Volume 2, Issue 1

In this study, varying amounts of NIPAAm and an ionic liquid (IL), namely 1-vinyl-3-isopropylimidazolium bromide ([ViPrIm] + [Br] − ), have been used to synthesize hybrid hydrogels by radical emulsion polymerization. Amounts of 70/30%, 50/50%, 30/70%, 15/85% and 5/95% (wt/wt) of PIL/pNIPAAm were used to produce hybrid hydrogels as well as the parental hydrogels. The adhesive strength was investigated and evaluated for mechanical characterization. Thermal properties of resulting hydrogels have been investigated using differential scanning calorimetry (DSC) in a default heating temperature range (heating rate 10 K min −1 ). The presence of poly ionic liquids (PIL) in the polymer matrix leads to a moved LCST (lower critical solution temperature) to a higher temperature range for certain hybrid hydrogels PIL/pNIPAAm. While pNIPAAm exhibits an LCST at 33.9 ± 0.3°C, PIL/pNIPAAm 5/95% and PIL/pNIPAAm 15/85% were found to have LCSTs at 37.6 ± 0.9°C and 52 ± 2°C, respectively. This could be used for controlled drug release that goes along with increasing body temperature in response to an implantation caused infection.

A major challenge in cardiovascular tissue engineering is the fabrication of scaffolds, which provide appropriate morphological and mechanical properties while avoiding undesirable immune reactions. In this study electrospinning was used to fabricate scaffolds out of blood proteins for cardiovascular tissue engineering. Lyophilised porcine plasma was dissolved in deionised water at a final concentration of 7.5% m/v and blended with 3.7% m/v PEO. Electrospinning resulted in homogeneous fibre morphologies with a mean fibre diameter of 151 nm, which could be adapted to create macroscopic shapes (mats, tubes). Cross-linking with glutaraldehyde vapour improved the long-term stability of protein based scaffolds in comparison to untreated scaffolds, resulting in a mass loss of 41% and 96% after 28 days of incubation in aqueous solution, respectively.

The usage of electrospun polymer scaffolds is a promising approach for artificial heart valve design. This study aims at the evaluation of biological performance of nanofibrous polymer scaffolds poly(L-lactide) PLLA L210, PLLA L214 and polyamide-6 fabricated by electrospinning via analyzing viability, adhesion and morphology of human umbilical vein endothelial cells (EA.hy926). Nanofibrous surface topography was shown to influence cell phenotype and cell viability according to the observation of diminished cell spreading accompanied with reduced cell viability on nonwovens. Among those, highest biocompatibility was assessed for PLLA L214, although being generally low when compared to the planar control surface. Electrospinning was demonstrated as an innovative technique for the fabrication of advanced biomaterials aiming at guided cellular behavior as well as the design of novel implant platforms. A better understanding of cell–biomaterial interactions is desired to further improve implant development.

Medical devices with small dimensions made of superelastic NiTi become more popular, but joining these parts remains challenging. Since laser welding was found to be an option, electron beam welding seems to be an interesting alternative as it provides additional advantages due to the precise beam positioning and the high vacuum. Superelasticity is influenced by microstructure and surface layer composition that are mainly affected by welding process and by heat treatment and therefore will be investigated in the present paper.

Silicone elastomers are well established in medical engineering and particularly in blood-contacting applications such as catheters and medical tubing. Still, their intrinsic surface properties have potential for improvement. For example, hydrophobicity reduction can be a way to provide better hemocompatibility. In this study, several bulk and surface modifications of silicone elastomers using polyethylene glycol (PEG) were investigated. All modifications induced long-term (2 months), stable wettability of the surface. Moreover, cytotoxicity testing demonstrated their suitability as implant material. Hemocompatibility was investigated through a thrombin generation assay as well as a platelet adhesion study combining an enzymatic assay and a scanning electron microscope analysis. That the hemocompatibility of silicone was considerably improved thanks to the PEG modifications could be shown. The study introduces easily processable, cost-efficient, and long-term stable hydrophilic modifications of silicone elastomer for improved hemocompatibility.

Conventional permanent stent systems for vascular applications are associated with long-term risks, such as restenosis and thrombosis. To overcome these limitations, novel approaches using various biodegradable materials for stent construction have been investigated. In this context, thermal treatment of polymer materials is investigated to adjust the mechanical properties of biodegradable stents. In this work polymeric tubular specimens of biodegradable poly(L-lactide) (PLLA) were extruded and subjected to a molding process using different temperatures above glass transition temperature T G . Physicochemical properties of the molded samples were analyzed using DSC measurements and uniaxial tensile tests. The molding process resulted in a weakening of the PLLA tubular specimens with a simultaneous increase in the degree of crystallinity ( χ ).

Sensitisation to immunologically active elements like chromium, cobalt or nickel and debris particle due to wear are serious problems for patients with metallic implants. We tested the approach of using a hard and thick ceramic coating as a wear-resistant protection of titanium implants, avoiding those sensitisation and foreign body problems. We showed that the process parameters strongly influence the coating porosity and, as a consequence, also its hardness.

To overcome challenges for manufacturing of modern smart medical plastic parts by injection molding, e.g. for active implants, the optimization of the interface between electronics and the polymer component concerning adhesion and diffusion behavior is crucial. Our results indicate that a nano-sized SiO x C y H z layer formed by plasma-enhanced chemical vapour deposition (PE-CVD) via open air atmospheric pressure plasma jet (APPJ) and by use of a hexamthyldisiloxane (HMDSO) precursor can form a non-corrosive, anti-permeable and biocompatible coating. Due to the open air character of the APPJ process an inline coating before overmolding could be an easy applicable method and a promising advancement.

The breakdown voltage of the biocompatible polymer Parylene C was determined after storage in 60°C saline solution and treatment by autoclave. It occurred that both, storage at 60°C in saline solution and autoclaving, lead to distinct decrease of dielectric strength by approximately 50%.

Open air atmospheric pressure plasma jet (APPJ) enhanced chemical vapour deposition process was used to deposit biocompatible SiO x /TiO x composite coatings. The as deposited films are hydrophilic and show visible light induced photocatalytic effect, which is a consequence of the formation of defects in the TiO x structure due to the plasma process. This photocatalytic effect was verified by the demonstration of an antimicrobial effect under visible light on E. coli as well as by degradation of Rhodamine B. The films are non-cytotoxic as shown by the cytocompatibility tests. The films are conductive to cell growth and are stable in DMEM and isopropanol. The structural evaluation using SEM, EDS and XPS shows a dispersion of TiO x phase in a SiO x CyHz matrix. These analyses were used to correlate the structure-property relationship of the composite coating.

Toxic volatile organic chemicals (VOCs), such as chloroform, are widely used in polymer manufacture in the field of implants and polymeric drug carriers. Several processes have to be carried out in order to remove toxic VOCs for patient safety without changing the thermal characteristics of the polymers. Therefore, we analyze the common commercial implant polymer poly(L-lactide) (PLLA) and screen different annealing- and rinsing processes considering influence on their morphology and thermal properties. For PLLA a rinsing step followed by annealing results in acceptable chloroform contents according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations. Annealing processes reveal the lowest chloroform content after one day, which did not further decrease significantly with extended annealing time.

The mechanisms of peri-implant de novo bone formation and contact osteogenesis are still largely unknown. In 1984 Donath et al. showed that macrophages were the first cells to colonize a titanium implant. Recently it was shown that that there are inflammatory (M1) and healing macrophages (M2), the latter of which can secrete BMP 2. In the context of data from a gap healing experiment a macrophage model of osseointegration is suggested.

Clinical diagnosis and prognosis usually rely on few or even single measurements despite clinical big data being available. This limits the exploration of complex diseases such as adolescent idiopathic scoliosis (AIS) where the associated low bone mass remains unexplained. Observed low physical activity and increased RANKL/OPG, however, both indicate a mechanobiological cause. To deepen disease understanding, we propose an in silico prognosis approach using clinical big data, i.e. medical images, serum markers, questionnaires and live style data from mobile monitoring devices and explore the role of inadequate physical activity in a first AIS prototype. It employs a cellular automaton (CA) to represent the medical image, micro-finite element analysis to calculate loading, and a Boolean network to integrate the other biomarkers. Medical images of the distal tibia, physical activity scores, and vitamin D and PTH levels were integrated as measured clinically while the time development of bone density and RANKL/OPG was observed. Simulation of an AIS patient with normal physical activity and patient-specific vitamin D and PTH levels showed minor changes in bone density whereas the simulation of the same AIS patient but with reduced physical activity led to low density. Both showed unchanged RANKL/OPG and considerable cortical resorption. We conclude that our integrative in silico approach allows to account for a variety of clinical big data to study complex diseases.

The human shoulder is one of the most complex joints of the human body, and due to the high range of motion and the complex soft tissue apparatus prone to injuries. Surgical therapies and joint replacements often lead to unsatisfactory results. To improve the understanding of the complex biomechanics of the shoulder, experimental investigations have to be conducted. For this purpose a new shoulder simulator with an innovative muscle force generation was developed. On the basis of a modular concept six artificial pneumatic muscles were integrated to represent the functionally most important muscles of the shoulder joint, whereby a free and controlled movement of the humerus can be conducted. For each muscle individual setpoints for muscle length control based on a user defined shoulder movement for any artificial or cadaver specimen are created by manual motion “Teach-In”. Additional to muscle forces and lengths, optical tracking and a joint force measurement is used to enable different biomechanical studies of the shoulder joint. This paper describes the technical setup as well as the control strategy and first results of its experimental functional validation.

Usability of medical devices is one of the main determining factors in preventing use errors in treatment and strongly correlates to patient safety and quality of treatment. This thesis demonstrates the usability testing and evaluation of a prototype for locomotor therapy of infants. Therefore, based on the normative requirements of the EN 62366, a concept combined of evaluation procedures and assessing methods was created to enable extensive testing and analysis of the different aspects of usability. On the basis of gathered information weak points were identified and appropriate measures were presented to increase the usability and operating safety of the locomotor prototype. The overall outcome showed an usability value of 77.4% and an evaluation score of 6.99, which can be interpreted as “satisfactory”.

In this work a microfluidic cell cultivation device for perfused hypoxia assays as well as a suitable controlling unit are presented. The device features active components like pumps for fluid actuation and valves for fluid direction as well as an oxygenator element to ensure a sufficient oxygen transfer. It consists of several individually structured layers which can be tailored specifically to the intended purpose. Because of its clearness, its mechanical strength and chemical resistance as well as its well-known biocompatibility polycarbonate was chosen to form the fluidic layers by thermal diffusion bonding. Several oxygen sensing spots are integrated into the device and monitored with fluorescence lifetime detection. Furthermore an oxygen regulator module is implemented into the controlling unit which is able to mix different process gases to achieve a controlled oxygenation. First experiments show that oxygenation/deoxygenation of the system is completed within several minutes when pure nitrogen or air is applied to the oxygenator. Lastly the oxygen input by the pneumatically driven micro pump was quantified by measuring the oxygen content before and after the oxygenator.

Radiofrequency ablation (RFA) is a standard clinical procedure for treating many cardiac arrhythmias. In order to increase the success rate of this treatment, the evaluation of lesion development with the help of intracardiac electrogram (EGM) criteria has to be improved further. We are investigating in-vitro the electrophysiological characteristics of cardiac tissue by using fluorescence-optical and electrical techniques. In this project, it is intended to create ablation lesions under defined conditions in rat atria or ventricle and to determine the electrical activity in the myocardium surrounding these lesions less than 1 s after the ablation. Therefore, we developed a semi-automatic RFA procedure, which was integrated into an existing experimental setup. Firstly, a controllable protection circuit board was designed to galvanically isolate the sensitive amplifiers for measuring extracellular potentials during the ablation. Secondly, a real-time system was implemented to control and to autonomously monitor the RFA procedure. We verified each component as well as the different sequences of the RFA procedure. In conclusion, the expanded setup will be used in future in-vitro experiments to determine new EGM criteria to assess lesion formation during the RFA procedure.

The microfabrication and packaging of novel, three-dimensional, polyimide-based, highly flexible, microscale electrocorticography multi-electrode arrays for enhanced epicortical recording of local field potentials is presented. A polyimide foil embeds metallic structures relating to 32 taper-type electrode sites, contact pads as well as interconnecting conductor paths which are integrated in the planar portion of the electrode substrate material. Circular exposed and, thus, active electrode sites are 50 μm in diameter and employed center-to-center pitches range from 250 μm to 1 mm, respectively. As-fabricated 3D-μECoG-MEAs provide taper heights of approximately 4 μm as well as 59 μm being distinguished by characteristic impedances of about 368.9 kΩ at 1 kHz measured in saline electrolyte. The applied packaging strategies favor flip-chip bonding and vapor phase soldering of the polymer substrates to customized printed circuit boards.

Diseases like schizophrenia and genetic epilepsy are supposed to be caused by disorders in the early development of the brain. For the further investigation of these relationships a custom designed application specific integrated circuit (ASIC) was developed that is optimized for the recording from neonatal mice [Bahr A, Abu-Saleh L, Schroeder D, Krautschneider W. 16 Channel Neural Recording Integrated Circuit with SPI Interface and Error Correction Coding. Proc. 9th BIOSTEC 2016. Biodevices: Rome, Italy, 2016; 1: 263; Bahr A, Abu-Saleh L, Schroeder D, Krautschneider W. Development of a neural recording mixed signal integrated circuit for biomedical signal acquisition. Biomed Eng Biomed Tech Abstracts 2015; 60(S1): 298–299; Bahr A, Abu-Saleh L, Schroeder D, Krautschneider WH. 16 Channel Neural Recording Mixed Signal ASIC. CDNLive EMEA 2015 Conference Proceedings, 2015.]. To enable the live display of the neural signals a multichannel neural data acquisition system with live display functionality is presented. It implements a high speed data transmission from the ASIC to a computer with a live display functionality. The system has been successfully implemented and was used in a neural recording of a head-fixed mouse.

Anatomical forceps are used for the handling of sensitive structures in medicine. Structures which are manipulated with these forceps can get damaged or slip out of the grip of the forceps. This paper presents a forceps using the bionic Fin-Ray-Effect inspired by fish-fins in order to handle vulnerable structures in particular. During the process of development, functional models of this forceps were designed, 3D-printed and evaluated.

The present work deals with the 3D printing of porous barium titanate ceramics. Barium titanate is a biocompatible material with piezoelectric properties. Due to insufficient flowability of the starting material for 3D printing, the barium titanate raw material has been modified in three different ways. Firstly, barium titanate powder has been calcined. Secondly, flow additives have been added to the powder. And thirdly, flow additives have been added to the calcined powder. Finally, a polymer has been added to the three materials and specimens have been printed from these three material mixtures. The 3D printed parts were then sintered at 1320°C. The sintering leads to shrinkage which differs between 29.51–71.53% for the tested material mixtures. The porosity of the parts is beneficial for cell growth which is relevant for future medical applications. The results reported in this study demonstrate the possibility to fabricate porous piezoelectric barium titanate parts with a 3D printer that can be used for medical applications. 3D printed porous barium titanate ceramics can especially be used as scaffold for bone tissue engineering, where the bone formation can be promoted by electrical stimulation.

Aim of this study was to prove the possibility of manufacturing patient specific root analogue two-part (implant and abutment) implants by direct metal laser sintering. The two-part implant design enables covered healing of the implant. Therefore, CT-scans of three patients are used for reverse engineering of the implants, abutments and crowns. Patient specific implants are manufactured and measured concerning dimensional accuracy and surface roughness. Impacts of occlusal forces are simulated via FEA and compared to those of standard implants.

Today’s 3D printing technologies offer great possibilities for biomedical researchers to create their own specific laboratory equipment. With respect to the generation of ex vivo vascular perfusion systems this will enable new types of products that will embed complex 3D structures possibly coupled with cell loaded scaffolds closely reflecting the in-vivo environment. Moreover this could lead to microfluidic devices that should be available in small numbers of pieces at moderate prices. Here, we will present first results of such 3D printed cell culture systems made from plastics and show their use for scaffold based applications.

There is great hope in 3D printing techniques to create patient specific scaffolds for therapeutic applications. The majority of these approaches rely on materials that both give support to cells and effectively mimic a tissue specific microenvironment. Hydrogels provide an exceptional support for cells but their physicochemical properties are not suited for conventional additive layer manufacturing. Their low viscosity and resulting fluidic nature inhibit voluminous 3D deposition and lead to crude printing accuracy. To enhance mechanical features, hydrogels are often chemically modified and/or mixed with additives; however it is not clear whether these changes induce effects on cellular behavior or if in vivo applications are at risk. Certainly it increases the complexity of scaffold systems. To circumvent these obstacles, we aimed for a 3D printing technique which is capable of creating scaffolds out of unmodified, pure hydrogels. Here we present a new method to produce alginate scaffolds in a viscosity- independent manner with high spatial resolution. This is achieved by printing in a sub-zero environment which leads to fast freezing of the hydrogels, thus preserving the printed shape and circumventing any viscosity dependent flows. This enables the user to create scaffolds which are able to reflect soft or stiff cell niches.

To establish photopolymers for the production of class II or class III medical products by additive manufacturing it is essential to know which components of photopolymeric systems, consisting of monomers, photoinitiators and additives, are the determining factors on their biocompatible properties. In this study the leachable substances of a cured photopolymeric system were eluted and identified by HPLC-MS detection. In addition the cured photopolymer was testes for cytotoxicity and genotoxicity according to DIN EN ISO 10993 for long time applications. The results showed that uncured residual monomers are the determining factor on the biocompatible properties of the photopolymeric system. Strategies to reduce these residual monomers in the cured photopolymer are presented.

Many conventional analysis techniques to detect chemical or biological species are able to achieve a high detection sensitivity, however, they are equipment- or time-expensive due to a multi-step procedure. In this work we describe sensor concepts using piezoresistive pressure sensor chips with integrated analyte-sensitive hydrogels, that enable inexpensive and robust biochemical sensors which are miniaturizable and in-line capable. Biocompatible hydrogels were developed and tested for pH- and glucose-monitoring during the chemical and biochemical processes. For that, monomer mixtures based on hydroxypropyl methacrylate HPMA, 2-(dimethylamino)ethyl methacrylate DMAEMA, tetraethylene glycol dimethacrylate TEGDMA and ethylene glycol EG were photo-polymerized. By means of carbodiimide chemistry, glucose oxidase was bound to the pH-sensitive HPMA/DMAEMA/TEGDMA/EG hydrogel squares causing the glucose-sensitivity. The crosslinked hydrogels were integrated in piezoresistive pressure sensors of different designs. pH- and glucose-depending reversible gel swelling processes were observed by means of the output voltage of dip sensors and of a novel implantable flexible sensor set-up. Due to its biocompatible components, the latter could be used inside the human body monitoring physiological blood values, for example glucose.

This paper reports on the development of a wireless system to monitor the thoracic cavity pressure in mammals. This project seeks to open a new field using the radio frequency (RF) technology in the studies of the interaction between breathing and locomotion in mammals. Furthermore, this study embodies the first step to develop a method of telemetry and remote monitoring based on implantable devices. In addition, it can be modified with other sensors to measure different physiological parameters.

Monitoring a person’s nutritional consumption is costly and complex. To solve this problem a new technique is proposed to draw conclusions of a person’s food intake. The air pressure signal, recorded in the external acoustic meatus, is used to detect swallow and chew events. A portable device has been developed to record this pressure signal. Due to the constraint of running on a low-power microcontroller, real-time algorithms, used in pattern and speech recognition, were used to develop methods to automatically detect swallow and chew events. A binary classifier was trained by means of manually annotated data sets. Direct comparisons with state of the art technology and tests with several subjects are provided for evaluation purposes.

MiRNAs are non-coding RNA molecules that control biological functions by reducing the translation of target proteins when binding to the mRNA. Alterations of the miRNA expression profile affect the cell metabolism, which can lead to distinctive disease patterns thus suggesting miRNA as an interesting biomarker. Here we present a SPR biosensor that utilizes disposable, injection-molded sensor chip/microfluidic hybrids combined with a lateral imaging optical system for parallel analysis of three one-dimensional spot arrays to detect miRNA-93. Using a RNA-DNA-hybrid antibody for signal enhancement we could reach a limit of detection of 10 pmol/l.

Recent studies show that vestibular implants have the potential to compensate the loss of functionality of the organ of equilibrium. The objective of this study was the development of a simulation framework which estimates the capability of various electrode arrangements and stimulation waveforms to selectively excite the ampullary nerves in the vestibular system. The choice of electrode configuration and stimulation waveform shows a significant influence in resulting selectivity, energy expenditure and injected charge in our simulations. This simulation environment could be beneficial in the development of safe and selective stimulation electrode designs.

Deep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro . Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABA A currents which can be verified using a GABA A antagonist. The results show that all the waveforms effectively increase the GABA A currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

This contribution addresses the question if imminent changes of the cortical state are predictable. The analysis is based on 1484 examples of microsleep (MS) and 1940 counterexamples of sustained attention (SA), both observed during overnight driving in the simulator. EEG segments (8 s in length) immediately before each respective event were included. Features were extracted by (i) modified periodogram and (ii) Choi-Williams distribution. Machine learning algorithms, namely the optimized learning vector quantization (OLVQ) and the support-vector machine with Gaussian kernel function (SVM), were trained in order to map signal features to the event type (MS or SA). Cross validation analysis yielded test set classification accuracies of 87.5 ± 0.1 % and 82.7 ± 0.1 % for feature set (i) and (ii), respectively. In general, SVM outperformed OLVQ. In conclusion, EEG contains enough information to predict immediately upcoming microsleep events.

Evaluating individual aerobic exercise capacity is fundamental in sports and exercise medicine but associated with organizational and instrumental effort. Here, we extract an index related to common performance markers, the aerobic and anaerobic thresholds enabling the estimation of exercise capacity from a conventional sports watch supporting beatwise heart rate tracking. Therefore, cardiac vagal threshold (CVT) was determined in 19 male subjects performing an incremental maximum exercise test. CVT varied around the anaerobic threshold AnT with mean deviation of 7.9 ± 17.7 W. A high correspondence of the two thresholds was indicated by Bland-Altman plots with limits of agreement −27.5 W and 43.4 W. Additionally, CVT was strongly correlated AnT (r p = 0.86, p < 0.001) and reproduced this marker well (r c = 0.81). We conclude, that cardiac vagal threshold derived from compression entropy time course can be useful to assess physical fitness in an uncomplicated way.

The goal of this research was to classify cardiac excitation patterns during atrial fibrillation (AFib). For this purpose, virtual models of intracardiac mapping catheters were moved across in-silico cardiac tissue to extract local activation times (LATs) of each catheter electrode from simulated cardiac action potential (AP) signals. The resulting LAT patterns consisting of the LATs of all electrodes resemble patterns measured in clinical cases. The LATs represent the input information for features that were used to separate four different excitation patterns during AFib. Those four excitation patterns were plane wave, ectopic focus (spherical wave), rotor (spiral wave) and block. A feature selection algorithm was used to investigate the features concerning their power to classify the different simulated excitation patterns. The scores of the selected features were used to train and optimize a support vector machine (SVM). The optimized and cross-validated SVM was then used to classify the simulated cardiac excitation patterns. The achieved overall classification accuracy of this SVM model was 98.4 %.

Atrial fibrillation is the most common cardiac arrhythmia. Many physicians believe in the hypothesis that persistent atrial fibrillation is maintained by centers of rotatory activity. These so called rotors are sometimes found by physicians during catheter ablation or electrophysiological studies but there are also physicians who claim that they did not find any rotors at all. One reason might be that today rotors are mainly identified by visual inspection of the data. Thus we are aiming at an algorithm for rotor detection. We first developed an algorithm based on the local activation times of the intracardiac electrograms recorded by a multielectrode catheter that can automatically determine the cycle length coverage. This was done to get an objective view on possible rotors and therefore help to quantify whether a rotor was found or not. The algorithm was developed and evaluated in two different simulation setups, where it could reliably determine cycle length coverage. But we found out that effects like wave collision and slow conduction have strong influence on cycle length coverage. This prevents cycle length coverage from being suited as the only parameter to quantify whether a rotor is present or not. On the other hand we could confirm that rotors imply a cycle length coverage of >70% if the multielectrode catheter is centered in an area of <5 mm away from the rotor tip. Therefore cycle length coverage can at least be used in some situations to exclude the presence of possible rotors.

Monitoring of cardiac and respiratory activity, is essential in several clinical interventions like bicycle ergometries. The respiration signal can be derived from the ECG if it is not recorded itself (ECG derived respiration, EDR). In this study, we tried to reconstruct breathing rates (BR) from stress test high resolution 12-channel-ECGs in nine healthy subjects using higher order central moments. A mean absolute error per subjects of 2.9/min and relatively high correlation (r p = 0.85) and concordance coefficient (r c = 0.79) indicated a quite accurate reproduction of respiratory activity. The analysis of the different test stages revealed an increase of BR errors while subjects were effortful cycling compared to rest. During incremental cycling exercise test the mean absolute error per subjects was 3.4/min. Compared to the results reported in other studies at rest in supine position, this seems adequately accurate. In conclusion, our results indicate that EDR using higher order central moments is suited for monitoring BR during physical activity.

The electrocardiogramm (ECG) is the state-of-the-art signal for gating in cardiovascular magnetic resonance imaging and patient monitoring. Using the ECG for gating and monitoring during the magnetic resonance imaging examination is a high challenging task due to the superimposition of the magnetohydrodynamic effect, radio-frequency (RF) pulses and fast switching gradient magnetic fields. The gradient induced artifacts hamper the correct QRS detection which is needed for correct gating and heart rate calculation and ECG displaying for patient monitoring. To suppress the gradient artifacts from the ECG signal acquired during MRI, a technique based on the Wilcoxon filter was developed. It was evaluated using ECG signals of 14 different subjects acquired in a 3 T MRI scanner. It could be shown reliable results for reducing gradient induced artifacts in the ECG signal in real-time.

Catheter ablation has become a very efficient strategy to terminate sustained cardiac arrhythmias like atrial flutter (AFlut). Identification of the optimal ablation spot, however, often proves difficult when scar from previous ablations is present. Although the application of electro-anatomical mapping systems allows to record thousands of intracardiac electrograms (EGMs) from each atrium, state-of-the-art techniques provide limited options for automatic signal processing. Goal of the presented research was the development of an algorithm to detect EGMs that present double potentials (DPs), as these often indicate functional or anatomical lines of block for cardiac excitation. Using an annotated database, we developed several features based on the morphological descriptors of DPs. These were used to train a binary decision tree which was able to detect DPs with a correct rate of over 90%.

Finite element analysis (FEA) of electric current distribution in the pelvis minor may help to assess the usability of non-invasive surface stimulation for continuous pelvic intraoperative neuromonitoring. FEA requires generation of quality volumetric tetrahedral mesh geometry. This study proposes the generation of a suitable mesh based on MRI data. The resulting volumetric mesh models the autonomous nerve structures at risk during total mesorectal excision. The model also contains the bone, cartilage, fat, skin, muscle tissues of the pelvic region, and a set of electrodes for surface stimulation. The model is ready for finite element analysis of the discrete Maxwell’s equations.

Two dimensional pelvic intraoperative neuromonitoring (pIONM ® ) is based on electric stimulation of autonomic nerves under observation of electromyography of internal anal sphincter (IAS) and manometry of urinary bladder. The method provides nerve identification and verification of its’ functional integrity. Currently pIONM ® is gaining increased attention in times where preservation of function is becoming more and more important. Ongoing technical and methodological developments in experimental and clinical settings require further analysis of the obtained signals. This work describes a postprocessing algorithm for pIONM ® signals, developed for automated analysis of huge amount of recorded data. The analysis routine includes a graphical representation of the recorded signals in the time and frequency domain, as well as a quantitative evaluation by means of features calculated from the time and frequency domain. The produced plots are summarized automatically in a PowerPoint presentation. The calculated features are filled into a standardized Excel-sheet, ready for statistical analysis.

In applied biomedical engineering and medical industry the transfer of established technology towards customers’ needs is essential for successful development and therefore business opportunities. In chronological order, we can show the transfer of scientific results of neurophysiological research into an existing neuromonitoring system and product which can be used by non-experts in medical technology in the operating room environment. All neurophysiology functions were realized in an intuitive graphical user interface. To stimulate the autonomous nerves, a specialized parameter paradigm was used, different from motor nerve stimulation. In the background, a complex signal processing algorithm recorded smooth muscle and bladder manometry data in synchronized time and automatically detected neurophysiological signals. The acquired data was then presented in real-time. With this effort a complex scientific task could be simplified to a Yes/No statement to the end-user. Beside all the reduction of complexity, the scientific challenge was still obtained, as raw-data is still possible to be recorded.

Camera-based photoplethysmography (cbPPG) is a novel technique that allows the contactless acquisition of cardio-respiratory signals. Previous works on cbPPG most often focused on heart rate extraction. This contribution is directed at the assessment of vasomotor activity by means of cameras. In an experimental study, we show that vasodilation and vasoconstriction both lead to significant changes in cbPPG signals. Our findings underline the potential of cbPPG to monitor vasomotor functions in real-life applications.

An ever increasing number of research is examining the question to what extent physiological information beyond the blood oxygen saturation could be drawn from the photoplethysmogram. One important approach to elicit that information from the photoplethysmogram is the analysis of its waveform. One prominent example for the value of photoplethysmographic waveform analysis in cardiovascular monitoring that has emerged is hemodynamic compensation assessment in the peri-operative setting or trauma situations, as digital pulse waveform dynamically changes with alterations in vascular tone or pulse wave velocity. In this work, we present an algorithm based on modern machine learning techniques that automatically finds individual digital volume pulses in photoplethysmographic signals and sorts them into one of the pulse classes defined by Dawber et al. We evaluate our approach based on two major datasets – a measurement study that we conducted ourselves as well as data from the PhysioNet MIMIC II database. As the results are satisfying we could demonstrate the capabilities of classification algorithms in the automated assessment of the digital volume pulse waveform measured by photoplethysmographic devices.

Being able to accurately monitor blood pressure in a reliable, truly non-invasive manner is a highly sought after goal within the biomedical community. In this paper we propose and assess a system, methodology and algorithm for unobtrusively obtaining true pulse transit time data from readily accessible peripheral locations, such as the hand, using a highly synchronous body-sensor-network encompassing an electrocardiogram- and dual mode photoplethysmogram sensor node. The results suggest the feasibility of acquiring such data, which strongly correlates with the recorded reference blood pressure, and can therefore be further employed to track changes thereof.

This paper describes an alternative design of linear phase low-pass differentiators with a finite impulse response (type III FIR filter). To reduce the number of necessary filter coefficients, the differentiator’s transfer function is approximated by a Fourier series of a triangle function. Thereby the filter’s transition steepness towards the stopband is intentionally reduced. It can be shown that the proposed design of low-pass differentiators yields to similar results as other published design recommendations, while the filter order can be significantly reduced.

Autonomic control of the heart rate was demonstrated to be complex and nonlinear. Respiratory sinus arrhythima plays a crucial role in heart rate vagal modulation. Here we present an approach of assessing nonlinear causal relationships in bivariate time series, called mutual compression entropy (MCE). We applied MCE to cardiorespiratory data of 29 patients with acute schizophrenia and 29 matched controls. The method is based on data compression and estimates to which extend a (target) time series can be compressed regarding another time series (driver). In schizophrenia an elevated sympathetic and reduced parasympathetic heart rate modulation was found. The nonlinear influence of respiration on heart rate variability was demonstrated by a highly significant reduction of MCE (0.816 vs. 0.808, p¡0.01). In healthy subjects MCE was mainly related to sympathovagal balance. We conclude, that this index has the potential to uncover physiological information beyond linear measures.

We address the correspondence problem which arises when applying empirical mode decomposition (EMD) to multi-trial and multi-subject data. EMD decomposes a signal into a set of narrow-band components named intrinsic mode functions (IMFs). The number of IMFs and their signal properties can be different between trials, channels and subjects. In order to assign IMFs with similar characteristics to each other, we compare two assignment methods, unbalanced assignment and k-cardinality assignment and two clustering algorithms, namely hierarchical clustering and density-based spatial clustering of applications with noise based on heart rate variability data of children with temporal lobe epilepsy.

Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the assessment of functional activity of the cerebral cortex. Recently fNIRS was also envisaged as a novel neuroimaging approach for measuring the auditory cortex (AC) activity in cochlear implant (CI) users. In the present study we report on initial measurements of AC activation due to spatial sound presentation with a first target to generate data for comparison with CI user and the future use in auditory diagnostics.

Quantifying cardiac functions in model organisms like embryonic zebrafish is of high importance in small molecule screens for new therapeutic compounds. One relevant cardiac parameter is the fractional shortening (FS). A method for semi-automatic quantification of FS in video recordings of zebrafish embryo hearts is presented. The software provides automated visual information about the end-systolic and end-diastolic stages of the heart by displaying corresponding colored lines into a Motion-mode display. After manually marking the ventricle diameters in frames of end-systolic and end-diastolic stages, the FS is calculated. The software was evaluated by comparing the results of the determination of FS with results obtained from another established method. Correlations of 0.96 < r < 0.99 between the two methods were found indicating that the new software provides comparable results for the determination of the FS.

In a large group of patients, it is impossible to measure blood pressure using an upper arm cuff. An alternative, non-invasive method of blood pressure measurement is required for patients with severe limb deformities or obesity, for amputees, and in the emergency medicine. The device proposed here measures blood pressure in the cheek using a small pressure pad and a pump to occlude the cheek artery – arteria facialis – and assesses blood flow with an infrared light source and a detector. The infrared light signal is analysed to assess the systolic and diastolic blood pressure of the patient. Manual evaluation of the light intensity signal showed a good agreement between cheek blood pressure measurement and a reference measurement using an upper arm cuff.

The estimation of respiratory rates from contineous respiratory signals is commonly done using either fourier transformation or the zero-crossing method. This paper introduces another method which is based on the autocorrelation function of the respiratory signal. The respiratory signals can be measured either directly using a flow sensor or chest strap or indirectly on the basis of the electrocardiogram (ECG). We compare our method against other established methods on the basis of real-world ECG signals and use a respiration-based breathing frequency as a reference. Our method achieved the best agreement between respiration rates derived from directly and indirectly measured respiratory signals.

Cardiac resynchronization therapy is an established therapy for heart failure patients. The aim of the study was to evaluate electrical left cardiac atrioventricular delay and interventricular desynchronization in sinus rhythm cardiac resynchronization therapy responder and non-responder. Cardiac electrical desynchronization were measured by surface ECG and focused transesophageal bipolar left atrial and left ventricular ECG before implantation of cardiac resynchronization therapy defibrillators. Preoperative electrical cardiac desynchronization was 195.7 ± 46.7 ms left cardiac atrioventricular delay and 74.8 ± 24.5 ms interventricular delay in cardiac resynchronization therapy responder. Cardiac resynchronization therapy responder New York Heart Association class improved during long term biventricular pacing. Transesophageal left cardiac atrioventricular delay and interventricular delay may be additional useful parameters to improve patient selection for cardiac resynchronization therapy.

The arterial blood pressure (ABP) holds a lot of information about the cardiovascular system. To analyse the ABP signal, at first the pulse wave has to be detected correctly. Due to influences, e.g. of noise, an accurate beat detection is a challenging task. In this work, a novel real-time ABP detector based on higher-order statistics is presented. The method uses the 4 th order cumulants for ABP-peak detection. To evaluate this detector, the Fantasia database freely available at physionet was used. In this database, 142,936 systolic peaks were available to check the efficiency of the beat detector. A sensitivity of 99.91% and a positive predictive value of 99.50% were achieved with the novel method.

During magnetic resonance imaging (MRI), a patient’s vital signs are required for different purposes. In cardiac MRI (CMR), an electrocardiogram (ECG) of the patient is required for triggering the image acquisition process. However, a reliable QRS detection of an ECG signal acquired inside an MRI scanner is a challenging task due to the magnetohydrodynamic (MHD) effect which interferes with the ECG. The aim of this work was to develop a reliable QRS detector usable inside the MRI which also fulfills the standards for medical devices (IEC 60601-2-27). Therefore, a novel real-time QRS detector based on integrated variance measurements is presented. The algorithm was trained on ANSI/AAMI EC13 test waveforms and was then applied to two databases with 12-lead ECG signals recorded inside and outside an MRI scanner. Reliable results for both databases were achieved for the ECG signals recorded inside (DB MRI : sensitivity Se = 99.94%, positive predictive value + P = 99.84%) and outside (DB InCarT : Se = 99.29%, + P = 99.72%) the MRI. Due to the accurate R-peak detection in real-time this can be used for monitoring and triggering in MRI exams.

The novel high-density mapping system Rhythmia TM Medical (Boston Scientific, Marlborough, USA) allows a fast and automatic acquisition of intracardiac electrograms (EGMs). For recording the ORION mini-basket catheter is used. Due to the small electrode surface, the spatial averaging is smaller than with other commonly used mapping catheters. This results in a higher quality of unipolar signals. However, these are still corrupted by noise such as high frequency interference. Within this project, methods were developed and benchmarked that can be applied to detect and remove these undesired components. An algorithm was implemented to detect and eliminate artificial peaks in the spectrum of the EGM. The filtered signals showed improved quality in time domain. The performance of the spectral peak detection resulted in a median sensitivity of 92.1% and in a median positive predictive value of 91.9%.

Computer simulation turns out to be beneficial when clinical data lack spatio-temporal resolution or parameters cannot be measured at all. To derive trustworthy results, these in-silico models have to thoroughly parameterized and validated. In this work we present data from a simplified in-vitro setup for characterizing ventricular electromechanics. Right ventricular papillary muscles from New Zealand rabbits were isolated and stretched from slack length to l max , i.e. the muscle length at maximum active force development. Active stress development showed an almost linear increase for moderate strain (90–100% of l max ) and a significant decrease for larger strain (100–105% of l max ). Passive strain development showed a nonlinear increase. Conduction velocity CV showed an increase of ≈10% between low and moderate strain and no significant decrease beyond. Fitting active active stress-strain relationship using a 5 th -order polynomial yielded adequate results for moderate and high strain values, whereas fitting using a logistic function yielded more reasonable results for low strain values. Passive stress-strain relationship was satisfactorily fitted using an exponential function.

Routine monitoring of blood pressure during general anaesthesia relies on intermittent measurements with a non-invasive brachial cuff every five minutes. This manuscript provides first experimental evidence that a physiology-based pulse wave analysis algorithm applied to optical data (as provided by a standard fingertip pulse oximeter) is capable of accurately estimating blood pressure changes in-between cuff readings. Combined with the routine use of oscillometric cuffs, the presented novel approach is a candidate technology to increase patient safety by providing beat-to-beat hemodynamic measurements without the need of invasive monitoring procedures.

Arteriosclerosis and associated cardiovascular disease remains the leading cause of mortality. Improved methods for vascular plaque detection allow early diagnose and better therapeutic options. Present diagnostic tools require intense technical expenditure and diminish value of modern screening methods. Our group developed an microwave sensor for on-site detection of plaque formation in arterial vessels. The sensor is an oscillator working around 27 GHz which is coupled to a microstrip stub line. The final flexible polyimid interposer has a length of 38 cm, a width of 1.2 mm and a thickness of 200 μm. Because of its minimal size the interposer completed a catheter with a diameter of 8F ready for further clinical use in cardiology and heart surgery.

This paper presents a special designed artificial blood circulatory (ABC) for studying gaseous embolism based on detection of gaseous emboli and their sizing using ultrasound (US) spectral Doppler. Blood mimicking fluid (BMF) was used in the circulatory to get valid results without using human blood. The additional necessary degassing circulatory shows a promising effect of decontaminating the BMF from air bubbles. This offers the base for detecting and sizing microemboli using special algorithms and finally leads to reliable calculations of dangerous embolism and its air volume. Standard US probes at an integrated tissue model and a new 8-MHz central catheter ultrasound (CCUS) probe inside a superior vena cava model (SVCM) are used and deliver the Doppler spectrogram as input for automatic emboli detection and further signal analysis. First results using the newly developed 8-MHz CCUS probe inside the SVCM and its Doppler spectrogram characteristics show promising results but need more detailed studies.

Microsleep events (MSE) are short intrusions of sleep under the demand of sustained attention. They can impose a major threat to safety while driving a car and are considered one of the most significant causes of traffic accidents. Driver’s fatigue and MSE account for up to 20% of all car crashes in Europe and at least 100,000 accidents in the US every year. Unfortunately, there is not a standardized test developed to quantify the degree of vigilance of a driver. To account for this problem, different approaches based on biosignal analysis have been studied in the past. In this paper, we investigate an electrocardiographic-based detection of MSE using morphological and rhythmical features. 14 records from a car driving simulation study with a high incidence of MSE were analyzed and the behavior of the ECG features before and after an MSE in relation to reference baseline values (without drowsiness) were investigated. The results show that MSE cannot be detected (or predicted) using only the ECG. However, in the presence of MSE, the rhythmical and morphological features were observed to be significantly different than the ones calculated for the reference signal without sleepiness. In particular, when MSE were present, the heart rate diminished while the heart rate variability increased. Time distances between P wave and R peak, and R peak and T wave and their dispersion increased also. This demonstrates a noticeable change of the autonomous regulation of the heart. In future, the ECG parameter could be used as a surrogate measure of fatigue.

The kink behavior of vascular stents is of particular interest for clinicians, stent manufacturers and regulatory as a kinked stent generates a lumen loss in the stented vessel and can lead to in-stent restenosis. In this study methods to determine the kink resistance of stents and stent delivery systems according to the ISO 25539-2 and FDA guidance no. 1545 were presented. The methods are applicable for balloon expandable stents as well as for self-expanding stents and determine the lumen loss and residual diameter change dependent on the specific bending radius.

Coronary diseases are the main reason for death in the western world. Bio-fluid mechanical correlations with arterial diseases are in the focus of our research. To treat occluded vessels, stents are implanted. Stent implantations can be associated with blood flow disruptions leading to restenosis or thrombosis formation. Numerical flow simulation is a promising tool to evaluate the hemodynamic performance of cardiovascular implants, but is resource-intensive in time and computational power. Therefore, a reduction in grid size would be beneficial due to economic exploitation of computational cost. The purpose of this numerical investigation is to substitute the computational domain of a distal stented bifurcation with a stented straight vessel by using the right inlet condition. The deviation of the results of the two different methods to simulate the blood flow situation in a bifurcation is marginal. This inlet can be used for standardised simulations of bifurcations were lesions commonly occur.

Stent implantation is the treatment of choice for cardiovascular diseases. By introduction of biodegradable thick strut stents investigations of thrombosis formation is one focus of research. This study deals with a transient Euler-Lagrange/DEM approach to simulate the flow field, platelet movement and clotting. The recirculation zones prolong particle residence time. As a result, the vicinity of stent struts shown a particularly higher risk for stent thrombosis.

Using the electrospinning process the geometry of a heart valve is not replicable by just one manufacturing process. To produce heart valve scaffolds the heart valve leaflets and the vessel have to be produced in separated spinning processes. For the final product of a heart valve they have to be mated afterwards. In this work an already existing three-axes laser was enhanced to laser weld those scaffolds. The automation control software is based on the robot operating system (ROS). The mechatronically control is done by an Arduino Mega. A graphical user interface (GUI) is written with Python and Kivy.

One of the greatest challenges in cardiovascular tissue engineering is to develop vascular grafts with properties similar to autologous vessels. A promising approach is the fabrication of scaffolds from biodegradable polymers by electrospinning. Unstructured vascular subs possess a weak dimensional stability resulting in lumen collapse when subjected to bending stress. In order to examine different structured grafts, a standardised test method is required. A manual test method, designed in a former study, was adopted in terms of standardisation and automation. Therefore, a control system was programmed to regulate the required electronics. The electronic circuit was then developed and put into service. To fix samples into the test bench a new sample holder and a new collector for electrospinning were designed. Subsequently, a validation showed the new systems’ improved functionality compared to the former test bench. The samples were manufactured with the new collector. They could be fixed to the sample holder with high repeatability. The demand for vascular grafts with biological and mechanical properties similar to autologous vessels requires a standardised test method to examine bendability. The new test system enables the scaffolds to be examined regarding bendability with low personal expense and a simultaneously high degree of reproducibility. In addition, the new collector geometry can be easily adapted to higher or lower inner diameters. Hence, a new sample geometry was developed within this work.

Thrombocytes can be concentrated in blood derivatives and used as autologous transplants e.g. for wound treatment due to the release of growth factors such as platelet derived growth factor (PDGF). Conditions for processing and storage of these platelet-rich blood derivatives influence the release of PDGF from the platelet-bound α-granules into the plasma. In this study Platelet rich plasma (PRP) and Platelet concentrate (PC) were produced with a fully automated centrifugation system. Storage of PRP and PC for 1 h up to 4 months at temperatures between −20°C and +37°C was applied with the aim of evaluating the influence on the amount of released PDGF. Storage at −20°C resulted in the highest release of PDGF in PRP and a time dependency was determined: prolonged storage up to 1 month in PRP and 10 days in PC increased the release of PDGF. Regardless of the storage conditions, the release of PDGF per platelet was higher in PC than in PRP.

For regenerative purposes, there is a high demand for viable and active cells. A big issue is to have enough viable cells available at any given time. One solution is cryopreservation. In this context, DMSO is used as cryoprotective agent (CPA) along with fetal bovine serum for nutrient supply and stress shielding effects. To use these cells for human clinical studies, it is important to eliminate the serum to prevent foreign immune reactions and virus transmittance and DMSO for its toxic effect. In this study a serum free cryopreservation solution and protocol has been established. The combination of methylcellulose and poloxamer 188 provide the basis for the new CPA. Other additves are α -tocopherol, ectoine, prolin and ascorbic acid. The CPAs were examined with 3T3-cells and multipotent stromal cells from the common marmoset monkey ( Callithrix jacchus) . The cells were preserved with various CPA concentrations, incubation times and different cooling rates. To enable a higher throughput of encouraging conditions a fluorescence microscopy analysis was used. The use of methylcellulose, poloxamer 188 and α -tocopherol enables the reduction of DMSO [up to 2.5% (v/v)] and the elimination of serum without viability losses compared to control.

Cultivation of human nasal septal chondrocytes in a self-established automated bioreactor system with a new designed reactor glass vessel and the results of a computational fluid dynamics model are presented. The first results show the effect of a homogeneous fluidic condition of the continuous medium flow and the resulting stresses on the scaffolds’ surface and their influence on the migration of the cells into the scaffold matrix under these conditions. For this purpose computational models, generated with the computational fluid dynamics software STAR-CCM+, and the results of alcian blue staining for newly synthesized sulphated glycosaminoglycans have been compared during cultivation in the new and a first version of the glass reactor vessel with inhomogeneous fluidic conditions, with the same automated bioreactor system and under similar cultivation conditions.

A successful cryopreservation is based on knowledge of the optimal cooling rate. So far, this is often determined by way of complex parameter studies. Alternatively, the identification of cell specific characteristics, such as osmotic behaviour, membrane hydraulic permeability and activation energy could be used to calculate the optimal cooling rate. These parameters should be determined for supra-zero and sub-zero temperatures. In this study cryomicroscopy was used. Mesenchymal stromal cells (MSCs) from bone marrow were analysed. The determined membrane hydraulic permeability for sub-zero temperatures is significantly lower than that for supra-zero temperatures. On the contrary the activation energy is significantly higher in the presence of ice. The addition of a cryoprotective agent (CPA) such as dimethyl sulfoxid (DMSO) shows an additional influence on the characteristics of the membrane of the cell. The optimal cooling rate was determined with these parameters. For cryopreservation without DMSO the optimal cooling rate was found to be 12.82 K/min. If the MSCs were frozen with 5% (v/v) DMSO the optimal cooling rate is 16.25 K/min.

Ensuring optimal climate conditions during cultivation is essential for successful and reproducible cell culture based investigation. Being the gold standard, carbon dioxide incubators fulfill this demand in various geometries and sizes to suit diverse cultivation applications. A door opening results in a climate breakdown followed by a restoration period during which optimal conditions cannot be guaranteed. The following paper investigates the influence of incubator door design to optimize climate retainment during the above mentioned event.

The issue of surgical site infections has become more critical during the last years. The number of airborne microbes depends on the number released by the staff in the room or supplied from neighbouring rooms. In order to minimize the risk of nosocomial infections during surgical procedures technical developments like ventilation systems were introduced in the operating room (OR). In this study several factors like clothing and types of ventilation systems have been investigated and their impact on the effectiveness for reducing microbial burden in the OR has been assessed. In case of OR-gowns we found a benefit for a disposable Swedish clothing concept regarding microbiological contamination in comparison with the German standard multiuse clothing. Moreover our study shows that there is comparable effectiveness of a fairly novel temperature controlled airflow ventilation system (TAF) compared to standard low turbulent uni-directional airflow (TAV).

Stress is a major influence on the quality of life in our fast-moving society. This paper describes a standardized and contemporary protocol that is capable of inducing moderate psychological stress in a laboratory setting. Furthermore, it evaluates its effects on physiological biomarkers. The protocol called “THM-Stresstest” mainly consists of a rest period (30 min), an app-based stress test under the surveillance of an audience (4 min) and a regeneration period (32 min). We investigated 12 subjects to evaluate the developed protocol. We could show significant changes in heart rate variability, electromyography, electro dermal activity and salivary cortisol and α -amylase. From this data we conclude that the THM-Stresstest can serve as a psychobiological tool for provoking responses in the cardiovascular-, the endocrine and exocrine system as well as the sympathetic part of the central nervous system.

The aim of this work was to analyse the medication process and the potential for errors during the process steps. For this purpose, a literature review was conducted and a questionnaire was developed to compare the results from the literature with the current medication process in Styrian hospitals. The questionnaire was divided into four different parts with a total of 29 questions. For the survey all 37 Styrian hospitals were contacted whereas 11 filled out the questionnaire. The survey showed that there is no standardized medication process defined and that the rate of medication errors is generally underestimated. In addition, technical solutions may help to reduce errors but are expected to be hardly used in clinical practice.

The main social priority is to reduce public debt and to streamline national health service (NHS) costs. Consequently, health managers need to acquire operating methods within their managerial structures so that all available resources are better planned in terms of effectiveness and efficiency, without compromising patient safety. In order to identify the information categories needed to know the whole surgical process is necessary to divide these in two main categories, supply and demand . Demand Information Group (DIG) contains the information that identify patients and its needs in terms of care. Instead Supply Information Group (SIG) contains information about hospital resources in order to cover the supply. The surgical process analyzed in terms such as industrial production process has the goal of produce the “ health product for the patient ” and its central part is performed in the operating room by a surgical team. This does not mean that the precedent and subsequent phases of the operating room have minor importance, in fact to obtain a high quality “ health product ” and reduce to a minimum the clinical risks related to the patient it is necessary that each phase of the process is carried out in the right way. The implementation of a Control Tower Approach allows for the management of productive process, able to guide hospital managers to identify the best strategies and to improve the risk management of patient safety in response to the guidelines of the World Health Organization.

The paper presents the development and test of a skull phantom, which can be used for the assessment of the radiographic visibility of neurovascular implants. State of the art methods are based on specimens of the human skull. These are highly individual and not suitable for comparison of different radiographic data sets. The development process of the skull phantom is described from data generation to image processing, design and manufacturing using 3D printing. An experimental setup is recommended to generate reproducible data sets for implant visibility assessment with bone mimicking structures of the phantom. The model is evaluated by qualitative comparison with equivalent data sets of the original human skull model. The results show, that contrast characteristics of the phantom and the human skull model are similar. X-ray attenuation of the human bone is higher than the polymeric phantom material. The introduced phantom allows the determination of X-ray attenuation characteristics of different neurovascular implants for medical approval and testing processes.

The presented work is an alternative to established measurement systems in surgical navigation. The system is based on camera based tracking of QR code markers. The application uses a single video camera, integrated in a surgical lamp, that captures the QR markers attached to surgical instruments and to the patient.

To avoid debris coming to the cerebral vessels during carotid artery stenting, embolic protection devices (EPD) are placed in front of the lesion. To evaluate their influence on the antegrade blood flow a test setup with a silicone tube simulating the internal carotid artery is realized. The pressure gradient of five different EPD was measured while particles were brought into the circuit and were caught by the systems. Additionally the microscopic structure of the systems was observed to correlate the morphology and the pressure gradient. The FiberNet device had the lowest pressure gradient. It was the only system that consists of fibers contrary to the systems RX Accunet, Angioguard RX, FilterWireEZ and EmboshieldNAV that contain porous membranes.

Severe gait abnormalities in patients with cerebral palsy are often treated by correction osteotomy. The established procedure of femoral derotation osteotomy (FDO) has proven effective to realign femur anteversion. Nevertheless, studies have revealed that therapy outcome is subject to substantial inter-patient variability and systematic loss of correction. Our previous work suggests that practical limitations in FDO may significantly contribute to this effect. In this work, we propose a novel computer assisted measurement system to support FDO with objective measurement (desired accuracy: ∼ ± 3°) and continuous monitoring of derotation. A prototype system based on the clinically emerging electromagnetic tracking technology is demonstrated which incorporates technical and operational considerations to enable continuous measurement in OR conditions while preserving the conventional workflow without disruptions. In phantom studies, the achieved measurement accuracy (standard error ≅±1.6)∘$\cong\pm 1.6{}^{\circ})$ proved high potential and may hugely benefit the quality of surgical execution. Currently, the prototype system is assessed under OR conditions in an in-vivo study with CP patients. Early experience shows high appreciation among surgeons and good potential for future application.

Infrared thermography can be used as a pre-, intra- and post-operative imaging technique during medical treatment of patients. Modern infrared thermal cameras are capable of acquiring images with a high sensitivity of 10 mK and beyond. They provide a planar image of an examined 3D object in which this high sensitivity is only reached within a plane perpendicular to the camera axis and defined by the focus of the lens. Out of focus planes are blurred and temperature values are inaccurate. A new 3D infrared thermography system is built by combining a thermal camera with a depth camera. Multiple images at varying focal planes are acquired with the infrared camera using a motorized system. The sharp regions of individual images are projected onto the 3D object’s surface obtained by the depth camera. The system evaluation showed that deviation between measured temperature values and a ground truth is reduced with our system.

In recent years, operating rooms (ORs) have transformed into integrated operating rooms, where devices are able to communicate, exchange data, or even steer and control each other. However, image data processing is commonly done by dedicated workstations for specific clinical use-cases. In this paper, we propose a concept for a dynamic service component for image data processing on the example of automatic image quality assessment (AQUA) of intraoperative cone beam computed tomography (CBCT) images. The service is build using the Open Surgical Communication Protocol (OSCP) and the standard for Digital Imaging and Communications in Medicine (DICOM). We have validated the proposed concept in an integrated demonstrator OR.

One of the oldest methods used in minimally invasive surgeries is the transurethral resection. This is an operation technique in which diseased tissue from the bladder or the prostate is removed using a resectoscope through the urethra [Schostak M, Blana A, Hrsg. Alternative operative Therapien in der Uroonkologie. Berlin, Heidelberg, Springer Berlin Heidelberg; 2016]. A resectoscope has a channel for the view of the surgeon, a liquid supply, a working channel and a hand piece which could rotate up to 360 degrees. A RF- electrode on the tip of the resectoscope is used to cut out pathological growths. For diseased tissue which is located in the bladder on the ventral side, a rotation of the resectoscope up to 180 degrees is necessary. This means on the one side tiring of the hands, wrist pain and a change of the position of the operating surgeon. On the other side a reorganization of the connected tubes and cables is necessary. To avoid these problems and integrate additional features a standard resectoscope was adapted with an easy to use twist mechanism. After discussion with experienced urological surgeons a complete new design of the resectoscope with a twist mechanism in combination with a gyro sensor and a reference display was realized.

There is an urgent need for in vitro dissolution test setups for intramuscularly applied dosage forms. Especially biorelevant methods are needed to predict the in vivo behavior of newly developed dosage forms in a realistic way. There is a lack of knowledge regarding critical in vivo parameters influencing the release and absorption behavior of an intramuscularly applied drug. In the presented work the focus was set on the simulation of blood perfusion and muscle tissue. A solid agarose gel, being incorporated in an open-pored foam, was used to mimic the gel phase of muscle tissue and implemented in a flow through cell. An aqueous solution of fluorescein sodium was injected. Compared to recently obtained in vivo results the distribution of the model substance was very slow. Furthermore an agarose gel of lower viscosity an open-pored foam and phosphate buffer saline pH 7.4 were implemented in a multi-channel-ceramic membrane serving as a holder for the muscle imitating material. Blood simulating release medium was perfused through the ceramic membrane including filling materials. Transport of the dissolved fluorescein sodium was, in case of the gel, not only determined by diffusion but also by convective transport processes. The more realistic the muscle simulating materials were constituted the less reproducible results were obtained with the designed test setups.

Drug delivery systems (DDS) ensure that therapeutically effective drug concentrations are delivered locally to the target site. For that reason, it is common to coat implants with a degradable polymer which contains drugs. However, the use of polymers as a drug carrier has been associated with adverse side effects. For that reason, several technologies have been developed to design polymer-free DDS. In literature it has been shown that micro-sized reservoirs can be applied as drug reservoirs. Inkjet techniques are capable of depositing drugs into these reservoirs. In this study, two different geometries of micro-sized reservoirs have been laden with a drug (ASA) using a drop-on-demand inkjet printhead. Correlations between the characteristics of the drug solution, the operating parameters of the printhead and the geometric parameters of the reservoir are shown. It is indicated that wettability of the surface play a key role for drug deposition into micro-sized reservoirs.

Functional electrical stimulation aims to help patients suffering from stroke or spinal cord injury to supplement lost motor function. Effective functional electrical stimulation requires precise placement of the stimulation electrode. Finding the correct placement, however, can be difficult and time consuming. Another common problem with functional electrical stimulation is early occurrence of muscle fatigue upon repetitive stimulation, limiting treatment efficiency. Both, precise electrode placement as well as the reduction of muscle fatigue can be achieved using multi-pad electrodes. Here we present a new standalone device for multi-pad functional electrical stimulation. The device is easy to use and designed to help patients recovering from stroke to train and perform opening of the hand.

Transcutaneous electrical stimulation is a common treatment option for patients suffering from spinal cord injury or stroke. Two major difficulties arise when employing electrical stimulation in patients: Accurate stimulation electrode placement and configuration of optimal stimulation parameters. Optimizing the stimulation parameters has the advantage to reduce muscle fatigue after repetitive stimulation. Here we present a newly developed system which is able to automatically find the optimal individual stimulation intensity by varying the pulse length. The effectiveness is measured with flex sensors. By adapting the stimulation parameters, the effect of muscle fatigue can be compensated, allowing for a more stable movement upon stimulation over time.

Human rely profoundly on tactile feedback from fingertips to interact with the environment, whereas most hand prostheses used in clinics provide no tactile feedback. In this study we demonstrate the feasibility to use a tactile display glove that can be worn by a unilateral hand amputee on the remaining healthy hand to display tactile feedback from a hand prosthesis. The main benefit is that users could easily distinguish the feedback for each finger, even without training. The claimed advantage is supported by preliminary tests with healthy subjects. This approach may lead to the development of effective and affordable tactile display devices that provide tactile feedback for individual fingertip of hand prostheses.

Neuromodulation using electrical stimulation is able to enhance motor control of individuals suffering an upper motor neuron disorder. This work examined the effect of sustained electrical stimulation to modify spasticity in the leg muscles. We applied transcutaneous spinal cord stimulation with a pulse rate of 50 Hz for 30 min. The subjects were assessed before and after the intervention using in a pendulum test setup. The motion of the free swinging leg was acquired through video tracking and goniometer measurements. The quantification was done through the R 2n index which shows consistency identifying the spasticity levels. In all incomplete SCI subjects having severe spasticity, the results show that electrical stimulation is effective to modify the increased muscle tone.

Real-time target localization with ultrasound holds high potential for image guidance and motion compensation in radiosurgery due to its non-invasive image acquisition free from ionizing radiation. However, a two-step localization has to be performed when integrating ultrasound into the existing radiosurgery workflow. In addition to target localization inside the ultrasound volume, the probe itself has to be localized in order to transform the target position into treatment room coordinates. By adapting existing camera calibration tools, we have developed a method to extend the stereoscopic X-ray tracking system of a radiosurgery platform in order to locate objects such as marker geometries with six degrees of freedom. The calibration was performed with 0.1 mm reprojection error. By using the full area of the flat-panel detectors without pre-processing the extended software increased the tracking volume and resolution by up to 80%, substantially improving patient localization and marker detectability. Furthermore, marker-tracking showed sub-millimeter accuracy and rotational errors below 0.1°. This demonstrates that the developed extension framework can accurately localize marker geometries using an integrated X-ray system, establishing the link for the integration of real-time ultrasound image guidance into the existing system.

Automated detection and tracking of subviral particles is a promising method to obtain insights in complicated virus-cell interactions. This paper describes the implementation of a linear assignment problem solver and a Kalman-filter in an existing particle tracking algorithm. Two different simulated image sequences are used for the evaluation of the algorithms. Tracking and detection results of the new implemented solver are compared to the results of the original algorithm. The improved algorithm is able to improve the results by closing gaps in the particle tracks.

Grading intraepithelial neoplasia is crucial to derive an accurate estimate of pre-cancerous stages and is currently performed by pathologists assessing histopathological images. Inter- and intra-observer variability can significantly be reduced, when reliable, quantitative image analysis is introduced into diagnostic processes. On a challenging dataset, we evaluated the potential of learning a classifier to grade anal intraepitelial neoplasia. Support vector machines were trained on images represented by fractal and statistical features. We show that pursuing a learning-based grading strategy yields highly reliable results. Compared to existing methods, the proposed method outperformed them by a significant margin.

Electrical Impedance Tomography (EIT) intends to obtain the conductivity distribution of a domain from the electrical boundary conditions. This is an ill-posed inverse problem usually solved on finite element meshes. Wavelet transforms are widely used for medical image reconstruction. However, because of the irregular form of the finite element meshes, the canonical wavelet transforms is impossible to perform on meshes. In this article, we present a framework that combines multi-scales wavelet transforms and finite element meshes by viewing meshes as undirected graphs and applying spectral graph wavelet transform on the meshes.

Susceptibility artefacts in magnetic resonance imaging (MRI) caused by medical devices can result in a severe degradation of the MR image quality. The quantification of susceptibility artefacts is regulated by the ASTM standard which defines a manual method to assess the size of an artefact. This means that the estimated artefact size can be user dependent. To cope with this problem, we propose an algorithm to automatically quantify the size of such susceptibility artefacts. The algorithm is based on the analysis of a 3D surface generated from the 2D MR images. The results obtained by the automatic algorithm were compared to the manual measurements performed by study participants. The results show that the automatic and manual measurements follow the same trend. The clear advantage of the automated algorithm is the absence of the inter- and intra-observer variability. In addition, the algorithm also detects the slice containing the largest artefact which was not the case for the manual measurements.

The densely innervated human cornea is the only superficial tissue of the human body in which nerve fibres are accessible in vivo by corneal confocal microscopy (CCM). Morphological parameters of the corneal sub-basal nerve plexus (SNP) derived from CCM images can potentially serve as a sensitive biomarker for early diagnosis of various neurodegenerative diseases. The evaluation of a single image with a typical field of view of 0.16 mm 2 is insufficient for robust morphometric assessment. Mosaicking approaches have therefore been proposed to examine the SNP on a larger scale. Here we present a highly automated technique that significantly facilitates the generation of mosaic images of the SNP and is suitable for clinical tests.

3D segmentation has become a widely used technique. However, automatic segmentation does not deliver high accuracy in optically dense images and manual segmentation lowers the throughput drastically. Therefore, we present a workflow for 3D segmentation being able to forecast segments based on a user-given ground truth. We provide the possibility to correct wrong forecasts and to repeatedly insert ground truth in the process. Our aim is to combine automated and manual segmentation and therefore to improve accuracy by a tunable amount of manual input.

The treatment of otitis media requires classifying the effusion in the tympanic cavity for choosing appropriate therapeutic strategies. Otoscopic examination of the middle ear depends on the expertise of the physician and is often hampered in case of inflammatory alterations of the tympanic membrane. In otologic research, optical coherence tomography is an innovative non-invasive imaging technique utilized for visualizing the tympanic membrane. This ex vivo study presents the possibility of OCT and Doppler-OCT for the detection of effusions in the tympanic cavity. Structural OCT imaging allows the direct visualization of scattering fluids behind the tympanic membrane. In addition, the measurement of the reduced oscillation amplitude by means of Doppler-OCT permits the indirect detection of scattering and transparent fluids.

The molecular processes behind pathological bone remodelling seen in diseases such as osteoporosis are unclear. However, a recently developed methodological platform known as Local in vivo Environment (LivE) imaging has been used to link cellular expression data to the local remodelling and mechanical environment in 2D sections of bone tissue. The method therefore can be used to give insight into which proteins are important for pathological bone remodelling. However, the cells within bone tissue exist as a 3D network. Therefore extension of LivE to accommodate 3D data may provide additional physiologically relevant information that is not possible to determine using 2D analysis alone. This will have implications for the further understanding of the cellular basis that underlies bone diseases such as osteoporosis. Here the LivE imaging technique is expanded to incorporate data from cells in a three dimensional manner via a serial sectioning technique. The methodological steps involved in the LivE imaging approach are defined and the optimisation steps performed are explained in detail.

Image guided minimal invasive treatment can have large benefits for patient recovery and is lowering hospitalisation costs. But an access path, minimizing patient’s risk, is needed to reach the target structure inside of the body. Beside the use of natural orifices like oral, vaginal or anal cavities, a percutaneous puncture is common to enter the body. Also an interstitial path can be selected but if the pathological structure is situated in the deep, a long accesses path is required. Thereby the risk of additional damage and affecting organ functionality is increased. A possible option to come closer to the target structure with less organ damage is by using the vascular system. Entering the vessel from an uncritical point, the vasculature can be used as “highway” to the target structures. For the treatment of these nearby structures, the vessel has to be punctured and occluded afterwards by a save procedure. We propose an Inside-Out access strategy using a new trans-vascular catheter approach.

Interventional MRI in closed bore high-field systems is a challenge due to limited space and the need of dedicated MRI compatible equipment and tools. A possible solution could be to perform an ultrasound procedure for guidance of the therapy tools outside the bore, but still on the MRI patient bed. That could track and subsequently combine the superior images of MRI with the real-time features of ultrasound. Conventional optical tracking systems suffer from line of sight issues and electromagnetic tracking does not perform well in the presence of magnetic fields. Hence, to overcome these issues a new optical tracking system called inside-out tracking is used. In this approach, the camera is directly attached to the US probe and the markers are placed onto the patient to achieve the location information of the US slice. The evaluation of our novel system of framed fusion markers can easily be adapted to various imaging modalities without losing image registration. To confirm this evaluation, phantom studies with MRI and US imaging were carried out using a point-registration algorithm along with a similarity measure for fusion. In the inside-out system approach, image registration was found to yield an accuracy of upto 4 mm, depending on the imaging modality and the employed marker arrangement and with that provides an accuracy that cannot be easily achieved by combining pre-operative MRI with live ultrasound.

For this study the impact of different co-registration procedures on MEG source localization of somatosensory evoked fields was evaluated. Two different co-registration procedures were used to calculate the transformation matrix which specifies how to align the MRI data to the MEG head coordinate system. In order to depict the differences, caused by the method, the Euclidian distance between the reconstructed sources was noted. It was shown that, erroneous MRI and MEG data co- registration effects source localization results. Most dipoles are located more posterior and superior when the more advanced registration procedure was applied. In conclusion the results show, that an iterative matching procedure allows an accurate knowledge of the MEG gradiometer sensor position relative to the head which is crucial to correctly reconstruct neuronal activity derived from MEG measurements.

In this paper, we propose a method to segment the thyroid from a set of 2D ultrasound images. We extended an active contour model in 2D to generate a 3D segmented thyroid volume. First, a preprocessing step is carried out to suppress the noise present in US data. Second, an active contour is used to segment the thyroid in each of the 2D images. Finally, all the segmented thyroid images are passed to a 3D reconstruction algorithm to obtain a 3D model of the thyroid. We obtained an average segmentation accuracy of 86.7% in six datasets with a total of 703 images.

Even today, dealing with motion artifacts in magnetic resonance imaging (MRI) is a challenging task. Image corruption due to spontaneous body motion complicates diagnosis. In this work, an MRI phantom for rigid motion is presented. It is used to generate motion-corrupted data, which can serve for evaluation of blind motion compensation algorithms. In contrast to commercially available MRI motion phantoms, the presented setup works on small animal MRI systems. Furthermore, retrospective gating is performed on the data, which can be used as a reference for novel motion compensation approaches. The motion of the signal source can be reconstructed using motor trigger signals and be utilized as the ground truth for motion estimation. The proposed setup results in motion corrected images. Moreover, the importance of preprocessing the MRI raw data, e.g. phase-drift correction, is demonstrated. The gained knowledge can be used to design an MRI phantom for elastic motion.

Intraoperative thermal neuroimaging is a novel intraoperative imaging technique for the characterization of perfusion disorders, neural activity and other pathological changes of the brain. It bases on the correlation of (sub-)cortical metabolism and perfusion with the emitted heat of the cortical surface. In order to minimize required computational resources and prevent unwanted artefacts in subsequent data analysis workflows foreground detection is a important preprocessing technique to differentiate pixels representing the cerebral cortex from background objects. We propose an efficient classification framework that integrates characteristic dynamic thermal behaviour into this classification task to include additional discriminative features. The first stage of our framework consists of learning this representation of characteristic thermal time-frequency behaviour. This representation models latent interconnections in the time-frequency domain that cover specific, yet a priori unknown, thermal properties of the cortex. In a second stage these features are then used to classify each pixel’s state with conditional random fields. We quantitatively evaluate several approaches to learning high-level features and their impact to the overall prediction accuracy. The introduction of high-level features leads to a significant accuracy improvement compared to a baseline classifier.

Computer aided classification of HEp-2 cell based indirect immunofluorescence (IIF) images is a recommended procedure for standardising autoimmune disease diagnostics. In this work a novel feature, the thresholded local binary count (TLBC) has been proposed to classify IIF images into one among six classes. The TLBC is rotational invariant and is insensitive to pixel quantization noise. It characterizes the local binary gray scale pixel information in an image. The proposed feature along with global features such as area, entropy, illumination level and mean intensity, when classified using a support vector machine gave an accuracy of 86%. This feature could help in improving the diagnostics of autoimmune diseases which is highly clinically significant.

In this work, an attempt has been made to differentiate muscle non-fatigue and fatigue conditions using sEMG signals and texture representation of the time-frequency images. The sEMG signals are recorded from the biceps brachii muscle of 25 healthy adult volunteers during dynamic fatiguing contraction. The first and last curls of these signals are considered as the non-fatigue and fatigue zones, respectively. These signals are preprocessed and the time-frequency spectrum is computed using short time fourier transform (STFT). Gray-Level Co-occurrence Matrix (GLCM) is extracted from low (15–45 Hz), medium (46–95 Hz) and high (96–150 Hz) frequency bands of the time-frequency images. Further, the features such as contrast, correlation, energy and homogeneity are calculated from the resultant matrices. The results show that the high frequency band based features are able to differentiate non-fatigue and fatigue conditions. The features such as correlation, contrast and homogeneity extracted at angles 0°, 45°, 90°, and 135° are found to be distinct with high statistical significance (p < 0.0001). Hence, this framework can be used for analysis of neuromuscular disorders.

In this work, we developed a method to handle the image quality test-tool precisely. This test-tool is important to evaluate the quality of the medical images for pre-treatment planning phase. But the achieved images are estimated by naked eyes, which does not provide the precise result. Our main goal is to get the desired image parameters numerically. This numerical estimation overcomes the limitation of naked eye observation. Hence, it enhances the pre-treatment planning. The ETR-1 test-tool is considered here. The contrast, the low contrast details and line-pairs (lp/mm) were estimated.

Compliant phantoms of the human aortic arch can mimic patient specific cardiovascular dysfunctions in vitro. Hence, phantoms may enable elucidation of haemodynamic disturbances caused by aortic dysfunction. This paper describes the fabrication of a thin-walled silicone phantom of the human ascending aorta and brachiocephalic artery. The model geometry was determined via a meta-analysis and modelled in SolidWorks before 3D printing. The solid model surface was smoothed and scanned with a 3D scanner. An offset outer mould was milled from Ebalta S-Model board. The final phantom indicated that ABS was a suitable material for the internal model, the Ebalta S-Model board yielded a rough external surface. Co-location of the moulds during silicone pour was insufficient to enable consistent wall thickness. The resulting phantom was free of air bubbles but did not have the desired wall thickness consistency.

Electrical impedance tomography (EIT) is used to monitor the regional distribution of ventilation in a transversal plane of the thorax. In this manuscript we evaluate the impact of different quantities of electrodes used for current injection and voltage measurement on the reconstructed shape of the lungs. Results indicate that the shape of reconstructed impedance changes in the body depends on the number of electrodes. In this manuscript, we demonstrate that a higher number of electrodes do not necessarily increase the image quality. For the used stimulation pattern, utilizing neighboring electrodes for current injection and voltage measurement, we conclude that the shape of the lungs is best reconstructed if 16 electrodes are used.

UWB microwave imaging has proven to be a promising technique for early-stage breast cancer detection. The extensive image reconstruction time can be accelerated by parallelizing the execution of the underlying beamforming algorithms. However, the efficiency of the parallelization will most likely depend on the grade of parallelism of the imaging algorithm and of the utilized hardware. This paper investigates the dependencies of two different beamforming algorithms on multiple hardware specification of several graphics boards. The parallel implementation is realized by using NVIDIA’s CUDA. Three conclusions are drawn about the behavior of the parallel implementation and how to efficiently use the accessible hardware.

Osteoradionecrosis (ORN) is a serious side effect of oncologic radiation therapy. Often, surgical removal of the affected skeletal tissue is indicated. In cranio-maxillofacial surgery, partial or total resection of the upper or lower jaw implies a severe impairment of the patient‘s quality of life. Up to now, clear display of ORN is still a challenge. This part of the project is dedicated to medical visualization of progressing ORN for clinical diagnosis. Currently, clinical diagnosis of ORN is mostly based on computer tomography (CT). With regard to its high advantages as e.g. reduced radiation dose, we additionally evaluate cone beam computer tomography (CBCT). After registration on a suitable reference and refined image processing and segmentation, all patient’s CT-/CBCT-data are subjected to various rendering techniques configured for the respective purpose, namely visualization of destructive and/or sclerotic skeletal alterations, consideration of cortical or trabecular bone, and analysis based on CT or CBCT. Recent achievements within the project were demonstrated with special focus on evaluation of both, CT and CBCT as well as on close cooperation with the clinical setting.

An accurate detection of anatomical structures in electrical impedance tomography (EIT) is still at an early stage. Aorta detection in EIT is of special interest, since it would favor non-invasive assessment of hemodynamic processes in the body. Here, diverse EIT reconstruction parameters of the GREIT algorithm were systematically evaluated to detect the aorta after saline bolus injection in apnea. True aorta position and size were taken from computed tomography (CT). A comparison with CT showed that the smallest error for aorta displacement was attained for noise figure nf = 0.7, weighting radius rw = 0.15, and target size ts = 0.01. The spatial extension of the aorta was most precise for nf = 0.7, rw = 0.25, and ts = 0.07. Detection accuracy (F1-score) was highest with nf = 0.6, rw = 0.15, and ts = 0.04. This work provides algorithm-related evidence for potentially accurate aorta detection in EIT after injection of a saline bolus.

In this study we evaluated open-source software for lung segmentation. Several parameters which emphasize on functionality, usability, image quality and 3D export are considered for this evaluation. Based on these parameters, a scoring system is generated. Our preliminary evaluation results indicated that the Pulmonary toolkit obtains the best overall performance according to the scoring system. However, the ranking of software shows a certain variation among different criteria. The selection of software should regard the focus and the specific interest of the user.

This paper describes a prototype of an automatic system for the detection and evaluation of Cystic fibrosis features (CF) in High resolution computed tomography (HRCT) Scans. The aim of this study lies in presenting this system as a decision support tool for radiologists in future. The CF features that have been detected and evaluated are Bronchiectasis and Mucus Plugging. This system recognizes Bronchiectasis as the presence of enlarged airways in pulmonary CF-CT slices whereas, Mucus Plugging has been recognized as clusters of high attenuation pixels. The dataset of this study consists of HRCT Scans of five CF patients of varying disease stages. Mean percentages of these CF features that were computed for each intercostal space, starting from the first to the fifth, fairly accurately match the different stages of the disease.

Analysis of multicellular patterns is required to understand tissue organizational processes. By using a multi-scale object oriented image processing method, the spatial information of cells can be extracted automatically. Instead of manual segmentation or indirect measurements, such as general distribution of contrast or flow, the orientation and distribution of individual cells is extracted for quantitative analysis. Relevant objects are identified by feature queries and no low-level knowledge of image processing is required.

There are various methods to synthesize superparamagnetic nanoparticles (SPIONs) useful for MPI (magnetic particle imaging) and in therapy (Hypothermia) such as co-precipitation, hydrothermal reactions etc. In this research, the focus is to analyse the effects of crucial parameters such as effect of molecular mass of dextran and temperature of the co-precipitation. These parameters play a crucial role in the inherent magnetic properties of the resulting SPIONs. The amplitude spectrum and hysteresis curve of the SPIONs is analysed with MPS (magnetic particle spectrometer). PCCS (photon cross-correlation spectroscopy) measurements are done to analyse the size distribution of hydrodynamic diameter the resulting SPIONs.

An experimental method for radiopacity evaluation of neurovascular implants is presented. State of the art methods are described for cardiovasular implants. To extend the methods to neurovascular devices, imaging parameters were determined from clinical radiography data sets and protocols. To reduce background noise, a thresholding method is introduced. This method is evaluated on a setup with four different laser cut and braided stents. The results are compared to current evaluation methods without filtering. It is shown that unfiltered methods underestimate the radiopacity by 0.89 mm ± 0.21 mm (aluminum equivalent). The introduced method is highly repeatable and uses modern clinical imaging technology. Thus an image evaluation under realisitc conditions is possible. Slightly visible vascular devices and implants can be compared with high accuracy.

Lifetime estimation of implanted electronics in hermetic packages requires the prediction of the humidity induced lifetime. Classical approaches are limited in applications where miniaturized packages and a buffered humidity at low values are being utilized. An approach to overcome these limitations is described and investigations on suitable materials and measurement setups are presented. The findings support the usability of a Zeolite-silicone based desiccant system as a dielectric for a new type of online sensor. The future exploitation of this new sensing principle can allow the monitoring and prediction of humidity conditions inside of highly reliable miniaturized hermetic implantable packages.

For the treatment of intracranial aneurysms with aneurysm clips, usually a follow-up inspection in MRI is required. To avoid any artifacts, which can make a proper diagnosis difficult, a new approach for the manufacturing of an aneurysm clip entirely made from fiber-reinforced plastics has been developed. In this paper the concept for the design of the clip, the development of a new manufacturing technology for the fiber-reinforced components as well as first results from the examination of the components in phantom MRI testing is shown.

The effects of alkaline pH on the initial adhesion of osteoblasts to titanium surfaces was analyzed by single cell force microscopy (SCFM). In the SCFM measurements, the same cells were used to compare their unspecific adhesion to uncoated titanium with their specific adhesion to collagen coated titanium. When the maximum detachment forces (MDFs) were compared at pH 7.4 and 8.0, only slight differences were found on pure titanium, while the MDFs were significantly increased at collagen coated surfaces at pH 8.0. Effects on the subsequent proliferation and gene expression were investigated in an in vitro model system consisting of an alkalizing polyvinyl alcohol (PVA) matrix and a perforated titanium disc. The sodium hydroxide releasing matrix maintained the medium pH between pH 7.6 and pH 8.4 during the entire experiment. Under these conditions, cell counts were significantly increased with respect to the control system after 7 days in culture. These results were supported by gene expression analyses, which showed an upregulation of proliferation-controlling genes of the EGFR1 and PI3K/AKT pathways after 14 days in culture. The SCFM data were complemented by findings of an intensive regulation of genes known to be associated with focal adhesion such as Itga8 and Tnn.

The understanding of the complex biomechanics of the knee is a key for an optimal implant design. To easily investigate the influence of prosthetic designs on knee biomechanics a rapid prototyping workflow for knee implants has been developed and evaluated. Therefore, different manufacturing technologies and post-treatment methods have been examined and overall seven different replica knee implants were manufactured. For evaluation, the manufacturing properties such as surface accuracy and roughness were determined and kinematic behaviour was investigated in a novel knee testing rig. It was carried out that PolyJet-Modelling with a sanded surface resulted in changed kinematic patterns compared to a usual CoCr-UHMWPE implant. However, fused deposition modelling using ABS and subsequent surface smoothening with acetone vapor showed the lowest roughness of the manufactured implants and only minor kinematic differences. For this reason this method constitutes a promising approach towards an optimal implant design for improved patient-satisfaction and long lifetime of the implant. Finally the workflow is not only limited to the knee.

Ultrahydrophilic titanium miniplates with sandblasted and acid etched (SLA) surfaces were protected from loss of hydrophilicity by an exsiccation layer of salt and stored in a dry state. Various salts in different concentrations were tested in respect to their conservation capacity and optical appearance. Potassium phosphate buffer in a specified composition appeared to be optimal. This optimal system was applied in a long time storage experiment showing no loss of hydrophilicity over years. It was also transferred with success to hyperhydrophilic dental implants.

New methodologies are a major driving force of scientific progress. In this case the finding that contact angles can be expressed as complex numbers offers the possibility of a much refined analysis beyond zero degrees of rough ultra-/superhydrophilic, (now called hyperhydrophilic), metal surfaces, which play a distinct role in dental and orthopedic implantology. The approaches, a short theoretical introduction and examples from medical applications are given.

Patient-specific bone and joint replacement implants lead to better functional and aesthetic results than conventional methods [1], [2], [3]. But extracting 3D shape information from CT Data and designing individual implants is demanding and requires multiple surgeon-to-engineer interactions. For manufacturing purposes, Additive Manufacturing offers various advantages, especially for low volume manufacturing parts, such as patient specific implants. To ease these new approaches and to avoid surgeon-to-engineer interactions a new design software approach is needed which offers highly automated and user friendly planning steps.

Carbon fiber reinforced polyetheretherketone (CFR-PEEK) has similar mechanical properties to human bone and is considered as the best alternative material to substitute titanium for spine cage implants. To compensate its poor osteogenic properties and limited bioinertness, CFR-PEEK was coated with a thin film of titanium. In the study, we investigated the biological response in vitro of titanium coated CFR-PEEK with different vacuum plasma pretreatments. The so modified surface revealed first hints for a good cell response by excellent cell adhesion and morphology of human osteoblast – like cells MG 63 (ATXX:’CRL-1427). Thus, the findings show that surface roughness of CFR-PEEK material has a profound effect on the biological activity via vacuum plasma treatment.

In this study we characterized the wear behavior of a tribological system with material combinations of the total intervertebral disc prosthesis InDisc (Institute of Medical and Polymer Engineering) – consisting of two laser sintered titanium alloy plates with an elastomer inbetween. For the tests a translatory oscillation test bench was used which simulates the kinematic and the physiological environment of the lumbar spine. In the interface between the elastomer (Silopren LSR 2670) and the laser sintered titanium alloy (Ti6Al4V) abrasion cords out of silicone rubber with a maximal area of 500 × 700 μm 2 were generated as well as individual particles with a size of 10 × 20 to 40 × 50 μm 2 . In the second prosthesis interface of Ti6Al4V and bone, bone particles with an area of 0.5 × 0.5 to 1 × 1 μm 2 were detected. The wear particles and the amount of wear volume influence the biological response of a total intervertebral disc prosthesis in the body.

Smart Devices, IoT and Co. are changing healthcare. The possibilities for pervasive sensing and analysis are fast increasing and new therapy concepts as well as business models are arising, related to the term “Digital Health”. The paper will give a brief overview on the history and ask, whether Digital Health is more than Telemedicine 4.0. Furthermore, we will ask for the prospective currency to participate in new preventive offer. Data is the new oil – Digital Biomarkers enable new value chains on health data and allow for the personalization of healthcare. We will present ongoing work of Fraunhofer ISST on a Digital Biomarker called beHealthy Health Score.

A close cooperation with users is necessary to ensure that interactive systems are robust, easy to use and accepted. Therefore, in medical technology, standards for usability are of fundamental importance. We investigated with the presented study how the concept of usability is currently understood and implemented in medical software companies. Interviews were conducted with 21 employees of German enterprises. Furthermore we extended an already existing quantitative online survey where 53 companies (including 24 from the health industry sector) participated in. Results show that the importance of usability is recognized by most of the respondents. Moreover, a wide variety of methods and approaches is known and implemented for exploring user needs and evaluating system prototypes. However, it was observed that human-centered design activities mainly focus on functionality, risk prevention and accessibility. Hedonic user needs and subjective perceptions (“user experience”) still play a minor role. Based on the results, practical requirements are derived and a “best case” for methodological approach is introduced.

The purpose of this research is to evaluate the detectability of defect membranes in intravenous (IV) infusion filter systems. The device under test (DUT) protects critical ill patients and has a high priority for the risk management of intensive care units. The developed quality control system stands out from other filter integrity methods because no method located on this topic represents such a simple, reliable, fast and non-destructive technique, examined without liquid. The invented method works as a pressure driven test and uses gas to identify defects. Previous studies have demonstrated the capability of detecting various types of errors. In this paper the influence of different test gases on the detectability of smallest defects is presented.

Development of wearable point-of-care medical devices faces many challenges. Besides technological and clinical issues, demands on robustness, miniaturization, and user interface design are of paramount importance. However, a systematic assessment of these non-functional but essential requirements is often impossible within the first product cycle. Later, surveys on user satisfaction with existing devices and user demands can offer significant input for device re-development and improvement. In this paper, we present a survey on satisfaction with and demands for a wearable medical device for percutaneous auricular vagus nerve stimulation (pVNS). We analyzed 36 responses from patients treated with pVNS and five responses from experienced physicians in order to devise a future concept of pVNS. Main shortcomings of a current pVNS device were identified to be lacking water resistance and mechanical robustness, both impairing daily activities. Painful sensation during pVNS application, unwanted side effects like skin irritations and strongly varying perception of the stimulation were reported. Results urge for more patient self-governance and an (automatic) adjustment of the stimulation to the current physiological state of the patient. Attained results support a strategic approach for future developments of pVNS towards personalized health care.

The pathway from the flash of a technological invention until its use as a medical device in every day care is tedious and burdensome. But the often postulated acceleration has to balance the speed of innovation and the indispensable product safety by an improved understanding of the innovation cycle. While several studies investigated the time course of pharmaceutical innovation, a comparable empirical analysis of medical devices is lacking. Thus we evaluated the time between the patent priority date and the corresponding receipt of the CE mark as a function of a medical device risk class in 61 cases. The statistical analysis yielded a time increment (trend) from medical devices in risk category I (median = 5.8 years) compared to risk category III (median = 10.4 years), which is close to literature reported values for drug development (9–12 years). The difference between products in risk classes I and II did not reach significance. To investigate the underlying facts, a text-mining approach especially to resolve the ambiguity of, e.g. patents, CE Marks etc. is suggested for increasing the sample size.

P-wave assessment is frequently used in clinical practice to recognize atrial abnormalities. However, the use of P-wave criteria to diagnose specific atrial abnormalities such as left atrial enlargement has shown to be of limited use since these abnormalities can be difficult to distinguish using P-wave criteria to date. Hence, a mechanistic understanding how specific atrial abnormalities affect the P-wave is desirable. In this study, we investigated the effect of left atrial hypertrophy on P-wave morphology using an in silico approach. In a cohort of four realistic patient models, we homogeneously increased left atrial wall thickness in up to seven degrees of left atrial hypertrophy. Excitation conduction was simulated using a monodomain finite element approach. Then, the resulting transmembrane voltage distribution was used to calculate the corresponding extracellular potential distribution on the torso by solving the forward problem of electrocardiography. In our simulation setup, left atrial wall thickening strongly correlated with an increased absolute value of the P-wave terminal force (PTF) in Wilson lead V 1 due to an increased negative amplitude while P-wave duration was unaffected. Remarkably, an increased PTF-V 1 has often been associated with left atrial enlargement which is defined as a rather increased left atrial volume than a solely thickened left atrium. Hence, the observed contribution of left atrial wall thickness changes to PTF-V 1 might explain the poor empirical correlation of left atrial enlargement with PTF-V 1 .

Radiofrequency ablation (RFA) is a widely used clinical treatment for many types of cardiac arrhythmias. However, nontransmural lesions and gaps between linear lesions often lead to recurrence of the arrhythmia. Intracardiac electrograms (IEGMs) provide real-time information regarding the state of the cardiac tissue surrounding the catheter tip. Nevertheless, the formation and interpretation of IEGMs during the RFA procedure is complex and yet not fully understood. In this in-silico study, we propose a computational model for acute ablation lesions. Our model consists of a necrotic scar core and a border zone, describing irreversible and reversible temperature induced electrophysiological phenomena. These phenomena are modeled by varying the intra- and extracellular conductivity of the tissue as well as a regulating zone factor. The computational model is evaluated regarding its feasibility and validity. Therefore, this model was compared to an existing one and to clinical measurements of five patients undergoing RFA. The results show that the model can indeed be used to recreate IEGMs. We computed IEGMs arising from complex ablation scars, such as scars with gaps or two overlapping ellipsoid scars. For orthogonal catheter orientation, the presence of a second necrotic core in the near-field of a punctiform acute ablation lesion had minor impact on the resulting signal morphology. The presented model can serve as a base for further research on the formation and interpretation of IEGMs.

Eikonal models are useful to compute approximate solutions of cardiac excitation propagation in a computationally efficient way. In this work the underlying conduction velocities for different cell types were computed solving the classical bidomain model equations for planar wavefront propagation. It was further investigated how changes in the conductivity tensors within the bidomain model analytically correspond to changes in the conduction velocity. The error in the presence of local front curvature for the derived eikonal model parametrization were analyzed. The conduction velocity simulated based on the bidomain model was overestimated by a maximum of 10%.

Anterior rhinomanometry is the current gold standard for the objective assessment of nasal breathing by determining the nasal resistance. However, computational fluid dynamics would allow spatially and temporally well- resolved investigation of additional flow parameters. In this study, measured values of nasal resistance are compared with measured values. An unclear discrepancy between the two methods was found, suggesting further investigation.

Respiratory system modelling can enable patient-specific mechanical ventilator settings to be found, and can thus reduce the incidence of ventilator induced lung injury in the intensive care unit. The resistance of a simple first order model (FOM) of pulmonary mechanics was compared with a flow dependent term of a non-linear autoregressive (NARX) model. Model parameters were identified for consecutive non-overlapping windows of length 20 breaths. The analysis was performed over recruitment manoeuvres for 25 sedated mechanically ventilated patients. The NARX model term, b 1 , consistently decreased as positive end expiratory pressure (PEEP) increased, while the FOM resistance behaviour varied. Overall the NARX b 1 behaviour is more in-line with expected trends in airway resistance as PEEP increases. This work has further verified the physiologically descriptive capability of the NARX model.

For patients with acute respiratory distress syndrome (ARDS), the use of mathematical models to determine patient-specific ventilator settings can reduce ventilator induced lung injury and improve patient outcomes. A non-linear autoregressive model of pulmonary mechanics was used to identify inspiratory and expiratory pressure-dependent elastance ( E i and E e ) as independent variables. The analysis was implemented on 19 data sets of recruitment manoeuvres (RMs) that were performed on 10 mechanically ventilated patients. At pressures p = 15–20 cmH 2 O the agreement between E i and E e was low. However, E i was a well-matched predictor of E e for p = 25–40 cmH 2 O, with R 2 ≥ 0.78, and there was no significant bias in the difference between E i and E e . Since many other models cannot uniquely identify E i and E e , the outcome may provide further insight into the characteristics of ARDS lungs in sedated patients.

Electrical impedance tomography (EIT) can be used to monitor regional lung ventilation. Due to its relatively high temporal resolution, EIT has already been applied during lung function tests in spontaneously breathing subjects with obstructive lung diseases like chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). In our study, ratios of the maximal volume exhaled in 1 s during forced expiration and forced vital capacity (FEV 1 /FVC) were calculated in predefined lung regions for five CF patients and five lung healthy subjects. The degree of FEV 1 /FVC homogeneity was assessed by using a slightly modified version of the global inhomogeneity index (GI FEV 1 /FVC ). CF patients showed a higher degree of inhomogeneity in pixel FEV 1 /FVC than lung healthy subjects. Since EIT is able to deliver regional information to assess airway obstruction in CF patients, it might represent a promising supplement to existing methods like spirometry providing global lung parameters.

Currently the surgical training of parietal bone graft techniques is performed on patients or specimens. Commercially available bone models do not deliver realistic haptic feedback. Thus customized parietal skull surrogates were developed for surgical training purposes. Two human parietal bones were used as reference. Based on the measurement of insertion forces of drilling, milling and saw procedures suitable material compositions for molding cortical and cancellous calvarial layers were found. Artificial skull caps were manufactured and tested. Additionally microtomograpy images of human and artificial parietal bones were performed to analyze outer table and diploe thicknesses. Significant differences between human and artificial skulls were not detected with the mechanical procedures tested. Highly significant differences were found for the diploe thickness values. In conclusion, an artificial bone has been created, mimicking the properties of human parietal bone thus being suitable for tabula externa graft lift training.

The numerical simulation of bone remodelling provides a great opportunity to improve the choice of therapy in particular for complex bone defects. Despite this fact, its use in clinical practice is not yet expedient because of several unresolved problems. In this paper a new bone remodelling algorithm based on standard computer tomography datasets and finite element analysis is introduced.

Thermoplastic polymers exhibit non-isochoric behaviour during tensile and compression testing as well as particular deformations like local necking (tension) or buckling (compression). A method for the determination of Cauchy stresses from tensile and compression tests is presented, that considers the actual deformations of the test specimens. The exact geometry of the specimens in the respective present configuration is determined in photographs, which are taken continuously throughout the test. The engineering stresses at several time points are converted into Cauchy stresses using newly developed formulas in consideration of the actual specimen geometry. For validation finite element analyses of the tensile and compression tests are performed using the identified stress-strain curves. The numerical results show good agreement with the experiments for the tested polymers. Thus a method for conversion of engineering to Cauchy stresses in tensile and compression tests could be established considering the non-isochoric deformation in plasticity. With this method “true” stress-strain curves as input for finite element material models can be identified for arbitrary materials.

Metallic implants in magnetic resonance imaging (MRI) are a potential safety risk since the energy absorption may increase temperature of the surrounding tissue. The temperature rise is highly dependent on implant size. Numerical examinations can be used to calculate the energy absorption in terms of the specific absorption rate (SAR) induced by MRI on orthopaedic implants. This research presents the impact of titanium osteosynthesis spine implants, called spondylodesis, deduced by numerical examinations of energy absorption in simplified spondylodesis models placed in 1.5 T and 3.0 T MRI body coils. The implants are modelled along with a spine model consisting of vertebrae and disci intervertebrales thus extending previous investigations [1], [2]. Increased SAR values are observed at the ends of long implants, while at the center SAR is significantly lower. Sufficiently short implants show increased SAR along the complete length of the implant. A careful data analysis reveals that the particular anatomy, i.e. vertebrae and disci intervertebrales, has a significant effect on SAR. On top of SAR profile due to the implant length, considerable SAR variations at small scale are observed, e.g. SAR values at vertebra are higher than at disc positions.

Transabdominal fetal pulse oximetry is an approach to measure oxygen saturation of the unborn child non-invasively. The principle of pulse oximetry is applied to the abdomen of a pregnant woman, such that the measured signal includes both, the maternal and the fetal pulse curve. One of the major challenges is to extract the shape of the fetal pulse curve from the mixed signal for computation of the oxygen saturation. In this paper we analyze the principle kind of connection of the fetal and maternal pulse curves in the measured signal. A time varying finite element model is used to rebuild the basic measurement environment, including a bulk tissue and two independently pulsing arteries to model the fetal and maternal blood circuit. The distribution of the light fluence rate in the model is computed by applying diffusion equation. From the detectors we extracted the time dependent fluence rate and analyzed the signal regarding its components. The frequency spectra of the signals show peaks at the fetal and maternal basic frequencies. Additional signal components are visible in the spectra, indicating multiplicative coupling of the fetal and maternal pulse curves. We conclude that the underlying signal model of algorithms for robust extraction of the shape of the fetal pulse curve, have to consider additive and multiplicative signal coupling.

Biorelevant in vitro test systems may be helpful to understand the in vivo behaviour of modern intravitreal dosage forms such as implants and injections. The already presented Vitreous Model (VM) in combination with the Eye Movement System (EyeMoS) was used to simulate the situation after a vitrectomy in combination with Siluron ® silicone oil (SO) insertion in vitro and to investigate the distribution of the model drug fluorescein sodium (FS) within the modified VM. The state after a vitrectomy was simulated in vitro by replacing half the volume of the gelled vitreous substitute by SO. Under consideration of simulated eye movements the position of SO towards the simulated vitreous body was examined. Furthermore, the influence of two different injection techniques was studied. On the one hand, FS was injected directly into the gel and on the other hand the injection was set through the gel in order to directly reach the SO. Independent of the injection technique, it was shown that the model drug distributed almost exclusively into the gel and not into the SO. This can be explained with the backflow of FS into the gel and the lack of solubility in the SO. Using the modified VM and EyeMoS, the in vitro characterization of drug release and distribution behaviour of intravitreal injections can be performed under consideration of a simulated vitrectomy.

Mathematical models can be employed to simulate a patient’s individual physiology and can therefore be used to predict reactions to changes in the therapy. To be clinically useful, those models need to be identifiable from data available at the bedside. Gradient based methods to identify the values of the model parameters that represent the recorded data highly depend on the initial estimates. The proposed work implements a previously developed method to overcome those dependencies to identify a three parameter model of gas exchange. The proposed hierarchical method uses models of lower order related to the three parameter model to calculate valid initial estimates for the parameter identification. The presented approach was evaluated using 12 synthetic patients and compared to a traditional direct approach as well as a global search method. Results show that the direct approach is highly dependent on how well the initial estimates are selected, while the hierarchical approach was able to find correct parameter values in all tested patients.

Atrial fibrillation is the most common arrhythmia. However, the mechanisms of AF are not completely understood. It is known that fractionated signals are measured in AF but the etiology of fractionated signals is still not clear. The central question is to evaluate the effects of segmented fibrotic areas in histological tissue sections on the extracellular potential in a simulation study. We calculated the transmembrane voltages and extracellular potentials from the excitation wave front around a 3D fibrotic area from mouse hearts that were reconstructed from histological tissue sections. Extracellular potentials resulted in fragmented signals and differed strongly by stimulations from different directions. The transmural angle of the excitation waves had a significantly influence on the signal morphologies. We suggest for future clinical systems to implement the possibility for substrate mapping by stimulations from different directions in sinus rhythm.

Computational fluid dynamics (CFD) is increasingly used by biomedical engineering groups to understand and predict the blood flow within intracranial aneurysms and support the physician during therapy planning. However, due to various simplifications, its acceptance remains limited within the medical community. To quantify the influence of the reconstruction kernels employed for reconstructing 3D images from rotational angiography data, different kernels are applied to four datasets with patient-specific intracranial aneurysms. Sharp, normal and smooth reconstructions were evaluated. Differences of the resulting 24 segmentations and the impact on the hemodynamic predictions are quantified to provide insights into the expected error ranges. A comparison of the segmentations yields strong differences regarding vessel branches and diameters. Further, sharp kernels lead to smaller ostium areas than smooth ones. Analyses of hemodynamic predictions reveal a clear time and space dependency, while mean velocity deviations range from 3.9 to 8%. The results reveal a strong influence of reconstruction kernels on geometrical aneurysm models and the subsequent hemodynamic parameters. Thus, patient-specific blood flow predictions require a carefully selected reconstruction kernel and appropriate recommendations need to be formulated.

For the development of a novel, user-friendly and low cost point-of-care diagnostic device for the detection of disease specific biomarkers a flow optimised design of the test system is investigated. For this, computational fluid dynamics and rapid prototyping methods are used. The result is a functional design, which can be used for further experimental investigations.

The fetal oxygen saturation is an important parameter to determine the health status of a fetus, which is until now mostly acquired invasively. The transabdominal, fetal pulse oximetry is a promising approach to measure this non-invasively and continuously. The fetal pulse curve has to be extracted from the mixed signal of mother and fetus to determine its oxygen saturation. For this purpose efficient algorithms are necessary, which have to be evaluated under constant and reproducable test conditions. This paper presents the improved version of a phantom which can generate artificial pulse waves in a synthetic tissue phantom. The tissue phantom consists of several layers that mimic the different optical properties of the fetal and maternal tissue layers. Additionally an artificial vascular system and a dome, which mimics the bending of the belly of a pregnant woman, are incorporated. To obtain data on the pulse waves, several measurement methods are included, to help understand the behavior of the signals gained from the pulse waves. Besides pressure sensors and a transmissive method we integrated a capacitive approach, that makes use of the so called “Pin Oscillator” method. Apart from the enhancements in the tissue phantom and the measurements, we also improved the used blood substitute, which reproduces the different absorption characteristics of fetal and maternal blood. The results show that the phantom can generate pulse waves similar to the natural ones. Furthermore, the phantom represents a reference that can be used to evaluate the algorithms for transabdominal, fetal pulse oximetry.

Unobtrusive medical instrumentation is a key in continuous patient monitoring. To increase compliance, multi-functional sensor concepts and measurement sites different from gold-standards are used. In this work, we aim to combine both approaches. We focus on minimally spaced electrode positions with high signal correlations to gold-standards. We present twofold experimental data from six and eleven healthy volunteers and provide chest positions with individual correlations up to 0.83 ± 0.06 for ECG and 0.73 ± 0.28 for the respiratory frequency. Using a performance index, we assess positions with correlations up to 0.77 ± 0.12 for ECG and 0.65 ± 0.35 for the respiratory frequency with 24 mm electrode distance.

Nasoalveolar moulding (NAM) has become a widely accepted and evidence-based treatment strategy for newborns with cleft lip and palate (CLP), attempting to reduce the cleft gap and to form an appropriately shaped alveolar arch by an intraoral patient-specific NAM plate and to erect the usually flattened nostrils towards a natural nose wing occurrence. The generation of such an appropriately shaped NAM plate requires, besides 3d information of the patient’s initially cleft lip and palate, an estimated target model of the maxilla. Previous studies showed the applicability of curve-based approaches to describe the maxilla during early infancy. We have developed an automated algorithm implemented with the programming language Python, describing the alveolar arch by an approximated ellipse. Therefore, the digitalized data sets of human maxillae were aligned to a global coordinate system with a total least square method and subsequently analyzed with the curvature-based algebraic point set surfaces (APSS) algorithm. The gathered information of height ratio and curvature allows the detection of points on the alveolar segments and therewith the fit of an ellipse describing the human maxilla. In 84.5% of 193 maxilla impressions of healthy newborns the fitted ellipses described the course of the maxilla within defined margins. Applying the algorithm to 38 newborns suffering from unilateral cleft lip and palate in 76.3% the fitted ellipses bridge the CLP alveolar segments, so that a harmonic alveolar arch can be deduced. Describing the alveolar arch by one or multiple ellipses allows (i) to automatically measure the dimensions of the maxilla, (ii) to derive a growth model during early infancy, (iii) to derive a healthy harmonic arch from CLP alveolar segments and (iv) to automatically generate a basic NAM device on the basis of the virtually modified maxilla.

Human-Machine Interfaces in rehabilitation engineering often use activity signals. Examples are electrical wheelchairs or prostheses controlled by means of muscle contractions. Activity signals are user-dependent and often reflect neurological weaknesses. Thus, not all users are able to operate the same control scheme in a robust manner. To avoid under- and overstraining, the interface ideally uses a control scheme which reflects the user’s control ability best. Therefore, we explored typical phenomena of activation signals. We derive criteria to quantify the user’s performance and abilities and present a routine which automatically selects and adapts one of three control schemes being best suited.

We examine the usefulness of event-based sampling approaches for reducing communication in inertial-sensor-based analysis of human motion. To this end we consider realtime measurement of the knee joint angle during walking, employing a recently developed sensor fusion algorithm. We simulate the effects of different event-based sampling methods on a large set of experimental data with ground truth obtained from an external motion capture system. This results in a reduced wireless communication load at the cost of a slightly increased error in the calculated angles. The proposed methods are compared in terms of best balance of these two aspects. We show that the transmitted data can be reduced by 66% while maintaining the same level of accuracy.

Inertial sensor networks enable realtime gait analysis for a multitude of applications. The usability of inertial measurement units (IMUs), however, is limited by several restrictions, e.g. a fixed and known sensor placement. To enhance the usability of inertial sensor networks in every-day live, we propose a method that automatically determines which sensor is attached to which segment of the lower limbs. The presented method exhibits a low computational workload, and it uses only the raw IMU data of 3 s of walking. Analyzing data from over 500 trials with healthy subjects and Parkinson’s patients yields a correct-pairing success rate of 99.8% after 3 s and 100% after 5 s.

During a magnetic resonance imaging (MRI) exam, a respiratory signal can be required for different purposes, e.g. for patient monitoring, motion compensation or for research studies such as in functional MRI. In addition, respiratory information can be used as a biofeedback for the patient in order to control breath holds or shallow breathing. To reduce patient preparation time or distortions of the MR imaging system, we propose the use of a contactless approach for gathering information about the respiratory activity. An experimental setup based on a commercially available laser range sensor was used to detect respiratory induced motion of the chest or abdomen. This setup was tested using a motion phantom and different human subjects in an MRI scanner. A nasal airflow sensor served as a reference. For both, the phantom as well as the different human subjects, the motion frequency was precisely measured. These results show that a low cost, contactless, laser-based approach can be used to obtain information about the respiratory motion during an MRI exam.

In almost any medical procedure respiratory motion is an issue and may result in image degradation. Most currently available devices and systems, which are intended to reduce respiratory influences do not come into operation however in clinics due to their high cost and complex operation. In our paper we evaluated an interactive breath hold control system that helps flat breathing to subsequently reduce respiratory motion during signal acquisitions or procedure treatments. With that the human subjects are enabled to regulate their own breath by following visual feedback via a specially designed display. That display shows biofeedback information about the respiratory excursion through air pressure deviations measured inside an air bellows belt. The system was assessed quantitatively in a laboratory setup and qualitatively by applications in real clinical procedures. The obtained results are very promising and can be further improved with additional developments to provide an easy to use and relatively inexpensive solution for respiratory motion related imaging problems.

The aim of the project is the development of an aid for blind or visually impaired people, considering economic aspects as well as easy adaptability to various daily situations. Distance sensors were attached to a walking frame (rollator) to detect the distance to obstacles. The information from the sensors is transmitted to the user via tactile feedback. This is realized with a number of vibration motors which were located at the upper belly area of the subject. To test the functionality of the aid to the blind, a testing track with obstacles has been passed through by a number of volunteers. While passing the track five times the needed time to pass through, as well as the number of collisions, were noticed. The results showed a decline in the average time needed to pass though the testing track. This indicates a learning process of the operator to interpret the signals given by the tactile feedback.

The mobility of the upper extremity is essential for everyday activities and for independent living. Shoulder disorders affect the range of motion, therefore a patient assistive system (PAS) for the shoulder joint can be used to compensate the restrictions. The developed PAS supports up to 120° of flexion and abduction. The portable dynamic orthotic consists of two levers and is attached to a hip belt. The upper arm of the patient is connected to the device using a brace. The prototype is driven by one motor and controlled by surface electromyography (EMG). The functionality of the system was successfully verified by tests with healthy subjects. For further development, a study with shoulder patients will be performed and health professionals will evaluate the PAS.

Realistic training of cardiologic interventions in a heart catheter laboratory is hardly achievable with simple tools and requires animal experiments. Therefore, first a simple mock circuit connected to a porcine heart mimicking the natural heart motion was developed. In a second step the setup was duplicated to drive both sides of the heart independently to generate motion and physiologic pressures and flows. Using this simple setup cardiologic interventions (arterial and ventricular septal defects ASD/VSD closure) were performed successfully and allowed realistic training under the C-arm, echocardiography, placement of catheters and repair of ASD/VSD. With the second setup flows of up to 4 l/min were achieved in both sides of the heart at maximum left and right ventricular pressures of 80 mm Hg and 30 mm Hg respectively. This method is inexpensive and represents a realistic alternative to training in animal experiments.