitudes towards the four digital technology fields considered here in relation to the levels and types of task-substitution. More specifically, if core carerelated work-tasks (e.g., direct care) are not substituted, nurses report stronger positive and less negative attitudes towards the supporting technologies and higher user behaviour.