Band 3, Heft 2

Ultrasound is being increasingly investigated for real-time target localization in image-guided interventions. Yet, in-vivo validation remains challenging due to the difficulty to obtain a reliable ground truth. For this purpose, real-time volumetric (4D) ultrasound imaging was performed simultaneously with electromagnetic localization of three wireless transponders implanted in the liver of a radiotherapy patient. 4D ultrasound and electromagnetic tracking were acquired at framerates of 12Hz and 8Hz, respectively, during free breathing over 8 min following treatment. The electromagnetic antenna was placed directly above and the ultrasound probe on the right side of the patient to visualize the liver transponders. It was possible to record 25.7 s of overlapping ultrasound and electromagnetic position data of one transponder. Good spatial alignment with 0.6 mm 3D root-mean-square error between both traces was achieved using a rigid landmark transform. However, data acquisition was impaired since the electromagnetic tracking highly influenced the ultrasound equipment and vice versa. High intensity noise streaks appeared in the ultrasound scan lines irrespective of the chosen frequency (1.7-3.3 MHz, 2/4 MHz harmonic). To allow for target visualization and tracking in the ultrasound volumes despite the artefacts, an online filter was designed where corrupted pixels in the newest ultrasound frame were replaced with non-corrupted pixels from preceding frames. Aside from these artefacts, the recorded electromagnetic tracking data was fragmented and only the transponder closest to the antenna could be detected over a limited period of six consecutive breathing cycles. This problem was most likely caused by interference from the metal holder of the ultrasound probe and was solved in a subsequent experiment using a 3D-printed non-metal probe fixation. Real-time wireless electromagnetic tracking was compared with 4D ultrasound imaging in-vivo for the first time. For stable tracking, large metal components need to be avoided during data acquisition and ultrasound filtering is required.

Diseases of lung tissue and the airways become a major task for medical care and health care systems in modern industrial countries in the future. Suitable treatment methods and strategies for lung support and artificial ventilation are of dare need. Besides the obvious importance as life-saving intervention, the effects of usually used over-pressure ventilation onto the sensitive alveolar tissue are insufficiently understood. Therefore, it is of great interest to characterize lung tissue during artificial ventilation at the alveolar level. Those measurements can be used to link micromechanics of alveolar structures to mechanical properties of the whole lung like compliance and resistance measured at the ventilator device. This can be done only in animal experiments due to the fact that imaging techniques used in human diagnostics like CT or MRT fail to resolve alveolar tissue structures. The disadvantage of high-resolution techniques like optical coherence tomography (OCT) or intravital microscopy (IVM) is the need of a surgical access to the lung due to the limitation in penetration depth of these techniques. Furthermore, imaging dynamic processes with high-resolution imaging techniques during uninterrupted artificial ventilation is a challenging task. In this study, we present a measurement setup for combined imaging of conventional pressure-controlled ventilated rats and the visualization of volume changes of alveolar structures during one cycle of breath. A custom-made OCT system in combination with a triggered scanning algorithm was used to acquire time-resolved 3D OCT image data. Furthermore, this system was combined with a self-adapting autofocus function for intravital microscopy to track the lung surface keeping the tissue in focal plane. The combination of new dynamic measurement modes for OCT and IVM allows new insights into alveolar tissue and will promote the understanding of mechanical behavior during artificial ventilation.

Measurement of the energy spectrum of secondary neutrons were carried out at the OncoRay Proton Therapy facility in Dresden, following an approach originating in neutron metrology which is well suited for both the characterization of secondary neutron fields at proton therapy facilities and the validation of Monte Carlo simulations. For the experiment, a brass target was placed in the proton beam and Bonner spheres measurements were made at a distance of 2 m from the target and at different angles, 15° to 120°, with respect to the incoming proton beam. The measured spectra were compared to Monte Carlo simulations.

Extracellular recordings of electrical neuronal sources with non-planar multichannel microelectrodes promise a high spatio-temporal resolution. We have developed signal-based algorithms, simulations and models to inversely estimate neuronal source positions and electrical properties by using multi-sensor recorded extracellular action potentials (EAP). Here, we analyse the dependence of electrode configurations on the position estimation by simulations. Estimations were simulated for various inter-electrode spacings, electrode-source distances and signal-to-noise ratios. The results show that inverse estimation depends on the electrode size or rather on the inter-electrode spacing. We find, as a rule, the larger the spacing, the larger the eligible source location area, but estimation quality of sources which are in the proximity of an electrode contact decreases. In addition, noise worsen the estimation and decreases the assessable distance between source and electrode. Thus, multichannel micro-electrodes should be selected towards signal and spatial sensitivity requirements.

The most common way to analyse heart rhythm is to calculate the RR-interval and the heart rate variability. For further evaluation, descriptive statistics are often used. Here we introduce a new and more natural heart rhythm analysis tool that is based on circular statistics and vector strength. Vector strength is a tool to measure the periodicity or lack of periodicity of a signal. We divide the signal into non-overlapping window segments and project the detected R-waves around the unit circle using the complex exponential function and the median RR-interval. In addition, we calculate the vector strength and apply circular statistics as wells as an angular histogram on the R-wave vectors. This approach enables an intuitive visualization and analysis of rhythmicity. Our results show that ECG-waves and rhythms can be easily visualized, analysed and classified by circular statistics and vector strength.

In this ex vivo feasibility study, endoscopic structural and functional optical coherence tomography (OCT) imaging with a field of view of 8 mm is presented allowing the inspection of nearly the entire tympanic membrane through the ear canal. The endoscope utilizes a gradient index optics for simultaneous OCT and video endoscopy. Additionally, Doppler-OCT allows the measurement of the tympanic membrane oscillation. Due to the fast image acquisition, only minor motion artifacts have been observed, which don’t affect the image quality. In conclusion, endoscopic OCT is considered as a promising tool for the comprehensive examination of the human middle ear.

In this paper, we presented a deep convolutional neural network (CNN) approach for forehead tissue thickness estimation. We use down sampled NIR laser backscattering images acquired from a novel marker-less near-infrared laser-based head tracking system, combined with the beam’s incident angle parameter. These two-channel augmented images were constructed for the CNN input, while a single node output layer represents the estimated value of the forehead tissue thickness. The models were – separately for each subject – trained and tested on datasets acquired from 30 subjects (high resolution MRI data is used as ground truth). To speed up training, we used a pre-trained network from the first subject to bootstrap training for each of the other subjects. We could show a clear improvement for the tissue thickness estimation (mean RMSE of 0.096 mm). This proposed CNN model outperformed previous support vector regression (mean RMSE of 0.155 mm) or Gaussian processes learning approaches (mean RMSE of 0.114 mm) and eliminated their restrictions for future research.

The ultimate goal of radiotherapy using external beams is to maximize the dose delivered to the tumor while minimizing the radiation given to surrounding healthy critical organs. Prompt Gamma Spectroscopy (PGS) has been proposed for range control of particle beams along with the determination of the elemental composition of irradiated tissues. We aim at developing a PGS system for the German Cancer Research Center – DKFZ that takes advantage of the superior selectivity of Helium and Carbon beams accelerated at the Heidelberg Ion-Beam Therapy Center. Preliminary tests with protons accelerated with an IBA C230 cyclotron located at the Universitäts Protonen Therapie Dresden were performed at OncoRay – National Center for Radiation Re-search in Oncology. We present results obtained with a PGS system composed of CeBr3 detectors ( Ø 2’’ × 2’’) and ( Ø 1.5’’ × 3’’) coupled to a Hamamatsu R13089 photomulti-plier tube and plugged to a Target U100 Spectrometer. Such system provides accurate time-of-flight measurements to increase the signal-to-noise ratio relative to neutron-induced background. First measurements resulted from the irradiation of PMMA and water phantoms, and graphite and aluminum bricks. Several PG energy lines ranging from 0.511 MeV up to 8 MeV were identified and compared with reference re-sults. Two further experiments consisted in irradiating PMMA phantoms in a slit- and semi-collimated configuration with mono-energetic proton beams of 165 MeV and 224 MeV, respectively. Results acquired by means of trans-versal PGS at different phantom depths, ranging from 6 cm before the Bragg peak (BP) to 3.5 cm beyond the BP in 5 mm steps with a 1 cm slit collimation (tungsten) showed a slight decrease of PG yields after the BP. Similar measurements with a semi-opened collimation configuration demonstrated a steeper decrease of PG yields after the BP.

For patients suffering from profound hearing loss or deafness still having respectable residual hearing in the low frequency range, the combination of a hearing aid with a cochlear implant results in the best quality of hearing perception (EAS – electric acoustic stimulation). In order to optimize EAS, ongoing research focusses on the integration of these stimuli in a single implant device. Within this study, the performance of piezoelectric actuators, particularly the dual actuator stimulation, in a scaled uncoiled test rig was investigated.

Developing an implantable, telemetric pressure measuring system for venous applications makes a high degree of miniaturization necessary. Thus the influence on the measurement environment is minimized and the risk of thrombosis at small flow blood velocities is decreased. But these systems are limited in terms of accuracy and resolution. The asked system requirements could only be reached by optimising the assembly and encapsulation techniques. To achieve the high degree of miniaturization numerical simulations were performed on the shape and size of the implant and led to the development of a specific metal housing consisting of two main components. A small measuring chamber will be placed into the portal vein and is rigidly fixed to a flat circular part that contains the pressure sensor chip and a transponder board and will be located outside on top of the vein. The main focus of the assembly process was based on a stress-free design and mounting of the components.

A functional device was developed to immediately show the localization of veins by detecting a temperature increase on the skin directly above them. Our new idea, compared to other developments, is the comparison of temperatures between a small, ideally punctiform, skin area, and a larger circularly surrounding area. This is realized by two infrared temperature sensors, one with a small field of view, and the other one with a larger field of view. The position of the vein is indicated by two laser modules, which beams cross in one spot, when the device is held in a defined distance to the skin. If the device is held over a vein, the laser spot lightens up. The device was tested in ten study participants. Cooling of the skin by disinfectant spray prior to the measurements increases the temperature gradient and thereby improves the efficiency of the device. Temperature profiles of four skin areas of each study participant were measured before and one minute after application of disinfectant spray. After application of disinfectant spray, a temperature difference of more than 0.3 K between a measuring point above a vein and points 15 mm next to this could be found in 36 out of 40 measurements (90%), compared to 26 out of 40 (65%) before disinfection. The mean temperature gradient could be increased from 0.476 K to 1.03 K (p < 0.001).

We resume the research for contactless in ovo sex determination of the domestic chicken, which has the final aim to provide an alternative to day-old cockerels culling in the layer industry. In ovo Raman and fluorescence spectroscopy of blood of eggs incubated until day 3.5 enables correct sexing rates over 90% barely affecting the hatching rate. Full automatization of the processes to guarantee high sexing speed and fulfill industrial demands is required to allow transferring the technology inside the hatcheries in the next future.

The deep understanding of cancer and tumor genesis, as well as the development of new therapy strategies still remains one of the emerging challenges in modern medicine. To meet these challenges it seems to be absolutely necessary to overcome the drawbacks of the established 2D in vitro models. Especially the missing microenvironment of the tumor, which means the absence of stroma and immune cells, results in a missing cell-cell and cell-stroma interaction as well as disrupted functional communication pathways. Modern 3D culture systems and 3D printing or rather bioprinting technologies attempt to solve this issue and aim to closely mimic natural tumor microenvironment. In this preliminary work we are going to present the first steps of establishing an artificial 3D tumor model utilising a low cost 3D printer. Therefore the printer had been modified with an open-source syringe pump to become a functional bioprinter using viscosity modulated alginate hydrogel. In the first attempts L929 mouse fibroblasts, which are an integral component of natural stroma, had been incorporated into the hydrogel matrix and printed into scaffolds. Subsequent to the printing process the scaffolds got ionically crosslinked with a 5% w/v aqueous solution of CaCl 2 to become mechanically stable. After three days of cultivation viability testing had been performed by utilising FDG staining and PET CT to obtain a volumetric viability measurement. The viability imaging showed vital cells homogeneously distributed in the scaffold and therefore stands as an evidence for a working low cost bioprinting process and a successful first step for the development of an artificial 3D tumor model.

The presented experimental in vitro approach was designed to assess the expansion behavior of stent systems in a resistant focal stenosis model with respect to a potential dog-boning effect. Five different stent systems (nominal diameter 3.0 mm) were investigated. The focal stenosis was simulated by a stainless steel tube (ID ≤ 1.20 mm). Stent expansion was performed using a proprietary test device consisting of a test chamber with 37 °C water, 2-axis laser scanner and a pressure controller. All stents could be properly expanded up to recommended maximum pressure (RBP). At nominal pressure (NP) maximum diameters ranged from 2.923 to 3.560 mm while at RBP the maximum diameters were 3.391 to 3.984 mm. Only minimal flaring of stent struts from the expanded balloon was observed. None of the stent systems failed under the extremely high stress at the edges of the focal stenosis.

The middle ear plays a crucial role in the quality of hearing. This complex construct performs different tasks like the protection against large air pressure input, the transmission of sound and its adaption to the inner ear impedance. Traumas, erosion by chronic otitis media or cholesteatoma, as well as other degenerative or damaging diseases, are reasons for a necessary reconstruction of specific middle ear structures. The reconstruction of the ossicular chain is very often performed by using rigid ossicular replacement prostheses made out of titanium, ceramics or bone. Tilting and dislocation of these passive implants are some of the known complications after middle ear surgery. They are related to loads at the implant coupling points in response to a tension change in the middle ear. The healing process, scar tension and ventilation problems are possible causes. To increase the sound transmission quality of total reconstructions and safety in case of pressure dependent movement of the tympanic membrane, a novel flexible total ossicular replacement prosthesis (TORP) with a silicone coated ball joint prototype was developed and investigated. Besides measurements of first middle ear transfer functions of temporal bones, the mechanical properties of the flexible TORP were examined with stress relaxation investigations. The novel silicone coated ball and socket joint TORP provides a sound transfer equivalent to the intact human middle ear at normal pressure and negative pressure in the middle ear. Together with the low stiffness values at an anatomically typical deflection of about 500 μm the prevention of a stiffening of the stapes annular ligament could be approved. Thus, improved acoustic transmission quality and reconstruction stability in comparison to common rigid titanium TORP could be determined. Nevertheless, further design improvements should be accomplished. The demonstrated flexible TORP can solve some common problems in middle ear reconstruction.

The realistic determination of effective dose of the staff in diagnostic radiology has been a challenge both for personal dosimetry and ambient dose measurement. A model for dosimetry of occupational exposure is presented that allows direct determination of effective dose from measured or even manufacturer given ambient dose distribution in front of the personnel. This model considers a wide range of radiation energies, different radiation protection situations, and gender effects.

To evaluate the possible range of application of the new InCise2 MLC for the CyberKnife M6 system in brain radiosurgery, a plan comparison was made for 10 brain metastases sized between 1.5 and 9cm3 in 10 patients treated in a single fraction each. The target volumes consist of a PTV derived by expanding the GTV by 1mm and were chosen to have diversity in the cohort regarding regularity of shape, location and the structures needed to be blocked for beam transmission in the vicinity. For each case, two treatment plans were optimized: one using the MLC and one using the IRIS-collimator providing variable circular fields. Plan re-quirements were: dose prescription to the 70% isodose line (18 or 20Gy), 100% GTV coverage, ≥98% PTV coverage, undisturbed central high dose region (95% of maximum dose) and a conformity index as low as possible. Plan com-parison parameters were: conformity index (CI), high-dose gradient index (GIH), low-dose gradient index (GIL), total number of monitor units (MU) and expected treatment time (TT). For all cases, clinically acceptable plans could be gen-erated with the following results (mean±SD) for CI, GIH, GIL, MU and TT, respectively for the MLC plans: 1.09±0.03, 2.77±0.26, 2.61±0.08, 4514±830MU and 27±5min and for the IRIS plans: 1.05±0.01, 3.00±0.35, 2.46±0.08, 8557±1335MU and 42±7min. In summary, the MLC plans were on average less conformal and had a shallower dose gradient in the low dose region, but a steeper dose gradient in the high dose region. This is accompanied by a smaller vol-ume receiving 10Gy. A plan by plan comparison shows that usage of the MLC can spare about one half of the MUs and one third of treatment time. From these experiences and results suggestions for MLC planning strategy can be de-duced.

The motor precision of today’s neuroprosthetic devices that use artificial generation of limb motion using Functional Electrical Stimulation (FES) is generally low. We investigate the adoption of natural co-activation strategies as present in antagonistic muscle pairs aiming to improve motor precision produced by FES. In a test in which artificial knee-joint movements were generated, we could improve the smoothness of FES-induced motion by 513% when applying co-activation during the phases in which torque production is switched between muscles – compared to no co-activation. We further demonstrated how the co-activation level influences the joint stiffness in a pendulum test.

Functional Electrical Stimulation (FES) facilitates the motor recovery of the hand function after stroke. The integration of biofeedback and other strategies to actively in-volve a patient in the therapy is important for the rehabili-tation progress. We introduce a combined control approach for a FES-driven neuroprosthesis using volitional electromyo-graphy (vEMG) and motion capturing via a novel inertial sensor network for patients that still possess a residual activity in the paralyzed muscles. A real-time vEMG measurement and signal processing in between stimulation pulses has been realized during active FES. Experiments showed that our system allows for quick adaption to individual users.

Inertial Measurement Units (IMUs) are increasingly used for human motion analysis. However, two major challenges remain: First, one must know precisely in which orientation the sensor is attached to the respective body segment. This is commonly achieved by accurate manual placement of the sensors or by letting the subject perform tedious calibration movements. Second, standard methods for inertial motion analysis rely on a homogeneous magnetic field, which is rarely found in indoor environments. To address both challenges, we introduce an automatic calibration method for joints with two degrees of freedom such as the combined radioulnar and elbow joint. While the user performs arbitrary movements, the method automatically identifies the sensor-to-segment orientations by exploiting the kinematic constraints of the joint. Simultaneously, the method identifies and compensates the influence of magnetic disturbances on the sensor orientation quaternions and the joint angles. In experimental trials, we obtain angles that agree well with reference values from optical motion capture. We conclude that the proposed method overcomes mounting and calibration restrictions and improves measurement accuracy in indoor environments. It therefore improves the practical usability of IMUs for many medical applications.

In neurovascular surgery the intraoperative fluorescence angiography has been proven to be a reliable contact-free optical imaging technique to visualize vascular blood-flow. This angiography is obtained by injecting a fluorescence dye e.g. indocyanine green and using an infrared camera system to visualize the fluorescence inside the vessel. Obviously this requires a medical approved dye and an additional camera setup and therefore generating risks and costs. Hence, the aim of our research is to develop a comparable technique for assessing the vascular function. This approach would not require dye nor an additional infrared camera setup. It is achieved by first preprocessing the video data of a camera that records only the visible spectrum and then filter it spatially as well as temporally. The prepared data is again processed to extract information about the vascular function and visualize it. This method would provide an option to compute and visualize the vascular function using the data recorded in the visible spectrum by the surgical microscopes. Given this contact-free optical imaging system, physiological information can be easily provided to the surgeon without an additional setup. In the case of comparable results with the state-of-the-art, this technique provides a straightforward optical intraoperative angiography. Further no drug approval is needed since no dye is injected.

Sudden cardiac death (SCD) is the leading single cause of death in the industrialized world. Current guidelines recommend a prophylactic implantation of an implantable cardioverter-defibrillator (ICD) in patients with reduced left-ventricular ejection fraction (LVEF ≤ 35%). However, most deaths after myocardial infarction (MI) occur in patients with normal or moderately reduced LVEF (>35%). There is a large body of evidence that cardiac autonomic dysfunction after MI is linked to increased susceptibility to malignant arrhythmias. Deceleration capacity of heart rate (DC) and periodic repolarization dynamics (PRD) are novel ECG-based risk markers, which capture different facets of cardiac autonomic dysfunction. Both parameters are strong and independent predictors of mortality and SCD after MI. Previous studies indicated that combined assessment of DC and PRD allows identification of a new high-risk group among post-infarction patients that is not addressed by current guidelines, thus opening new perspectives for biosignal-guided personalized therapies.

Not only in the technological world (“Industry 4.0”), but also in medicine, a paradigmatic change is taking place: We are already on the threshold of “Medicine 4.0”. Molecular biology has long played a leading role in life sciences. Scientists now realise that, with increasing miniaturisation, microelectronic systems downsized to the dimensions of cellular systems will facilitate new therapeutic approaches. But conventional telecommunications systems can also be equipped with sensors and transformed into intelligent medical monitoring devices that can help patients become part of the diagnostic and therapeutic process. This article illustrates development trends that will lead to modern, electronically supported healthcare concepts.

Radiotracers offer unique options for brain imaging of functional and molecular processes related to hearing. Such imaging can be applied in a broad spectrum of situations from preclinical research to clinical patient care. Functional imaging to assess activation in brain regions and networks involved in auditory processing uses markers of blood flow or energy-metabolism in well-defined conditions with and without auditory stimulation. Molecular markers can be used in hearing research for example to study changes in inhibitory neurotransmission systems related to hearing loss. For imaging either positron emission tomography (PET) or single-photon emission computed tomography (SPECT) are employed. Data analysis can encompasses voxel-wise statistical analysis of activation and calculation of quantitative parameters like receptor binding-potentials based on bio-kinetic modeling. Functional imaging has been frequently used in the context of auditory implantation. Before implantation it aims to assess intactness of the central auditory pathway and prognosis. After implantation it is used to improve understanding of the outcome with respect to auditory function and finally speech understanding, e.g. by measuring correlates of central auditory processing and neuroplasticity.

Smoke in laparoscopic videos usually appears due to the use of electrocautery when cutting or coagulating tissues. Therefore, detecting smoke can be used for event-based annotation in laparoscopic surgeries by retrieving the events associated with the electrocauterization. Furthermore, smoke detection can also be used for automatic smoke removal. However, detecting smoke in laparoscopic video is a challenge because of the changeability of smoke patterns, the moving camera and the different lighting conditions. In this paper, we present a video-based smoke detection algorithm to detect smoke of different densities such as fog, low and high density in laparoscopic videos. The proposed method depends on extracting various visual features from the laparoscopic images and providing them to support vector machine (SVM) classifier. Features are based on motion, colour and texture patterns of the smoke. We validated our algorithm using experimental evaluation on four laparoscopic cholecystectomy videos. These four videos were manually annotated by defining every frame as smoke or non-smoke frame. The algorithm was applied to the videos by using different feature combinations for classification. Experimental results show that the combination of all proposed features gives the best classification performance. The overall accuracy (i.e. correctly classified frames) is around 84%, with the sensitivity (i.e. correctly detected smoke frames) and the specificity (i.e. correctly detected non-smoke frames) are 89% and 80%, respectively.

Planning of interventions to treat cardiac arrhythmia requires a 3D patient specific model of the heart. Currently available commercial or free software dedicated to this task have important limitations for routinely use. Automatic algorithms are not robust enough while manual methods are time-consuming. Therefore, the project attempts to develop an optimal software tool. The heart model is generated from preoperative MR data-sets acquired with contrast agent and allows visualisation of damaged cardiac tissue. A requirement in the development of the software tool was the use of semi-automatic functions to be more robust. Once the patient image dataset has been loaded, the user selects a region of interest. Thresholding functions allow selecting the areas of high intensities which correspond to anatomical structures filled with contrast agent, namely cardiac cavities and blood vessels. Thereafter, the target-structure, for example the left ventricle, is coarsely selected by interactively outlining the gross shape. An active contour function adjusts automatically the initial contour to the image content. The result can still be manually improved using fast interaction tools. Finally, possible scar tissue located in the cavity muscle is automatically detected and visualized on the 3D heart model. The model is exported in format which is compatible with interventional devices at hospital. The evaluation of the software tool included two steps. Firstly, a comparison with two free software tools was performed on two image data sets of variable quality. Secondly, six scientists and physicians tested our tool and filled out a questionnaire. The performance of our software tool was visually judged more satisfactory than the free software, especially on the data set of lower quality. Professionals evaluated positively our functionalities regarding time taken, ease of use and quality of results. Improvements would consist in performing the planning based on different MR modalities.

High-throughput microscopy makes it possible to observe the morphology of zebrafish on large scale to quantify genetic, toxic or drug effects. The image acquisition is done by automated microscopy, images are evaluated automatically by image processing pipelines, tailored specifically to the requirements of the scientific question. The transfer of such algorithms to other projects, however, is complex due to missing guidelines and lack of mathematical or programming knowledge. In this work, we implement an image processing pipeline for automatic fluorescence quantification in user-defined domains of zebrafish embryos and larvae of different age. The pipeline is capable of detecting embryos and larvae in image stacks and quantifying domain activity. To make this protocol available to the community, we developed an open source software package called „ZebrafishMiner“ which guides the user through all steps of the processing pipeline and makes the algorithms available and easy to handle. We implemented all routines in an MATLAB-based graphical user interface (GUI) that gives the user control over all image processing parameters. The software is shipped with a manual of 30 pages and three tutorial datasets, which guide the user through the manual step by step. It can be downloaded at https://sourceforge.net/projects/scixminer/.

In this work a procedure is proposed to determine an optimal distribution of b-values in diffusion MRI measu-rements. The optimization procedure uses a method of Maximum Likelihood Estimation which can operate on any given number of b-values, values of the diffusion coefficients (ADC) and measurement noise strengths. Optimal b-values are calculated for white and gray brain matter. An optimi-zation for more than one ADC is demonstrated using multiple target values.

Automatic detection and tracking of subviral particles in image sequences is an indispensable supportive method for modern medicine research programs. This paper describes the development of a highly adaptable camera-to-world system motion invariant tracking algorithm. A translation compensation is obtained by cross correlations. Particles are detected by an implemented existing algorithm. The detected particles are linked by solving a Linear Assignment Problem. For highly stable results the tracks are improved by Kalman filtering. The algorithm is tested on simulated sequences. The results show a great ability for stable tracking.

Prostate cancer (PCa) is one of the most common cancer diseases in men in the western countries [1]. Besides the palpation, and the amount of prostate-specific-antigen’s (PSA) inside the blood, the current diagnostic imaging technologies are not appropriate. Early diagnosis defining the exact tumor location, spread and margins could make efficient targeted biopsies and image-guided surgery. A multimodal imaging technique containing a transmit-receive surface coil for anatomical MR imaging, a (S)PET detector module, consisting of silicon photomultipliers (SiPM), for functional imaging and an ultrasound (US) probe are placed as close as possible to the prostate designed as an endorectal tube to increase sensitivity and spatial resolution. All materials that are used are non-magnetic. Advantages of the SiPM are diversified, like non-sensitive to magnetic fields, higher gain (10 5 –10 6 ) than standard avalanche photodiodes (APD), good timing properties and compactness. The PET detector should reach approximately 1mm3 spatial resolution together with 60ps FWHM Time-of-Flight resolution and a high efficiency to reduce scanning time and injected dose. A home-made transmit-receive coil surrounding the PET module improves signal-to-noise-ratio (SNR) with respect to standard coils will be present. The system will be used as a MRI-insert and be able to visualize anatomic and metabolic information together. The US-probe is guiding examination for correct overlapping of the multimodal images. This procedure will save time, costs and the need of co-registration. By combining all advantages of each system, it will necessarily update the non-invasive treatment of PCa. The system is adapted and tested to a 3 Tesla MR scanner called Trio A Tim system and Allegra system from the company Siemens healthcare with a larmor frequency of 123.2 MHz and an input of 50 Ω free from artifacts. First results on homogeneity of the transmit-receive coil will be presented. Preliminary measurements showing the proposed device is challenging but feasible.

Improving the accuracy and reproducibility during patient positioning is of paramount importance. Hence, the goal of this work is to characterize the aspects of image blurring occurring during carbon target bremsstrahlung portal imaging and to assess the applicability of a deconvolution algorithm. Blurring effects involved in this method of portal imaging are electron scattering inside the EPID, geometric blurring due to the photon source size and photon scattering inside the patient. These effects can all be described by convolutions using as the convolutional kernel a Lorentz function, whose FWHM is 2λ. The λ values measured for these effects range from 0.2 mm to 0.45 mm, and an iterative 2D-deconvolution of carbon target portal images was performed accordingly. A significant decrease in the image blurring of test objects has been achieved and confirmed by analyzing the RMTF. However for clinical images, the deconvolution method is presently faced with the problem of the associated increase of image noise.

We present an approach for polarization sensitive optical coherence tomography (PS-OCT) that solely requires a modification of the light source, a buffered swept source laser. For this purpose a single-mode fiber-based Fourier domain mode locked laser is extended by fourfold buffering with manual fiber polarization controllers to emit alternating sweep polarizations, while the polarization contrast calibration is realized by a high-speed polarimeter. As the introduced setup utilizes standard scanning and detection units, the proposed method is a promising way to enhance various swept source OCT systems by polarization sensitive imaging. Preliminary measurements of a human finger nail with different polarization contrasts demonstrate the feasibility of the concept.

Medical applications like vascular endoscopy can provide additional diagnostic value for future procedures [1]. For these applications an optimal compromise between image quality and fibre flexibility has to be identified. Image quality of endoscopes is normally estimated using flat test objects or charts. For the application of vascular endoscopy a tubular test set up seems to be more beneficial. We compare three fibre endoscopes with different diameters and number of integrated fibre according to image quality and flexibility. Based on the results a recommendation for possible applications in vascular endoscopy is given.

Incremental innovation, something better or cheaper or more effective, is the standard innovation process for medical product development. Disruptive innovation is often not recognized as disruptive, because it very often starts as a simple and easy alternative to existing products with much reduced features and bad performance. Innovation is the invention multiplied with a commercial use, or in other words something that eventually provides a value to a clinical user or patient. To create such innovation not a technology push (technology delivered from a technical need perspective) but rather a pull (by learning and working with the clinical users) is required. Medical technology students need to understand that only through proper observation, procedure know-how and subsequent analysis and evaluation, clinically relevant and affordable innovation can be generated and possibly subsequently used for entrepreneurial ventures. The dedicated laboratory for innovation, research and entrepreneurship- INNOLAB ego.-INKUBATOR IGT (Image Guided Therapies) is financed by the state of Sachsen-Anhalt as part of the European ego.-INKUBATOR program with (EFRE funds) at the university clinic operated by the technical chair for catheter technologies and image guided surgeries. It forms a network node between medicine, research and economics. It teaches students to lead innovation processes, technology transfer to the user and is designed to stimulate the start-up intentions.

The so-called Laryngeal Adductor Reflex (LAR) protects the respiratory tract from particle intrusion by quickly approximating the vocal folds to close the free glottal space. An impaired LAR may be associated with an increased risk of aspiration and other adverse conditions. To evaluate the integrity of the LAR, we recently developed an endoscopic prototype for LAR triggering by shooting accelerated droplets onto a predefined laryngeal target region. We now modified the existing droplet-dispensing system to adapt the fluid system pressure as well as the valve opening time to user-chosen values autonomously. This has been accomplished using a microcontroller board connected to a pressure sensor and a mechatronic syringe pump. For performance validation, we designed a measurement setup capable of tracking the droplet along a vertical trajectory. In addition to the experimental setup, the influence of parameters such as system pressure and valve opening time on the micro-droplet formation is presented. Further development will enable the physician to adjust the droplet momentum by setting a single input value on the microcontroller-based setup, thus further increasing usability of the diagnostic device.

Cardiac resynchronization therapy with biventricular pacing is an established therapy for heart failure patients with sinus rhythm, reduced left ventricular ejection fraction and electrical ventricular desynchronization. The aim of the study was to evaluate electrical interventricular delay and left ventricular delay in right ventricular pacemaker pacing before upgrading to cardiac resynchronization therapy. Heart failure patients with right ventricular pacing, DDD pacemaker, DDD defibrillator and 24.5 ± 4.9 % left ventricular ejection fraction were measured by surface ECG and transesophageal bipolar left ventricular ECG before upgrading to cardiac resynchronization therapy. Interventricular and intraventricular desynchronization in right ventricular pacemaker pacing were 228.2 ± 44.8ms QRS duration, 86.5 ± 32.8ms interventricular delay and 94.4 ± 23.8ms left ventricular delay. Cardiac resynchronization therapy was optimized by impedance cardiography. Transesophageal electrical interventricular delay and left ventricular delay in right ventricular pacemaker pacing may be additional useful ventricular desynchronization parameters to improve patient selection for upgrading right ventricular pacemaker pacing to cardiac resynchronization therapy.

Noise reduction or denoising is the process of removing noise from a signal. If some signal properties are known linear filtering is often useful. Fourier, wavelet and similar transform approaches remove unwanted signal components in the codomain. For this, predefined eigen-functions, e.g. wavelets, are used. Here we use singular value decomposition in order to compute a signal driven re-presentation (eigendecompositon). By removing unwanted components of the representation the signal can be denoised. We introduce the new method, apply it to signals and discuss its properties.

Automatic relevance determination (ARD) was applied to two-channel EOG recordings for microsleep event (MSE) recognition. 10 s immediately before MSE and also before counterexamples of fatigued, but attentive driving were analysed. Two type of signal features were extracted: the maximum cross correlation (MaxCC) and logarithmic power spectral densities (PSD) averaged in spectral bands of 0.5 Hz width ranging between 0 and 8 Hz. Generalised learn-ing vector quantisation (GRLVQ) was used as ARD method to show the potential of feature reduction. This is compared to support-vector machines (SVM), in which the feature reduction plays a much smaller role. Cross validation yielded mean normalised relevancies of PSD features in the range of 1.6 – 4.9 % and 1.9 – 10.4 % for horizontal and vertical EOG, respectively. MaxCC relevancies were 0.002 – 0.006 % and 0.002 – 0.06 %, respectively. This shows that PSD features of vertical EOG are indispensable, whereas MaxCC can be neglected. Mean classification accuracies were estimated at 86.6±b 1.3 % and 92.3±b 0.2 % for GRLVQ and SVM, respectively. GRLVQ permits objective feature reduction by inclusion of all processing stages, but is not as accurate as SVM.

Invasive electric stimulation of sacral somatic and autonomic outflow is used for treatment of urinary and anorectal functional disturbances and selective monitoring of the autonomic nerve-sparing technique in pelvic surgery, the so called pelvic intraoperative neuromonitoring. The aim of this experimental study was to investigate a less invasive approach for simultaneous stimulation of sacral somatic and autonomic outflow and concomitant recording of feedback. A newly developed multifunctional surface probe for simultaneous transrectal stimulation and electromyography (EMG) of external (EAS) and internal anal sphincter (IAS) was investigated in a consecutive series of six male pigs. The probe (cathode) was designed for intra-anal/-rectal application. An additional surface anode was placed on the animals´ back at the level of the sacrum. Each animal underwent autonomic nerve-sparing low anterior rectal resection. The transrectal stimulations followed a standardized protocol. Further direct stimulation of the surgically exposed pelvic autonomic nerves was carried out with a hand-guided bipolar microfork probe. In all six experiments, the transrectal stimulation resulted in significantly increased EMG signals of the somatically innervated EAS (21.0 μV (interquartile range (IQR): 17.8; 64.4) before stimulation vs. 375.8 μV (IQR: 103.4; 895.9) during stimulation, p = 0.004) and autonomically innervated IAS (35.1 μV (IQR: 27.9; 41.7) before stimulation vs. 1115.7 μV (IQR: 420.1; 2920.3) during stimulation, p = 0.008). Subgroup analysis of the observed IAS EMG signals under transrectal stimulation and hand guided direct stimulation revealed no significant differences between both methods (70.5 μV (IQR: 31.5; 322.7) vs. 320.3 μV (IQR: 204.0; 358.0), p = 0.109). The newly developed multifunctional surface probe enabled successful transrectal stimulation of sacral somatic and autonomic outflow under EMG feedback control. The clinical value of this less invasive approach for the treatment of functional disturbances needs further investigations.

Telemedicine approaches in the treatment of COPD can be useful for the detection of upcoming exacerbations. Specifically productive cough can serve as an effective monitoring parameter. By using modern technologies, we developed a smartphone application to record and analyze nocturnal cough in an outpatient environment. All results will be displayed through a web interface by patients, physicians and relatives. Monitoring cough could lead to an individual therapy and an increased quality of life.

The interest in hybrid systems combining magnetic resonance imaging and medical linear accelerator (MR-Linac) is rapidly increasing due to the clinical availability of different systems. Reference dosimetry is a critical issue for integrating these devices into clinical practice. However, the response of ionization chambers changes according to the distinct orientation of the chamber with respect to the magnetic field. In this study, we have carried out Monte Carlo simulations to identify an optimal orientation for thimble type chambers in MRgRT reference dosimetry. Our findings suggest that an orientation where the chamber axis is parallel to the magnetic field axis should be preferred.

For daily CyberKnife QA a Winston-Lutz-Test (Automated-Quality-Assurance, AQA) is used to determine sub-millimeter deviations in beam delivery accuracy. This test is performed using gafchromic film, an extensive and user-dependent method requiring the use of disposables. We therefore analyzed the usability and accuracy of high-resolution detector arrays. We analyzed a liquid-filled ionization-chamber array (Octavius 1000SRS, PTW, Germany), which has a central resolution of 2.5mm. To test sufficient sensitivity, beam profiles with robot shifts of 0.1mm along the arrays' axes were measured. The detected deviation between the shifted and central profile were compared to the real robot's position. We then compared the results to the SRS-Profiler (SunNuclear, USA) with 4.0mm resolution and to the Nonius (QUART, Germany), a single-line diode detector with 2.8mm resolution. Finally, AQA variance and usability were analyzed performing a number of AQA tests over time, which required the use of specially designed fixtures for each array, and the results were compared to film. Concerning sensitivity, the 1000SRS detected the beam profile shifts with a maximum difference of 0.11mm (mean deviation = 0.03mm) compared to the actual robot shift. The Nonius and SRS-Profiler showed differences of up to 0.15mm and 0.69mm with mean deviation of 0.05mm and 0.18mm, respectively. Analyzing the variation of AQA results over time, the 1000SRS showed a comparable standard deviation to film (0.26mm vs. 0.18mm). The SRS-Profiler and the Nonius showed a standard deviation of 0.16mm and 0.24mm, respectively. The 1000SRS seems to provide equivalent accuracy and sensitivity to the gold standard film when performing daily AQA tests. Compared to other detectors in our study the sensitivity as well as the accuracy of the 1000SRS appears to be superior and more user-friendly. Furthermore, no significant modification of the standard AQA procedure is required when introducing 1000SRS for CyberKnife AQA.

An integrated system of a linear accelerator and a magnetic resonance imaging (MRI) device may provide real-time imaging during radiotherapy treatments. This work investigated changes affecting the dose deposition caused by a magnetic field (B-field) transverse to the beam direction by means of Monte Carlo simulations. Two different phantoms were used: A water phantom (Ph1) and a water-air phantom (Ph2) with a 4-2-4 cm water-air-water cross section. Dose depositions were scored for B-field values of 0 T, 0.35 T, 0.5 T, 1.5 T, 3 T and 5 T. Beams were based on a precalculated photon spectrum taken from an earlier simulated Elekta 6 MV FFF accelerator. All lateral profiles in Ph1 showed a Lorentz force driven shift w.r.t. the B-field strength, presenting a steeper penumbra in the shift's direction. Depositions were shifted up to 0.3 cm for 5 T, showing a constant central axis plateau-dose or an increase by 2.3 % for small fields. Depth-dose curves in Ph1 showed a shift of the dose maximum towards the beam entrance direction for increasing B-field of up to 1.1 cm; the maximum dose was increased by 6.9 %. In Ph2, an asymmetric dose increase by up to 36.9 % was observed for 1.5 T at the water-air boundary, resulting from the electron return effect (ERE). In our scenario, B-field dependent dose shifts and local build-ups were observed, which consequently affect the resulting dose distribution and need to be considered in magnetic resonance guided radiotherapy treatment planning.

An Elekta Synergy LINAC was used to investigate the beam quality index Q and the beam quality correction factor kQ, which is used for absolute dosimetry, in off-axis photon fields. It was found that the beam quality index Q of the photon energies with flattening filter decreases with increasing distance to the central axis, at 6 MV by 4.27% and at 15 MV by 3.98% inside a range of 15 cm off-axis. The beam quality index for flattening filter free photon fields also decreases with increasing distance to the central axis. In this case Q changed only by 1.01% inside the above range.

Electrical Impedance Tomography (EIT) is an imaging technique used for monitoring of ventilation distribution in the lung. Small alternating currents are injected and resulting voltages are measured on the body surface with electrodes fixed around the thorax. Two-dimensional EIT (2D-EIT) is the most common technique in clinical applications but enables visualization of only one horizontal slice of the thorax. However, additional information in the cranio-caudal direction is necessary to more comprehensively assess the ventilation distribution. 3D-EIT systems address this issue, but clinically approved systems are not yet available. The aim of this study is to realize a multi-layer EIT-system with several electrode planes. An approved EIT system functions as basis for this development (PulmoVista 500, Dräger, Lübeck, Germany). Two planes were used for the technical realization of the multi-layer EIT-system. The alternation between the planes was realised using analog switches, which were controlled via a frequency generator and transfer the injected current and the measured voltages between the different electrode planes and the EIT device. The multi-layer EIT-System was applied to a phantom tank for first pilot measurements. Results on the phantom tank with non-conductive targets at different heights reveal that the system is capable of providing information in the cranio-caudal direction. The high frame rates of EIT images combined with the high switching speed of the used analog switches enable real-time acquisition of ventilation at different thoracic planes. Thus, the modified EIT device makes it possible to comprehensively monitor the redistribution of air in the lungs during a breathing cycle, not only in a single plane, but also in the cranio-caudal direction.

The development of an optical sensor for non-invasive measurements in humans requires a test setup, where the optical properties of tissue and blood can be adjusted and measured standardized. The goal of this work is to develop a simplified device based on an integrating sphere setup to evaluate the optical properties of tissue and blood phantoms with respect to static as well as flow conditions. Furthermore, the measurement system is intended to be used at different locations such as laboratories and operating theaters. We evaluate the absorption μ a and reduced scattering μ s ' coefficients of specimens, with the developed integrating sphere setup. The measurement is regulated by a microcontroller for averaging and processing the data. The system is housed in a lightproof box and powered by a battery and therefore transportable. Due to this construction, no calibration is necessary between transports of the system. Calculations are executed with the inverse adding doubling algorithm. In order to basically calibrate and evaluate the setup before first transportation, a dilution series with Intralipid and India ink serve for the test. The results were consistent with precedent studies (mean absolute deviation for μ s ' of 0.75 mm-1) and demonstrate that this method might be able to produce liquids with adjustable optical properties, as required for further research. Furthermore, a first dilution series of heparinized heamoglobin (5 to 15 g/dl) with oxygen saturation of 98 % was measured with this system under flow conditions. We observed a linear increase of μ a and μ s ' with the increment of the haemoglobin concentration. As light sources, laser diodes in the range from 780 to 980 nm were introduced. Static and flow measurements indicated that the system is capable for evaluating optical properties under the selected conditions.

The risk of ventilator induced lung injury in mechanically ventilated (MV) critically ill patients can be mitigated by patient-specific optimisation of ventilator settings. Recent studies have shown that driving pressure, i.e. the difference between plateau pressure ( P plat ) and PEEP, is a strong indicator for survival in MV patients suffering from ARDS. However, to measure P plat , an extended end-inspiratory pause (EIP) has to be applied, possibly interrupting ventilation therapy. This study presents a method for predicting P plat from normal breaths in MV patients. A total of 859 MV breaths with a 5 second EIP were recorded in 27 MV patients with ARDS. Two methods for determining P plat were tested, one using an exponential fit of the pressure data and the other using a four-parameter viscoelastic model (VEM). Each method was identified using various lengths of data after the peak inspiratory pressure (PIP). Using the identified parameters, both methods were then used to predict the P plat recorded at 5 seconds. The exponential method showed a median coefficient of variation (CV) from the real P plat of 42.9% using data from PIP to 0.5 seconds after PIP, 24.9% using 1 second of data and 15.2% using 1.5 seconds of data. The respective VEM prediction median CVs were of 17.2%, 9.7% and 8.4%. Therefore, the VEM showed a better prediction than the non-physiological exponential model, allowing it to be used to reduce the clinical burden of determining P plat by reducing the required length of the EIP to 1.5 seconds.

Clinical observation revealed deformations of the local vasculature due to implanted devices related to treatment of intracranial aneurysms. Pre- and post-interventional image data is reviewed and segmented. Based on Computational Fluid Dynamics (CFD) the effect of the vessel deformation on the intra-aneurysmal hemodynamics is investigated. The simulations incorporate the vessel trees with aneurysm excluding the device itself in order to consider the isolated effect of geometric modifications. As a result, the aneurysm inflow jet is redirected, changing the local flow quantities. Finally, a neck inflow rate reduction of 52.5 % is archived. Thus, a targeted vessel straightening as a novel tool for treatment planning appear to be an idea worth to discuss in the community.

The pressure drop over a pathological vessel section can be used as an important diagnostic indicator. However, it cannot be measured non-invasively. Multiple approaches for pressure reconstruction based on velocity information are available. Regarding in-vivo data introducing uncertainty these approaches may not be robust and therefore validation is required. Within this study, three independent methods to calculate pressure losses from velocity fields were implemented and compared: A three dimensional and a one dimensional method based on the Pressure Poisson Equation (PPE) as well as an approach based on the work-energy equation for incompressible fluids (WERP). In order to evaluate the different approaches, phantoms from pure Computational Fluid Dynamics (CFD) simulations and in-vivo PC-MRI measurements were used. The comparison of all three methods reveals a good agreement with respect to the CFD pressure solutions for simple geometries. However, for more complex geometries all approaches lose accuracy. Hence, this study demonstrates the need for a careful selection of an appropriate pressure reconstruction algorithm.

The obstructive sleep apnoea syndrome (OSAS) is characterized by a collapse of the upper respiratory tract, resulting in a reduction of the blood oxygen- and an increase of the carbon dioxide ( CO 2 ) - concentration, which causes repeated sleep disruptions. The gold standard to treat the OSAS is the continuous positive airway pressure (CPAP) therapy. The continuous pressure keeps the upper airway open and prevents the collapse of the upper respiratory tract and the pharynx. Most of the available CPAP-devices cannot maintain the pressure reference [1]. In this work a model predictive control approach is provided. This control approach has the possibility to include the patient’s breathing effort into the calculation of the control variable. Therefore a patient-individualized control strategy can be developed.

CFD has gained significant attention as a tool to model aortic hemodynamics. However, obtaining accurate patient-specific boundary conditions still poses a major challenge and represents a major source of uncertainties, which are difficult to quantify. This study presents an attempt to quantify these uncertainties by comparing 14 patient-specific simulations of the aorta (reference method), each exhibiting stenosis, against simulations using the same geometries without the branching vessels of the aortic arch (simplified method). Results were evaluated by comparing pressure drop along the aorta, secondary flow degree (SFD) and surface-averaged wall shear stress (WSS) for each patient. The comparison shows little difference in pressure drop between the two methods (simplified-reference) with the mean difference being 1.2 mmHg (standard deviation: 3.0 mmHg). SFD and WSS, however, show striking differences between the methods: SFD downstream of the stenosis is on average 61 % higher in the simplified cases, while WSS is on average 3.0 Pa lower in the simplified cases. Although unphysiological, the comparison of both methods gives an upper bound for the error introduced by uncertainties in branching vessel boundary conditions. For the pressure drop this error appears to be remarkably low, while being unacceptably high for SFD and WSS.

Converting energy from human upper limb motions into electrical energy is a challenge, as low frequency movements have to be converted into repetitive movements to effectively drive electromechanical generators. The prototype of an electromagnetic linear generator with gyrating mass is presented. The mechanical motion model first was simulated and the design was evaluated during different activities. An average power output of about 50 μW was determined with a maximum power output of 2.2 mW that is sufficient to operate sensors for health monitoring.

In this survey we propose a new hybrid simultaneous integrated boost (SIB) delivery method for breast radiotherapy that was implemented in our department of Radiation Oncology. This technique encompasses non-modulated tangential fields as well as VMAT-arcs and combines the robustness and the dose confinement properties of tangential opposed fields with the benefits of a complex VMAT-technique. The results of the dosimetric evaluation indicate that the proposed technique enables a balanced mix between dose coverage, homogeneity and conformity versus the exposure of the organs-at-risks. More precisely, the proposed technique is on par with other recently published SIB techniques for breast radiotherapy.

We simulated a doublet of permanent magnet quadrupoles (PMQs) to estimate the sensitivity on positioning precision and its impact on the spectral properties of transported protons. The study guided the construction and testing of a focusing setup for laser-accelerated proton bunches with energies between 6 and 10 MeV. Our results shed light on possible applications that may arise from broad input particle spectra.

Laser-driven acceleration of particle beams is an emerging modality under research for biomedical applications. The spatially resolved diagnostics of laser-accelerated proton bunches is crucial for their application. The RadEye detector, featuring up to 10 cm x 5 cm area of online complementary metal-oxide-semiconductor (CMOS) detector made of 48 μm pixels, is established for x-ray, proton and ion beam diagnostics. We exploit the usually undesired ‘Image lag’ phenomenon of incomplete pixel reset to generate 2D-images with a larger dynamic range than the single frame range of 12-bit. Using 532 nm laser pulses and computer simulations for single-slit diffraction, calibration factors to stack multiple readouts were successfully derived to quantitatively reconstruct spatial information about an optical beam and hence extend the dynamic range of the detector compared to a single frame. The final goal is focus quantification for a permanent magnet quadrupole system for protons and terawatt (TW-class) laser focus diagnostics.

Background: Despite of the use of tangential beam directions during the irradiation of mammary carcinomas, a dose reduction of the heart cannot always be achieved. This is decivise for the increased risk of heart diseases and the associated mortality. Especially affected is the cardiac apex. However, by using respiratory gated treatment techniques, like the deep inspiration breath-hold (DIBH), a dose sparing of this area can be reached. Material and Methods: The Elekta ABC system was used to control the respiratory stop of early staged breast cancer patients. The treatment planning was implemented by a 3D and VMAT technique. The focus was the optimization of irradiation plans and the evaluation of the respective dose exposure to the heart, the left ventricle and the left anterior descending coronary artery (LAD artery). A planning concept of 28 x 2,25 Gy in the SIB and 28 x 1,8 Gy in the left breast was used. Results: The results showed that a dose reduction of 30-40% in mean and maximal in all structures is possible by using the VMAT technique in combination with the ABC system. In the case of 3D irradiation planning, a substantial relief can only be seen at the mean dose exposure of approximately 50%. Also, only a maximum dose reduction of 13% could be achieved. Conclusion: The mean dose reduction was mainly achieved by the increased distance between the heart and the thorax wall. The maximum dose was reduced by the volumentric optimization algortihm of the VMAT and the resulting steeper dose fall-off at the inner thoracic wall. Due to the lack of this optimization and thus the greater dose drop, the maximum dose of the 3D plans could only reduced by 13%.

The use of coatings based on diamond like carbon (DLC) for medical applications was established during the last years. Main advantages of these coatings are its high hardness, good wear and friction behavior and its biocompatibility. Using low-energy electron-beam treatment, we addressed the surface modification of DLC coatings. The aim was to generate new biofunctional surface characteristics that are long-term stable. Electron-beam modification resulted in significantly increased surface hydrophilicity, giving rise to the conclusion, that biological reaction on these surfaces will also be influenced by the modification. Furthermore, the stability of the surface modification was investigated. Therefore, the modified samples were stored for 8 weeks under ambient conditions. Additionally, the samples were stored in physiological saline solution at 37°C for 8 weeks. The stability of the modification was analyzed by contact angle measurement confirming no changes over the whole period of storage. In addition, the stability against standard cleaning and sterilization procedures was investigated. The durability of the modification to withstand these cleaning procedures was also proven. With these findings, the low-energy electron-beam modification seems to be a suitable tool for surface modification of DLC coatings. Thereby, the very good long-term stability is a great improvement in comparison to conventional surface modification methods like plasma treatment. In order to investigate the suitability of the modified coatings for biomedical applications, the cellular response was investigated using human fibroblasts, revealing a significantly reduced cell count on modified surfaces while maintaining their biocompatibility. By modification of the DLC surfaces, it is possible to adapt the cell adhesion on the treated surface areas. These findings demonstrate electron-beam treatment to be applicable for partial surface modification and functionalization within biomedical applications.

The risk of infection via microbiologically contaminated surfaces has already been demonstrated by other publications. In this work two different antibacterial surface technologies transition metalloacids (AMiSTec) and TiO2/AgNO3 (Health Complete) were compared regarding feasibility as well as their advantages and disadvantages. The examination of the antimicrobial activity was assessed according to the JIS Z 2801. We could demonstrate that all of our tested samples showed a strong antimicrobial activity (>log 3 germ reduction) in the JIS experiments. Furthermore this strong antibacterial effect could be shown already after <30min incubation and at low light intensity (approx. 300 Lux) for the TiO 2 /AgNO 3 samples. Both technologies provide a high potential for an improved infection control for example in a high risk environment like operation rooms or intensive care units.

Wound healing represents a complex biological repair process. Established 2D monolayers and wounding techniques investigate cell migration, but do not represent coordinated multi-cellular systems. We aim to use wound surface area measurements obtained from image acquisition and planimetry systems to establish our wounding technique and in vitro organotypic tissue. These systems will be used in our future wound healing treatment studies to assess the rate of wound closure in response to wound healing treatment with light therapy (photobiomodulation). The image acquisition and planimetry systems were developed, calibrated, and verified to measure wound surface area in vitro. The system consists of a recording system (Sony DSC HX60, 20.4 M Pixel, 1/2.3″ CMOS sensor) and calibrated with 1mm scale paper. Macro photography with an optical zoom magnification of 2:1 achieves sufficient resolution to evaluate the 3mm wound size and healing growth. The camera system was leveled with an aluminum construction to ensure constant distance and orientation of the images. The JPG-format images were processed with a planimetry system in MATLAB. Edge detection enables definition of the wounded area. Wound area can be calculated with surface integrals. To separate the wounded area from the background, the image was filtered in several steps. Agar models, injured through several test persons with different levels of experience, were used as pilot data to test the planimetry software. These image acquisition and planimetry systems support the development of our wound healing research. The reproducibility of our wounding technique can be assessed by the variability in initial wound surface area. Also, wound healing treatment effects can be assessed by the change in rate of wound closure. These techniques represent the foundations of our wound model, wounding technique, and analysis systems in our ongoing studies in wound healing and therapy.

To improve cell vitality, sufficient oxygen supply is an important factor. A deficiency in oxygen is called Hypoxia and can influence for example tumor growth or inflammatory processes. Hypoxia assays are usually performed with the help of animal or static human cell culture models. The main disadvantage of these methods is that the results are hardly transferable to the human physiology. Microfluidic 3D cell cultivation systems for perfused hypoxia assays may overcome this issue since they can mimic the in-vivo situation in the human body much better. Such a Hypoxia-on-a-Chip system was recently developed. The chip system consists of several individually laser-structured layers which are bonded using a hot press or chemical treatment. Oxygen sensing spots are integrated into the system which can be monitored continuously with an optical sensor by means of fluorescence lifetime detection. Hereby presented is the developed hard- and software requiered to control the oxygen content within this microfluidic system. This system forms a closed-loop control system which is parameterized and evaluated.

Hereby a microfluidic system for cell cultivation is presented in which human pluripotent stem cell-derived cardiomyocytes were cultivated under perfusion. Besides micro-perfusion this system is also capable to produce well-defined oxygen contents, apply defined forces and has excellent imaging characteristics. Cardiomyocytes attach to the surface, start spontaneous beating and stay functional for up to 14 days under perfusion. The cell motion was subsequently analysed using an adapted video analysis script to calculate beating rate, beating direction and contraction or relaxation speed.

Novel approaches in regenerative medicine and tissue engineering are highly promoted by human induced pluripotent stem cells. Typical workflows include the expansion, differentiation and/or cryopreservation of these cells. Often, the differentiation, cytotoxicity tests or disease modelling rely on multicellular aggregates. Here, we present the novel bag-based system “Labbag®” to address workflows required for these applications. As a unique feature, the Labbag® provides a chemical spot pattern to allow the formation of several hundreds of hanging droplets within a few seconds with standard laboratory equipment. In this study, we describe the general concept of the Labbag® and show aggregate formation of stem cells as first stem cell workflow successfully transferred.

Implant-based drug delivery necessitates a rigorous quantitative assessment and quality control of the drug release behavior. In this context, a fast simultaneous UV-VIS spectrometer quantification method was developed for an antibiotic dual drug system. Particular challenges arose from interfering spectra, as well as different solubility and stability of the drugs. The test system used here consists of the antibiotics Minocycline and Rifampin, which are used as an antibiotic combination approach in a growing number of device applications, such as impregnation of venous or urethral catheters. Two suitable wavelengths for this test system were identified. At a wavelength of 475 nm only Rifampin shows an absorption maximum, which was used to determine the concentration of Rifampin in the mixture. At 245 nm both antibiotics have a local extremum, a maximum for Minocycline, and a minimum for Rifampin. The developed UV-VIS spectrometer method for Rifampin and Minocycline dissolved in Sörensen buffer showed good results for small concentrations of Minocycline. For stability tests, a mixture of both antibiotics (1:1) was stored at 37°C for up to 144 h in NaCl solution (0.9%), and in Sörensen buffer, respectively. At defined time points, UV-VIS spectra were recorded, and feasibility of this quick simultaneous quantification method for these two widely used antibiotics was demonstrated.

For a long-term efficient drug-eluting stent for vascular applications, the development of drug-loaded coating, combining the effective inhibition of smooth muscle cell proliferation while promoting the re-endothelialization, is a promising concept. However the mostly required simultaneous incorporation of drugs can influence decisively the stability, efficacy and release of the respective drug. Therefore, the mutual influence of a dual local drug delivery coatings based on poly(L-lactide-co-ε-caprolactone) (PLLA-co-CL) containing vascular endothelial growth factor (VEGF 165 ) coupled to the surface and an embedded drug, such as fluorescein diacetate (FDAc) instead of Paclitaxel (PTX) on the in vitro drug release was investigated. Surprisingly, for the investigated coating the immobilized VEGF loading was enhanced and the release profile was accelerated by FDAc incorporation. Even a manifold increase for the in vitro released amounts of VEGF was detected. In contrast, the immobilization of VEGF seems to have a negligible influence on the in vitro FDAc release profiles.

Cartilage tissue is avascular with less regeneration potential and therefore, cartilage regeneration is still a major challenge for therapeutic approaches. Commonly used treatment strategies involve the transplantation of autologous chondrocytes into the defect. Before that, it is required to increase the cell number in vitro resulting in unwanted chondrocyte dedifferentiation. This could impair subsequent tissue regeneration. Both growth factors TGF-ß1 and IGF-1 are used as strong inducer of chondrogenic redifferentiation, however, a controlled application of TGF-ß1 is essential to avoid adverse effects. Therefore, in the present study, we investigated the time-dependent influence of TGF-ß1 administration on chondrocyte redifferentiation. Human chondrocytes were embedded in alginate and cultured in serum-free DMEM containing ascorbic acid, dexamethasone, ITSTM and IGF-1. TGF-β1 was supplemented for 3, 7 and 21 days. Afterwards, cell viability and synthesis of extracellular matrix (ECM) proteins was analyzed by histological staining. Live/dead staining of chondrocytes incubated with TGF-β1 for 21 days displayed an enhanced proliferation and formation of cell clusters resulting in excessive outgrowth of fibroblastic-like cells. However, exposure to TGF-β1 over only 7 days caused also cell clustering with moderate cell proliferation. Additionally, after 21 days of cultivation proteoglycan synthesis was identified by alcian blue staining after both TGF-β1 supplementation for 21 and also 7 days. Aggrecan was also detected in the periphery of the cell clusters after TGF-β1 incubation for only 7 days. Chondrocytes lacked proteoglycan expression after three-day TGF-β1 administration. We could show, that prolonged administration of TGF-β1 results in massive proliferation of chondrocytes which is accompanied by cell outgrowth. We found that TGF-ß1 exposure for seven days is sufficient for achievement of cell clustering without excessive cell proliferation, which is important for inducing subsequent chondrogenic differentiation. Results indicate that even an initial TGF-β1 administration could be sufficient for inducing chondrocyte proliferation and differentiation in vitro .

Fused deposition modeling as an additive manufacturing technique has gained great popularity for the fabrication of medical devices as well as pharmaceutical dosage forms over the last years. Particularly the variety of geometries that can be printed determines the attractiveness of this technique enabling a shape adaption of e.g. implants. In the presented work the soft hydrogel material glycerol gelatin was investigated towards its applicability in 3D-printing as an alternative to the commonly applied and mostly rigid polyesters. Model implants loaded with the model drug quinine and with the shape of a hollow cylinder were printed via an extrusion based technique utilizing the piston feed in a hydrogel filled heatable syringe. Glycerol gelatin hydrogels need to be crosslinked to avoid gel-sol-transition at body temperature. For this purpose three different crosslinking methods (insertion, dipping, spraying) with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) were evaluated regarding their crosslinking efficiency and drug losses during the crosslinking process. Dipping of the implant into an aqueous solution with at least 50 mM EDC and 10 mM NHS was found to be the most efficient crosslinking technique in conjunction with a smaller drug loss during processing compared to inserting. However, the use of hydrogels also causes problems as an intense and highly variable swelling of the printed structures during crosslinking (120.7 % ± 11.9 % for 10 times dipping in 50mM EDC/10 mM NHS) and a great dependency of the volume on storage conditions complicate the preparation of tailor-made implants. The release of the model drug quinine from printed and crosslinked implants was fast and nearly completed within 6 hours.

The Fraunhofer IMS has recently developed a technique for producing nanoelectrodes that are generated by atomic layer deposition (ALD) in a via deep reactive ion etching (DRIE) structured sacrificial layer. This method enables the fabrication of CMOS- and biocompatible nanoelectrodes with suitable ALD-materials. Improvements of the established fabrication processes and the electrochemical characterization of such electrodes are presented. In the frame of the Fraunhofer-Max-Planckcooperation project ZellMOS different types of nanoelectrodes are studied. Their diameter is in the range of 200 nm and thereby sufficiently small to be taken up by living cells. In addition, the electrodes are mechanically enforced by an oxide layer at the nanoelectrodes’ bottom.

Fibrin glue is a two-component adhesive used to stop bleeding, seal wound edges and for scaffolds in tissue engineering. Autologous products result in reduced risk of contamination and immunological responses compared to commercially available fibrin glue. However, reproducibility due to patient dependent sealant properties of autologous fibrin glue preparation is low. In this study a fully automated production process for both the fibrinogen and thrombin component from small blood volumes was developed. The resulting fibrinogen concentration, thrombin activity and sealant properties of the fibrin glue were determined. The fully automated and closed production system proved to be a promising tool for fast and easy production of autologous fibrin glue with an effective adhesive quality.

A precise relative stopping power map of the patient is crucial for accurate particle therapy. Charged particle imaging determines the stopping power either tomographically – particle computed tomography (pCT) – or by combining prior knowledge from particle radiography (pRad) and x-ray CT. Generally, multiple Coulomb scattering limits the spatial resolution. Compared to protons, heavier particles scatter less due to their lower charge/mass ratio. A theoretical framework to predict the most likely trajectory of particles in matter was developed for light ions up to carbon and was found to be the most accurate for helium comparing for fixed initial velocity. To further investigate the potential of helium in particle imaging, helium computed tomography (HeCT) and radiography (HeRad) were studied at the Heidel-berg Ion-Beam Therapy Centre (HIT) using a prototype pCT detector system registering individual particles, originally developed by the U.S. pCT collaboration. Several phantoms were investigated: modules of the Catphan QA phantom for analysis of spatial resolution and achievable stopping power accuracy, a paediatric head phantom (CIRS) and a custom-made phantom comprised of animal meat enclosed in a 2 % agarose mixture representing human tissue. The pCT images were reconstructed applying the CARP iterative reconstruction algorithm. The MTF 10% was investigated using a sharp edge gradient technique. HeRad provides a spatial resolution above that of protons (MTF10 10% =6.07 lp/cm for HeRad versus MTF 10% =3.35 lp/cm for proton radiography). For HeCT, the spatial resolution was limited by the number of projections acquired (90 projections for a full scan). The RSP accuracy for all inserts of the Catphan CTP404 module was found to be 2.5% or better and is subject to further optimisation. In conclusion, helium imaging appears to offer higher spatial resolution compared to proton imaging. In future studies, the advantage of helium imaging compared to other imaging modalities in clinical applications will be further explored.

A current FDA guidance demands the validation of cleaning and disinfecting protocols even for non-sterile medical devices. The aim of this work is to clarify whether this is already possible using the guidance itself as well as the German DIN EN ISO 17664. An angiography system (Artis Zeego / Pheno - Siemens) was selected as a test object for the validation of a cleaning and disinfection protocol for medical devices in a hybrid operating room. In pilot study prior to the trial, critical points of the system were evaluated by means of questionnaires to clinical users (OTA, surgical technicians). An initial assessment of the in-house cleaning protocols used in the hospitals was done by using a fluorescence assay. The microbiological examination took place subsequently by contact plates and swabbing to determine the amount and type of germs on the surfaces of the system. These experiments were done at three different clinical sites. It was found that there was a significant germ count on several surfaces of the product even after in-house cleaning and disinfection (C&D). After application of an enhanced C&D plan, these germs could be greatly reduced at all verified sites. In addition, it could be shown that DIN EN ISO 17664 can in principle be applied to non-sterile medical products.

Healthcare associated infections in surgical procedures have long been the focus of scientific research. In Germany, more than 225,000 patients suffer from such infections each year [1]. However, the reduction of the microbiological contamination is not only limited by cleaning and disinfecting measures. The choice of the ventilation system in the operating room or the type of the clothing of the personnel during the operation is also an important factor contributing to patient safety and infection control. Currently there are different approaches for assessing the hygienic situation in an operating room. In Germany, the air quality and cleanliness is evaluated by the DIN 1946-4: 2008-12 [2] and is based on the measurement of particles in the operating theatre. Other countries i.eSweden. focus on the biological contamination and use microbiological methods for the assessment and surveillance of the operating room ventilation (SIS-TS 39: 2015) [3].

This paper presents initial steps towards an auto-mated analysis for pain-related evoked potentials (PREP) to achieve a higher objectivity and non-biased examination as well as a reduction in the time expended during clinical daily routines. While manually examining, each epoch of an en-semble of stimulus-locked EEG signals, elicited by electrical stimulation of predominantly intra-epidermal small nerve fibers and recorded over the central electrode (Cz), is in-spected for artifacts before calculating the PREP by averag-ing the artifact-free epochs. Afterwards, specific peak-latencies (like the P0-, N1 and P1-latency) are identified as certain extrema in the PREP’s waveform. The proposed automated analysis uses Pearson’s correlation and low-pass differentiation to perform these tasks. To evaluate the auto-mated analysis’ accuracy its results of 232 datasets were compared to the results of the manually performed examina-tion. Results of the automated artifact rejection were compa-rable to the manual examination. Detection of peak-latencies was more heterogeneous, indicating some sensitivity of the detected events upon the criteria used during data examina-tion.

Analyzing directed interactions within brain networks of high spatial resolution is always associated with a limited interpretability due to the high amount of possible connections. Here, module detection algorithms have proven to helpfully subsume the information of the resulting networks for each proband. However, the between-subject comparison of clusters is not straightforward since identified modules are not matched to each other across different subjects. Tensor decomposition has successfully been applied for the detection of group-wide connectivity patterns. Yet, a thorough investigation of the effect of the involved analysis parameters and data properties on decomposition results has still been missing. In this study we filled this gap and found that - given appropriate parameter choices - tensor decomposition of functional connectivity data reveals meaningful, group-specific insights into the brain's information processing.

The main purpose of this work is to propose a new method for characterization and visualization of FHR deceleration episodes in terms of their depth, length and location. This is performed through the estimation of a progressive baseline computed using a median filter allowing to identify and track the evolution of decelerations in cardiotocographic CTG recordings. The proposed method has been analysed using three representative cases of normal and pathological CTG recordings extracted from the CTU-UHB database freely available on the PhysioNet Website. Results show that both the progressive baseline and the parameterized deceleration episodes can describe different time-variant behaviour, whose characteristics and progression can help the observer to discriminate between normal and pathological FHR signal patterns. This opens perspectives for classification of non-reassuring CTG recordings as a sign of foetal acidemia.

Introduction: In radiotherapy, tumors may move due to the patient’s respiration, which decreases treatment accuracy. Some motion mitigation methods require measuring the tumor position during treatment. Current available sensors often suffer from time delays, which degrade the motion mitigation performance. However, the tumor motion is often periodic and continuous, which allows predicting the motion ahead. Method and Materials: A couch tracking system was simulated in MATLAB and five prediction filters selected from literature were implemented and tested on 51 respiration signals (median length: 103 s). The five filters were the linear filter (LF), the local regression (LOESS), the neural network (NN), the support vector regression (SVR), and the wavelet least mean squares (wLMS). The time delay to compensate was 320 ms. The normalized root mean square error (nRMSE) was calculated for all prediction filters and respiration signals. The correlation coefficients between the nRMSE of the prediction filters were computed. Results: The prediction filters were grouped into a low and a high nRMSE group. The low nRMSE group consisted of the LF, the NN, and the wLMS with a median nRMSE of 0.14, 0.15, and 0.14, respectively. The high nRMSE group consisted of the LOESS and the SVR with both a median nRMSE of 0.34. The correlations between the low nRMSE filters were above 0.87 and between the high nRMSE filters it was 0.64. Conclusion: The low nRMSE prediction filters not only have similar median nRMSEs but also similar nRMSEs for the same respiration signals as the high correlation shows. Therefore, good prediction filters perform similarly for identical respiration patterns, which might indicate a minimally achievable nRMSE for a given respiration pattern.

Mapping the effective transverse relaxation time T 2 * represents an emerging MRI tool for non-invasive myocardial tissue characterization and holds the promise to provide means for assessing myocardial (patho)physiology in vivo. This work takes advantage of the linear increase of susceptibility effects with magnetic field strength which renders it appealing to perform T 2 * mapping at ultrahigh magnetic fields and enables temporally resolved T 2 * mapping. Recognizing this potential this study examines the applicability of myocardial CINE T 2 * mapping in healthy volunteers and hypertrophic cardiomyopathy (HCM) patients at 7.0 Tesla and investigates its capability to distinguish between healthy myocardium and myocardium affected by HCM.

Standard pulse oximetry only measures the functional derivatives oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) to calculate the arterial oxygenation. However, the two dysfunctional hemoglobin derivatives carboxyhemoglobin (COHb) and methemoglobin (MetHb) are of much interest. The gold standard detecting abnormal concentration of COHb or MetHb is the blood gas analysis (BGA). In this paper a non-invasive method for measuring these derivatives and a setup for validation is presented. A standard pulse oximeter utilizes a sensor with two LEDs at the wavelengths 660 nm and 905 nm. For achieving information about the other hemoglobin derivatives, the new sensor is equipped with additional wavelengths between 500 nm and 1400 nm. An artificial blood-flow-model is used to simulate the blood flow through tissue. In this model a variation of the concentrations O2Hb, MetHb and COHb is feasible. The reflection of emitted light is measured for wavelengths between 500 nm and 600 nm, whereas transmission is measured for emitted light above 600 nm. An algorithm was designed to calculate the different hemoglobin derivatives independently. Therefore, the perfusion for each wavelength is computed and combined in a linear regression model. An in-vivo animal study with 18 pigs confirmed previous simulations. The pigs were ventilated with a respiratory minute volume of 4 l. To induce hypoxia (minimal SaO2 70 %), the inhaled air was mixed with nitrogen. Ventilating with 100 % oxygen reoxygenated the pigs. An increase of MetHb up to 35 % was induced by sodium nitrite. Afterwards methylene blue decreased the concentration. Carbon monoxide was mixed with the inhaled air to raise the COHb concentration up to 40 %. Different combinations of concentrations were performed. The references were achieved via BGA. It is shown that this setup is capable of measuring COHb, MetHb and O2Hb non-invasively. The setup is accurate even when manipulating hemoglobin derivatives in parallel.

We propose a novel method for the automated formal analysis of on-demand medical device networks communicating via an open communication protocol. The resulting toolbox aims at assisting operators of cross-vendor medical device networks in the complex process of conformity assessment. The method is based on the notion of timed, extended finite automata and employs existent TCTL model checking techniques by use of MATLAB and UPPAAL. We evaluate our methodology in a real-life application similar to a user experience published by the U.S. Food and Drug Admninistration. The method revealed a flaw in the connector design for the Surgical Real Time Bus of the OR.Net project.

Intraoperative neurophysiological monitoring (IONM) can be used to monitor the neural integrity and help the surgeon to reduce iatrogenic patient damage. We present a networked digital assistance system based on real-time IONM data. The system automatically reduces the power of active medical ablation instruments when they endanger neural structures. We integrated a nerve monitor into a real-time network of medical devices. In doing so, neurophysiological signals are available to all connected medical devices in real-time. With the IONM data a so-called function module Neuro Control calculates and controls the maximum allowed power for active instruments like an ultrasonic dissector.

As a by-product of nonlinear amplification in the cochlea, the inner ear emits sound waves in response to two tones with different frequencies. These sound waves are measurable in the ear canal as distortion-product otoacoustic emissions (DPOAEs). DPOAEs putatively consist of two components emerging at different locations in the cochlea. Wave interference between the two components limits the accuracy of DPOAEs as a noninvasive measure of cochlear function. Using short stimulus pulses instead of continuous stimuli, the two DPOAE components can be separated in the time domain due to their different latencies. The present work utilizes a nonlinear hydrodynamic cochlea model to simulate short-pulse DPOAEs in the time domain. When adding irregularities to the mechanical parameters of the model, the simulated DPOAE signals show two distinguishable components and long-lasting beat tones, similar to band-pass filtered experimental data from normal-hearing human subjects. The model results suggest that the beat tones can occur solely due to interference of the coherent-reflection component with the fading nonlinear-distortion component.

Magnetic fluid hyperthermia (MFH) is a promising approach for organ-confined tumor treatment. In MFH, magnetic nanoparticles (MNP) are magnetically targeted at the tumor site and heated in an alternating magnetic field. The heat produced by the MNP is used to cause tumor cell death. At the tumor site, MNP bind to the cell membrane and form agglomerates before they are internalized into the intracellular compartments. Intracellular immobilization and the formation of agglomerates influence heating properties of MNP making it difficult to control the local heating inside the tumor. In this study, we investigated MNP agglomerated samples for their heating efficiency. We found an increase in heating of 22 % upon agglomeration. If MNP are additionally immobilized, however, the heating decreases by 30 %. Consequently, due to the binding of bigger MNP agglomerates at cellular level, heating efficiency inside tumors is assumed to decrease.

Current research shows, that light directly influences the course of the inner biological rhythm. Light synchronizes the biological clock by controlling the concentration of various hormones in the human body. A well-known example is the discharge of melatonine due to increased blue spectral parts in daylight. Light affects the quality of sleep, general performance and even the phenomenon Season Affected Disorder (SAD).

Drug coated balloons (DCB) are used in the therapy of coronary as well as peripheral artery disease. The success of drug transfer to the vessel wall depends on the excipient used in combination with paclitaxel as antiproliferative drug. Although in-vivo studies show very good results with this technology, there is a lack of in-vitro test methods for characterization of various DCB available on the market. This study describes a method to gain information about the drug transfer and the particle release of three different DCB based on cetylpyridinium salycate (Cetpyrsal), hyaluronic acid and iopromide within a porcine in-vitro model. The Cetpyrsal-based DCB showed promising results with the highest drug transfer while producing the lowest number of particles.

Deformable image registration is gradually becoming the tool of choice for motion extraction during adaptive radiotherapy. Achieving a motion vector field that accurately represents the anatomical changes requires a tissue specific transformation model. Therefore, widely used spline based models most likely fail in appropriately reproducing large anatomical changes such as the arms of the patient being positioned up and down. We present the application of a tissue specific biomechanical model with the goal to mimic patient motion even in presence of large motion. Based on the planning CT, delineated bones are used to represent the rigid anatomy of the patient. We implement ball-and-socket joints between corresponding bones in order to achieve mobility of the skeleton. An inverse kinematics approach enables the propagation of motion between individual bones across their joints, leading to an articulated skeleton that can be controlled by feature points on one or more bones. The transformation of each bone initializes a chainmail based soft tissue model to also propagate the motion into the surrounding heterogeneous soft tissue. Representation of different postures like arms up and down can be achieved within less than 1 s for the skeleton and ∼10 s for the soft tissue. Especially for large anatomical changes, the kinematics approach benefits from the direct articulation at specific joints, considerably lowering the degrees of freedom for motion description. Being the input for the chainmail based soft tissue model, the transformed bones guarantee for its meaningful initialization. The proposed biomechanical skeleton model is promising to facilitate the registration of patients’ anatomy, being positioned with arms up and arms down. The results encourage further refinement of the joints and the soft tissue model.

Glioblastoma multiforme is the most frequent and most aggressive malignant brain tumor with de facto no long term curation by the use of current multimodal therapeutic approaches. The efficacy of brachytherapy and enhancing interstitial hyperthermia has been demonstrated. RF heating at ultrahigh fields (B 0 =7.0T, f=298MHz) has the potential of delivering sufficiently large thermal dosage for hyperthermia of relatively large tumor areas. This work focuses on electromagnetic field (EMF) simulations and provides realistic applicator designs tailored for simultaneous RF heating and MRI. Our simulations took advantage of target volumes derived from patient data, and our preliminary results suggest that RF power can be focused to both a small tumor area and a large clinical target volume.

An increasing number of missions in emergency medical services and a progressive utilization rate of emergency physicians also require the use of the benefits of telemedicine in prehospital emergency medicine. Through modern technology, such as the transmission of vital data in real time and a secure audio-visual contact, paramedics can be quickly connected to an experienced emergency physician from a distance and supported in diagnostics and therapy of a patient. This tele-emergency services physician is established in the Aachen emergency service since 2014 and has already had numerous successful missions.

The role of physiological signals has a large impact on driver monitoring systems, since it tells something about the human state. This work addresses the recursive probabilistic inference problem in time-varying linear dynamic systems to incorporate invariance into the task of heart rate estimation from face videos under realistic conditions. The invariance encapsulates motion as well as varying illumination conditions in order to accurately estimate vitality parameters from human faces using conventional camera technology. The solution is based on the canonical state space representation of an Itô process and a Wiener velocity model. Empirical results yield to excellent real-time and estimation performance of heart rates in presence of disturbing factors, like rigid head motion, talking, facial expressions and natural illumination conditions making the process of human state estimation from face videos applicable in a much broader sense, pushing the technology towards advanced driver monitoring systems.

For people with lower limb amputation, a user-specific human-machine interaction with their prostheses is required to ensure safe and comfortable assistance. Especially during dynamic turning manoeuvres, users experience high loads at the stump, which decreases comfort and may lead to long-term tissue damage. Preliminary experiments with users wearing a configurable, passive torsional adaptor indicate increased comfort and safety achieved by adaptation of torsional stiffness and foot alignment. Moreover, the results show that the individual preference regarding both parameters depend on gait situation and individual preference. Hence, measured loads in the structure of the prosthesis and subjective feedback regarding comfort and safety during different turning motions are considered in a user-specific human-machine interaction strategy for a prosthetic shank adaptor. Therefore, the interrelations of gait parameters with optimal configuration are stored in an individual preference-setting matrix. Stiffness and foot alignment are actively adjusted to the optimal parameters by a parallel elastic actuator. Two subjects reported that they experienced appropriate variation of stiffness and foot alignment, a noticeable reduction of load at the stump and that they could turn with less effort.

By 2025, the number of diabetic patients worldwide could rise by more than 50 percent from now 250 million to about 380 million. With about 6 million patients, diabetes mellitus is one of the greatest national diseases in Germany. Type 1 diabetes is a mostly genetically induced autoimmune disease, type 2 diabetes is a civilization disease and arises due to lack of exercise and poor diet. Regardless of the type of diabetes, it is important for those affected to manage their own insulin production of the body and to harmonize these with appropriate possibilities. Because of the harmful side effects of exogenous insulin doses, the major focus should be on a sustainable behavioral change and low-threshold nutritional coaching. The most important side effects of diabetes are damage to the vascular system with possible consequences: myocardial infarction, stroke, kidney weakness, nasal damage and erectile dysfunction. A concept for a knowledge-based expert system for the therapy of diabetes mellitus is presented, in which genetic, anatomical and physiological parameters are recorded, evaluated and visualized by means of a model-based approach to specific therapeutic recommendations. The "user interface" is a digital avatar, which can display the model parameters in various "abstraction levels" as a metamodel.

Systems medicine is a data-oriented approach in research and clinical practice to support study and treatment of complex diseases. It relies on well-defined information management processes providing comprehensive and up to date information as basis for electronic decision support. The authors suggest a three-layer information technology (IT) architecture for systems medicine and a cyclic data management approach including a knowledge base that is dynamically updated by extract, transform, and load (ETL) procedures. Decision support is suggested as case-based and rule-based components. Results are presented via a user interface to acknowledging clinical requirements in terms of time and complexity. The systems medicine application was implemented as a prototype.

The ISO 80369-series replace Luer-connectors in five application areas to fight misconnections. Although the standard avoids the mechanical problem of misconnections, the design of products and packages remains arbitrary. So, packages and products with same functions but different connectors could have similar designs and hence could be mixed-up. To ascertain whether standardization is needed for marking non-distinguishable products and packages, a risk management and usability engineering process were carried out, partly. The ensuing risk analysis created nine unacceptable risks relating to non-distinguishable packages and lookalike-products. Based on this, risk control (standardization) is needed for lookalikes with the following proposed measures: colour allocation and haptic textures for products, colour allocation and symbols for packages. Furthermore, three scenarios were planned for summative evaluation. An additional consideration of the efficiency of proposed combinations of measures and products relying on measures would be helpful.

Assessment of hydrodynamic performance of transcatheter aortic valve prostheses (TAVP) in vitro is es-sentially in the fields of development and approval of novel implants. For the prediction of clinical performance, in vitro testing of TAVP allows for benchmarking of different devic-es, likewise. In addition to the implant itself, also the testing environment has a crucial influence on leaflet dynamics and quantitative test results like effective orifice area (EOA) or aortic regurgitation. Therefore, within the current study we developed simpli-fied physiological and pathophysiological vessel models of the aortic root as a tool for in vitro hydrodynamic testing of TAVP in idealized and worst case conditions. We used 3D printing and silicone cast molding for manufacturing of aortic root models with variable degree of stenosis. Design of aortic roots with normal, mild and severe stenosis was developed according to Reul et al . For manufacturing of tripartite cast-ing molds, a 3D printer was used. Both outer mold parts and the mold core were manufactured from polylactide filament and water soluble polyvinylalcohol filament, respectively. In vitro hydrodynamic performance testing of an exemplary commercially available TAVP implanted in different aortic root models was conducted according to DIN EN ISO 5840-3:2013, using a pulse duplicator system. Manufactured aortic root models were highly transparent, dimensionally stable and therefore suitable for hydrodynamic testing of TAVP. Both, EOA and regurgitant fraction in-creased with increasing degree of stenosis from 1.6 ± 0.1 cm 2 to 1.8 ± 0.1 cm 2 and 8.6 ± 6.5% to 20.2 ± 4.2% ( n = 30 cy-cles), respectively. We successfully developed a testing environment ena-bling sophisticated evaluation of hydrodynamic performance of TAVR in pathophysiological worst case conditions.

Electrical Impedance Tomography (EIT) is a novel medical imaging technology which is expected to give valuable information for the treatment of mechanically ventilated patients as well as for patients with obstructive lung diseases. In lung-EIT electrodes are attached around the thorax to inject small alternating currents and to measure resulting voltages. These voltages depend on the internal conductivity distribution and thus on the amount of air in the lungs. Based on the measured voltages, image reconstruction algorithms are employed to generate tomographic images reflecting the regional ventilation of the lungs. However, the ill-posedness of the reconstruction problem leads to reconstructed images that are severely blurred compared to morphological imaging technologies, such as X-ray computed tomography or Magnetic Resonance Imaging. Thus, a correct identification of the particular ventilation in anatomically assignable units, e.g. lung-lobes, is often hindered. In this study a 3D-FEM model of a human thorax has been used to simulate electrode voltages at different lung conditions. Two electrode planes with 16 electrodes at each layer have been used and different amount of emphysema and mucus plugging was simulated with different severity in the lung lobes. Patient specific morphological information about the lung lobes is used in the image reconstruction process. It is shown that this kind of prior information leads to better reconstructions of the conductivity change in particular lung lobes than in classical image reconstruction approaches, where the anatomy of the patients’ lungs is not considered. Thus, the described approach has the potential to open new and promising applications for EIT. It might be used for diagnosis and disease monitoring for patients with obstructive lung diseases but also in other applications, e.g. during the placement of endobronchial valves in patients with severe emphysema.

The use of optimised CT protocols regarding radiation exposure is a legal requirement. Since low contrast visibility is intrinsically varying within the CT slice, there is no adequate method for optimisation of dose and image quality. We developed a method to access image quality in a way that represents the situation closer to a real patient. This method is based on a novel difference detail curve (DDC) phantom with low contrast objects representing native tissue contrast and contrast media with different densities and diameters. The position of the contrast objects have been evaluated by a noise level analysis of CT slices of different manufactures. The dose – length – product can be measured within the phantom simultaneously. For all tested manu-factures and CT protocols, the noise analysis revealed a similar spatial variation of the signal -to-noise ratio (SNR). For the DDC method, contrast steps of 6 (4-8) Hounsfield Units (HU) are adequate. For the different CT units, comparable low contrast detectability is associated with remarkably varying dose levels (CTDI range from 8 to 18 mGy for native contrast and 9-16 mGy for contrast media). The novel DDC phantom is sensitive to protocol optimisations and therefore suitable for rating subtle effects caused by protocol optimisation.

Video-based smoke detection in laparoscopic surgery has different potential applications, such as the automatic addressing of surgical events associated with the electrocauterization task and the development of automatic smoke removal. In the literature, video-based smoke detection has been studied widely for fire surveillance systems. Nevertheless, the proposed methods are insufficient for smoke detection in laparoscopic videos because they often depend on assumptions which rarely hold in laparoscopic surgery such as static camera. In this paper, ten visual features based on motion, texture and colour of smoke are proposed and evaluated for smoke detection in laparoscopic videos. These features are RGB channels, energy-based feature, texture features based on gray level co-occurrence matrix (GLCM), HSV colour space feature, features based on the detection of moving regions using optical flow and the smoke colour in HSV colour space. These features were tested on four laparoscopic cholecystectomy videos. Experimental observations show that each feature can provide valuable information in performing the smoke detection task. However, each feature has weaknesses to detect the presence of smoke in some cases. By combining all proposed features smoke with high and even low density can be identified robustly and the classification accuracy increases significantly.

During radiotherapy, posture changes and volume changing deformations like growing or shrinking tissue result in anatomical deformations. The basis for investigating the impact of such deformations on dose uncertainties, are model-based tools for deformation analysis. In this context, we propose a transformation model based on the information of CT-images, which allows an on-the-fly calculation of voxel volumes. Our model is based on the concept of the chainmail algorithm and describes deformation on voxel-level. With an exemplary input of a set of landmark pairs, generated by a kinematic head-and-neck skeleton model, CT-images (512x512x126 voxel) can be deformed with an on-the-fly volume calculation in less than 70s. The volume calculation delivers insight into model-characteristic volume changes and is a prerequisite for implementing tissue growth and shrinkage.

Double diffusion encoding (DDE) MRI is a technique in which two diffusion weighted periods are applied between excitation and acquisition. This allows to acquire structural information (as pore size and shape) and molecular exchange between compartments, in terms of apparent exchange rate (AXR). However, it has not been well investigated yet whether the diffusion restriction underlying DDE size estimation may compromise AXR results. Numerical simulations for impermeable spheres have shown that in case of small pores (diameter < 10 μm) the restriction effect may be neglected. Yet, for larger pores, the restriction effect can be relevant and needs to be considered in the analysis of experiments. Here, we present experiments performed on a 3 T clinical MRI system using a water-in-oil emulsion in which no exchange between compartments is expected. The results show that a nonzero apparent exchange rate may be estimated in a sample with impermeable pores. This shows that, as predicted in simulations, the restriction effect affects the AXR results. The use of perpendicular diffusion gradients may be a solution for this problem in isotropic samples.

Accurate optic disc (OD) segmentation and fovea detection in retinal fundus images are crucial for diagnosis in ophthalmology. We propose a robust and broadly applicable algorithm for automated, robust, reliable and consistent fovea detection based on OD segmentation. The OD segmentation is performed with morphological operations and Fuzzy C Means Clustering combined with iterative thresholding on a foreground segmentation. The fovea detection is based on a vessel segmentation via morphological operations and uses the resulting OD segmentation to determine multiple regions of interest. The fovea is determined from the largest, vessel-free candidate region. We have tested the novel method on a total of 190 images from three publicly available databases DRIONS, Drive and HRF. Compared to results of two human experts for DRIONS database, our OD segmentation yielded a dice coefficient of 0.83. Note that missing ground truth and expert variability is an issue. The new scheme achieved an overall success rate of 99.44% for OD detection and an overall success rate of 96.25% for fovea detection, which is superior to state-of-the-art approaches.

Tracking of subviral particles with automated methods enables the analysis of intracellular processes exhibited by viruses. A linear assignment problem solver and a Kalman-filter have been added to an existing particle tracking algorithm. First results produced with simulated image sequences showed that the improved algorithm is able to improve tracking results by closing gaps in the particle’s trajectories. Here we report on the evaluation of the LAP-Kalman algorithm using real fluorescence-microscopic images. The results from the original and improved algorithm have been compared to the results of manual tracking. Evaluation results indicate that the improved algorithm is capable to reconstruct missing parts of particle tracks in difficult conditions. However, the evaluation of the algorithms and the manual tracking is a complex task because of the low image contrast and high object density with intersecting tracks in the live-cell images.

The Origin Ensemble method allows image reconstruction of photon-limited emission tomography data to be performed entirely in the image domain. This offers attractive perspectives such as including scatter events for image reconstruction in Positron Emission Tomography . In this work, the probability of single Compton scatter along a line-of-response is estimated by the Single Scatter Simulation algorithm; for every event a decision is made whether this event is reconstructed along a line or an area confined by two circular arcs holding potential scatter points. First results of 2D simulations show visual agreement with the reference and locally increased contrast recovery coefficient values.

Automation of the image acquisition process via robotic solutions offer a large leap towards resolving ultrasound’s user-dependency. This paper, as part of a larger project aimed to develop a multipurpose 4d-ultrasonic force-sensitive robot for medical applications, focuses on achieving real-time remote visualisation for 4d ultrasound image transfer. This was possible through implementing our software modification on a GE Vivid 7 Dimension workstation, which operates a matrix array probe controlled by a KUKA LBR iiwa 7 7-DOF robotic arm. With the help of robotic positioning and the matrix array probe, fast volumetric imaging of target regions was feasible. By testing ultrasound volumes, which were roughly 880 kB in size, while using gigabit Ethernet connection, a latency of ∼57 ms was achievable for volume transfer between the ultrasound station and a remote client application, which as a result allows a frame count of 17.4 fps. Our modification thus offers for the first time real-time remote visualization, recording and control of 4d ultrasound data, which can be implemented in teleoperation.

We examined if ECG-based features are discrimi-native towards drowsiness. Twenty-five volunteers (19–32 years) completed 7×40 minutes of monotonous overnight driving simulation, designed to induce drowsiness. ECG (512 s-1) was recorded continuously; subjective ratings of drowsiness on the Karolinska sleepiness scale (KSS) were polled every five minutes. ECG recordings were divided into 5-min segments, each associated with the mean of one self- and two observer-KSS ratings. Those mean KSS values were binarized to obtain two classes not drowsy and drowsy . The Q-, R- and T-waves in the recordings were detected; R-peak positions were manually reviewed; the Q- and T-detection method was tested against the manual annotations of Physio-net’s QT database. Power spectral densities of RR intervals (RR-PSD) and quantiles of the empirical distribution of heart-rate corrected QTc intervals were estimated. Support-vector machines and random-holdout cross-validation were used for the estimation of the classification error. Using either RR-PSD or QTc features yielded mean test errors of 79.3 ± 0.3 % and 82.7 ± 0.5 %, respectively. Merging RR and QTc features improved the accuracy to 88.3 ± 0.2 %. QTc intervals of the class drowsy were generally prolonged com-pared to not drowsy . Our findings indicate that the inclusion of QT intervals contribute to the discrimination of driver sleepiness.

It was investigated whether cognitive performance shows a circadian rhythm during a 50 h-long forced desynchrony sleep-wake-schedule. We asked whether it would be possible to estimate the circadian period of cognitive performance under such circumstances and how strong it correlates to subjective sleepiness rating as well as body temperature. Cognitive performance was evaluated using the Bowles-Langley test (BLT), which estimates cognitive performance by capturing reaction time and counting errors in a 2-choice visual search task. Power spectral densities (PSD) were estimated by the Lomb-Scargle periodogram [1]. The circadian period τ c was estimated from peak PSD. PSD of BLT scores showed lowest, yet distinct, circadian amplitude. In addition to the circadian period estimation we analyzed the correlation of the acquired variables against each other. Pearson’s correlation coefficients were significant but varied strongly at a commonly low level. Despite the obstacle of a plethora of influencing factors [2] BLT scores are sensitive to the circadian rhythm and provide correct estimates of τ c compared to rectal body temperature (RBT) as reference. Subjective measures failed estimating τ c .

Wearable accelerometers are lightweight, affordable, and allow for even smaller form factors than 9D inertial measurement units. They are therefore a promising tool for assessing the quality of movement of patients during daily life activities. While generic signal features such as signal power and frequency content are widely used, the derivation of kinematic (angular and spatial) quantities remains a challenge. We consider a chain of body segments, such as the arm, equipped with 3D accelerometers and propose a method for calculation of the inclination and relative height of the distal segment. For validation of the method against an optical motion capture system, we consider a setup with accelerometers on the forearm and the upper arm of a subject, who performs a sequence of drinking motions and pick-and-place motions. We obtain a root-mean-square deviation of about 2.5 cm for the wrist height relative to the shoulder and about 6° for the inclination angles of the forearm. We conclude that the proposed method yields measurements of kinematic quantities that are accurate enough for classification of functional versus non-functional motions or well-performed motions versus incomplete motions.

In the area of care in general but especially in the care of elderly, there is a great interest in deriving patient parameters preparation free. For this purpose, a load cell functionalized nursing bed has been developed at Niederrhein University of Applied Science. The system allows analysis and recognition of the persons’ positions and actions in the bed. The Hidden Markov Toolkit (HTK) based posture recognition system was initially presented at the BMT 2015 by our research group. The initial system shows good results but to draw conclusions about the patient's condition, a minimum possible error rate should be achieved. For this purpose, a two-step retrospective analysis of the initial results was developed as an extension to improve the accuracy of the system. In a first step, the results of the initial recognition are analysed and classified into correct or incorrect results. This is done by means of probability based distance measure. The distances are calculated by the Viterbi algorithm. Based on these distance measures, errors and so called ‘secure support points’ are determined in the recognition result and the associated parameters are extracted. The second part of the extension deals with a retrospective recognition method to improve the error rate of the initial recognition step. Based on the determined support points, the errors are analysed again applying syntactic relation. To this end, a special parameter set to control the recognition system, the so-called ‘syntax’, is generated individually for each erroneous recognition result based on the preceding secure support point. The new parameterized recognition system is then used to improve the initial erroneous results by re-classification. Finally, the corrected recognition results are combined with the preliminary recognition result.

The ability to predict when a person is about to fall asleep is an important challenge in recent biomedical research and has various possible applications. Sleepiness and fatigue are known to increase pupillary fluctuations and the occurrence of eye blinks. In this study, we evaluated the use of the pupil diameter to forecast sleep episodes of short duration (>1s). We conducted multi-channel physiological and pupillometric recordings (diameter, gaze position) in 91 healthy volunteers at rest in supine position. Although they were instructed to keep their eyes open, short sleep episodes were detected in 20 participants (16 males, age: 26.2±5.6 years), 53 events in total. Before each sleep event, pupil size was extracted in a window of 30s (without additional sleep event). Mean pupil diameter and its standard deviation, Shannon entropy and wavelet entropy in the first half (15s) were compared to the second half of the window (15s). Linear and nonlinear measures demonstrated an elevation of pupil size variability before sleep onset. Most obviously, WE and SD increased significantly from 0.054±0.056 and 0.38±0.16 mm to 0.113±0.103 (T(102)=2.44, p<0.001) and 0.46±0.18 mm (T(104)=3.67, p<0.05) in the second half of each analysis window. We were able to identify 83% of the pre-sleep segments by linear discriminant analysis. Although our data was acquired in an experimental condition, it suggests that pupillary unrest might be a suitable predictor of events related to transient sleep or inattentiveness. In the future, we are going to involve the other recorded physiological signals into the analysis.

In recent years, the analysis of the photoplethys-mographic (PPG) pulse waveforms has attracted much research focus. However, the considered signals are primarily recorded at the fingertips, which suffer from reduced peripheral perfusion in situations like hypovolemia or sepsis, rendering waveform analysis infeasible. The ear canal is not affected by cardiovascular centralization and could thus prove to be an ideal alternate measurement site for pulse waveform analysis. Therefore, we developed a novel system that allows for highly accurate photoplethysmographic measurements in the ear canal. We conducted a measurement study in order to assess the signal-to-noise ratio of our developed system Hereby, we achieved a mean SNR of 40.65 dB. Hence, we could show that our system allows for highly accurate PPG recordings in the ear canal facilitating sophisticated pulse waveform analysis. Furthermore, we demonstrated that the pulse decomposition analysis is also applicable to in-ear PPG recordings.

Perfusion computed tomography (CTP) images tumor angiogenesis and can assess tumor aggressiveness. However, the CTP examinations are dose intensive. This study aimed to optimize a routinely used CTP protocol for the head and neck region in oncology in order to reduce the effective dose to the patient and simultaneously achieve the same image quality. The Alderson phantom was scanned on a GE Revolution CT scanner. A scan with our standard protocol for head and neck cancer patients was used (100kV, 80mAs, 5mm slice thickness and backprojection algorithm) and in seven predefined regions (ROI) the signal to noise ratio (SNR) was measured. For the dose optimized protocol, the tube voltage was lowered and the mAs adaptation protocol was used. To improve image quality different percentage of an adaptive statistical iterative reconstruction (ASiR) was applied. For a better resolution we set the slice thickness to 2.5 mm. The mAs adaption range and the percentage of the ASiR reconstruction were varied until we found a combination with the same median SNR in the seven defined ROIs as for our old protocol. For the old and the optimized protocol dose measurements were performed using 25 LiF-TLDs. Organ doses were calculated and the effective dose was determined based on the weighting factors of ICRP103. The optimized scanning protocol used a voltage of 80kV, a mAs range between 15 and 80, a noise level of 10%, and 50% ASiR reconstruction. The median SNR ratio was slightly better (14% better SNR) with the new protocol. An effective dose of 8 mSv was measured with the original protocol and 4 mSv with the optimized scanning protocol. For organs in the scanning field the dose was reduced by a factor of 2 and outside the field by a factor of 2.2. Advanced reconstruction algorithms allow a significant dose reduction and an improvement of image resolution, while maintaining the image quality.

When performing electrocorticography, reliable recordings of bioelectrical signals are essential for signal processing and analysis. The acquisition of cellular electrical activity from the brain surface of mice requires a system that is able to record small signals within a low frequency range. This work presents a recording system with self-developed software and shows the result of a technical characterization in combination with self-developed electrode arrays to measure electrocorticograms of mice.

Magnetic particle spectrometry (MPS) is a novel technique used to measure the magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs). Therefore, it is one of the most important tools for the characterization of the SPIONs for imaging modalities such as magnetic particle imaging (MPI) and Magnetic Resonance Imaging (MRI). In MPS, change in the particle magnetization induces a voltage in a dedicated receive coil. The amplitude of the signal can be very low (ranging from a few nV to 100 μV) depending upon the concentration of the nanoparticles. Hence, the received signal needs to be amplified with a low noise amplifier (LNA). LNA’s paramount task is to amplify the received signal while keeping the noise induced by its own circuitry minimum. In the current research, we purpose modeling, design, and development of a prototyped LNA for MPS. The designed prototype LNA is based on the parallelization technique of Op-amps. The prototyped LNA consists of 16 Op-amps in parallel and is manufactured on a printed circuit board (PCB), with a size of 110.38 mm × 59.46 mm and 234 components. The input noise of the amplifier is approx. 546 pV/√Hz with a noise figure (NF) of approx. 1.4 dB with a receive coil termination. Furthermore, a comparison between the prototyped LNA and a commercially available amplifier is shown.

Alteration of the flow characteristics in coronary vessels is correlated with coronary heart disease (CHD). In particular, wall shear stress (WSS) appears to be a hemody-namic key factor in the genesis of CHD. Since computational fluid dynamics (CFD) is a well-known method for the inves-tigation of WSS, it may be a valuable tool for the prediction of CHD. Latest imaging techniques, such as optical coher-ence tomography (OCT) in conjunction with angiography deliver precise 2D data sets of patient-specific vessel geome-try, which can be used for CFD analysis. Current CFD stud-ies utilize patient-specific geometries, but are lacking well defined physiologic inflow conditions. In this study, we present an inflow mapping method for patient-specific arterial vessels, which is capable of consider-ing the influence of bifurcations located proximal of the OCT-data set. At first, the patient-specific vessel was recon-structed. For this purpose the OCT-based vessel cross sec-tions were arranged along an angiographic based vessel pathway. Secondly, we simulated the flow field in a generic bifurcation model by means of CFD. Thereafter the flow field of a side branch was extracted and transferred (mapped) to the inlet of the patient-specific vessel. To evaluate the influence of the physiological inlet the WSS distribution of the same patient-specific vessel was calculated using an axial-symmetric inflow condition. Analy-sis of the simulation data yielded deviations of the WSS distribution in the proximal vessel segment. A bifurcation, located upstream of the relevant vessel segment strongly affects the flow in the OCT-based vessel reconstruction and has a strong influence on the results of the numerical analy-sis. Therefore, it is important to implement not only the pa-tient-specific geometry, but also an inlet boundary condition adapted to the upstream velocity distribution reflecting the actual proximal flow situation of the vessel.

The clinical performance of an implant, e.g. for the treatment of large bone defects, depends on the implant material, anchorage, surface topography and chemistry, but also on the mechanical properties, like the stiffness. The latter can be adapted by the porosity. Whereas foams show isotropic mechanical properties, digitally modelled scaffolds can be designed with anisotropic behaviour. In this study, we designed and produced 3D scaffolds based on an orthogonal architecture and studied its angle-dependent stiffness. The aim was to produce scaffolds with different orientations of the microarchitecture by selective laser melting and compare the angle-specific mechanical behaviour with an in-silico simulation. The anisotropic characteristics of open-porous implants and technical limitations of the production process were studied.

Fractures or other major bone defects in the mandible are commonly treated by mounting a reconstruction plate at the fracture site. To avoid complications due to loosening of the implant or the fixation screws, electrical stimulation presents a possibility to accelerate bone healing. The aim of this study was to investigate different combinations of activated electrodes and plate designs regarding their feasibility for electrostimulation of the mandibular bone. The electric field distribution for multiple implant designs was computed using the finite element method. The results suggest that the electrode insulation renders a crucial parameter, which influences substantially the stimulation impact and its power consumption.

For the development of a novel, user-friendly and low cost point-of-care diagnostic device for the detection of disease specific biomarker a flow optimised design of the test system has to be investigated. The resulting test system is characterised by a reduced execution period, a reduction of execution steps and an integrated waste management. Based on previous results, the current study focused on the design implementation of the fluidic requirements, e. g. tightness, inside the test device. With the help of fluid flow simulations (CFD – computational fluid dynamics) the flow behaviour inside the test device was analysed for different designs and arrangements. Prototypes generated from additive manufacturing technologies (PolyJet modeling) are used for validating the simulation results and further experimental tests.

The Bauschinger effect is a phenomenon metals show as a result of plastic deformation. After a primary plastic deformation the yield strength in the opposite loading direction decreases. The aim of this study is to investigate if there is a phenomenon similar to Bauschinger effect in thermoplastic polymers for stent application that would influence the mechanical properties of these biodegradable implants. Combined uniaxial tensile with subsequent compression tests as well as conventional compression tests without prior tensile loading were performed using biodegradable polymers for stent application (PLLA and a PLLA based blend). Comparing the results of compression tests with prior tensile loading to the compression-only tests a decrease in compressive strength can be observed for both of the tested materials. The conclusion of the performed experiments is that there is a phenomenon similar to Bauschinger effect not only in metallic materials but also in the examined thermoplastic polymers. The observed reduction of compressive strength as a consequence of prior tensile loading can influence the mechanical behaviour, e.g. the radial strength, of polymeric stents after sustaining a complex load history due to crimping and expansion.

Double diffusion encoding is a magnetic resonance technique with applications in measuring microstructure. In many tissues, cell size (which is of a few micrometers) is an important biological parameter. Estimating an arbitrary pore size distribution from a diffusion attenuated signal usually relies on varying a single experimental setting. This inversion process is numerically unstable. Numerical simulations are presented, where multiple experimental settings are varied concomitantly. The inversion’s results show good agreement with ground truth.

For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses are increasingly used, especially for elderly patients. The current generation of devices is based on xenogenic leaflet material, involving limitations with regard to calcification and durability. Artificial polymeric leaflet-structures re-present a promising approach for improvement of valve performance. Within the current work, finite-element ana-lysis (FEA) design studies of polymeric leaflet structures were conducted. Design of an unpressurized and axially-symmetric trileaflet heart valve was developed based on nine parameters. Physiological pressurization in FEA was specified, based on in vitro hydrodynamic testing of a commercially available heart valve prosthesis. Hyper-elastic constitutive law for polymeric leaflet material was implemented based on experimental stress strain curves resulting from uniaxial tensile and planar shear testing. As a result of FEA, time dependent leaflet deformation of the leaflet structure was calculated. Obtained leaflet dynamics were comparable to in vitro performance of the analyzed prosthesis. As a major design parameter, the lunula angle has demonstrated crucial influence on the performance of the polymeric leaflet structures. FEA represented a useful tool for design of improved polymeric leaflet structures for minimally invasive implantable heart valve prostheses.

The biplanar diode arrays Delta4PT and Delta4+ has been used in our hospital since the introduction of the TomoTherapy in 2013 to ensure a good agreement between the calculated and the measured dose distributions in patient-related QA with helical TomoTherapy. The aim of this presentation is to evaluate the quality of the measurement procedure with the Delta4 phantoms Delta4PT and (since January 2016) Delta4+. This includes the influence of a cross calibration with a treatment plan with low modulation. Two analyses were performed: (i) All treatment plans in a period of three months (n=86) were not only calculated and measured with Delta4PT or Delta4+ but also with an ionization chamber (Exradin A1SL) in the homogeneous “cheese phantom”. (ii) All data measured from January 2016 to April 2017 (Delta4+, n=132) were analyzed regarding median dose deviation, Gamma analysis and others. The comparison with chamber measurements shows that all measurements with Delta4 and almost all with the ionization chambers (79 of 86) yield a deviation of measured vs. planned dose in the PTV of less than 2.5%, but with a lower variation of the Delta4 measurements. However, a strong correlation between both was not observed. The separate analysis of the measurements with the newer Delta4+ (since January 2016) shows a mean dose deviation in the PTVs of only 0.14% with a standard deviation (S.D.) of 0.69%. Before every measurement a cross calibration has been performed. Without this cross calibration, the deviation would be 0.96% with an increased standard deviation of 0.93%. It is concluded that the Delta4 systems are well suited for patient-related QA for helical TomoTherapy treatment plans. The comparison with chamber measurements shows a plausible accordance between both systems whereas the variation of single measurements is quite different. With the help of a daily cross calibration the variability of the Delta4 results is further decreased and the results show higher accuracy and reliability. According to our experience, a daily cross calibration is mandatory for a reliable patient-related QA.

In phase I of the survey a planning intercomparison of patient-related QA was performed at 12 institutions. The participating clinics created phantom based IMRT and VMAT plans which were measured utilizing the ArcCheck diode array. Mobius3D (M3D) was used in phase II. It acts as a secondary dose verification tool for patient-specific QA based on average linac beam data collected by Mobius Medical Systems. All Quasimodo linac plans will be analyzed for the continuation of the intercomparison. We aim to determine if Mobius3D is suited for use with diverse treatment techniques, if beam model customization is needed. Initially we computed first Mobius3D results by transferring all plans from phase I to our Mobius3D server. Because of some larger PTV mean dose differences we checked if output factor customization would be beneficial. We performed measurements and output factor correction to account for discrepancies in reference conditions. Compared to Mobius3D's preconfigured average beam data values, these corrected output factors differed by ±1.5% for field sizes between 7x7cm 2 and 30x30cm 2 and to −3.9% for 3x3cm 2 . Our method of correcting the output factors turns out good congruence to M3D's reference values for these medium field sizes.

Carbon nanotube (CNT) is a new technology used to generate gamma photons in X-ray tubes. CNTs, in comparison to other small X-ray sources, produce high X-ray intensities and as they are not based on a thermionic principle they considered cold electron sources with a very high conversion of electrical to photon energy. Their small size and other interesting properties could make them feasible for use in intraoperative radiation therapy applications. In this study, physical characteristics of the photon beam generated by the CNT-based X-ray source were assessed. A soft X-ray ionization chamber and a flat panel detector was used to measure dose and photon counts, respectively. The repetitively produced pulses had almost the same photon intensities with differences of less than 1% between them. For a typical selected pulse, the variation in the pulse amplitude was also insignificant, which shows a stable radiation exposure of the tube during the ON-mode. When moving from the center of the beam profile to the lateral distance of 25 mm, both intensity profile and dose profile showed a falling trend by a factor of almost 3 in the measured values. We also tested the miniature tube with our novel radiation beam shaping collimator designed for a possible application to treat larynx tumor, which showed the possibility of interventional radiation therapy using this miniature source. An endoscopic camera attached to the system can also make it possible to optically visualize the radiation exposed area. In conclusion, CNT-based X-ray source with suitable attached collimator to shape the beam of the source, seems to provide an opportunity to deliver radiation to a desired tumor area in minimally invasive image guided medical procedures mainly in the normal cavities of the body.

This study investigates differences between treatment plans generated by Ray Tracing (RT) and Monte Carlo (MC) calculation algorithms in homogeneous and heterogeneous body regions. Particularly, we focus on the head and on the thorax, respectively, for robotic stereotactic radiotherapy and radiosurgery with Cyberknife. Radiation plans for tumors located in the head and in the thorax region have been calculated and compared to each other in 47 cases and several tumor types. Assuming MC as the algorithm of highest accuracy it is shown that based on selected dose parameters, RT slightly underestimates the dose in homogeneous regions and overestimates in heterogeneous regions. In addition, deviations occur due to tumor size rendering large differences for small tumors. We conclude that dose prescriptions for radiotherapy treatments should differentiate between RT and MC calculation algorithm. This is especially important for small tumors in heterogeneous body regions.

Objective : For commissioning of source path mo-dels for ring tubes of Nucletron (now Elekta) CT/MR ring applicators, a method was established using a source position simulator (SPS) and a CT scanner. Methods : An acrylic glass support for ring tubes was constructed serving as defined coordinate system. With SPS, 40 positions were set in the ring in steps of 2.5mm from proximal to distal direction. In each position a CT-series was taken with ring plane inside scan plane using a GE Optima 580 scanner (slice width 0.625mm). Evaluation was done in multiplanar recon-struction mode under display settings revealing dummy source shape. With a 3D-cursor dwell position coordinate (center of Ir-192 core) was determined. Measurements were validated by film autoradiography in selected positions. Four rings were investigated: 60° Φ26, 45° Φ26, 60° Φ30, and 45° Φ30 with figures denoting angle between ring plane and stem and ring diameter in mm. Results : The method is feasible to reconstruct source dwell positions with an overall accuracy of ±0.3mm. Detected coordinates are consistent and in excel-lent agreement with those obtained by autoradiography. Comparison with Elekta’s source path models, however, re-vealed mean deviations of up to 3.5mm. Discussion : It is advisable to measure individual source paths and have them added to the data base of the treatment planning system.

A Compton camera prototype for ion beam range monitoring via prompt (< 1 ns) gamma detection in hadron therapy is being developed and characterized at the Medical Physics Department of LMU Munich. The system consists of a large (50x50x30 mm3) monolithic LaBr3(Ce) scintillation crystal as absorber component to detect the multi-MeV Compton scattered photons, together with a stack of 6 double-sided silicon strip detectors (DSSSD) acting as scatterer component. Key ingredient of the γ-source reconstruction is the determination of the γ-ray interaction position in the scintillator, which is read out by a 256-fold segmented multi-anode photomultiplier tube (PMT). From simulations an angular resolution of about 1.5o for the photon source reconstruction can be expected for the energy range around 3 – 5 MeV, provided that a spatial resolution of 3 mm can be reached in the absorbing scintillator [1]. Therefore, particular effort was dedicated to characterize this latter property as a function of the γ-ray energy. Intense, tightly collimated 137 Cs and 60 Co photon sources were used for 2D irradiation scans (step size 0.5 mm) as prerequisite for studying the performance of the “k-Nearest-Neighbors” algorithm developed at TU Delft [2] (together with its variant ”Categorical Average Pattern”, CAP) and extending its applicability into the energy range beyond the original 511 keV. In this paper we present our most recent interaction position analysis in the absorbing scintillator, leading to a considerably improved value for the spatial resolution: systematic studies were performed as a function of the k-NN parameters and the PMT segmentation. A trend of improving spatial resolution with increasing photon energy was confirmed, resulting in the realization of the presently optimum spatial resolution of 2.9(1) mm @1.3 MeV, thus reaching the design specifications of the Compton camera absorber. The specification goal was reached also for a reduced PMT segmentation of 8x8 anode segments (each with 6x6 mm 2 active area), thus allowing to reduce the complexity of the signal processing while preserving the performance.

Imaging in radiation therapy has become an important part of clinical routine. In order to evaluate and compare the image quality of verification images from different imaging modalities, one needs objective criteria like the modulation transfer function (MTF). The aim of our study was to compare the resolution properties of three generations of electronic portal imaging devices (EPIDs), namely one fluoroscopic-optical system and two different flat-panel imaging systems.

This study deals with comparison of conventional and 4D CT (GE Lightspeed) planning on the tumour control probability (TCP), using the TCP model of the AAPM-Report Task Group 166. In the first step a VMAT treatment plan was calculated (Varian Eclipse 13.7) on basis of conventional CT data. This treatment plan was transferred to the complete 4D CT, which represents the tumour volume in motion. Due to the increased volume and the resulting decrease of tumour coverage the TCP went down from 97,6% to 91,2%. After adding an internal target volume (ITV, ICRU 62) to the conventional CT according to our clinical protocols (1,0 cm cc and 0,3 cm axial plane) the TCP increased to 98,0% when applying the conventional plan to the 4D CT. This finding demonstrates the need of 4D CT for moving tumours in chest and abdomen region. Average IPs with increasing width have been created to evaluate the impact on the TCP and the non-malignant tissue. Our observations had shown that heart, lung and spinal cord radiation exposure did not correlate to chosen respiration segment. This could be explained by the extremely slight ratio of the planning target volume and the irradiated normal tissue. This procedure enables us to evaluate the efficacy of treatment plans. Furthermore, optimizing trials like the influence of respiration-gated RT, setting individual margins and fitting planning objectives and parameters are still under investigation.

The response to the synaptic release of γ-Aminobutyric acid (GABA) in the central nervous system is mediated by the GABA B receptor, inter alia dependent on the formation of receptor oligomers. Spatial intensity distribution analysis (SpIDA) is an image analysis method measuring the oligomerization and density of proteins. It was used to quantify the oligomerization of GABA B receptors in the rodent spinal cord under conditions of chronic pain and inflammation. SpIDA reports a lowered density of tetrameric GABA B receptor entities in GABAergic neurons of the dorsal horn under these conditions compared to sham samples. The soma of neurons in the ventral horn is shown to be populated by single entities of the GABA B receptor. The findings underline the role of receptor oligomerization, as well as the membrane environment in regulating receptor function.

Flexible polyimide probes, used for neuronal signal acquisition, are thought to reduce signal deteriorating gliosis, improving the quality of recordings in brain machine interfacing applications. These probes suffer from the disadvantage that they cannot penetrate brain tissue on their own, owing to their limited stiffness and low buckling forces. A microfluidic device as an external micro-drive which aids in the insertion of flexible polyimide neural probes in 0.6% Agarose gel is presented here.

Due to serious side effects of traditional chemotherapeutic treatment, novel treatment techniques like targeted drug delivery, which allows a reduction of the overall dosage of drugs, are investigated. It is worth mentioning that at the same time, precise drug delivery offers an increased dosage of chemotherapeutic drugs in the tumorous area employing the EPR effect. Therefore, vehicles smaller than 400 nm can be used to pass the poorly aligned endothelial cells of tumour vessels passively through their fenestrations. In a subsequent step, the chemotherapeutic drugs need to be released. One possibility is an ultrasound-based release via inertial cavitation. Thereby, it is desirable to restrict the drug release to a narrow range. Thus, the cavitation inducing ultrasound wave has to be focused to that region of interest. Ultrasound frequencies of more than 500 kHz enable sufficient focusing, however, inertial cavitation occurs primarily at much lower frequencies. In order to afford inertial cavitation at 500 kHz, either bigger particles in the range of micrometres are needed as cavitation nucleus, which is not possible due to the EPR effect or high acoustic pressure is needed to generate inertial cavitation. Nevertheless, this high pressure is inappropriate for clinical applications due to thermal and mechanical effects on biological tissue. We have produced Poly-(L)-lactic acid (PLLA) nanoparticles by a solvent evaporation technique that serve as nucleus for inertial cavitation at moderate acoustic pressure of 800 kPa and at high frequencies of 800 kHz after the particles have been freeze-dried. In this contribution, we characterize the designed particles and present the production process. Moreover, we show that these particles enable inertial cavitation at an acoustic pressure and at acoustic frequencies which are commonly used in clinical ultrasound units. We also show that other particles with the same size at the same acoustic parameters do not induce cavitation activity.

Cell-cell and cell-extracellular matrix (ECM) adhesion regulates fundamental cellular functions and is crucial for cell-material contact. Adhesion is influenced by many factors like affinity and specificity of the receptor-ligand interaction or overall ligand concentration and density. To investigate molecular details of cell-ECM and cadherins (cell-cell) interaction in vascular cells functional nanostructured surfaces were used Ligand-functionalized gold nanoparticles (AuNPs) with 6-8 nm diameter, are precisely immobilized on a surface and separated by non-adhesive regions so that individual integrins or cadherins can specifically interact with the ligands on the AuNPs. Using 40 nm and 90 nm distances between the AuNPs and functionalized either with peptide motifs of the extracellular matrix (RGD or REDV) or vascular endothelial-cadherins (VEC), the influence of distance and ligand specificity on spreading and adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) was investigated. We demonstrate that RGD-dependent adhesion of vascular cells is similar to other cell types and that the distance dependence for integrin binding to ECM-peptides is also valid for the REDV motif. VEC-ligands decrease adhesion significantly on the tested ligand distances. These results may be helpful for future improvements in vascular tissue engineering and for development of implant surfaces.

The use of the electrospinning technique is a promising and versatile method for producing fibrous nonwovens from various polymers. Here we present fibre formation via direct electrospinning of a soluble polyimide, a class of polymers that is typically insoluble. In this study solution parameters as the solvent and the polymer concentration are investigated. Furthermore relevant process parameters are varied for optimization of the performance. The presented data indicate polyimide as a promising material for the fabrication of nanofibrous nonwovens via direct electrospinning.

In the last decades PLLA-based copolymers have been among the most attractive polymeric candidates used to fabricate devices for drug delivery and stent applications in the cardiovascular system. PLLA is biocompatible and biodegradable, exhibits a wide range of erosion times and has tunable mechanical properties. Therefore, the influence of drug incorporation on the physicochemical properties of biodegradable PLLA copolymers were examined in this study using Fluorescein diacetate (FDAc) and Paclitaxel (PTX). A percental amount of these drugs (17.5 %) were incorporated into poly(L-lactide-co-glycolide) (P(LLA-co-GA)) and poly(L-lactide-co-ε-caprolactone) (P(LLA-co-CL)) made via spray coating. The polymer surface properties, such as surface morphology and hydrophilicity were also examined and remained rather unchanged for both polymers after drug loadings. Furthermore, also the contact angle changed rather marginally. However, both polymers have already different thermal properties without the drug embedded, especially the glass transition temperature (TG) is for P(LLA-co-CL) under 37°C and for P(LLA-co-GA) considerable above with around 66°C. An rather high increase in TG achieved by addition of FDAc or PTX, crucial influences the drug release profiles for P(LLA-co-CL) in contrast to P(LLA-co-GA). Besides these results preliminarily experiments of additional coupling of other drugs on the polymer surface were performed and we obtained an influence of FDAc or PTX. The drug incorporation and physicochemical characterization data obtained in this study is relevant in optimizing the incorporation or coupling of further drugs on the polymer surface and delivery properties of these potential multi drug delivery coatings.

For the development of intelligent implant systems hydrogels (HG) from crosslinked ionic liquids feature a high potential to be utilised as a drug depot. Biocompatibility of the HGs is one key prerequisite for biomedical applications. HGs were polymerised from a variety of different ionic monomers based on methacrylate, methacrylamide, styrene or vinyl imidazolium derivatives in aqueous solution. N,N'-methylenebisacrylamide was used as crosslinker. CellQuanti-Blue™ Cell Viability Assay Kit was implemented to proof viability of L929 mouse fibroblasts. The predominant part of the HG eluates generated only a marginal reduction of less than 15% cell viability at 100% eluate concentration. This underlines the excellent suitability of these HGs for biomedical applications and revealed some promising candidates for the development of drug depots for implants.

Development of new implant coatings with temperature-controlled drug release to treat infections after device implantation can be triggered by highly elastic hydrogels with adequate stability and adhesive strength in the swollen state. By using an ionic liquid (IL [ViPrIm] + [Br] − ) as additive to N-isopropylacrylamide (NIPAAm) unique effects on volumetric changes and mechanical properties as well as thermoresponsive drug release of the obtained hybrid hydrogels were observed. In this context, rheological measurements allow the monitoring of gelation processes as well as chemical, mechanical, and thermal treatments and effects of additives. Hybrid hydrogels of pNIPAAm and poly (ionic liquid) (PIL) were prepared by radical emulsion polymerization with N,N′-methylenebis(acrylamide) as 3D crosslinking agent. By varying monomer, initiator and crosslinker amounts the multi-compound system during polymerization was monitored by oscillatory time sweep experiments. The time dependence of the storage modulus (G′) and the loss modulus (G″) was measured, whereby the intersection of G′ and G″ indicates the sol-gel transition. Viscoelastic behavior and complex viscosity of crosslinked and non-crosslinked hydrogels were obtained. Within material characterization rheology can be used to determine process capability and optimal working conditions. For biomedical applications complete hydrogelation inter-connecting all compounds can be received providing the possibility to process mechanically stable, swellable implant coatings or wound closures.

Xenogenic leaflet material, bovine and porcine pericardium, is widely used for the fabrication of surgically implanted and transcatheter heart valve prostheses. As a biological material, long term durability of pericardium is limited due to calcification, degeneration and homogeneity. Therefore, polymeric materials represent a promising approach for a next generation of artificial heart valve leaflets with improved durability. Within the current study we analyzed the mechanical performance of polymeric structures based on elastomeric materials. Polymeric cast films were prepared and nonwovens were manufactured in an electrospinning process. Analysis of cyclic stress-strain behavior was performed, using a universal testing machine. The uniaxial cyclic tensile experiments of the elastomeric samples yielded a non-linear elastic response due to viscoelastic behavior with hysteresis. Equilibrium of stress-strain curves was found after a specific number of cycles, for cast films and nonwovens, respectively. In conclusion, preconditioning was found obligatory for the evaluation of the mechanical performance of polymeric materials for the use as artificial leaflet material for heart valve prostheses.

The particle generation of medical implants and drug coated balloons (DCB) is evaluated by simulating the implantation process and collecting the released particle material. In addition to size and particle counts their material composition is of interest. Raman spectroscopy and micros-copy are established methods for chemical identification. For the manual analysis of the particles different filter or rather background materials are suitable because different require-ments in height and intensity of the spectra can be compen-sated by the user. The aim of this study was to find suitable background materials for automatic particle identification. Raman analysis of background and spherical polystyrene standard particles on filters and plain surfaces was performed manually to receive evaluable spectra for automation. Auto-matic analysis was done by a) single-point spectrum meas-urement using the coordinate list of all particles, and b) scan-ning a large sample area pixel by pixel measuring back-ground and particles. For automatic analysis with method a) the polycarbonate membrane provided best results. With method b) the polysty-rene spectrum of the particles could be found on both plain surfaces and the polycarbonate membrane. Influences from the background spectrum could be kept small by thoroughly defining the focal plane with a wavelength specific autofocus mode for method a) and manually for method b).

Thin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting). The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

Aspects and approaches for the design of systems for simultaneous signal and energy transmission for medical implants are presented. The main focus is on the consideration of the mutual influence on both transmission lines. To minimize the influence of capacitive as well as inductive paths, that affect the transmission, reducing the number of components is discussed. In order to increase the degree of miniaturization and reliability, the realization of certain functionalities is based on the so-called parasitics of electrical components. An implementation example is presented.

Recent advancements in implant technology include increasing application of electronic systems in the human body. Hermetic encapsulation of electronic components is necessary, specific implant functions and body environments must be considered. Additional functions such as wireless communication systems require specialized technical solutions for the encapsulation. In this paper 3 different implant strategies based on the material groups silicone, ceramics and titanium alloys are evaluated. With the background of a specific application the requirements for the encapsulation are defined and include the implementation of electrical feedthroughs, wireless communication and wireless energy transfer as well as biomedical specifications such as hermetic sealing, mechanical stability and biocompatibility. The encapsulations are manufactured and qualified experimentally.

The remote determination of vital parameters can contribute to the field of ambient assisted living (AAL) to face the challenges of a steadily ageing society. In this study, we examined the possibility to remotely measure the four vital parameters heart rate, respiration rate, oxygen saturation and blood pressure in AAL environments. For this, we evaluated the state of the art, implementations and concepts. While, the determination of heart and respiration rate is ready for usage, further attention has to be paid to the determination of oxygen saturation and blood pressure.

In the project I-CARE a technical system for tablet devices is developed that captures the personal needs and skills of people with dementia. The system provides activation content such as music videos, biographical photographs and quizzes on various topics of interest to people with dementia, their families and professional caregivers. To adapt the system, the activation content is adjusted to the daily condition of individual users. For this purpose, emotions are automatically detected through facial expressions, motion, and voice. The daily interactions of the users with the tablet devices are documented in log files which can be merged into an event list. In this paper, we propose an advanced format for event lists and a data analysis strategy. A transformation scheme is developed in order to obtain datasets with features and time series for popular methods of data mining. The proposed methods are applied to analysing the interactions of people with dementia with the I-CARE tablet device. We show how the new format of event lists and the innovative transformation scheme can be used to compress the stored data, to identify groups of users, and to model changes of user behaviour. As the I-CARE user studies are still ongoing, simulated benchmark log files are applied to illustrate the data mining strategy. We discuss possible solutions to challenges that appear in the context of I-CARE and that are relevant to a broad range of applications.

The project fast care is working on a real-time capable sensor data analysis-framework in the fields of "Ambient Assisted Living" (AAL), "Human-Technology Interaction" (MTI) and "eHealth". The aim is to provide a medical valid - integrated real-time picture of the patient’s situation by using an ad hoc interconnected sensor – actor infrastructure with a latency period of less than 10 ms.

Main target of fast care is the development of a real-time capable sensor data analysis framework for intelligent assistive systems in the field of Ambient Assisted Living, eHealth, Tele Rehabilitation, and Tele Care. The aim is to provide a medically valid integrated situation model based on a distributed, ad-hoc connected, energy-efficient sensor infrastructure suitable for daily use. The integrated situation model combining physiological, cognitive, and kinematic information about the patient is grounded on the intelligent fusion of heterogeneous sensor data on different levels. The model can serve as a tool for quickly identifying risk and hazards as well as enable medical assistance systems to autonomously intervene in real-time and actively give telemedical feedback.

In this paper we investigate which pulse wave pick-up technologies are well suited for blood pressure trend estimation. We use custom built hardware to acquire electrocardiographic, applanation-tonometric, photo- and impedance-plethysmographic signals during low intensity workouts. Beat-to-beat features and pulse wave runtimes are correlated to the reference arterial blood pressure. Temporal lag adjustment is performed to determine the latency of feature response. Best results are obtained for systolic arterial blood pressure. These suggest that every subject has a range of well-performing features, but it is not consistent among all. Spearman Rho values reach in excess of 0.8, with their significance being validated by p-values lower than 0.01.

The state-of-the-art blood pressure measurement is beside common cuff-based methods the cuff-less estimation of pulse-transit-time, which is the time a blood pressure wave requires to travel from left ventricle of the heart to another peripheral point in the cardiovascular system. Within this work we present a novel estimation method for cuff-less blood pressure measurement by analysing a single photoplethysmographic signal in the frequency domain. The harmonic phase-shift of the fundamental frequency and the first harmonic within the photoplethysmographic signal has proven a strong correlation of r = 0.8514 and r = 0.9315 with systolic and diastolic blood pressure respectively.

Development of preparation-free functionalized furniture based patient monitoring systems for use in the area of home- or stationary- care is often empirically driven. In particular, functionalization of furniture by means of different sensors is strongly affected by this development methodology. As a result, the systems are often not extensive-ly extendable or cannot be optimized because basic mechanisms are not comprehensible. In order to support development or optimization, a modelling approach is often useful. Thus, using a more comprehensive approach the required sensitivity of the sensors as well as their position in the system can be derived from a simulation model. In order to solve this problem, a multi-stage model was introduced at the BMT conference in 2014 by the authors, which allows the designer to model the entire system. The model has been extended and improved in the meantime and the achieved progress is presented in this work. The presented modelling approach can be divided into three main components. These are the person under supervision, the furniture (in our case a nursing bed) and the sensors (force measuring cells) which are modelled separately. In this work the main focus will be on improving the modelling of the human movement process and its implementation. Furthermore, the modelling of the sensor behavior in the nursing bed is described in detail with regard to their oscillation behavior and the influence on the model.

Restoration of hearing is a demanding surgical task which requires the insertion of a cochlear implant electrode array into the inner ear while preserving the delicate basilar membrane inside the cochlea for an atraumatic insertion. Already shortly after the first clinical success with early versions of cochlear implants the desire for a controlled insertion of the electrode array arose. Such a steerable electrode should be in its shape adaptable to the individual path of the helical inner ear in order to avoid any contact between the implant and the surrounding tissue. This article provides a short overview of concepts and actuator mechanisms investigated in the past and present with the objective of developing a steerable electrode array for an individualized insertion process. Although none of these concepts has reached clinical implementation, there are promising experimental results indicating that insertion forces can be reduced up to 60% compared to straight and not steerable electrodes. Finally, related research topics are listed which require considerable further improvements until steerable electrodes will reach clinical applicability.

Biomedical engineering innovations towards the reconstruction of biological functions seek to improve the quality of patients’ lives. The coordinated research project “RESPONSE – Partnership for Innovation in Implant Technology” (BMBF program Twenty20 – Partnership for Innovation, 2014 - 2021) is focusing on the development of novel concepts for (i) cardiovascular scaffolds, glaucoma and ENT stents, (ii) transcatheter heart valves and venous valves, (iii) polymeric implants and polymer/drug formulations. Current clinical paradigm shifts, fostered by the progress in implant technology and a growing global demand, frame the background for the joint research efforts of academia and industry in the RESPONSE consortium.

Computational fluid dynamics (CFD) is a powerful tool to extent knowledge of biomechanical processes in cardiovascular implants. To provide a standardized method the U.S. Food and Drug Administration (FDA) initialized a CFD round robin study. One of the developed benchmark standard models is a generic nozzle geometry, consisting of a cylindrical throat with a conical collector and sudden expansion on either side. Several fluid mechanical data obtained from international institutes by means of CFD and particle image velocimetry (PIV) measurements under different flow regimes ( Re = 500, 2000, 3500, 5000 and 6500) are freely available. This database includes only steady state simulations. In this study we performed pulsatile CFD simulations to consider the physiological environment of the coronary vessels. Furthermore, the nozzle geometry was scaled down to coronary dimension (D inlet = 12 mm to 3 mm) while retaining the average Reynolds number Re = 500 constant. The pulsatile character is described by a Womersley number of Wo = 2.065. Our CFD code was previously validated by using FDA’s data for steady state inflow conditions. It could be shown that time averaged wall shear stress and shear stress values agree well with steady state results. We conclude that steady state simulations are valid for hemodynamic analyses if only time averaged values are needed. This could save computational costs of future hemodynamic investigations. In addition, this study expands FDA’s benchmark case by pulsatile inlet condition for further code validation. This could be necessary for the development of new numerical methods as well as for validation of CFD codes used in the approval process of medical devices.

Glaucoma is the leading cause of irreversible blindness worldwide. An increased intraocular pressure (IOP) is known as major risk factor. Currently, drainage devices that are implanted by means of minimally invasive glaucoma surgery (MIGS) represent a promising approach for IOP low-ering. Commercially available devices for MIGS suffer from unregulated drainage involving ocular hypotony. Further-more, long term drainage capability of current devices is limited by fibrotic encapsulation processes. Therefore, our group focusses on the development of a valved drug-eluting microstent for MIGS. Within the current work, we developed two alternative injector devices for minimally invasive mi-crostent implantation. Both injector devices were based on a cannula in which the microstent is loaded and a mandrel inside the cannula. Injector device A is designed to push the microstent out of the cannula and injector device B is de-signed to withdraw the cannula above the microstent. Manu-facturing of injector devices was conducted using rapid prototyping. Simplified polymeric microstents were manu-factured from polycarbonate based silicone elastomer. Simulated use was performed in a silicone eye model. The presented injector devices were suitable for minimally in-vasive ab interno microstent implantation into suprachoroidal space. Ongoing miniaturization of the microstent system will allow the use of a 22 G cannula in future ex vivo experiments.

A multitude of different applications for magnetic nanoparticles were already investigated. Most prominent are drug delivery, imaging and several diagnostic in-vitro methods. To implement nanotechnological applications into clinics it is advantageous to cover all development stages starting from synthesis over characterization to the production of respective material under quality controlled conditions (cGMP)

For stereotactic irradiation, both, penumbra and MLC leaf width make an impact on the sparing of healthy tissue around the target. Mostly, MLC design is regarded as the one influenceable parameter. However, also penumbra can be varied by choosing different distances between the source of radiation and the patient. The authors investigate the distance- dependent penumbra effects of idealized collimators as well as for real 5 mm MLCs. Test objects are small spherical targets of varying diameters to be irradiated under differing prescription conditions. A method to calculate exact stereotactic radial dose distributions from beam profiles or 2D dose distributions of single beams is developed for circular and MLC shaped targets. Also, a planning study is performed using a Pinnacle3™ planning system. Also, in a theoretical analysis perfect top hat profile beams and beams with varying penumbra are compared for better understanding of penumbra effects with respect to radial dose distributions. It is shown, that the penumbra changes for small targets are more relevant than the beam shaping by 5 mm MLCs. Quasi-isotropic irradiated MLC shaped (quadratic) beams at virtual SAD 700 mm produce steeper radial dose decrease than ideal circular beam shapes with a penumbra typical for SAD 1000 mm. A reduced source-to-patient distance allows better sparing of healthy tissue because of two reasons: The smaller effective leaf width but even more due to steeper penumbra. First, the authors suggest for future recommendations on stereotactic irradiations to specify not only MLC widths but also penumbra characteristics. Second, a so-called “virtual isocentre” could be useful to take advantage of the penumbra effect: Dependent on gantry angle and isocentric couch angle, the couch should be steered automatically in a way that the central axes of all beams always intersect in the same point at the same distance from the source.

With improvements in CT technology, the need for reliable patient-specific dosimetry increased in the recent years. The accuracy of Monte-Carlo simulations for absolute dose estimation is related to scanner specific information on the X-ray spectra of the scanner as well as the form filter geometries and compositions. In this work a mobile measurement setup is developed, which allows both to determine the X-ray spectra and equivalent form filter of a specific scanner from just one helical scan in less than 2 minutes.

OSA is characterized by repetitive collapses of the upper airways during sleep. Computational fluid dynamics can be used to investigate the abnormal pressure distribution in the patient’s airways. The computational costs and model reconstruction effort can be reduced by focusing the simulations on the pharynx and replacing the nasal cavity by a simple pipe structure. In this work, the effects of the mentioned replacement on the simulated flow are evaluated. Airflow simulations using the k-ω turbulence model are performed in the anatomically correct airway of a patient having a high difference in the inspiratory volume flow rates of both nostrils, as well as in a model with replaced nasal cavity by a simple pipe structure. The simulated pressure distributions of both models are in very good agreement indicating the acceptability of replacing the nasal cavity by simple pipe structures in in-silico airflow analyses of OSA patients.

In dentofacial surgery, augmentation procedures employing xenografts have become a reliable treatment. Recent studies, however, have shown significant enhance-ments of the in vivo bone tissue augmentation using mesenchymal stem cells loaded into bone grafts. We conducted experimental and numerical investigations in flow perfusion systems to determine flow conditions which allow for homogenous stem cell distribution in BioOss Block (Geistlich Pharma AG, Switzerland) xenografts. Pressure gradient-velocity characteristics and flow distributions were investigated experimentally and numerically at steady state flow conditions with Reynolds numbers ( Re ) ranging from 0.01 ≤ Re ≤ 0.40. Distilled water at 20°C with a dynamic viscosity of 1.002 mPa.s and a density of 998 kg/m3 was used. The geometry utilized in three-dimensional computa-tional fluid dynamics (CFD) simulation was obtained by means of micro-computed tomography (μCT). Results of CFD analysis are in good accordance with experimental data. The comparison of the pressure gradient-velocity characteris-tics for experimental and numerical data yields a relative error of 3.6%. According to Darcy’s law for creeping fluid flow the experimentally determined permeability is 2.55.10 -9 m 2 . Moreover, numerical flow distribution analysis shows an increasingly heterogenic streamline distribution for increasing Reynolds numbers. Experimentally validated CFD simulations introduced in this study provide a tool to assess optimal flow conditions for a homogenous stem cell distribution in perfusion flow systems.

Today, hybrid systems of linear accelerator and MRI scanner are clinically available. Therefore it is important to investigate the feasibility of reference dosimetry with ionization chambers in the presence of a magnetic field and determine correction factors. In this work, correction factors under various conditions that influence the chamber response were experimentally investigated, using a conventional 6 MV linear accelerator together with a stand-alone magnet. We found that the correction factor for a PTW31010 ionization chamber ranges from 0.9873 to 1.009 depending on the magnetic field strength, magnetic field orientation and magnetic field size. The phantom material also does have an influence on the measured signal. Therefore, reference dosimetry with ionization chambers in the presence of a magnetic field is feasible, but requires dedicated correction factors, which depend on the experimental setup.

We present an automated approach for rating HER2 over-expressions in given whole-slide images of breast cancer histology slides. The slides have a very high resolution and only a small part of it is relevant for the rating. Our approach is based on Convolutional Neural Networks (CNN), which are directly modelling the whole computer vision pipeline, from feature extraction to classification, with a single parameterized model. CNN models have led to a significant breakthrough in a lot of vision applications and showed promising results for medical tasks. However, the required size of training data is still an issue. Our CNN models are pre-trained on a large set of datasets of non-medical images, which prevents over-fitting to the small annotated dataset available in our case. We assume the selection of the probe in the data with just a single mouse click defining a point of interest. This is reasonable especially for slices acquired together with another sample. We sample image patches around the point of interest and obtain bilinear features by passing them through a CNN and encoding the output of the last convolutional layer with its second-order statistics. Our approach ranked second in the Her2 contest held by the University of Warwick achieving 345 points compared to 348 points of the winning team. In addition to pure classification, our approach would also allow for localization of parts of the slice relevant for visual detection of Her2 over-expression.

Automatic relevance determination (ARD) was applied to two-channel EOG recordings for microsleep event (MSE) recognition. 10 s immediately before MSE and also before counterexamples of fatigued, but attentive driving were analysed. Two type of signal features were extracted: the maximum cross correlation (MaxCC) and logarithmic power spectral densities (PSD) averaged in spectral bands of 0.5 Hz width ranging between 0 and 8 Hz. Generalised learn-ing vector quantisation (GRLVQ) was used as ARD method to show the potential of feature reduction. This is compared to support-vector machines (SVM), in which the feature reduction plays a much smaller role. Cross validation yielded mean normalised relevancies of PSD features in the range of 1.6 - 4.9 % and 1.9 - 10.4 % for horizontal and vertical EOG, respectively. MaxCC relevancies were 0.002 - 0.006 % and 0.002 - 0.06 %, respectively. This shows that PSD features of vertical EOG are indispensable, whereas MaxCC can be neglected. Mean classification accuracies were estimated at 86.6±b 1.3 % and 92.3±b 0.2 % for GRLVQ and SVM, respec-tively. GRLVQ permits objective feature reduction by inclu-sion of all processing stages, but is not as accurate as SVM.

Normal Pressure Hydrocephalus (NPH) has become a common disease in the elderly coming along with typical symptoms of dementia, gait ataxia and urinary incontinence, which make the differential diagnosis with other forms of dementia difficult. Furthermore the pathogenesis of NPH is still not understood. About 10% of all demented patients might be suffering from NPH [1]. Many hypotheses suggest that modified biomechanical boundary conditions affect the craniospinal dynamics inducing the pathogenesis of NPH. We present a novel approach for an in-vitro model of the craniospinal system to investigate important hydrodynamic influences on the system such as (dynamic) compliance of the vascular system and especially the spinal subarachnoid space (SAS) as well as reabsorption and hydrostatics. The experimental set-up enables the individual adjustment of relevant parameters for sensitivity analyses regarding the impact of resulting CSF dynamics on the pathogenesis of NPH.

In polysomnography, an oronasal thermal airflow sensor and respiratory inductance plethysmography (RIP) belts at thorax and abdomen are used to detect central sleep apnoea. These sensors are uncomfortable to wear, can disturb the patient’s sleep, and data quality can be significantly di-minished if a sensor slips off the patient. Contactless meas-urements would be a desirable alternative. We utilized a 3D time-of-flight sensor to monitor respiratory-related chest movements to decipher epochs of normal breathing and ap-noea in ten adult patients with a total of 467 apnoea events. Time-synchronized comparisons of 3D measurements of chest movements due to respiration to polysomnography signals from rip belts and nasal airflow proved that the 3D sensor provided largely equivalent results. This new tech-nique could support the diagnosis of central sleep apnoea and Cheyne-Stokes respiration.

Intracardiac electrogram recordings during atrial fibrillation (AFib) are characterized by irregular rhythms and complex morphologies. Hence, analysis in the time domain is a difficult task. The so called dominant frequency DF is a spectrum based approach that aims at finding the most relevant frequency in a signal providing information about the rate and dynamics of AFib. However, in recent years various studies reported controversial results regarding the clinical relevance of the DF . In this work, a definition of the DF at a fundamental scale is proposed as the rate at which action potentials are triggered in atrial cells. The most common method to estimate the DF in literature, labeled as DF Spec , is examined in comparison to the proposed definition. A signal processing study using synthetic signals verified that the DF Spec is stable for all changes in morphology of atrial activations. However, it is also demonstrated that the DF Spec becomes unstable for variations above 20% in the cycle length of a signal. Spectrum based DF estimation should be interpreted in a critical manner and is not advisable for study endpoints or clinical markers.

Recent studies about the development of endocardial radiofrequency (RF) ablation lesions (ALs) tried to identify reliable electrogram (EGM) markers for assessment of lesion transmurality. Additional clinically relevant information for physicians can be provided by examining endocardial EGM parameters like signal morphology, amplitude or time points in the signal. We investigated EGM features of the pulmonary vein ostia before and after RF ablation for three point-shaped lesions. Using high-density (HD) mapping, local activation time (LAT) and voltage maps were created, which provided information about the RF ALs regarding the lesion size and showed activation time delay as well as low-voltage areas with bipolar peak-to-peak voltages smaller than 2mV. The time delay of the depolarization front comparing the activation times anterior and posterior to the RF AL was up to 51.5 ms. In a circular area with 5mm radius around an RF AL the mean peak-to-peak voltage decreased by 62-94% to about 0.12-0.44mV and the mean maximal absolute EGM derivative was reduced by 65-96 %. Comparing the results of this study with EGMs of similar clinical settings confirmed our expectations regarding the low-voltage areas caused by the ablation procedure. An improved understanding of the electrophysiological changes is of fundamental importance to provide more information for enhanced RF ablation assessment.

The Purkinje system is part of the fast-conducting ventricular excitation system. The anatomy of the Purkinje system varies from person to person and imposes a unique excitation pattern on the ventricular myocardium, which defines the morphology of the QRS complex of the ECG to a large degree. While it cannot be imaged in-vivo , it plays an important role for personalizing computer simulations of cardiac electrophysiology. Here, we present a new method to automatically model and customize the Purkinje system based on the measured electrocardiogram (ECG) of a patient. A graphbased algorithm was developed to generate Purkinje systems based on the parameters fibre density, minimal distance from the atrium, conduction velocity, and position and timing of excitation sources mimicking the bundle branches. Based on the resulting stimulation profile, the activation times of the ventricles were calculated using the fast marching approach. Predescribed action potentials and a finite element lead field matrix were employed to obtain surface ECG signals. The root mean square error (RMSE) between the simulated and measured QRS complexes of the ECGs was used as cost function to perform optimization of the Purkinje parameters. One complete evaluation from Purkinje tree generation to the simulated ECG could be computed in about 10 seconds on a standard desktop computer. The measured ECG of the patient used to build the anatomical model was matched via parallel simplex optimization with a remaining RMSE of 4.05 mV in about 16 hours. The approach presented here allows to tailor the structure of the Purkinje system through the measured ECG in a patient-specific way. The computationally efficient implementation facilitates global optimization.

Multimodal imaging is gaining in importance in the field of personalized medicine and can be described as a current trend in medical imaging diagnostics. The segmentation, classification and analysis of tissue structures is essential. The goal of this study is the evaluation of established segmentation methods on different medical image data sets acquired with different diagnostic procedures. Established segmentation methods were implemented using the latest state of the art and applied to medical image data sets. In order to benchmark the segmentation performance quantitatively, medical image data sets were superimposed with artificial Gaussian noise, and the mis-segmentation as a function of the image SNR or CNR was compared to a gold standard. The evaluation of the image segmentation showed that the best results of pixel-based segmentation (< 3%) can be achieved with methods of machine learning, multithreshold and advanced level-set method - even at high artificial noise (SNR< 18). Finally, the complexity of the object geometry and the contrast of the ROI to the surrounding tissue must also be considered to select the best segmentation algorithm.

Cardiac arrhythmias are a widely spread disease in industrialized countries. A common clinical treatment for this disease is radiofrequency ablation (RFA), in which high frequency alternating current creates a lesion on the myocardium. However, the formation of the lesion is not entirely understood. To obtain more information about ablation lesions (ALs) and their electrophysiological properties, we established an in-vitro setup to record electrical activity of rat myocardium. Electrical activity is measured by a circular shaped multielectrode array. This work was focused to gain more information by developing algorithms to process the measured electrical signals to collect different features, which may allow us to characterize an AL. First, pacing artefacts were detected and blanked. Subsequently, data were filtered. Afterwards, activations in atrial signals were detected using a non-linear energy operator (NLEO) and templates of these activations were generated. Finally, we determined different features on each activation in order to evaluate changes of unipolar as well as bipolar electrograms and considered these features before and after ablation. In conclusion, the majority of the signal features delivered significant differences between normal tissue and lesion. Among others, a reduction in peak to peak amplitude and a diminished spectral power in the band 0 to 100 Hz may be useful indicators for AL. These criteria should be verified in future studies with the aim of estimating indirectly the formation of a lesion.

A common treatment of focal ventricular tachycardia is the catheter ablation of triggering sites. They have to be found manually by the physician during an intervention in a catheter lab. Thus, a method for determining the position of the focus automatically is desired. The inverse problem of electrocardiography addresses this problem by reconstructing the source of the ectopic beats using the surface ECG. This problem is ill-posed and therefore needs specific methods for solving it. We propose a machine learning approach for localisation of the ectopic foci in the heart to assist cardiologists with their therapy planning.We simulated 600 120-lead ECGs with different known excitation origins in the heart using a cellular automaton followed by a forward calculation. Features from the ECGs were used as input for a support vector regression (SVR). We assumed a functional relation between features from the ECG and the excitation origin. To benchmark SVR, we also used the well-known Tikhonov 0th order regularisation to reconstruct the transmembrane potentials in the heart and detect the location of the ectopic foci. Parameters for SVR and regularisation were chosen using a grid search minimising the error between estimated and true excitation origin. Compared to the Tikhonov regularisation method, SVR achieved a smaller deviation between estimated and real excitation origin evaluated with 6-fold cross validation. Future work could investigate on the behaviour on data from simulations with other torso and electrophysiological models, the influence of other methods for feature extraction and finally the evaluation with clinical data.

Acquiring adequate mapping data in patients with atrial fibrillation is still one of the main obstacles in the treatment of this atrial arrhythmia. Due to the lack of catheters with both a panoramic field of view and sufficient electrode density for simultaneous mapping, electrophysiologists are forced to fall back on sequential mapping techniques. But, because activation patterns change rapidly during atrial fibrillation, they cannot be mapped sequentially. We propose that mapping tissue properties which are time independent, in contrast, allows a sequential approach. Here, we use the shortest measured electrogram cycle length to estimate the effective refractory period of the underlying tissue in a simulation study. Atrial fibrillation was simulated in a spherical model of the left atrium comprised of regions with varied refractory period. We found that the minimal measured electrogram cycle length correlates with the effective refractory period of the underlying tissue if the regions with distinct refractory properties are large enough and if the absolute difference in effective refractory periods is sufficient. This approach is capable of identifying regions of lowered effective refractory period without the need for cardioversion. Those regions are likely to harbor drivers of atrial fibrillation, which emphasizes the necessity of their localization.

A treatment gap exists for moderately displaced pediatric distal forearm fractures (DFF), which carry a potential risk of improper reduction when treated conservatively. Currently, no standard method for the correction of the initial reduction of pediatric DFF is available. A novel closed reduction method has been proposed to correct and maintain a successful reduction throughout the healing process. This study further develops this novel cast system and evaluates its mechanical behavior through the design, construction, and testing of a biomechanical CAD model and pediatric forearm phantom. Initial results support the novel system as an improved treatment for pediatric fractures. Both the CAD model and tissue phantom indicate the ability of the system to manipulate a 15° fracture, with 0-1° of residual angulation.

Radiofrequency ablation is the gold standard for treating cardiac arrhythmias. However, the success rate of this procedure depends on numerous parameters. Wet lab experiments provide the opportunity to investigate cardiac electrophysiology under reproducible conditions. To evaluate the electrophysiological changes of ablated myocardium in these studies it is necessary to consider the three-dimensional (3D) geometry of the lesions. For this purpose, we investigated the usage of different magnetic resonance imaging (MRI) sequences as well as an image processing procedure to analyze in-vitro preparations. To differentiate signal intensities between nonablated and ablated tissue we evaluated FISP (fast imaging with steady-state precession; delivering dominantly T 1 -weighted images) and RARE (rapid acquisition with relaxation enhancement; delivering dominantly T 2 -weighted images). After image processing, the ablated tissue was segmented in each image slice forming a 3D volume. The geometry of the lesion was modeled by the boundary of this volume. It was generally feasible to distinguish between healthy myocardium and ablated tissue as well as to determine lesion transmurality. The analysis of the reconstructed lesion geometries from FISP and RARE MRI showed a high agreement, however T 2 -weighted sequences showed larger lesion volumes as well as higher variations in segmentation compared to T 1 - mapping. FISP with higher quality may be used to reconstruct the 3D geometry of the ablation lesions.

Camera-based photoplethysmography (cbPPG) is an innovative measuring technique that enables the remote extraction of vital signs using video cameras. Most studies in the field focus on heart rate detection while other physiological quantities are often ignored. In this work, we analyzed the relation between the pulse pressure and the pulsation strengths of cbPPG signals for 70 patients after surgery. Our results show a high correlation between the two measures ( r = 0.54). Furthermore, the influence of technical and medical factors was tested. The controlled impact of these factors proved to enhance the correlation by between 9 and 27 %.

Future fully digital surgical visualization systems enable a wide range of new options. Caused by optomechanical limitations a main disadvantage of today’s surgical microscopes is their incapability of providing arbitrary perspectives to more than two observers. In a fully digital microscopic system, multiple arbitrary views can be generated from a 3D reconstruction. Modern surgical microscopes allow replacing the eyepieces by cameras in order to record stereoscopic videos. A reconstruction from these videos can only contain the amount of detail the recording camera system gathers from the scene. Therefore, covered surfaces can result in a faulty reconstruction for deviating stereoscopic perspectives. By adding cameras recording the object from different angles, additional information of the scene is acquired, allowing to improve the reconstruction. Our approach is to use a fixed four-camera setup as a front-end system to capture enhanced 3D topography of a pseudo-surgical scene. This experimental setup would provide images for the reconstruction algorithms and generation of multiple observing stereo perspectives. The concept of the designed setup is based on the common main objective (CMO) principle of current surgical microscopes. These systems are well established and optically mature. Furthermore, the CMO principle allows a more compact design and a lowered effort in calibration than cameras with separate optics. Behind the CMO four pupils separate the four channels which are recorded by one camera each. The designed system captures an area of approximately 28mm × 28mm with four cameras. Thus, allowing to process images of 6 different stereo perspectives. In order to verify the setup, it is modelled in silico. It can be used in further studies to test algorithms for 3D reconstruction from up to four perspectives and provide information about the impact of additionally recorded perspectives on the enhancement of a reconstruction.

Nowadays, the surgical microscope is the goldstandard for microsurgical procedures. Additional functionalities such as surgical navigation, data injection or imageoverlay are providing additional valuable information to the surgeon. For substituting the conventional optical system by a fully-digital multi-camera setup the three dimensional (3D) reconstruction of the scenery in the field of view is required. However, for in camera-based systems, an exact alignment of the cameras is a challenging task. Therefore, a final adjustment through a digital image rotation becomes necessary. Even though the digital rotation is a commonly used procedure, it leads to unavoidable errors because of the discretized grid of the image. Previous research reported in literature has demonstrated that the method of digitally rotating the images combined with the Fourier interpolation delivers the results of best quality. Nevertheless, the performance evaluation of this algorithm was carried out rotating an image in multiple threestep rotations to a total of 90 or 180 degrees and comparing it to the original image rotated in one step. This is a valid approach because a rotation of 90 or 180 degrees does not produce rotation artifacts. In this research project, we verify the performance of the three-step rotation algorithm using recorded images for which the test pattern was rotated as ground truth. A series of photographs with a rotation angle of 3 to 45 degrees was created. The advantage of this setup is that the result of the digital rotation can be directly compared to the recorded image. In addition, with the knowledge obtained about the interpolation error, we can improve pixel matching in the further triangulation used for 3D reconstruction. By doing so, the estimation of the interpolation error helps to reduce the triangulation error.

This paper presents the design of implantable electronics as a part of a system for prosthetic hand control. Purpose of the implant is the sensing of electrical signals originating from biological tissue and the actuation of the same, therefore closing the loop and allowing for an improved control of the prosthetic hand. The implant contains two integrated circuits for eight channel EMG monitoring and four channel stimulation, respectively. An on-board microcontroller allows for local pre-processing. All intracorporeal to extracorporeal communications are running through and are directed by the main processing platform. The external components of the control system include, in addition to the main processing and control platform, the inductive power transfer circuits and the pressure sensors for the sensory feedback. Different assembly and encapsulation options are taken into account for the implantable electronics and are unified in a single PCB design.

Lung ventilation and perfusion analyses using chest imaging methods require a correct segmentation of the lung to offer anatomical landmarks for the physiological data. An automatic segmentation approach simplifies and accelerates the analysis. However, the segmentation of the lungs has shown to be difficult if collapsed areas are present that tend to share similar gray values with surrounding non-pulmonary tissue. Our goal was to develop an automatic segmentation algorithm that is able to approximate dorsal lung boundaries even if alveolar collapse is present in the dependent lung areas adjacent to the pleura. Computed tomography data acquired in five supine pigs with injured lungs were used for this purpose. First, healthy lung tissue was segmented using a standard 3D region growing algorithm. Further, the bones in the chest wall surrounding the lungs were segmented to find the contact points of ribs and pleura. Artificial boundaries of the dorsal lung were set by spline interpolation through these contact points. Segmentation masks of the entire lung including the collapsed regions were created by combining the splines with the segmentation masks of the healthy lung tissue through multiple morphological operations. The automatically segmented images were then evaluated by comparing them to manual segmentations and determining the Dice similarity coefficients (DSC) as a similarity measure. The developed method was able to accurately segment the lungs including the collapsed regions (DSCs over 0.96).

In this paper, we present a method for locating and tracking players in the game of squash using Gaussian mixture model background subtraction and agglomerative contour clustering from a calibrated single camera view. Furthermore, we describe a method for player re-identification after near total occlusion, based on stored color- and region-descriptors. For camera calibration, no additional pattern is needed, as the squash court itself can serve as a 3D calibration object. In order to exclude non-rally situations from motion analysis, we further classify each video frame into game phases using a multilayer perceptron. By considering a player’s position as well as the current game phase we are able to visualize player-individual motion patterns expressed as court coverage using pseudo colored heat-maps. In total, we analyzed two matches (six games, 1:28h) of high quality commercial videos used in sports broadcasting and compute high resolution (1cm per pixel) heat-maps. 130184 manually labeled frames (game phases and player identification) show an identification correctness of 79.28±8.99% (mean±std). Game phase classification is correct in 60.87±7.62% and the heat-map visualization correctness is 72.47±7.27%.