AV III
Artificial Vision III
Topic: Machine Learning and Model Based Approaches
Room: Room 6 "Zoo Duisburg" (Location: Meeting Room 6)
Chairs: Paul Werginz and John PezarisTue
26 Sep
08:30 - 10:00
Submissions:
1
08:30 - 08:45
Introduction
Sensory encoding converts information from sensors into stimulation parameters of sensory prostheses. In visual implants, one key aspect of image encoding is to downsample the images captured by a camera to match the specifics of implantable neural interfaces. Although several studies developed image encoding pipelines, the natural transformation occurring within the retina is generally not considered.Methods
We utilized a learning-based approach with a neural network for the optimization of the downsampling process. The model consists of an actor-network prepended to a forward-network, both of which are convolution neural networks. The forward-network acts as the digital twin of a biological retina which we used to optimize the actor-network. We first train the forward-network using experimental data of retinal ganglion cells' response to projected images. Then we train the actor-network to downsample a given image in a way that, when presented to a retinal, elicits a neuronal response similar to that of a high-resolution image.Results
Here we show that with a learning-based approach accounting for the retinal image transformation, our model could distil pertinent features of effective downsampling. Compared with the performance of a learning-free approach like pixel-space averaging, our proposed method generated higher neuronal reliability validated both in-silico and ex-vivo. These results indicate that our method generates downsampled images which elicit a neuronal response more similar to the high-resolution images. We also reveal contrast as a crucial feature for effective downsampling.Conclusion
The implications of our research are far-reaching and we anticipate our method will serve as a guide for future image encoding research to account for biological processes using a learning-based image encoding approach. Ultimately, this study holds promise in aiding the advancement of retinal prosthesis, bringing us closer to a future where retinal prosthesis can help restore vision to those who have lost it.
Mr. Franklin Leong
EPFL
#visual prosthetics #sensory encoding #image encoding #Artificial Neural Network #Convolutional neural network #machine learning
2
08:45 - 09:00
Introduction
The resolution of the electrode array in retinal implants is a bottleneck in the signal transmission pipeline from the camera to the brain. To address this issue, we applied an inverse model as a preprocessing step before transmitting signals to the electrode array. We investigated the performance of a neural network-based inverse model as the encoder in a retinal implant. Our rationale for this study is that downsampling input images to the resolution of the electrode array does not construct an inverse function, which in theory is the optimal encoder.
Methods
Using two psychophysically validated computational models, scoreboard and axon-map, we generated percepts from images (or stimulations, which are the current signals on the electrode array) from the MNIST dataset and two randomly generated datasets of continuous values and ternary values {0, 0.5, 1}, respectively. Ideally, the percept should be identical with the input image. With this assumption, the convolutional neural network-based inverse model, which was trained from stimulations to percepts, received the original image as input and generated the encoded stimulation signals on the electrode array as output during inference. The loss function used was the pixel-wise mean squared error (MSE).Results
We evaluated the reconstruction performance between the normalized input image and the predicted percept using MSE on the test set. With the scoreboard model, we achieved MSEs of 0.016 and 0.009 using a 3-level and a 5-level U-Net, respectively. With the axon-map model, we achieved MSEs of 0.0013 and 0.0005 using a 2-block and a 4-block VGG, respectively.Conclusion
Our results suggest that the convolutional neural network-based inverse encoder is feasible for optimizing the retinal prosthetic stimulation signals on the electrode array with different datasets, both visually and numerically.Mr. Yuli Wu
RWTH Aachen University
#retinal implant #Convolutional neural network
3
09:00 - 09:15
Introduction
In future electronic retinal implants, the selective stimulation of specific Retinal Ganglion Cell (RGC) subclasses will be of great importance to mimic the natural response of neurons to light. To be able to determine the selectivity success of the stimulation, a robust cell-type classification of evoked spiking activity is required. To achieve this, a deep learning neural network approach is used.Methods
To ensure a robust classification, a sufficient amount of recorded light stimulation responses is required as training data for the neural network. This data, which is already labeled with the respective cell-type class, was acquired from the "RGC Typology Database", which is available at rgctypes.org. The dataset was split into ON-/OFF-clusters to ensure a homogeneous spike distribution within the respective recording, having a standardised length of 1 second. Afterwards a fully connected deep learning model was trained using the raw neural spike train recording as its input and the matching cell-type as its output.Results
It was determined that the most effective configuration for this task was a neural network incorporating three hidden layers, utilising the ReLU activation function for the hidden layers and the SoftMax function for the output layer. A dropout rate of 10% was used to prevent overfitting. Using this configuration, a correct classification rate of 92% could be reached on average for a broader distinction into functional cell classes (ON/OFF, transient/sustained, DS). Applying a specific distinction into the respective subtypes (n = 42), an average accuracy of 72% could be reached.Conclusion
Neural networks are a powerful tool for the classification of contained cell-types within raw neural recordings. For 1 second spike trains a satisfying accuracy could be reached, enabling this approach to be used for closed-loop retinal stimulation systems. Future trainings will focus on single spike classifications and the hardware integration of the resulting model.Mr. Philipp Löhler
University of Duisburg-Essen
#neural network #Artificial Intelligence #rgc spikes #closed-loop stimulator
4
09:15 - 09:30
Introduction
Optic nerve stimulation has the potential to produce visual perceptions spanning the whole visual field, providing thus a valuable alternative to retinal and cortical stimulation. Nonetheless, the produced phosphenes are very elongated and it is difficult to organize them into meaningful perceptions. Automatic optimization of stimulation based on biophysically-accurate computational models would allow to explore in an efficient way the large space of stimulation parameters, but its use is limited by the complexity of said models. Here, we propose how to substitute biophysically-accurate models with machine learning-based surrogate models to enable stimulation optimization.
Methods
We propose to predict the firing rate of optic nerve fibers under the independent electrical stimulation from multiple stimulating sites using machine learning. Specifically, we compare support vector machines, multilayer perceptrons, random forests, and more recent machine learning algorithms like XGBoost and LightGBM in terms of accuracy and speed of prediction. Finally, we propose cascading a classifier to predict recruitment with a regressor to find the firing rate of recruited fibers.Results
We find that random forest-based methods excel both in terms of accuracy and speed of prediction (LightGBM, RMSE for active fibers: 6.27 Hz, RMSE for inactive fibers: 3.00 Hz). The goodness of predictions is further improved on inactive fibers cascading a classifier and a regressor (LightGBM classifier then regressor, RMSE for active fibers: 6.44 Hz, RMSE for inactive fibers: 1.80 Hz). The use of such methods increases the speed of prediction of several orders of magnitudes with respect to traditional models (0.2 s for 25,000 samples), and enables the in silico optimization of stimulation parameters in an automatic way in a simplified model of optic nerve stimulation.
Conclusion
Machine learning-based surrogate models allow to accurately predict the firing rates of optic nerve fibers and can replace traditional models enabling automatic, model-based optimization of electrical stimulation parameter.Mr. Simone Romeni
#optic nerve #electrical stimulation #machine learning #firing rate
5
09:30 - 09:45
Introduction
Serious eye diseases significantly impact the lives of those affected. Eye correction devices and surgical procedures have been developed to address these challenges. However, these do not provide a definite solution for severe eye conditions such as glaucoma. Instead, cortical prostheses have possible solutions. These aim to restore vision by stimulating the visual cortex because stimulation in the cortex produces phosphenes, and thus the vision of light flashes within the visual field. This abstract discusses our progress in developing our custom vision prosthetic system to restore partial vision where the patient can recognize objects by boundaries.Methods
Our design comprises four modules, 1) headset, 2) subcutaneous control unit, and 3) optogenetic probes driven by 4) our custom ASIC design. The headset with a camera captures incoming visuals (images at a defined framerate) for bio-inspired processing and powers the control unit using wireless power transmission. The processed visuals are then sent (in a compressed form) to the control unit using Bluetooth Low-Energy (BLE). This unit therefore embodies the BLE module, a low-power microcontroller (MCU) and a wireless power receiver with dedicated power management.Results
The MCU first decompresses these images and then based on the contents of each image dynamically reconstructs the frame map used to drive the ASIC and then the probes. This is done to be sure that the probes operate with an even power distribution to avoid excessive current damage to the tissues. Finally, the control unit transmits the generated frame map to the ASIC, which controls the probes blinking (temporally and spatially) to stimulate the nerves, drives LEDs for optogenetic stimulation, drives electrodes to recording, resulting in closed-loop control.Conclusion
Preliminary experimental results show that the processed images, which reduce the instantaneous peak power by 30-50%, are ready to be tested in a future controlled environment.Mr. Yu Liu
School of Engineering, Newcastle University
#Visual prosthesis #Image processing #Control system
Tue
26 Sep
10:15 - 12:00
AV IV
Artificial Vision IV
Topic: Preclinical data on stimulation and new devices
Room: Room 6 "Zoo Duisburg" (Location: Meeting Room 6)
Chairs: Takeshi Morimoto and Sandra JohnenSubmissions:
1
10:15 - 10:30
Introduction
In treatment of blindness causing retinal dystrophies i.e., Retinitis pigmentosa (RP) retinal implants showed promising results. In recent years, larger devices restoring a greater field of vision were introduced. With larger size, implantation became more difficult. In this study, a novel implantation device was developed, fabricated, and tested in ex-vivo implantation surgeries in porcine & rabbit eyes. The goal was to demonstrate a reproducible, safe, and compared to current methodology, superior implantation method.Methods
3D design software was used for design, modeling, and fabrication. Anatomical dimensions of rabbit, pig and human eyes were collected from anatomical and histological data sources. The 3D-printed large-array port system (3D-PLAPS) was fabricated using 3D printing. Implantation surgery was performed on cadaveric porcine as well as rabbit eyes. 3D-PLAPS was tested for implantation of a large-array epiretinal stimulator, developed by this group. A standardized ophthalmologic surgical procedure was established. Intraocular pressure was measured at different time points during surgery.Results
3D PLAPS was manufactured with a length of 9.0 mm and adapted to the curvature of an emmetropic human eye with a diameter of 24.0 mm. The elliptically shaped aperture is 7.0 mm long and 1.0 mm wide at its widest points. Apertures for scleral fixation were added. Further, a sealing plug closing the central aperture was introduced. In ex-vivo experiments, 3D-PLAPS improved the stability of the eye, sealed the incision, and withstand increased intraocular pressures during surgery. It is suitable for foldable retinal stimulators up to 14.0 mm and up to 7.0 mm in diameter in non-foldable state, respectively.Conclusion
The new implantation device proves to be feasible for implantation of large epiretinal stimulators. The newly established implantation methodology will be tested in further in-vivo experiments.The project is funded by the Research Training Group 2610/1 of the German Research Foundation (DFG).
Mr. Frederic Balcewicz
RWTH Aachen University, University Hospital
#retinal implants #retinal prostheses #ophthalmologic surgery #implantation device #port system #3D-printing #medical engineering #vitreoretinal surgery
2
10:30 - 10:45
Introduction
Retinitis pigmentosa (RP) is a class of inherited disorders caused by the progressive death of photoreceptors in the retina, for which treatments remain limited. Retinal prostheses are a therapeutic approach to restore vision for RP patients, which rely on an intact and organized visual pathway. Alterations of anatomy and function along the visual pathways from the retina to the visual cortex upon blindness are well studied. However, little is known about plasticity on a molecular level.Methods
The Royal College of Surgeons (RCS) rats were used as the retinal degeneration model for this study. Along the process of retinal degeneration, experiments were conducted at P30 (30 days), P50, 3M (3 months), 6M, and 12M of age. Optomotor response was tested to track the visual performance of the RCS rats. We further analyzed the receptor density of GABAAR, mGluR5, and 5-HTR2A, as they were implicated in cortical plasticity, by the specific binding of selective radioligands [3H] Flumazenil, [3H] ABP-688 and [3H] MDL100907, respectively, on brain slices.Results
In RCS rats at P30 and P50, scotopic and photopic vision were comparable to wild-type rats. Scotopic vision was initially completely lost in 6M RCS rats with some detectable photopic vision at contrast 1. This high contrast photopic vision was subsequently completely impaired at 12M. A transient increase of 30% of GABAAR density was found in the superior colliculus of RCS rats at P50, compared with wild-type rats, but not in the visual cortex. The GABAAR density in RCS rats dropped to a normal level at 3M. No difference was found in the receptor density of mGluR5 and 5-HT2AR between RCS and wild-type rats.Conclusion
Scotopic and photopic vision were completely impaired in 6M and 12M RCS rats, respectively. A transient increase in GABAAR density was found in the superior colliculus of RCS rats at P50.
Ms. Jing Wang
Institute of Neuroscience and Medicine (INM-4)
Forschungszentrum Jülich
#retinitis pigmentosa #cortex plasticity #visual cortex #receptors #metabolites #RCS rat
3
10:45 - 11:00
Introduction
Artificial vision to treat retinitis pigmentosa is based on directly stimulating surviving retinal cells to create visual perceptions. However, retinal degeneration is associated with remodeling processes, which impair the efficacy of artificial vision. Gene therapy is a promising approach to treating retinal diseases. Our aim is to develop an efficient and safe gene therapy to counteract the process and effects of retinal remodeling. We have analyzed non-viral Sleeping Beauty (SB) transposon-based gene transfer into degenerated retinas using electroporation.Methods
Different stages of rd10 mouse retinas (P25 to P180) and age-matched wild-type (WT) retinas (C57BL/6J) were electroporated with the SB100X transposase plasmid and the pT2-CAGGS-Venus transposon plasmid using NEPA21 electroporator. Transfection efficiency was assessed by fluorescence microscopy one day after incubation. Retinal integrity and transfected cell types were evaluated and identified by hematoxylin & eosin and immunofluorescence staining, respectively. Fluorescein isothiocyanate-dextran (FITC-dextran, 4 kDa) was used to further investigate the electroporation effect.Results
The ideal electroporation settings were: 10 V (voltage), 5 ms (length), 50 ms (interval), 2 (number), 10% (decay rate), +/- (polarity) for the poring pulse; 10 V (voltage), 50 ms (length), 50 ms (interval), 5 (number), 40% (decay rate), +/- (polarity) for the transfer pulse. Transfection efficiency was improved using 0.1 µg/µl plasmid mixture with Opti-MEM electroporation buffer. Retinas from rd10 mice older than P61 were easily transfected. Thickness and number of retinal cell layers were maintained under the optimal electroporation parameters. The transfected cells were Müller cells. Retinas from young rd10 (P25) and WT mice were difficult to transfect; however, FITC-dextran was able to enter both young rd10 and WT retinal cells after electroporation.Conclusion
This non-viral electroporation-based gene transfer enables distinct transfection in degenerated rd10 retinas. Increased Müller cell transfection might be due to hypertrophy of Müller cell endfeet during the process of retinal remodeling in rd10 mice.Ms. Jiao Zhang
RWTH Aachen University
#Retinal degeneration #Retinal remodeling #Gene therapy #Electroporation
4
11:00 - 11:15
Introduction
Retinopathia pigmentosa is an inherited retinal dystrophy that leads to blindness. Previous retinal prostheses have had limited efficacy, in part because the remaining retinal layers remodel as the disease progresses. In recent years, gene therapy has emerged as a promising approach to treat genetic disorders. Currently, viral vectors are the main method for gene transfer; however, they also have drawbacks. Here, the non-viral Sleeping Beauty (SB) transposon system was used to transfer the genes encoding yellow-fluorescent protein, pigment epithelium-derived factor (PEDF), and brain-derived neurotrophic factor (BDNF) by electroporation, resulting in stable integration into the cell genome.Methods
The SB100X transposase plasmid and the corresponding transposon plasmid (1:16 ratio, 420 ng/µl) were introduced into the glioblastoma cell line A-172. Two electroporation devices were used: a capillary-based system for cells in suspension and a system for adherent cells. Transfection efficiency, transgene expression, and cell viability were assessed by flow cytometry, ELISA, qPCR, and a luminescence assay.Results
The best transfection efficiency (62.4%) for cells in suspension was achieved at 1100 V, 30 ms, and 2 pulses. Increasing the voltage resulted in higher transfection efficiency but lower cell viability. An increase in PEDF/BDNF transgene expression and protein secretion was observed compared to non-transfected cells. For transfection of adherent cells, voltages of 125 V to 275 V were used. A poring and a transfer pulse (+ or +/- polarity) were applied. The best efficiency (4 %) was observed with a poring pulse with + polarity and a transfer pulse with +/- polarity at 200 V for 5 ms.Conclusion
Transfection of cells in suspension resulted in higher efficiencies than adherent cells, which might be due to a better distribution of the electric field. Nevertheless, transfection of adherent cells helps in further development of intraocular chips with a dual function of electroporation and stimulation.Mr. Saishreyas Iyer
Uniklinik RWTH Aachen (RTG 2610 InnoRetVision)
#non-viral #Electroporation #transfection #retinitis pigmentosa #cell suspension #cells on surfaces #Sleeping Beauty #SB100X #PEDF #BDNF
5
11:15 - 11:30
Introduction
Retinal prostheses have shown the restoration of a coarse form of vision in patients affected by retinitis pigmentosa, such as letters discrimination and object recognition. However, despite some progress in retinal prosthetics, several challenges remain open.Methods
POLYRETINA device exploits photovoltaic wireless stimulation to overcome these challenges. For the preclinical validation of the POLYRETINA prostheses we used blind Göttingen minipigs.Results
We generated a model of retinal blindness by intravenous injection of iodoacetic acid (IAA) in Göttingen minipigs. Anatomical and physiological alterations were verified using in-vivo spectral-domain optical coherence tomography (SD-OCT), in-vivo evoked electroretinograms (fERGs) and flash visual evoked cortical potentials (fVEP), and postmortem histological assays. Then, we developed a minimally invasive injection procedure to insert the large epiretinal implant into the eye through a 6.5-mm long corneal incision. The epiretinal fixation was achieved using two custom-made stainless-steel retinal tacks. Postoperative echography images showed that POLYRETINA matched the eye curvature with tight adhesion to the retina.Then, we showed that POLYRETINA restores light-evoked cortical responses at safe irradiance levels in blind Göttingen minipigs unilaterally implanted. We recorded flash electrical evoked potentials (fEEPs) to demonstrate the recovery of light responses in implanted blind Göttingen minipigs. Electrophysiological recordings were performed acutely before (fVEPs) and after (fEEP) POLYRETINA implantation. Recordings before surgery showed no detectable fVEPs induced by light. After POLYRETINA implantation, fEEPs were recovered. Last, postmortem histological assays showed a low level of acute immune response compared to normal minipigs (2 weeks after implantation). The level of immune response was comparable to unimplanted minipigs but treated with IAA. We concluded that POLYRETINA does not worsen the inflammatory state caused by degeneration.
Conclusion
These results indicate that POLYRETINA holds the potential for artificial vision in totally blind patients affected by retinitis pigmentosa.Mr. Dr. Diego Ghezzi
Hôpital ophtalmique Jules-Gonin - Fondation Asile des Aveugles
#Retinal implants #Photovoltaic stimulation #retinal prostheses
6
11:30 - 11:45
Introduction
Throughout the last decades, researchers worldwide have been trying to artificially restore vision in blind patients affected by retinal degenerative diseases. Our group has been pushing forward a new generation of retinal implants: Flexible bidirectional microelectrode arrays (BiMEAs), penetrating the retinal tissue for simultaneous recording and stimulation. With the aim of in-vivo trials in mind, this work presents the in-vitro and cadaveric validation of 3D retinal implants.Methods
Flexible implants are fabricated using thin-film technology and surface micromachining processes. Experiments were carried out with healthy wildtype (WT) rats, and additionally with diseased RCS rats as a model for retinitis pigmentosa. An Open-Sky approach and pars-plana implantation were tested in a cadaveric setting as surgical methods. Resistivity measurements at the implantation site are used to prove successful insertions.Results
3D flexible implants were successfully tested in ex-planted in-vitro WT and RCS retinae to prove their recording and stimulating feasibility. The resistivity values were mapped to electrophysiological recordings showing spontaneous activity when the electrode was close to the ganglion cell layer and no activity when placed at deeper locations. The resistivity values peak at the OPL/ ONL layer with values of 1.68 +/- 0.12 for RCS and 2.89 +/- 0.15 W m (mean +/- SEM) for WT rats. In cadaveric rats and rabbits, the feasibility of an open-sky and pars-plana surgical approach were tested using the resistivity measurements to demonstrate the implantation depth.Conclusion
Proving the surgical implantation by resistivity measurements in cadaveric settings for healthy and diseased retinae paves the way for future in-vivo validation with 3D retinal implants.Ms. Marie Jung
Research Center Jülich
#Retinal implants #Neural implants
7
11:45 - 12:00
In the rd10 mouse model, an intrinsic oscillatory activity is observed at a frequency of 3-6Hz in the local field potential and retinal ganglion cell (RGC) firing that compromises the efficiency of electrical stimulation. It was suggested that the loss of photoreceptor-mediated glutamatergic input causes depolarization of ON cone bipolar cells and through electrical coupling, also of AII amacrine cells (AII), allowing the activation of voltage-gated Na+ channels and oscillations. As oscillations compromise the stimulation efficiency, in this study, we seek to identify approaches to abolish oscillations.
Methods:
In vitro recordings from retinas of 5-6 months old C57BL/6J wild-type (wt) and rd10 mice were obtained using multi electrode arrays. The effect of different pharmacological drugs on the oscillatory activity was determined.
Results:
Blocking excitatory ionotropic glutamate receptors or decoupling gap junctions abolished oscillations. However, both methods reduced RGC spiking, indicating that RGCs might be less excitable. The inhibitory neurotransmitters GABA and glycine also abolished oscillations, probably by shifting the AII membrane potential to a range that does not allow oscillations.
Oscillations were abolished by activating specifically GABAA receptors using benzodiazepines and THIP, but not by targeting GABAB receptors or by increasing the GABA concentration in the synapse by blocking either GABA re-uptake or GABA catabolism.
Conclusion:
Our data indicate that the activation of GABAA receptors abolishes oscillations. Clinically approved GABAA receptor agonists like benzodiazepines would be suitable candidates to improve stimulation efficiency of a retinal implant.
Ms. Nruthyathi Nruthyathi
Forschungszentrum Jülich,
Jülich, Germany 52428
#Retinal degeneration #Retinal implants #pathological oscillations #rd10
Tue
26 Sep
10:00 - 10:15
Break
Tue
26 Sep
11:45 - 12:45
Break
Break + YoungNet "Lunch with Leaders"
Chairperson for YoungNet "Lunch with Leaders"
Ms Lena Hegel
Ms Lena Hegel
Room: Lobby 2 (Location: Lobby 2)
Chair: Lena HegelTue
26 Sep
13:45 - 15:15
AV V
Artificial Vision V
Topic: Effects of Novel Stimulation Protocols
Room: Room 6 "Zoo Duisburg" (Location: Meeting Room 6)
Chairs: Günther Zeck and Shelley FriedSubmissions:
1
13:45 - 14:00
Introduction
Phosphenes in electrically-based visual prostheses are created from microstimulation to individual contacts in electrodes implanted in the visual pathway so as to bypass the impaired site and provide restoration of function. Objects are conveyed through patterns of stimulation driven by images from the external world, subject to device designs that can, for example, limit the number of simultaneously activated electrodes. In this experiment, we investigate the effect of temporal skew of individual phosphenes on perception in a simulation of artificial vision, with quantitative measurements made through a reading task. We hypothesized that synchronously presented phosphenes will result in higher performance than asynchronous phosphenes.Methods
We had normal, sighted subjects perform a simple reading task based on the MNREAD test of visual acuity, viewed through a high-performance simulation of artificial vision. Sentences in the task were presented at varying font sizes (1.1–1.4 logMAR) to measure reading performance under different levels of phosphene temporal noise.Results
Phosphene temporal noise significantly affected reading performance: higher levels of asynchrony created lower reading scores. A significant negative impact on reading scores was also observed for an overall increase in phosphene latency.Conclusion
Text perception, and by extension, object binding, is optimized with synchronously presented phosphenes, and degrades with increasing levels of asynchrony. Our observations are important for the design of effective stimulation patterns required for high-fidelity artificial vision.Mr. Dr. John Pezaris
Massachusetts General Hospital, Harvard Medical School
#visual prosthesis #timing #electrical stimulation
2
14:00 - 14:15
Introduction
Retinitis pigmentosa (RP) comprises a group of inherited retinal diseases associated with progressive visual loss. Currently, there is no standard treatment available. To preserve or restore vision, gene-replacement therapies, stem cell therapies, optogenetic therapies and electronic implants are under development. An alternative treatment route is neuroprotective therapy using transcorneal electrical stimulation (TcES). In an exploratory analysis, the hypothesis of a current-strength dependent slowing of loss of visual field area (VFA) by TcES was tested (Stett et al., Trans. Vis. Sci. Tech. 2023).Methods
The data for the a posteriori analysis come from a study conducted at the University of Tübingen from 2011 to 2014 (Schatz et al., IOVS, 2017). In the randomised controlled trial (clinicaltrials.gov: NCT01837901), 52 RP patients were monocularly stimulated with biphasic current pulses (pulse duration 5ms/5ms, amplitudes 0.0 to 1.0 mA, 20 Hz) with the OkuStim system once a week for one year. In the reanalysis the percentage reduction in VFA (measured with semi-automatic kinetic perimetry) at the end of treatment was compared with the untreated contralateral eyes and correlated with current amplitude.Results
After one year, the TcES-treated eyes had a mean VFA loss of 2.1%, while the untreated contralateral eyes had lost 5.8% and the placebo-treated eyes had lost 7.5%. Thus, the loss of VFA was 64 % less in the stimulated eyes than in the untreated contralateral eyes (p = 0.013) and 72% less than in the placebo-treated eyes (p = 0.103). The slowing effect correlated linearly with current amplitude (p = 0.047), and the visual field was stable on average in patients receiving 0.8 - 1.0 mA.Conclusion
TcES is an electroceutical that can slow down the progressive VFA loss in RP. Further studies are needed to confirm its long-term effectiveness and to elucidate the neuroprotective mechanism of action of TcES treatment.Mr. Dr. Alfred Stett
Okuvision GmbH
#retinitis pigmentosa #Retinal degeneration #neuroprotection #transcorneal electrical stimulation #visual field
3
14:15 - 14:30
Electrical retinal implants have been employed for partial restoration of sight in the past. However, although partially successful, the visual percepts restored so far have not been proven useful enough in the day to day life of patients. Therefore, optimal stimulation protocols avoiding stimulation at remote positions are still highly needed. In this sense, achieving preferential and local activation of retinal ganglion cells is assumed to provide a sufficiently high acuity of the visual percept.
Methods:
In this study, we search for a window of opportunity, which efficiently stimulates retinal ganglion cell (RGC) somata while avoiding activation of axons of passage in ex vivo retinae of a photoreceptor-degenerated (rd10) adult mouse model of retinitis pigmentosa.
We make use of a CMOS-based microelectrode array which allows for continuous electrical stimulation and simultaneous electrical recording of RGC spiking activity. The CMOS-MEAs used here enable precise localization of RGC somata and of axons at a spatial resolution of 16 µm. Sinusoidal electrical stimulation was applied to electrodes positioned underneath the cell soma or underneath the axons.
Results
We were able to identify RGC spiking during electrical stimulation. Variation of the sinusoidal stimulation frequency and amplitude allowed us to identify cell-specific stimulus-response relations and to identify a window of opportunity for stimulation of the cell somata while avoiding axons.
Conclusion:
Our results indicate specific parameters, i.e. a window of opportunity which might be used in future to avoid axonal stimulation in epiretinal prostheses.
Ms. Andreea Cojocaru
TU Wien
#epiretinal electrical stimulation, CMOS-MEA, sinusoidal stimulation
4
14:30 - 14:45
Introduction
Visual prostheses that stimulate electrically the retina have allowed partial vision restoration in blind patients with retinal degenerative diseases. Nonetheless, current retinal implants do not give feedback on the efficiency of electrical stimulation therapies and do not adjust to the remodelling processes of the diseased retina. To improve the efficiency of electrical stimulation, this work builds upon the bidirectional approach proposed before [1] and characterizes further the capability of evoking electrical responses from the inside of the retina with different current-controlled stimulation configurations.Methods
Parylene-C-based intraretinal probes [2] with four 145-185 µm-long penetrating shanks, each one containing three 15-µm diameter-recording electrodes (REs) and one 25-µm diameter-stimulating electrode (SE) are used in vitro in explanted healthy (WT) and diseased rd10 mouse retinae. Intraretinal placement comprises SEs at the inner plexiform layer and REs along the inner retina and ganglion cell layer. Monopolar/bipolar, biphasic, and first cathodic vs. first anodic pulses were tested with stimulation currents between ± 0.5–10 µA and pulse widths between 0.1–5 ms.Results
Simultaneous recording and stimulation inside the retina are feasible with charge injection thresholds as low as 0.05 nC. Excitatory and inhibitory, monotonic, non-monotonic, and saturated neural responses, are captured upon electrical stimulation. Electrically evoked potentials with latencies between 5–25 ms to 150 – 400 ms are captured, implying therefore indirect responses of the retina. Furthermore, the excitability of WT and rd10 retinae is increased for both when using bipolar biphasic first-anodic charged balanced pulses. Moreover, the use of bipolar stimulation uncovered the possibility of significant responses within single neuronal columns.Conclusion
Multisite intraretinal probes allow simultaneous recording and electrical stimulation of the retina, exposing electrically evoked neural responses using electrodes with single-cell dimensions and low-charge injection thresholds.[1] Rincón Montes et al. Front. Neurosci., 2019
[2] Rincón Montes et al. Sci Rep, 2020
Ms. Dr. Viviana Rincón Montes
Institute of Biological Information Processing (IBI-3) - Bioelectronics, Forschungszentrum Jülich
#Electrical stimulation #Intraretinal implants #Retinal implants
5
14:45 - 15:00
Introduction
Intracortical microstimulation (ICMS) is a technique for restoring lost sensory perception, such as vision and touch, and for relieving the symptoms of certain neurological disorders. To recreate complex firing patterns, ICMS devices should have a large number of small electrodes that can stimulate at high spatial resolution. This work aimed to use computational modeling both to study neuron responses to intracortical electrical stimulation and to compare various stimulating electrode geometries (carbon fiber electrode, Utah electrode, and an ideal point source) with realistic 3D morphologies.Methods
A biophysical model of a cortical neuron was combined with a volume conductor model of the head, with several realistic electrode designs included. The neuron model is a multi-compartmental conductance-based cable model of a pyramidal neuron with realistic 3D morphologies from Blue Brain library. The head volume conductor is finite element model of a head with four layers. Anodic-first, cathodic-first and cathodic-first asymmetric charge balanced biphasic single pulses were used with pulse widths of between 50 µs and 2 ms. Electrodes were placed at 80 different locations around the pyramidal neuron in a 3D grid. Threshold in µA for a given pulse width was calculated at each electrode location.Results
The average threshold difference between a carbon fiber electrode and an ideal point source was less than 5.3%, 4.1% and 4.2% for anodic-first, cathodic-first and cathodic-first asymmetric charge balanced biphasic pulses respectively. Utah electrode had thresholds 38%, 37% and 38% times higher than the carbon fiber electrode. Moreover, cathodic-first pulses consistently activated the neuron with lower thresholds compared to anodic-first pulses. It was also seen that threshold current is directly proportional to the distance between the electrode and action potential initiation point. Chronaxie and rheobase calculations supported findings related to threshold predictions. Utah electrode thresholds predicted by the model are similar to clinical findings.Conclusion
This study demonstrates the importance of using realistic electrode geometry for modeling ICMS. Additionally, the use of realistic neuron models with 3D morphologies are promising instead of simpler models.Mr. Asst. Prof. Mahmut Emin Çelik
Gazi University
#Intracortical microstimulation #carbon fiber electrode #multi compartmental #modeling #neuron
6
15:00 - 15:15
Introduction
To improve psychophysical outcomes with retinal implants, it will be necessary to better reproduce the complex signaling patterns used naturally by the retina. Re-creating such patterns with a prosthesis is challenging however as neurons are heterogeneous and closely spaced and therefore individual cell types need to be selectively targeted. Unfortunately, thresholds to conventional pulsatile stimulation are similar between different types of RGCs. However, different RGC types exhibit sensitivity differences to stimulation delivered at higher rates, e.g., 2000 Hz. The factors shaping these differences are not well understood and are investigated here.Methods
A combination of cell-attached and whole-cell patch clamp recordings were used to correlate spiking and voltage responses to both low and high frequencies of stimulation. A computational model was then developed that allowed the biophysics underlying observed responses to be examined.Results
Low frequencies produced hyperpolarization of Vm regardless of amplitude while higher frequencies tended to produce hyperpolarization at lower amplitudes but depolarization at higher amplitudes. Conditions that produced hyperpolarization also generated robust spiking while those that produced depolarization, especially at stronger levels, resulted in weaker spiking responses. Modeling revealed that the depolarizing vs. hyperpolarizing shifts arose from changes in the relative contributions of voltage-gated sodium vs. potassium channels. Interestingly, ON cells enter depolarization block at a more depolarized level of Vm than OFF cells. While this suggested that OFF cells should reach depolarization block at a lower level of stimulus amplitude, the level of depolarization produced by a given level of HFS was higher in ON cells, with the result that the peak responses of ON cells occurred at lower stimulus amplitudes than those of OFF cells.Conclusion
These results suggest that previously reported non-monotonic responses arise from depolarization block and that the sensitivity differences between ON and OFF types arise from differences in the properties of intrinsic ion channels.Mr. Associate Professor Shelley Fried
Massachusetts General Hospital
Dept of Neurosurgery
#electrical stimulation #RGCs #selective targeting #retina
Tue
26 Sep
15:30 - 17:00
AV VI
Artificial Vision VI
Topic: Perception in Artificial Vision
Room: Room 6 "Zoo Duisburg" (Location: Meeting Room 6)
Chairs: Gislin Dagnelie and Penelope AllenSubmissions:
1
15:30 - 15:45
Introduction
The ICVP is a novel device for creating visual percepts in blind individuals. We tested the hypothesis that the implantee could discriminate horizontal and vertical orientations of smallest gratings of Berkeley-Rudimentary-Vision-Test (BRVT).Methods
The ICVP consists of multiple wireless floating microelectrode arrays (WFMAs), each with 16 stimulating electrodes. Twenty-five WFMAs were implanted in the right occipital visual cortex of a participant with only bare light perception in an FDA-approved Phase 1 clinical trial (NCT04634383). Groups of electrodes within WFMAs were evaluated across 9 months to measure current thresholds and phosphene positions and persistence (at 200 Hz, 200 µs cathodic phase duration and currents up to 60 µA). An off-the-shelf pair of glasses with an integrated camera was used for stimulation with 6 selected WFMAs. During 2 days of exploratory testing, the 50 M BRVT grating was tested at 25 cm in front of the participant (0.15 cycles/degree) in either horizontal or vertical orientation, with 30 balanced, randomized forced-choice trials.Results
Thresholds under 60 µA were found for 233 electrodes. Thresholds varied across days, but remained stable on average. Of the 6 WFMAs used for camera testing, 4 produced phosphenes within a 4° cluster centered 4° below and left of fixation, and the others located 4° below and 20° left of the central cluster. Phosphene sizes varied within 0.3–6° across, generally increasing in size with distance from fixation. The participant correctly determined the orientation of the 50 M grating in 27/30 trials (p < 10−5, binomial test), corresponding to an acuity of 2.3 logMAR or better, responding within 24 s on average (range: 6–91 s). In recent tests, the participant successfully placed checkers pieces on magnetic boards, located small objects and walked a short mobility course.Conclusion
In the first human-implanted ICVP system, patients achieved a grating acuity of 2.3 logMAR or better.Mr. Gislin Dagnelie PhD
Johns Hopkins University
I am a medical physicist by training, working with blind and profoundly visually impaired individuals, performing research in two principal areas: 1) Developing assessments of functional vision that can be used as clinical trial outcomes and markers of rehabilitation progress; 2) Psychophysical assessment and analysis of the properties of partially restored vision by means of electronic visual prostheses.
#Intracortical microstimulation #Visual prosthesis #Electrical stimulation
2
15:45 - 16:00
Objective: To compare accuracy of the L2 method to the face detection (FaD) and available chair detection (ChD) methods, in recipients of the second-generation (44-channel) suprachoroidal retinal prosthesis in laboratory and real-world environments.
Methods: Four implant recipients with profound vision loss due to retinitis pigmentosa were acclimatised to L2, FaD and ChD methods (#NCT05158049). For face localisation, one or two mannequins were positioned forward (face visible) or backward (face not visible) in the right, middle, and/or left position(s) in a square room (4x4m). Participants identified forward-facing mannequins (40 trials). For available chair localisation, two mannequins were seated facing forward in two of three chairs (right, middle, left). Participants localised and navigated to the available chair (36 trials). Functional Low-Vision Observer Rated Assessment (FLORA) tasks were performed in their home and surrounds.
Results: The FaD method (total 80.0 ± 8.9% correct) performed significantly better than L2 (total 34.1 ± 4.2%) for face localisation regardless of whether zero (p=0.019), one (p=0.021) or two (p=0.013) faces were presented (Kruskal-Wallis). The ChD method (87.5 ± 14.6% correct) performed significantly better than L2 (19.4 ± 13.2%), p=0.020 (Kruskal-Wallis) for localisation of available chairs. FLORA demonstrated a trend towards improved functionality with FaD and ChD compared to L2 for tasks relating to locating faces and chairs.
Conclusions: FaD and ChD methods performed better than the L2 method for specifically detecting faces and available chairs, respectively. Hence there is potential for these methods to be incorporated into the vision processing system to aid social interaction and navigation.
Ms. Assoc. Prof Penelope Allen
Centre for Eye Research Australia
The University of Melbourne
The Royal Victorian Eye and Ear Hospital
#retinal prosthesis
3
16:00 - 16:15
Methods : PRIMA has been implanted in 5 subjects with atrophic AMD in a feasibility trial in France. After mechanical, optical and electronic adjustment of the external components, the subjects were trained to use the device. Subjects underwent visual testing, including Octopus visual field, visual acuity tests with Landolt rings and ETDRS charts. Subjects were able to benefit from the image processing, including zoom. We report about the follow up over up to 48 months.
Results: In all 5 patients, the implant has been successfully placed under the central retina. The visual field test demonstrated that all subjects had perception elicited by the implant in the scotoma area. Visual acuity measurement with Landolt rings demonstrated an improvement of up to logMAR 0.87 (with vs without the system). ETDRS measurement demonstrated that subjects are able to recognize letters and sequences of letters with a visual acuity improvement of up to 37 letters (logMAR 0.74). The peripheral visual acuity did not decline after the surgery over a review period of up to 48 months following surgery.
Conclusions: The subretinal implantation of PRIMA in subjects with geographic atrophy due to AMD is feasible and safe, with no reduction of natural peripheral visual acuity Visual acuity measure mets showed that patients are able to reliably recognize letters and sequences of letters with a clinically meaningfull visual acuity improvement.
Mr. Dr Yannick Le Mer
Hopital Fondation A. de Rothschild, Paris
#Articial retina, geographic atrophy, treatment, vision recovery
4
16:15 - 16:30
Introduction
Simulations of artificial vision are used in visual prosthesis design, with normal-sighted subjects performing psychophysical tasks to give insight on capabilities and the trajectory of improvement over time. Previously, we observed substantial training effects in a longitudinal study of daily practice with a reading task. Here, we sought to quantify and compare the training effects in a more passive task, with the expectation that activities like watching videos are likely to dominate post-implant experience.Methods
Eight subjects used a simulation of a thalamic visual prosthesis with 1000 phosphenes to watch episodes of classic American television in daily, 25-minute sessions, for a period of about one month (21 total episodes) while we periodically measured their reading accuracy and reading speed through a simple reading task using six font sizes (logMAR 0.9-1.4). Sigmoidal fits to reading task performance across font sizes allowed estimation of equivalent acuity that was longitudinally tracked. A carefully designed schedule allowed independent extraction of the learning effects of video viewing from the interleaved reading tests.Results
Population reading accuracy improved significantly with passive experience leading to a 0.15 ± 0.05 logMAR visual acuity change. When normalized by the amount of time spent training, the per-minute improvement was about one third the rate of the interleaved reading tests. Population reading speed, on the other hand, did not change significantly over the duration of the experiment.Conclusion
While passive viewing tasks may be useful for post-implant rehabilitation, active tasks are likely to be substantially more effective.Ms. Katerina Eleonora Rassia
Department of History and Philosophy of Science, National and Kapodistrian University of Athens, Greece
#Visual prosthesis #Thalamic prosthesis #Simulation #Passive training
5
16:30 - 16:45
Methods: Eighteen right-handed patients (10 men, 8 women) with advanced RP, mean age 64.4 ± 11.5 years, participated. Visual acuity ranged from hand motion to bare light perception. Informed consent was obtained, and the study was approved by the Ethics Committee of Osaka University Hospital. TES used a stimulating electrode, measuring electrical current thresholds for initial phosphene perception. The square localization test involved touching white square targets with a 10° visual angle on a monitor screen, measuring the average absolute deviation.
Tests were performed one eye at a time, focusing on right eye results. If the right eye couldn't perceive phosphenes, left eye results were used. Correlations between visual acuity, phosphene threshold, and localization test results were calculated.
Results: The mean threshold for initial phosphene perception was 1.25 ± 0.6 mA (±SD). Mean absolute deviation was 16.0 ± 6.7°. No significant correlations were found between visual acuity, TES results, and localization test results. Patients were divided into four groups based on a threshold of 1 mA and a deviation of 15 degrees. The group with deviation <1 mA and >15 degrees showed the highest potential for visual function improvement with a retinal prosthesis.
Conclusions: Combining the TES and localization tests can effectively evaluate visual function and identify suitable retinal prosthesis candidates among advanced RP patients where traditional ophthalmologic exams are insufficient.
Mr. Dr Takeshi Morimoto MD, PhD
Osaka university graduate school of medicine
#retinal function #retinitis pigmentosa
Tue
26 Sep
12:45 - 13:45
BMT O-02
Plenary
Room: Philharmonie (Location: Philharmonie)
Chair: Karsten SeidlSubmission:
1
12:55 - 13:35
Mr. Roland Zengerle
#Molecular Diagnostics
Tue
26 Sep
08:00 - 08:30
BMT O-01
Welcome Address
Room: Philharmonie (Location: Philharmonie)
Chairs: Karsten Seidl and Gudrun StockmannsTue
26 Sep
17:00 - 19:00
BMT O-10
Opening Ceremony
Room: Philharmonie (Location: Philharmonie)
Chairs: Karsten Seidl and Gudrun StockmannsSubmission:
1
17:10 - 17:50
Mr. Florian Solzbacher
#Inflection points
Tue
26 Sep
18:45 - 20:00
BMT O-11
BMT Get-Together
Room: Foyer Philharmonie (Location: Foyer Philharmonie)
Tue
26 Sep
08:30 - 10:05
BMT S-01
Ultrasound
Room: Room 1 "Terahertz" (Location: Meeting Room 1)
Chairs: Steffen Tretbar and Andreas MelzerSubmissions:
1
08:30 - 08:42
Mr. Dr. Arne Bokemeyer
UKE
#Sonographie
2
08:42 - 08:55
Introduction
Deep brain stimulation (DBS) is a well established method for therapy of brain-related neurological disorders (Parkinson´s, essential tremor). It consists in inserting an electrode designed for delivering a stimulus into the brain. Ultrasound can be a non-invasive alternative to these surgical methods. While HIFU therapy (high intensity ultrasound) will permanently damage brain tissue by coagulation, LIFUP (low-intensity focused ultrasound pulsation) therapy is based on a neuromodulating or –suppressing effect while being in the energy range of diagnostic ultrasound.Methods
The TRUST-system (MR-Instruments Inc., Licensed by Fraunhofer IBMT) is a novel multi-channel electronics device including two matrix array transducers for 3D beam steering developed by Fraunhofer IBMT. The 256 transmit channels with up to 16 W/channel and DC up to 100% can be individually programmed. The matrix arrays have 256 elements in a circular configuration and allow steering up to 20°. The probes allow integration into an MR head coil and are equipped with MR markers for easy localization in MR planning data. Each probe is equipped with an active cooling, so that heating of the aperture is prevented.Results
Pressure distribution field measurements were performed to characterize the system. A focal pressure of >8 MPa was obtained for a focus of 3 mm x 20 mm (x/z respectively). The acoustic output inter-element variability was less than 20 % (standard deviation). The array allows steering in a range of approximately +/- 20°. The system safety was assessed both when it comes to compliance with medical device standards (IEC 60601) and thermal aspects (system, probe and cable heating).Conclusion
A novel ultrasound neuromodulation system based on a programmable multichannel platform with high DC capabilities and two matrix array probes allowing precise focusing with more than 8 MPa focal pressure has been developed, characterized and tested according to medical device standards.Mr. Marc Fournelle
Fraunhofer Institute for Biomedical Engineering IBMT
Mr. Dipl.-Ing. Steffen Tretbar
Fraunhofer IBMT
#ultrasound #neurostimulation #array technology
3
08:55 - 09:08
Introduction
Focused Ultrasound (FUS) can be used as a drug delivery application for localized chemotherapy to treat cancer. The effect of ultrasound-induced inertial cavitation (IC) is promising to trigger drug release from nanocarriers. After release, the drug is quickly absorbed by the surrounding tissue. Therefore, the drug is released only in the area targeted by FUS, although the drug is present throughout the body’s vasculature. To investigate this drug release effect in vivo, usually, a passive cavitation detection setup is employed. However, applying such a setup is challenging for in vivo experiments, as the test object may require its fixation inside the water tank. Thus, this work presents a prototype of a coupling device simplifying these experiments. Since the presented setup favors unwanted sound wave interference leading to superimposed sound pressure amplitudes exceeding the Mechanical Index, we additionally investigated different signal lengths. The occurring standing wave effects can be observed in the changing cavitation activity.Methods
In this work, we integrated the FUS transducer and the passive cavitation detector in the coupling device and attached the setup to a tissue-mimicking phantom made of polyvinyl alcohol. As a test sample, we used a talcum-water suspension. Degassed and deionized water served as a negative control. To investigate the interference of the ultrasound signal, we employed 750 kHz monofrequent sinusoidal burst sequences of different cycles 2-100. The applied peak rarefaction pressure corresponded to an MI = 1.2.Results
Standing waves can occur for this setup at a signal length of 44 cycles, proven by our calculations. Furthermore, our experiments have revealed a mean increase of the cavitation activity by ≈5.1 % , which indicated the occurring interferences.Conclusion
We can summarize that the here presented prototype of a coupling device can be employed for IC experiments redundantizing a water tank, which simplifies in vivo IC experiments.Mr. Benedikt George
University of Freiburg,
Department of Microsystems Engineering – IMTEK,
Laboratory for Electrical Instrumentation
#Coupling device #Focused ultrasound #Inertial cavitation #Drug delivery
4
09:08 - 09:21
Magnet Resonance-imaging guided Focused Ultrasound (MRgFUS) is of interest due to real-time co-registration of targeted brain regions with ultrasound transducer, as well as possible direct visualisation of FUS-effects. Based on the need for versatile mobile MRgFUS systems for any MRI, this study presents first steps towards a clinical MRgFUS neuronavigated system.
MRgFUS research system consists of rolling table for flexible transportation with monitor and amplifier for connection of MR-compatible and beam steering capable mobile FUS-system with a 256-channel matrix transducer (MRInstruments). Transducer size of 10x10x11 cm fit into most head coils. To identify optimal insonation window for FUS to cross the patients skull, phase aberration was investigated on human calvaria in a self-built acoustic scanning tank with fiber optic hydrophone (Precision Acoustics). System is equipped with MR-compatible optical tracked navigation system (Localite). For MR-based transducer tracking semi-active resonant fiducial markers were improved at the transducer housing and investigated for directionality and visibility in T1- weighted gradient-echo sequences (GRE (*fl2d1), FA=1°,10°,20°,40°,60°,90°, TR=100ms, TE=3.53ms, FoV=133*214mm, AM=0\192\120\0, FS=3T). MR measurements were performed in Biograph mMR PET/MRI (Siemens Healthineers) based on modified ASTM sequences. Treatment planning and transducer placement was tested on a phantom using ACCESS head coil, and DuoFlex Quadrupole coils (MRInstruments).
The integrated semi-active MR markers showed a >12 times increased brightness of >4095 at FA=10° compared to standard passive Gd-filled markers at 338. The SNRin air ranged from 531 (FA=1°) to >1165 (FA=90°).
Most components of the set-up were made from mostly 3d-printed plastic parts with non-magnetic electronic components, thus achieving full MR-compatibility.
The feasibility of the mobile versatile MRgFUS-system was shown and various measurements are being performed to verify that a safe operation on human subjects is possible in the particularly difficult and sensitive area of the brain.
Mr. Andreas Melzer
Innovation Center Computer Assisted Surgery (ICCAS), Faculty of Medicine, University of Leipzig
#neurostimulation #MRgFUS #MR compatability
5
09:21 - 09:34
Introduction
In orthopaedic technology unilateral leg amputees are provided with prosthesis attached through a shaft to the remaining part of the leg. The prosthesis legs are built according to manufacturer’s specifications and adjusted to the patient´s needs by means of gait analysis. Even if the prosthesis is adjusted correctly the chance to develop arthritis in the remaining knee joint is increased. The goal of this paper is to establish a procedure based on acoustic emission to detect early signs of arthritis in the remaining knee joint and to control secondary disabling conditions like misfit of the socket and misalignment of the prosthesis.Methods
The measurement system consists of the acoustic emission – measurement device, a force plate to measure ground reaction forces. Two handles on a test rig - with strain gauges to measure hand force attached – allow the patient to compensate for the muscular imbalance. And two video cameras which record the movement from front and side. The amputee performs a standard movement of three knee bends in ten seconds.Results
While the ground reaction forces show the load distribution between the remaining leg and the prosthesis, the hand forces give clues on the amputee´s balance. In correlation with the acoustic emission it is possible to assess the condition of the joint.Conclusion
In a pilot study the influence of the prosthesis type and the foot inclination is investigated under the conditions of a possible standard procedure.Once assessed it’s possible to regularly monitor the remaining knee joint for defects and evaluate the quality of the socket fit and prosthetic alignment.
Mr. Prof. Dr. rer. nat. Joerg Subke
Univeristy of Applied Sciences THM
Wiesenstr. 14
D-35390 Giessen
Germany
#Acoustic emission analysis #monitoring #unilateral leg amputee #adjusted prosthesis #gonarthritis
6
09:34 - 09:47
Introduction
Focused ultrasound on the thalamus is employed to relieve tremor in movement disorders. The treatment efficacy is currently assessed by subjective observation of patient tremor during hand movements. The purpose of this study was to create a simple quantitative method to assess tremor based on traditional pen-and-paper spiral drawing that could be employed during treatment and follow-up visits.Methods
Image processing was employed to automatically and rapidly clean scanned spiral and line drawings and to isolate the minimal part of the drawing that could provide sufficient data for tremor detection. Sobel edge detection and easily-interpretable statistics of the distribution of edge-angle orientations in the spirals relative to the spiral centres were used as tremor measures. The method was applied to scanned drawings of 122 tremor patients before treatment and in follow-up visits. Discrimination analysis of the tremor measure between drawings in the session before treatment and the follow-up sessions was carried out.Results
The processing yielded correctly cropped and clean spirals. The tremor measure demonstrated consistent tremor reduction in the treated hand drawings in all five follow-up visits during the first year following treatment date in 76% patients from the study cohort.Conclusion
In this study we developed a computational method that rapidly computed tremor severity estimate in an explainable and clinically useful manner from a traditional pen-and-paper spiral drawing.This rapid quantitative and objective tremor assessment can easily be implemented during focused ultrasound treatment and replace the subjective assessment currently employed.
Ms. Prof. Vered Aharonson
School of Electrical and Information Engineering, University of the Witwatersrand, Johannesburg
#Parkinson's disease #essential tremor #thermal lesion #unilateral ablation #FUS
7
09:47 - 10:00
Introduction
Theranostic agents are materials that act both as tracers during diagnostic imaging and as vehicles carrying and releasing therapeutics during treatment. Ultrasound-triggered theranostic agents comprise shell-encapsulated microbubbles that pulsate during low-amplitude ultrasonic imaging and release their payload upon higher-amplitude sonication whilst simultaneously assisting in the permeation of target tissue. High-amplitude release may be undesirable due to unwanted side effects related to inertial cavitation. However, low-amplitude release from microbubbles typically requires thin encapsulating shells, which in turn may be permanently disrupted under diagnostic imaging conditions. The purpose of this study was to investigate the suitability for theranostic applications of a novel microbubble agent with thick shells composed of calcium carbonate.Methods
Hydrophobised calcium carbonate-encapsulated microbubbles of radii between 1.0 µm and 11 µm were subjected to short ultrasound pulses of 1-MHz ultrasound at acoustic amplitudes of 0.5 MPa or less, which corresponds to low mechanical indices. During sonication, high-speed video footage was recorded at a frame rate of ten million frames per second.Results
We observed pulsations but no gas release at a 0.1-MPa amplitude and intra-encapsulation fragmentation during sonication at a 0.3-MPa amplitude. At 0.5-MPa amplitude sonication, release was observed from more than 70% of the microbubbles in the field of view. This finding indicates that the microbubbles were stable scatterers during 0.1-MPa sonication, but instable vehicles during 0.5-MPa sonication.Conclusion
The pressures used in this study to observe release were too low to allow for unwanted inertial cavitation. In conclusion, therefore, the microbubbles studied were a promising theranostic agent whose contents could be released at moderate acoustic amplitudes.Mr. Dr Craig S. Carlson
BioMediTech, Faculty of Medicine and Health Technology, Tampere University
Mr. Prof. Dr.-Habil. Michiel Postema
BioMediTech, Faculty of Medicine and Health Technology, Tampere University
Ms. Miss Nicole Anderton
Tampere University
#controlled release #CaCO3 #low-MI sonication #LIFU #toothpaste
Tue
26 Sep
08:30 - 10:00
BMT T-11
Education and Training I
Room: Room 2 "Innenhafen Duisburg" (Location: Meeting Room 2)
Chair: Marc KraftSubmissions:
1
08:30 - 08:45
Introduction
Colonoscopy is considered as gold standard in colorectal cancer screening with the highest sensitivity and specificity. The quality indicators of colonoscopy are reaching the caecum, a withdrawal time over 6 minutes, and an adenoma detection rate (ADR) of ≥ 20%. ADR can be significantly improved by training. The goal of this work is to develop a colonoscopy training model for intraprocedural polyp detection with feedback. The simulator will be evaluated with a study.Methods
Colorectal datasets were first processed using graphics software, transition areas were designed and polyps implemented. The organs were 3D printed, immersed in latex, and photoresistors were attached. The positioning and morphology of the polyps are according to human pathology. The organs were fitted into a foam block and a chassis, followed by installation and programming of the electronics. The recorded data in comma-separated values format were analysed with Excel.Results
The colonoscopy simulator was evaluated with n = 29 participants. The developed model is suitable for colorectal examination and detection of pathologies. Intubation of the caecum and measurement of the withdrawal time are possible. Further, the user interface provides numerical and visual information about the required time and the number of detected polyps. The model achieved a score of 1.6 (Scale: very good to not realistic, 1 – 6). During the standardized examination, the participants required an average of 7.4 minutes for withdrawal and detected 6.6 of 10 polyps. Participants with a withdrawal under 6 minutes detected 48% of the polyps. Participants with a withdrawal over 6 minutes detected 74.7% of the polyps.Conclusion
With this mechanical model, colonoscopy training can be performed in a good, standardized manner with the detection of polyps by implemented photoresistors. The evaluation provides a good suitability of the simulator for training. The results show a higher number of polyps detected with an examination time over 6 minutes.Ms. Anja Lachenmaier
University of Tübingen
Mr. Benedikt Duckworth-Mothes
Department for General, Visceral and Transplantation Surgery at the University Hospital of Tübingen, Workgroup for Experimental Endoscopy, Development and Training; Waldhörnlestrasse 22, 72072 Tübinge
Mr. Ulrich Schweizer
Department for General, Visceral and Transplantation Surgery at the University Hospital of Tübingen, Workgroup for Experimental Endoscopy, Development and Training; Waldhörnlestrasse 22, 72072 Tübinge
Ms. Dr. Dörte Wichmann
University Hospital of Tübingen
#colonoscopy #training #polyp detection
2
08:45 - 09:00
Introduction
The project aims to develop a realistic training system for thoracic surgery, applicable for both open and minimally invasive procedures.Methods
Central components are (I) a modular thorax model based on real CT data, whose ribs are connected by a plug-in system, and a (II) simulation trainer for abdominal interventions. The design process was based on the guidelines of the VDI and the usability requirements of the MDR. Various concepts were designed and manufactured. The selection of a preferred variant was made by the head of the thoracic surgery department at Magdeburg University Hospital. The components were manufactured additively with PETG and TPU, to provide a flexible organ tray.Results
The training system consists of a holder on which a right hemithorax and a synthetic skin can be attached. It can be combined with a P.O.P Trainer (Optimist GmbH), which allows the use of animal organs including their perfusion as a Wet Lab application. A flexible grid is connected to the bottom to keep animal organs in an anatomically correct position. The evaluation employed criteria that were derived from general requirements for medical training systems. In addition, a tabular comparison was made with other products. The model met the criteria and convincingly represented clinical conditions compared to other thoracic simulators. The geometry and modular system of the thoracic model provides advantages over other systems. Furthermore, it mimics the arrangement and functioning of organs more realistically, especially by imitating the vertical movement of the heart through pulmonary ventilation. Therefore, the proof of concept could be carried out successfully.Conclusion
The design should be improved in order to simplify handling and the soft tissue shell should become more realistic. Aligning with high standards set by VDI and MDR creates the prerequisites for future approval as a valid training option.Mr. Tim Weiß
#Thoracic Surgery Simulation #Wet Lab #Surgical Education
3
09:00 - 09:15
Introduction
Keeping up student engagement throughout a whole-semester course is a challenge which can be addressed by including gamification into the course structure. We evaluate the application of gamification to a second-year B.Sc. ''Biosignal Processing'' course (5 ECTS, 3 semester hours/week) in an Applied Computer Science study degree. We analyze whether there were different types of learners and the impact on student satisfaction.Methods
We applied gamification by providing different ways to earn points (max: 1,405) as prerequisite for the exam. Studens were eligible upon reaching 600p. These could be earned by taking a quiz after each lecture (first 50p, then 5p each), submitting solutions for Jupyter Notebook exercise sheets (100p each), presenting a solution orally in front of the class (100p), or answering questions to a scientific paper as a group task (100p). For each student we compared the achieved points to the grade in an online, open-book exam. Additionally, we conducted a questionnaire evaluation at the end of the course using Likert scales (1-6).Results
The exam was taken by 22 students with an average of 75% (std: 21%, range: 54-96%). During the course, we observed different types of behaviour, e.g. "competitive" (aim: maximize points) vs. "cost-effective" (aim: reach 600 points), and roles, e.g. "busy bees" (early submissions) vs. "procrastinators" (late submissions). The course was evaluated by 7 students with an average of 2.0 for the whole course and 1.7 for the combination of lectures and gamification tasks. 6/7 rated the various options as motivating and 3/7 expressed that they tried to earn as many points as possible.Conclusion
The overall evaluation of the course was improved by 0.6 compared to previous years with same content but without gamification. In the future we will incorporate more types of tasks appealing to more types of learners.Ms. Theresa Bender
University Medical Center Göttingen
#Gamification #Biosignal Processing #Student Engagement
4
09:15 - 09:30
Introduction
Machine learning (ML), especially neural networks (NN), play an increasingly important role in medicine. This implies the integration of this topic into the curriculum of the course of study in biomedical engineering and related courses of study. At the Westsächsische Hochschule Zwickau a practical course was developed, which introduces the students to the concept of ML.Methods
The practical course takes place in a computer room. For the exercises, the students create web-based interactive Jupyter Notebook documents and program in the language Python. Basic programming skills are a prerequisite. Each unit of the course takes 90 minutes and covers a different topic of ML. It was taken care, that there are no special requirements regarding the hardware and that the used software is free of charge.Results
In total, six units were developed for the course covering topics such as introduction to important Python libraries (Numpy, Matplotlib and Pandas), supervised learning applied to tabular data of diabetic patients using the k-NN-algorithm and supervised learning applied to tabular data using deep learning realised with the library Keras (including the development and evaluation of a model for a NN). In two final units supervised learning implemented with the library TensorFlow is used to classify image data like CT images of brain tumours.Conclusion
The practical course covers selected important topics of ML and is able to teach the concept of this field. Despite the limited period of time the students are able to solve practical problems in a unit. Students of biomedical engineering evaluating the course listed the programming as the biggest challenge, which is likely due to their limited education in computer science. They also stressed the importance of an accompanying lecture teaching the theoretical background of ML.Mr. Ralf Hinderer
Westsächsische Hochschule Zwickau
#practical course #machine learning #supervised learning
5
09:30 - 09:45
Introduction
For engineering students heading for the medical device industry, knowledge in engineering subjects should be complemented by the basic concepts of regulatory affairs for medical devices (RA for MDs). Since the development of digital learning objects (DLOs) needs time and money, the type of DLO should be carefully chosen to achieve high pedagogic quality. Former work led to a list of types of DLOs, which are suitable to deliver teaching content in the field of RA for MDs. Each item included a preliminary estimation of its acceptance by students. This work aims at giving a a first impression of the influence of the type of DLO on the learning outcome of the participants.Methods
For three different topics in the field of RA for MDs, three different DLOs with high popularity rankings were investigated:- A text was provided in a webbased format with junctions and possibilities to go into more detail.
- Lecture with embedded quizzes
- Animated picture story with characters
- Pre-test for the first topic,
- Usage of one of the DLOs (1-3),
- Post-test.
To estimate the learning outcome the results of the pre- and posttests were compared.
Results
The procedure provided a ranking of the DLOs (1-3) with regard to their effectiveness in the learning process.Conclusion
The effect on the learning outcome as a selection criteria is added to the suitability and the popularity ranking. Thus it enlarges the basis for decision regarding the selection of DLOs in the field of RA for MDs.Ms. Dr. Maria Henke
Institute for Robotics and Cognitive Systems
#Regulatory Affairs
6
09:45 - 10:00
Introduction
The digitizing of medical education has been winning more support in recent years. One of the options is the implementation of Augmented Reality to complement or replace conventional methods in medical training and to create a more efficient learning environment for medical students and prospective staff in healthcare.Methods
In this work a Digital Tutor in Augmented Reality in medical training is evaluated with the aim of finding out whether it offers an additional value compared to conventional learning and teaching methods. Therefore, an application for medical training was arranged and a user survey with (n = 24) students from the Faculty of Life Sciences at the University of ANONYMIZED was carried out. The utilized application had two versions. One version included the Digital Tutor, who verbally delivered the instructions, and the other version included a text box with written instructions.Results
The students evaluated these two applications through a questionnaire. Further, to validate this work an expert interview was conducted with a person in charge of designing concepts for the digitizing of education for the ANONYMIZED university. Through the survey and interview it was concluded that the Digital Tutor has an additional value compared to the text box.Conclusion
In summary, the digital tutor has proven a higher learning success than the textbox. In the future the interactivity of the Digital Tutor with the students should be improved and a larger study should be done to further validate this outcome.Mr. M.Sc. Christian Gießer
Universität Siegen
#Augmented Reality #Digital Tutor #Education #Magic Leap #SkillsLab
Tue
26 Sep
08:30 - 10:00
BMT T-08
Additive Manufacturing and Bioprinting
Room: Room 3 "Landschaftspark Duisburg-Nord" (Location: Meeting Room 3)
Chairs: Verena Scheper and Nina EhlertSubmissions:
1
08:30 - 08:45
Introduction
Injuries to the bone/tendon junctions can lead to various pathologies in the musculoskeletal system, which can be caused by aging or metabolic diseases. Melt electrospinning (MES) has been increasingly used to produce graded polymeric fiber scaffolds that can aid in the reconstruction of tissue interfaces. One of the key advantages of MES is the ability to control the deposition of polymer fibers, allowing for the creation of scaffolds with a reproducible, three-dimensional structure. This study aims to fabricate and assess the mechanical behavior and cell compatibility of melt-electrospun fiber mats with varying fiber geometries.Methods
Electrospun fiber scaffolds were manufactured from a polycaprolactone (PCL, MW=45kDa) melt, with different fiber geometries, including non-oriented (i), grid-patterned (mesh width 20µm) (ii), and graded scaffolds with fibers of different deposit densities (iii). For fabrication of the graded scaffold, the collector speed was changed during the process. To investigate the mechanical behaviour both unaxial and dynamic tensile tests were conducted. Additionally, cytocompatibility tests werde conducted with hMSC. Cell viability was measured after 1,3 and 7days.Results
The average diameter of the fiber scaffolds varied depending on the scaffold type, with values of 25µm, 22.2µm, and 28µm for types (i), (ii), and (iii), respectively. Uniaxial tensile tests showed a force at break of 15N for (i), 17.5N for (ii), and 20,2N for (iii). Cell viability significantly increased in short-term (1d) cell attachment for scaffold type (iii) compared to (i), and long-term viability and proliferation of hMSC was comparably high for scaffold types (i) and (iii), whereas lower survival rates were observed for type (ii).Conclusion
This study demonstrates that MES can be used to produce graded fiber scaffolds with varying fiber geometries that exhibit improved mechanical stability and good cytocompatibility. These findings have important implications for the development of tissue engineering strategies to treat musculoskeletal injuries.Ms. Gesine Hentschel
Leibniz University Hannover
#Melt Electrospinning #musculoskeletal system #fiber scaffolds #hMSC
2
08:45 - 09:00
Manufacturing replicas for replacing missing or defective body parts also incorporates 3D technology, including scanning, image processing and printing. Rehabilitation engineering covers principles to develop technological solutions and devices to assist individuals with disabilities. The goal is to recover physical and/or cognitive functions lost because of disease or injury.
- Methods
In the case of the ears, both aesthetics and functionality play a significant role. This paper presents a workflow pipeline developed for manufacturing outer ear and nose replicas based on accurate 3D scanning, post-processing of the images and printing. Furthermore, mechanical properties of prototypes will be discussed, and two actual use cases highlighted.
Hand-held scanners were tested that are commercially available. Scanned images using the Go!SCAN and the SIMSCAN 3D devices were post-processed in MeshLab software. Post-processing tasks of the images include: cutting and resizing, deleting unwanted elements of the skull, filling the holes in the mesh, giving “thickness” to the mesh, and converting it to a printer friendly format. In addition, mirroring plays a significant role. We are interested in using affordable, easily accessible materials and printers. The Craftbot Flow XL and the Craftbot Flow Idex machines, and three different kinds of elastic materials: Formlabs Flexible 80A, Formlabs Elastic 50A (synthetic resins), and a general purpose hard polymer with water-soluble filament as support material were selected for printing. Mechanical testing included tensile and temperature testing.
- Results and conclusion
All samples proved to be appropriate for everyday environmental conditions. Hand-held scanners delivered accurate images for post-processing of the mesh and for printing in a cost- and time efficient way, allowing the technology to be available for the general population.
Mr. Dr. György Wersényi
Széchenyi István University
György wersényi was born in 1975 in Győr, Hungary. He received his MSc degree in electrical engineering from the Technical University of Budapest in 1998 and PhD degree from the Brandenburg Technical University in Cottbus, Germany. Currently, he is a full professor, member of the European Acoustics Association and the Audio Engineering Society. His research focus is on acoustic measurements, virtual and augmented reality solutions, sonification, cognitive infocommunications, and assistive technologies.
#3D printing #Image processing #Outer ear #Reconstruction #Biomaterial
3
09:00 - 09:15
In this context, 3D-printed imaging phantoms, which have specific requirements relevant to AI models, can play a
crucial role. Due to its unique ability to create phantoms of almost any complexity, 3D printing technology seems a suitable
approach for the quality control of AI models in medical imaging.
The following reviews some of the works that used 3D-printed technology to create custom-built phantoms for use
in Computed Tomography (CT), nuclear imaging, Magnetic Resonance Imaging (MRI), and ultrasound imaging. The focus
of this short review is on the accuracy of 3D-printed technology in creating imaging phantoms. In the end, the potential
of the 3D-printed phantoms in testing and quality control of AI-based algorithms in radiology is discussed.
Mr. Dr. Ali Pashazadeh
Otto von Guericke University Magdeburg
#medical imaging phantoms #3D printing technology #artificial intelligence #quality control
4
09:15 - 09:30
Introduction
The use of 3D printing technology for medical applications is becoming increasingly popular. Recent stereolithography (SLA)-based printing methods allow the generation of complex structures with a high surface quality. This is particularly useful for applications in the neurovascular field, where sophisticated structures are involved.
Methods
In this study patient-specific intracranial aneurysm models are extracted based on medical image data und printed as thin-walled vascular phantom models. For this purpose, two commercially available 3D printers are used to print flexible vascular models with three different silicone-like elastic resins (Ultracur3D FL 300, Prusament Flex80 and Formlabs Elastic 50A) of various Shore hardness. Three aneurysm models of different size and complexity are chosen. To evaluate the geometric accuracy of the flexible models, angiographic measurements are performed for an exemplary case and morphological parameters are extracted from the generated 3D models.Results
The printed results demonstrate a successful generation of hollow aneurysm phantoms. There are dependencies regarding the print quality from the model to platform positioning for two materials. The quantitative geometric accuracy analysis shows notable differences between the materials. The extracted morphological parameter values for all materials show a mean decrease compared to the original reference model of aneurysm volume (4.5 %) and maximum diameter (1.0 %) as well as an increase of ostium area (6.0 %) and maximum height (4.9 %). However, Formlabs Elastic 50A in particular exhibits just slight reductions with respect to the reference model, with a mean decrease for all parameters of 5.7 % as well as no dependence on printing position and resulting artifacts.Conclusion
The study investigates the feasibility of using SLA-based 3D printing to generate realistic flexible aneurysm phantoms. In this context, the Formlabs Elastic 50A could be identified as potentially applicable for phantom creation in terms of reproducible quality and geometric validity.Mr. Janneck Stahl
Department of Fluid Dynamics and Technical Flows, Research Campus STIMULATE, University of Magdeburg
#intracranial aneurysms #3D printing #vascular phantom models #stereolithography #flexible resin
5
09:30 - 09:45
Introduction
One key challenge in 3D cell culture remains the supply of nutrients and oxygen. The aim of this study was to explore the use of stereolithography for the production of easy-to-produce scaffold structures with perfusion channels for low-cost cell culture of larger constructs.Methods
Scaffold structures and perfusion channels were constructed by CAD and subsequently 3D printed on a Caligma200 UV hot stereolithography system using the manufacturers photoresin material Pre019. Polymer components were post-processed and analyzed via microscopy. All materials applied were tested for cytotoxicity by means of MTT- and Live/Dead-assays prior to cell culture experiments testing the supply of cell culture medium via perfusion channels.Results
Cubic lattice scaffold structures were produced with web thickness of 199.3 ± 2.8 µm and pore sizes of 581.0 ± 15.4 µm and perfusion channels with an inner diameter of 797.0 ± 5.6 µm and channel pores with a 327.5 ± 5.6 µm. A minimum flow rate by hydrostatic pressure was determined to be 5.2 ± 0.3 ml/h. All materials exhibit no cytotoxic effects in eluate and direct contact tests. Perfusion channel supply of cell culture medium for cell culture is demonstrated.Conclusion
Scaffold and perfusion channels can be produced by stereolithography with high accuracy and resolution with reasonable effort. 3D Cell culture using a perfusion channel was demonstrated but shows a rather limited nutrient supply only in the vicinity and needs to be improved in further research.Mr. Klaus Kreuels
Chair for Laser Technology LLT, RWTH Aachen University
#Stereolithography #Scaffolds #Perfusion Channel #3D Cell Culture
Tue
26 Sep
08:30 - 10:00
BMT T-02
Devices and Systems for Surgical Interventions
Room: Room 4 "Sportpark Duisburg" (Location: Meeting Room 4)
Chair: Karin Somerlik-FuchsSubmissions:
1
08:30 - 08:45
Introduction
Insufficient screw anchorage in trabecular bone of poor quality leads to early implant failure. Osteoporosis is both, cause for frequent fragility fractures and, when internal fixation is attempted, the reason for compromised (screw) implant load bearing capabilities. Implant loosening and failure are due to decreased bone density and impaired trabecular structure. This is especially critical in spine surgery, where good bone anchorage of pedicle screws is critical for sufficient primary stability in instrumented segmental fixation for reliably achieving posterolateral fusion. This study was designed as proof of principle and safety test of the novel technique, the Immediate Stabilization System (ISS). The technique is designed to immediately stabilize polymer-augmented pedicle screws (PAS) in deficient bone and avoid complications of loosening pedicle screws at the bone-screw interface, especially in osteoporotic patients.Methods
A polymer sleeve was designed as augmentation to improve screw anchorage after drilling the screw hole. By applying ultrasonic energy, the polymeric tube was molded into the pores of the host bone forming a strong and uniform bond with the adjacent bone. The original screw was then implanted into the denser bony environment leading to an enhanced immediate stability. The ISS-treated implants were compared to conventionally placed pedicle screws in ex-vivo cadaver bones (2 sheep spines, n = 6 implants per spine, total 12 screws) and in-vivo in a spinal sheep model (Swiss alpine sheep, n = 5, 4 implants per animal, total 20 screws).Results
After eight weeks implantation, no bone resorption in the proximity of any polymer-augmented screw was observed. The primary stability of ISS-treated pedicle screws was increased in ex-vivo bone (+24% insertion torque (IT)) and in-vivo (+32.9% IT) in sheep spine. Removal torque (RT) was higher ex-vivo (+24% RT), however, lower in the in PAS tested for 8 weeks in-vivo (-21% RT).Conclusion
The ISS technology demonstrated improved anchorage of pedicle screws in ex-vivo cadaver bones as well as in-vivo studies in sheep spine compared to native screws. The ISS technology proved to be safe to use with in-vivo experiments in sheep. As a platform technology, it could be used in dental, trauma, spinal and other orthopaedic applications without any change of original implants or surgical instruments. This novel technology has the potential to improve the treatment of osteoporotic bone fractures or situations with disturbed bone metabolism, clinically allowing for more time for fusion and mobilization.Mr. Michael de Wild
University of Applied Sciences Northwestern Switzerland, FHNW
School of Life Sciences HLS
Institute for Medical Engineering and Medical Informatics IM2
#screw anchorage #primary stability
2
08:45 - 09:00
Introduction
The global shortage of healthcare staff has led to high workloads and subsequent risks to patient well-being. One of the professions affected is that of the scrub nurse. Scrub nurses must perform various tasks, such as instrument handling or the documentation of surgical procedures. Robotic scrub nurse systems have the potential to reduce workload and to assist in handling surgical instruments. Existing approaches mostly use two-finger grippers or electromagnetic grippers. However, it is assumed that a granular jamming gripper is more suitable for handling various surgical instruments, regardless of material and shape. Therefore, a gripping unit based on two granular jamming grippers is presented and assessed.Methods
For evaluation, an articulated robotic arm was equipped with the gripping unit and six different surgical instruments were repeatedly gripped and transported. The number of successful/failed transfers was recorded.Results
Both, the pick-up of instruments from a table surface and from a hand is possible. During assessment, the granular jamming gripper was found to be suitable for picking up and transferring most of the surgical instruments, however, handling very flat instruments turned out to be challenging.Conclusion
The preliminary tests of the gripping unit allow to derive a basic suitability for the handling of surgical instruments. However, the gripping performance needs to be improved to ensure safe and reliable instrument transfers. The presented gripping unit has the potential to be inexpensive and thus, designed as a sterile disposable product, particularly safe. In future work, open challenges, such as the combination with an image-based object detection and a contact-free user interface need to be addressed.Mr. Max B. Schäfer
University of Stuttgart
#robotic scrub nurse #granular jamming gripper #instrument handling #robot-assisted surgery
3
09:00 - 09:15
Mr. Witold Serwatka
AGH University of Science and Technology
Ms. Katarzyna Heryan
AGH University of Science and Technology
Mr. Prof. Dr. Michael Friebe
#Signal Processing #Audio guidance #Tissue characterisation #Vibroacoustics #Acoustic guidance #Interventional therapy #Minimal-invasive procedures #Convolutional Neural Networks
4
09:15 - 09:30
Introduction
Future operating rooms will increasingly utilise integrated intelligent systems that can process and analyse data streams of multiple perspectives. A potentially valuable application of the intelligent systems inside the OR is the automatic generation of surgical reports such as the anaesthesia report. Indeed, Automatic generation of intraoperative anaesthesia reports has great potential to generate accurate and efficient documentation and allow the anaesthesiologists to utilize their time more optimally. In this paper, a computer-assisted system for anaesthesiology report generation during laparoscopic surgery is proposed.Methods
The system relied on acquiring data from surgical devices, anaesthesia machine and patient monitor.Information that describes the vital signs of the patient and the settings of the anaesthesia machine through the surgical procedure was documented at adjustable regular intervals automatically from the data streams. Additionally, the system enables the anaesthesiologist to manually enter some information such as the airway management method and the size of the airway tube. Moreover, additional information that describes the surgical procedure (e.g., current surgical phase) was added by analysing surgical data such as the laparoscopic video.
Results
A qualitative comparison between a hand-written anaesthesiology protocol and an automatically generated protocol proved that the proposed system prototype was able to generate more accurate, efficient, and better readable reports compared to hand-written ones by clinicians.Conclusion
Automatically generated anaesthesia protocol showed great potential of using computer-assisted reports to help anaesthesiologists and enhance data reliability.Mr. Nour Aldeen Jalal
Institute of Technical Medicine (ITeM), Furtwangen University
#Anaesthesia Protocol #Data Fusion #Operating Room #Context-aware System #Medical Report
5
09:30 - 09:45
Introduction
In conventional open surgery, sensory modalities provide vital information. However, these senses are strongly affected in laparoscopic and robotic-assisted surgery due to restricted access and limited direct contact between the surgeon’s hand and the target structure. Surgical Audio Guidance (SURAG) is a new concept that exploits a new source of information inherent to any surgical procedure. Every medical instrument tip interacting with tissue generates a vibroacoustic (VA) wave that naturally propagates through the instrument’s shaft without the necessity of any active component. By connecting a sensing module at the proximal end of the instrument, SURAG can acquire a wave rich in haptic information. In this paper, we investigate the application of SURAG in laparoscopic surgery by analyzing the characteristics of the instrument-tissue interactions VA signals produced during various surgical tasks performed on different tissue samples.Methods
Experiments were conducted using a dedicated phantom covered in dense foam. Three trocars were inserted into the phantom to place the endoscopic camera and two laparoscopic instruments. A human user performed palpation and cutting tasks over tissue samples with different characteristics placed inside the phantom. The VA signals were displayed and recorded simultaneously with the endoscopic video and were analyzed using time-domain and spectral-domain representation.Results
The time domain and time spectral energy dynamics were studied for cutting events. The differences in frequency components were analyzed for palpation events. The results showed that the VA signals were sensitive to the types of tissue and the performed tasks. In addition, the cutting events produced different kinds of dynamic changes compared to palpation events.Conclusion
The VA signals can provide valuable information about the characteristics of surgical tool-tissue interactions. The results show that different tasks performed over different tissue samples produce VA excitations that involve different signal dynamics, making VA signals a promising tool for surgical monitoring applications.Ms. Nazila Esmaeili
Justus Liebig University of Giessen
Mr. Dr. Axel Boese
Otto-von-Guericke University Magdeburg
Medical Faculty
#Vibro-acoustic Sensing #Surgery Augmentation #Haptic Information #Laparoscopy
6
09:45 - 10:00
Introduction
Conventional mechanical drilling for implant placement is limited to specific geometry and orientation, resulting in incorrect positioning and inadequate anchoring in thin or porous bone. This study presents the development of a laser-based ablation process and an applicator technology for precise and fast laser drilling in the oral cavity.Methods
For the process development, a CO2 laser with a wavelength of 10.6 μm was used. Pulse durations between 10 μs and 400 μs were investigated for fast laser drilling with low thermal impact. For efficient ablation and cooling of the bone tissue, we applied a fine water spray.Results
The laser applicator is designed with an integrated scanning module, focusing optics and a compact water spray system with three spray nozzles in the applicator tip. The geometry of the cavities was analyzed using digital microscopy and scanning electron microscopy, allowing to measure the ablated volume and depth as well as investigating the bone microstructure. This study demonstrates a laser ablation process capable to generate cavities with an ablation rate of 1.75 mm³/s which is about 80% higher than previously reported. At this ablation rate the melted zones were smaller than 30 μm.Conclusion
This paper demonstrates a concept for a dental laser drilling system with a fast ablation process and a highly integrated applicator for treatment in the oral cavity.Ms. Christina Giesen
Fraunhofer Institute for Laser Technology ILT
Mr. Lazar Bochvarov
Fraunhofer-Institut für Lasertechnik
#Dental Implantology #Implantation #Laser Ablation #Laser Drilling #Applicator #Handpiece #Laser Surgery #Digitalisation #Laser Osteotomy
Tue
26 Sep
08:30 - 10:00
BMT T-01
Digital Health and Care
Room: Room 5 "Tiger & Turtle" (Location: Meeting Room 5)
Chairs: Bruno Ristok and Thomas WittenbergSubmissions:
1
08:30 - 08:45
A diagnostic medical tool is described that allows patients to non-invasively observe, describe and document their own retinal blood vessels using the Purkinje vascular entoptic test. We envision key applications of the Purkinje retinal image stabilization (PRIS) device in monitoring of diabetic retinopathy and cost-effective assessment of retinal visual acuity. The success of previously used entoptic techniques is limited by the interaction between patient and examiner. As a result, the entoptic perception and description may vary from patient to patient.
Methods
The subjective Purkinje appearance becomes both quantifiable and objective by a stabilized entoptic image combined with assistance methods for the patient. Assistance is provided by the examiner or a physician and additionally by a guiding app for self-diagnosis. To optimize our PRIS principle, we have developed a benchtop device with interchangeable light modules. The modular design is intended to provide maximum flexibility for determining appropriate PRIS stimulation parameters with individually software-controlled light emitting diodes (LEDs).
Results
Different geometric LED arrangements were prepared for testing two types of light spot movement. Light modules are adapted to the geometry of a closed human eye for optimal placement. A majority of self-testers (67%, n = 10) experienced a pleasant and stable entoptic perception when a green luminous light spot moves on a circular path 5 mm in diameter.
Conclusion
The entoptic perception of retinal vessels and their disease related pathologies is enabled by a simple diagnostic tool and can lead to a standardization of previous methods. Clinical studies in patients with and without diabetes are intended to provide information on what assistance needs to be given to a patient to optimize Purkinje self-diagnosis and documentation. Self-test findings need to be verified with fundoscopic examination. The challenging part is to derive an objective diagnosis from a subjective phenomenon.
Mr. Dr. Carsten Tautorat
Institute for Biomedical Engineering, Rostock University Medical Center
#entoptic phenomenon #purkinje #retinal visual acuity #diabetes #retinopathy #aneurysm
2
08:45 - 09:00
Introduction
Falls and gait disorders often result in hospitalization and immobilization. Near-falls may be one of the earliestsigns of increased fall risk. In the literature, several sensor positions are used for fall detection, but few studies include the head as a sensor position. Hearables and hearing aids are increasingly equipped with inertial measurement units (IMUs) and are therefore of particular interest for measuring the risk of falling in everyday life.
Methods
Therefore, we investigate the suitability of the ear as a sensor position for near-fall detection in comparison to the standard sensor positions. The motion data of one study participant (female, 63 years) was exemplary analyzed. The participant walked at her individually preferred gait speed on a perturbation treadmill while nine different perturbations (anterior-posterior, medio-lateral and pitch) were applied with a time interval of 20-30 seconds. We used seven IMUs during the measurement at the positions ear, sternum, lumbar, wrist (left/right), foot (left/right).Results
The absolute acceleration signals at the seven different positions show the periodicity of the normal gait before the perturbation. During and after the perturbation changes in the motion pattern can be seen, whereby the response to the perturbation occurs with a slight time lag. The Pearson correlations show that the sensor positions sternum, lumbar and ear correlate well with each other and thus show similar signal characteristics in the reaction to this perturbation.Conclusion
This provides evidence that the ear sensor position is at least comparable to the preferred sensor positions in the literature on the torso. However, these results were obtained under laboratory conditions. Further research is needed to investigate the sensor position at the ear in everyday life.Ms. Lea Feld
Carl von Ossietzky University of Oldenburg
#hearables #mobile health #fall risk #near-falls #gait assessment
3
09:00 - 09:15
Introduction
Dizziness is a common symptom in medicine. The anamnesis and clinical examination including nystagmus detection are essential to identify a vertigo’s pathogenesis. A nystagmus is an involuntary, rapid, rhythmic oscillatory eye movement induced by a dynamic, patterned visual stimulus or malfunction in the vestibular system. Diagnostics are complex, expensive and not always available across the board. A mobile videonystagmography (VNG) can reduce the level of discomfort and improve the self-determination of vertigo patients.Methods
To simplify neurootological diagnostics for medical staff and to offer immediate support for patients, the feasibility of a location- and time-independent smartphone-based application for VNG that does not require additional hardware was tested. The app uses artificial intelligence for eye tracking and to detect a horizontal nystagmus. The app uses Google‘s MediaPipe for detecting facial landmarks. A convolutional neural network was trained to detect the eye pupil centre in an eye‘s image. A feasibility study of the mobile VNG with 13 healthy volunteers was performed at a university clinic within the Department of Otorhinolaryngology (ENT). Each participant underwent a caloric vestibular testing to provoke the presence of a vestibular nystagmus. Anonymised videos of 20 seconds were taken with and without medical face masks as well as with front and rear camera to evaluate the feasibility, limits and differences.Results
A sensitivity of 90%, specificity of 32%, and positive predictive value of 61% was analysed. A nystagmus‘ direction is assigned in alignment with the ENT specialist‘s evaluation in 62% of the cases. Neither wearing a medical face mask nor using the front instead of rear camera affected the VNG.Conclusion
It could be shown that smartphone-based videonystagmography is possible. Future studies with vertigous patients are needed. Further, the software will be extended to compute angular velocities as is the case for the gold standard VNG.
Ms. Dr. med. Sophia Reinhardt
Universitätsklinikum Düsseldorf
#Vertigo #deep Learning #eye tracking #videonystagmography #nystagmus #dizziness #digital health
4
09:15 - 09:30
Introduction
Due to varying symptoms, early diagnosis of Parkinson's disease (PD) and objective measurement of medication effect is challenging. We investigated which features of mobile phone voice recordings can differentiate between participants with and without PD (PDCLASS) and identify pre- and post-medication conditions (PRE/POST).Methods
We formed 4 classes ‘With PD’(3758), ‘Without PD’(4001), ‘BeforeMedication’(1324) and ‘AfterMedication’(1602) from 10-second recordings of /a/-vowel phonation from the mPower dataset (https://doi.org/10.1038/sdata.2016.11). We extracted 60 features and grouped them into jitter, shimmer, non-linear dysphonia, mel-cepstral-coefficients, amplitude, frequency-power, temporal, wavelet, pitch, and tremor. To identify the most salient features, we performed a cyclical analysis using a multilayer perceptron classifier for each classification.Groups were added one-by-one during a 5-fold cross-validation, updating the feature vector if accuracy increased. The most informative groups were those that the most often increased accuracy. Features were then removed one-by-one and, if the average accuracy remained unchanged or increased, removed definitively. Then all remaining unused features were randomly added one-by-one and, if the average accuracy increased, included. Finally, we build two classifiers with the selected features and demographics (age,sex).
Results
The number of features reduced from 60 to 7 (PDCLASS) from 3 groups (amplitude, temporal and pitch) and to 9 (PRE/POST) from 4 groups (tremor, mel-cepstral-coefficients, frequency-power and pitch). The AUC of PDCLASS was 95.1%, which was slightly higher than the 82.6% achieved with 5 features plus demographics. The AUC for PRE/POST was 59.1%. This may be explained by the fact that extracted features don't include a sufficient number of useful information.Conclusion
PDCLASS requires different voice features than PRE/POST medication detection.Ms. Khrystyna Semkiv
Ulm University
#Parkinson's disease #Voice Recordings #Mobile Data #Feature Extraction #Classification
5
09:30 - 09:45
Introduction
With the ongoing work on the Health Level Seven (HL7) standards and the IEEE 11073 Service-oriented Device Connectivity (SDC) family, the demand for open integration of medical devices in the operating room (OR) has become clear. Nevertheless, there are very few interoperable medical devices available to date. This work describes a practical example of connecting an intraoperative neuromonitoring (IONM) device with a radiofrequency (RF) surgical device based on SDC and with the hospital information system (HIS) based on HL7.Methods
Before starting the surgery, patient-related data must be entered into the neuromonitoring system. To minimize manual input, we integrated an automized patient data query based on HL7, which completes all other necessary data provided by the HIS after entering the patient identification number. During the surgery, while mapping neural structures in the situs using IONM, the parallel operation of RF devices for coagulation generates artifacts in the neuromonitoring signals, which makes a reliable interpretation of the IONM signals impossible. Therefore, we developed an IEEE 11073 SDC interface for the neuromonitoring device and implemented an SDC-based OR control panel. While placing the hand probe for mapping neural structures in the situs, the OR control panel suppresses the coagulation of the electrosurgical instrument and only reenables it, after the mapping has been terminated. After the surgery, the generated IONM report can be uploaded into the HIS using HL7. Therewith it is assigned automatically to the previously selected patient.Results
In a demonstration OR we performed the surgical workflow of an integrated, interoperable neuromonitoring system using IEEE 11073 SDC and HL7.Conclusion
With the SDC- and HL7-enabled neuromonitoring system, we showed a practical use case of interoperable medical devices to optimize surgical workflow.Ms. Lea Weßbecher
inomed Medizintechnik GmbH
#IEEE 11073 SDC #HL7 #Neuromonitoring #IONM #interoperability
6
09:45 - 10:00
Introduction
The documentation landscape for care data in German is predominantly heterogeneous and unstructured. Therefore, insightful methods such as Artificial Intelligence (AI)[DH1] are difficult to implement. We propose a stepwise- approach that identifies relevant information from theory and care practice and maps it to a standardized care core data set to enable data-based improvement of nursing care. Our approach can enable the use of AI while leveraging consensus and evidenced-based expert knowledge from nursing science.Methods
The approach of developing a common, uniform data model is mainly based on processes of requirements engineering. We raise requirements for a care core data set and propose a stepwise method on how to proceed. We apply this developed method to propose a core data set module for a use case that is relevant in the field of nursing science.Results
In the first step of our approach, evidence-based care knowledge is formalized. The second step consists of the standardized structuring of care data for prevention measures. In the subsequent step, the data is mapped to the knowledge model to obtain a semantic structure on which AI algorithms can be applied. Another aspect of our method includes the description of the existing data in care facilities. The result of our work is the description of a process that captures, consolidates, and evaluates theoretical care knowledge and available care data and transforms it into a technical modelling.Conclusion
In the future, technical modeling representation of care knowledge and care data will play an increasingly important role, as they enable the basis for technical support of the care process, for example, through the use of artificial intelligence. We offer a blueprint for a data modelling process on the example of risk detection and prevention that can be transferred to various care domains.Ms. Maren Warnecke
Fraunhofer ISST
#Fall prevention #cross-facility data set #core data set #care data set
Tue
26 Sep
08:30 - 10:00
BMT T-04
Medical Device Regulation and Innovation
The high regulatory requirements hinder the market success of medical devices. With the entry into force of the new Europen Medical Device Regulation (MDR), the situation has worsened not only for manufacturers but also for research. The extensive documentation constraints make the transferability of research and development results considerably more difficult. In this session, we will discuss how medical technology can remain innovative despite regulatory requirements.
Room: Gerhardt Mercator-Lounge (Location: Gerhardt Mercator-Lounge)
Chairs: Cord Schlötelburg and Zeynep SchreitmüllerSubmissions:
1
08:30 - 08:45
Introduction
The MDR states the objectives of the law in the preface. There you will find, among other things, a consideration of small and medium-sized enterprises as well as high health protection and an innovative effect. Therefore, the question arises to what extent these goals have been achieved so far or can be achieved in the foreseeable future. The planned extension could be helpful but will not solve all problems.Methods
To this end, a systematic literature review was conducted to present the perspectives of various stakeholders in the healthcare sector.Results
Critical situations certainly arise for certain manufacturers, Notified Bodies and certain patient groups.Conclusion
The adopted extension of the transitional periods could be helpful but will not solve all problems.Mr. Prof. Dr. Michael Scholtes
Technische Hochschule Mittelhessen
#Medical Device Regulation #Socioeconomic Impact
2
08:45 - 09:00
Introduction
Remote patient monitoring (RPM) has become an important medical innovation in recent years. Despite its potential benefits, the collection and storage of sensitive medical data makes the security and privacy of patient data a top priority. RPM offers promising prospects for the health economy, creating new opportunities for medical tools and technologies that can enhance healthcare delivery, particularly for patients in medically underserved communities.Methods
Data exchange and RPM applications in Germany were to be examined. This led to the research question of what current applications are available in Germany and how different legal systems affect data exchange in RPM. It is summarized how remote patient monitoring is already being used, paying special attention to Germany and its regulatory framework. A SWOT analysis was done to highlight the potential of telemedicine.Results
Results show that health insurance and social care insurance in Germany are governed by different statutes, making it difficult to exchange data. Furthermore with the use of telemedicine, doctors may track patients' health state in real-time and identify changes as soon as they happen. For patients with long-term illnesses like diabetes or heart disease, where early identification of changes in health status might stop consequences, this can be extremely helpful.Conclusion
In conclusion, this paper highlights the potential and challenges of RPM in Germany. While there are promising developments in the field, such as remote monitoring and the electronic patient record, data protection and regulatory issues must be addressed for the widespread adoption of RPM in Germany. One potential solution is the creation and implementation of a uniform electronic patient record that contains all pertinent patient information and can be used by all involved healthcare providers and care facilities.Mr. Alexander Keil
University of Siegen
Ms. Faduma Ikar
University of Siegen
Ms. Jessica Bui
University of Siegen
Ms. Nafisa Musse
University of Siegen
Mr. Kai Hahn
University of Siegen
#remote patient monitoring #telemonitoring #vital data #data security #health infrastructure
3
09:00 - 09:15
Introduction
Next to the increase of regulatory requirements, poor screening-to-recruitment ratios, lack of patient engagement, and long timelines for contracting and institutional review board (IRB) approval are leading to an outflow of clinical trials in the EU. Patient registries are a potentially rich source of data, especially for evaluating the course of rare diseases and effects of new treatments. In the sectors of regulatory assessments of medical devices they are greatly underused. Health-related real world data provide crucial support for regulatory decision-making, particularly post-market assessments of medical products. Registries can be used not only for observational studies, but also for conducting experimental study designs.Methods
Register-based randomized controlled trials (RRCTs) are of particular importance here, as they can combine the advantages of randomized controlled trials (RCT) and registers.Results
Medical Device Regulators has recommended that a medical device registry should have a case ascertainment of at least 95%, if it is to be accepted as providing high-quality data that is sufficiently robust to inform regulatory decisions. Challenges of registry-based randomized controlled trials such as registry data quality, ethical issues and methodological challenges have to be taken into consideration before conducting RRCTs.Conclusion
The government's financial support and reduction of regulatory barriers to the implementation of registry-based RCT are incentive factors for manufacturers to let their medical devices (re-)certified. Furthermore, it is essential that the necessary criteria are already taken into account when setting up the German implant registry in order to enable future RRCTs. The factors outlined in this paper are intended to ensure that patient registry data are used to adequately support regulatory assessments in the future.Mr. Matthias Leuchter
Institute for ImplantTechnology and Biomaterials e.V.,
Rostock-Warnemünde, Germany
#Medical Device Regulation #post-market clinical follow-up #registries #Mregulatory affairs
4
09:15 - 09:30
Introduction
Extended time to market, late failure finally in clinical implementation, and declining innovation in healthcare –these are all symptoms of the translational crisis in biomedical engineering.Far too often, innovative medical devices are lost in the valley of death due to complexity and the lack of connection to clinical demand, typical for the technology push approach. Although demand driven innovations are more likely to get marketed, hardly any procedures have been established to effectively find an optimized technological solution from a given clinical need with the greatest possible technology openness.
Therefore, we explored the potential of AI-based mining of published knowledge to find demand matching technological solutions for a real oncological use case.
Methods
Starting from a scoping review, two different seed-document-based and automated search procedures, bag-of-words (Bow) and a readily available semantic PubMedBERT model trained on sentence similarity task, are engaged on localized PubMed and PATSTAT databases. A final machine learning classifier is trained using scoping results to accelerate the relevance screening. A workshop of experts contributed to evaluate and embed the AI based steps into a process leading from clinical demand to substantial funding or investment.Results
While the Bow approach revealed 91% work-saved-over-sampling and overall recall at 76% on publications, it performed weak on patents. Here the semantic BERT approach showed its strength. The manual synthesis suggested three possible feasibility projects to be conducted simultaneously and finally guided by e.g. regulatory experts towards venture team building and pitching.Conclusion
The results point the way to a comprehensively modified innovation path starting from unmet medical needs. But to shape such a disruptive demand driven innovation path, technology openness, parallelism in early innovation phases, and a reduced sector structure in public research funding must be instituted..
Mr. DR. Robert Farkas
AME - Institute of Applied Medical Engineering
- Helmholtz Institute -
RWTH Aachen University | University Hospital Aachen
#Translational Gap #Innovation Process #Textmining #Machine Learning #Resilience #Medical technology
Tue
26 Sep
08:30 - 10:00
BMT T-07
Hospital Engineering
Room: Philharmonie (Location: Philharmonie)
Chair: Sebastian BuhlSubmissions:
1
08:30 - 08:45
Mr. Dr. Sebastian Buhl
Ostbayerische Technische Hochschule Amberg-Weiden
#Introductory lecture
2
08:45 - 09:00
Introduction
The disinfecting effect of UV-C radiation on microorganisms has long been known [1]. The technology is already being used in some areas such as water treatment. Recently, another field has been developing, namely autonomously acting UV-C robot systems [2]. In this work the disinfecting potential of such an UV-C System (HERO21, ICA Traffic GmbH) was investigated for the possibility of disinfection in a clinical setting. Such systems could be an additional factor in infection prevention and patient safety.Methods
The UV-C robot system was tested in the Research OR (OTH, Amberg-Weiden) for its effectiveness. For this purpose, standardized soiling with a solution of test bacteria (Staphylococcus aureus, ATCC 6538; 1*106 CFU/ml) was applied and the residual contamination after UV-C disinfection was determined by contact plates. In a second test run, the implementation of the system in hospital setting was investigated. Therefore, surfaces were contaminated in a patient room following the routine measures anaolgous to the first test and the efficiveness of the UV-C robot system was evaluated in a real clinical environment.Results
The evaluation showed effective germ reduction by the system. Due to the test concept and set-up, the maximum germ reduction of >3.7 log levels could be achieved at almost all test sites. The tests in the hospital under clinical conditions also showed similar results. Lower reduction rates were achieved at test sites difficult to clean and reach by UV-light (drawers, backs of surfaces, etc.).Conclusion
The study could prove the effectiveness and feasibility of integrating such a system into clinical settings. However, in a realistic clinical environment, limitations of the application also become apparent. Further investigations are needed to clarify how the use of such a UV-C robot can support the clinical staff in infection prevention and control in the future.Mr. M.Sc. Alexander Stich
Technical University of Applied Science Amberg-Weiden, 92637 Weiden, Germany
#UV-C disinfection #hygienic measures #clinical hygiene #germ reduction
3
09:00 - 09:15
Introduction
We have developed an enhanced version of the FLow-controlled EXpiration (FLEX) system for linearizing expiratory flow that is usable in conjunction with a conventional ventilator and with spontaneously breathing patients. Being demonstrated an important option for lung-protective ventilation already, we hope that linearization of the expiratory flow based on closed-loop control will further improve patient outcomes and provide a more effective impact of mechanical ventilation for studies in patients with lung diseases.
Methods
We have developed our improved FLEX system based on self-designed 3D-printed parts, as well as a flow sensor and up to three pressure sensors. These sensors enable comprehensive monitoring of respiratory parameters and fine-tuning of expiratory flow. The system employs a rotating disc within a tube to adjust the size of an aperture. This disc is magnetically connected to an external hollow-shaft stepper motor, enabling contactless flow adjustment. This design allows for precise linear step-wise flow control, and by serving as a media-separated flow control valve, it eliminates the need for electronic components in the breathing tubes. We tested the new FLEX system with various mechanical ventilators and different test lungs and in large animal experiments.
Results
The system effectively linearized expiratory flow, even at high expiratory flow rates up to 100 liters/min, and with various ventilation modes. In animal studies, our system was able to linearize the expiration in lung-healthy and lung-injured pigs, even with respiratory rates up to 50/min.
Conclusion
We have developed an improved FLEX system that provides a more accurate and reliable means of linearizing expiratory flow even at high flow rates and high respiratory rates, which makes it particularly effective in achieving lung-protective ventilation. Furthermore, due to the contactless control of the aperture the gas-carrying tube remains intact. This would allow a save use in patients without risk for leak.
Mr. Prof. Stefan Schumann
Department of Anaesthesiology and Critical Care, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
#mechanical ventilation #closed-loop system #flow control #lung-protective ventilation
4
09:15 - 09:30
Introduction
Small animals, especially mice and rats, are mostly used in pre-clinical studies. For all models where the respiratory system is depressed or subject of analysis, mechanical ventilation is indispensible. However, commercial small animal ventilators are both expensive and limited in their functionality, as they only provide limited ventilation patterns. The development of a low-cost small animal ventilator comprising exclusively of commercially available components that allows for more comprehensive ventilation options could greatly benefit the research community.
Methods
We have developed a small animal ventilator based on a cylinder pump system (Festo), which is driven by a linear motor with a lead screw (Nanotec). This system allows for precise and controlled delivery and removal of a defined volume of gas to and from the animal's lungs. Valves (Bavaria Fluid Systems) are used to enable fresh gas supply and a variable positive end-expiratory pressure (PEEP). The system is capable of generating respiratory rates up to 120/min with tidal volumes up to 4ml in ventilation mode, and also tidal volumes up to 15ml with lower respiratory rates, e.g. for recruitment maneuvers. The ventilation patterns can be customized by choosing different inspiration and expiration curves following any mathematically representable curves.
Results
The small animal ventilator was confirmed to deliver the desired tidal volumes and respiratory rates with an external flow and pressure measurement at various ventilation patterns including linear, exponential and sinusoidal flow patterns in inspiration and expiration. The results showed that the delivered tidal volumes, respiratory rates, PEEP and ventilation curves were in agreement with the set parameters and independent of the chosen ventilation pattern. Total component costs were about 650€.
Conclusion
In summary, this system allows labs to set up a small animal ventilator at a significantly lower price than commercially available models and to customize ventilation patterns with any mathematically representable curves.
Mr. Prof. Stefan Schumann
Department of Anaesthesiology and Critical Care, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
#small animal ventilator #microcontroller system #low-cost system #ventilation research
Wed
27 Sep
08:30 - 10:00
BMT S-03
Terahertz in Medicine
Room: Room 1 "Terahertz" (Location: Meeting Room 1)
Chairs: Andreas Prokscha and Niels BensonSubmissions:
1
08:30 - 08:45
Introduction
Remote sensors for environmental monitoring can play an important role in pathogen detection in the future. The development of remote sensors is complicated by various requirements such as high sensitivity, long reading range, compactness, and low cost. Electromagnetic (EM) sensors have the advantage that they can use the same radiation for sensing, communication, and localization. Among various EM sensors, terahertz (THz) photonic crystals (PhC) can achieve high sensitivity and long communication range simultaneously.Methods
The proposed remote sensor consists of a PhC resonator for sensing and a dielectric rod antenna (DRA) for efficient coupling from the free-space. Pathogens can be identified and quantified by a frequency shift of the resonance. The signal from the resonator is radiated from the DRA and can be extracted by a read-out device and post-processing steps.The PhC chip is fabricated with alumina using lithography-based ceramic manufacturing technique and characterized using a vector network analyzer connected to a horn antenna. The chip is placed in front of the horn antenna at a distance of 0.5 m. 1.5 µL of different concentrations of protein solution as a mock-up for the pathogen is pipetted onto the resonator.
Results
The resonance frequency can be wirelessly detected with a high signal-noise-ratio. The dried protein leads to a resonance shift. The resonance shift is linearly related to the protein concentration with a slope of 5.2 MHz µL µg-1.Conclusion
The proposed PhC chip can detect biomolecules with long range wirelessly. In addition, the proposed chip has the advantage of being non-electronic, having a long lifetime, and being suitable for harsh environments.Mr. Yixiong Zhao
University of Duisburg-Essen
#terahertz #wireless #biosensors
2
08:45 - 09:00
Introduction
Rehabilitation aiming at patient mobilization often requires mechanical guidance, using equipment such as motorized exoskeletons or prosthetics. The state of the art enables this using complicated setups, where sensors are a vital part of the human machine interface. Yet, as typically one sensor is attached to one cable, depending on the complexity of the system, this has strong limitations in terms of errors, interference and patient comfort. Epidermal electronics is a potential solution, conforming directly to the surface of the skin and capable of integrating a multitude of sensors without negatively impacting patient comfort. Yet, despite all its promise, real world applications have eluded epidermal electronics so far, due to Young's modulus, silicon front end and substrate breathability challenges.Methods
Here, we introduce a concept, which completely rethinks epidermal electronics to address above issues, and to enable passive, wireless exoskeleton or prosthetics control. Our approach makes use of the unique THz properties of Graphene, which are tuneable by electronic gating, such as by muscle induced skin surface potential variation, enabling the efficient control of THz reflection and absorption. This makes passive and wireless epidermal electronics possible, relying only on an external THz transceiver, e.g. exoskeleton or prosthetic integrated, which measures muscle movement in reflection from a graphene based passive and chipless epidermal electronic matrix.Results
A proof of principle of this concept will be demonstrated, using a Reconfigurable Intelligent Surface (RIS) based on Al / AlOx / Graphene / Au stack, where the Au electrode features graphene windows, allowing THz reflection measurements in dependence of the potential difference between the two electrodes. This is evaluated in the 500GHz to 3THz range, using a TDS system with a spectral range >6 THz and a single shot dynamic range of up to 60dB.Conclusion
By controlling the skin surface potential dependent THz absorption and reflection of Graphene, a novel chipless and passive epidermal electronics concept becomes feasible, for which as a proof of principle is demonstrated here using a gateable RIS.Mr. Prof. Dr. Niels Benson
University of Duisburg-Essen
#Epidermal Electronics #Body Motion #Graphene
3
09:00 - 09:15
Ms. Dr. Mandana Jalali
General and Theoretical Electrical Engineering (ATE), Faculty of Engineering, University of Duisburg-Essen,
and CENIDE – Center for Nanointegration Duisburg- Essen, D-47048 Duisburg, Germany
#Diabetes #Glucose sensing #Fingernail bed #Cole-Cole model #THz radiation #THz-TDS
4
09:15 - 09:30
Based on the assumption that muscle activity causes skin deformations, a non-contact camera-based method is developed that can capture multiple images of the skin surface of a preferred body part. By using a photogrammetry tool and computing a 3D model of the body part, time-varying deformations can be represented that can be attributed to muscle activity. To do this, a 3D printer and tripod were used to create a camera mount that can vary in height and also change orientation. For the camera system itself, the Raspberry Pi Camera Module 3 Wide with an image resolution of 12 megapixels was selected according to specially defined evaluation criteria.
The first images showed promising results in terms of simultaneous recording and transmission of images to a central computer.
The next step is to finalize the measurement system. Afterwards, the photogrammetric part can start to enable the measurement of muscle activity. In the future, this stand-alone system will serve as ground truth for a contactless THz-based system to be developed in the terahertz.NRW initiative. The envisioned THz-based approach for muscle sensing will enable reflectance measurements with a THz beam directly on the skin surface. Since skin deformation also plays a significant role here, it makes sense to include a reference system such as the camera system to properly evaluate the results.
Mr. Sabisan Santhakumaran
University of Duisburg-Essen
Ms. Prof. Dr. Elsa Andrea Kirchner
University of Duisburg-Essen
#muscle activity # skin deformation # photogrammetry # THz reflectance measurement
5
09:30 - 09:45
Terahertz – based non-contact vital sign measurements (Diana Goller, Christian Wiede, Karsten Seidl)
Introduction
Vital signs are essential indicators of a person's physiological status and overall health. Regular monitoring of vital signs enables early detection of health issues, guides treatment decisions, and aids in assessing the effectiveness of interventions. Conventional methods have the disadvantage of being contact-based, which leads to low comfort when worn especially for people with sensitive skin. In recent years, terahertz technology has emerged as a promising candidate for contactless vital sign measurement. We are presenting an overview of our latest research that investigates the feasibility and accuracy of using terahertz technology for assessing vital signs without contact.Methods
Our approach to non-contact measurement uses terahertz-based reflection measurements at 230 - 320 GHz. Terahertz reflection measurements give the possibility of evaluating accurate distances. That can be used to determine heart rate and respiration rate, as the heart beats, the blood flow induces minute movements of the body, including the chest, and the skin. These movements can be measured by the system.Similarly, during respiration, the expansion and contraction of the chest result in movements that can be detected by the measurement system. By analyzing the resulting signals, the respiratory rate can be calculated.
Results
We successfully determined and evaluated the heart rate and respiration rate in clinical and care environment. In particular, the use of neural networks allows to detect critical conditions and changes over time.Conclusion
Our approach highlights the potential of terahertz technology for non-invasive and contactless measurement of vital signs. The results indicate that terahertz-based-systems can measure more accurately than classical radar-systems. They can detect and monitor changes in heart rate and respiratory rate. Furthermore it gives the oppurtunity to be miniaturized in future due to the higher frequencys. By using artificial intelligence, critical conditions can be detected and changes over time can be analyzed.Ms. Diana Goller
Fraunhofer IMS
#vital parameters #Artificial Intelligence #terahertz
Tue
26 Sep
10:15 - 11:45
BMT W-02
Professor at a university of applied sciences: Career paths for female academics - Workshop: How can I actively approach this career path?
...
Room: Room 1 "Terahertz" (Location: Meeting Room 1)
Chairs: Gudrun Stockmanns and Sandra LaumenTue
26 Sep
10:15 - 12:00
BMT S-05
Nanomedicine and Theranostics I
Room: Room 2 "Innenhafen Duisburg" (Location: Meeting Room 2)
Chair: Fabian KiesslingSubmissions:
1
10:15 - 10:30
Methods: Drug delivery systems (DDS) have been developed to improve biodistribution and therapeutic index.
Results: The number of new drug approvals and investigational applications based on DDS has steadily increased, but setbacks have triggered discussions about the future of anticancer DDS design and clinical translation.
Conclusion: In this session we will discuss strategies to overcome the current challenges in the field of anticancer DDS development and to explore therapeutic and theranostic scenarios that lead to improved patient outcomes. These include pharmacological or physical treatments that modulate tumor blood vessels and the microenvironment to improve drug delivery, strategies to boost the efficacy of immunotherapy and the use of companion diagnostics and nanotheranostics for patient stratification.
Mr. Prof. Dr. Fabian Kiessling
RWTH Aachen University
Fabian Kiessling studied Medicine in Heidelberg. Until 2008, he worked in the Departments of Radiology and Medical Physics in Radiology of the German Cancer Research Center. In parallel, he did his clinical training at the University of Heidelberg and received the board certification as Radiologist. Since 2008 he is leading the Institute for Experimental Molecular Imaging at the RWTH Aachen University. Aim of his research is the development of novel diagnostic probes and imaging tools for a disease specific diagnosis and therapy monitoring. He authored over 400 publications and book chapters, edited four books, and received multiple research awards and honours. 2019-2021 he has been on the list of Clarivate’s Highly Cited Researchers (web of Science).
#Nanoparticles
2
10:30 - 10:45
Introduction
Despite the essential role of animal experimentation in biomedical research, ethical considerations motivate efforts to develop physiologically-relevant in vitro models that mimic the tissue-scale and organization of human solid malignancies. We present a novel 3D bio-printed artificial tumor model that self-organizes into functional and perfusable vascular structures.Methods
We utilized extrusion-based bio-printing techniques and gelatin mixed with EC as vascular and fugitive bioink. The printing was conducted into a custom-designed PEEK bioreactor that is imaging-compatible. An ECM-mimicking collagen-fibrin hydrogel blend mixed with stromal cells was casted between the printed gelatin strands, where a multicellular tumor spheroid was positioned. After gelatin liquefaction, the bioreactors were cultivated for up to three weeks under physiological flow conditions in a recirculating fluid loop, and capillary network formation and functionality were assessed by the use of red blood cells and microbeads.
Results
We successfully bioprinted tumor feeding vessels that mimic natural vessel conformation, including anastomoses, curves, and variations in lumen size. Our PEEK bioreactor with optically transparent windows enabled real-time monitoring of cell growth, and its inner spaces of centimeter thickness could contain sufficient volumes of hydrogel for long-term durability while facilitating growth of biological material beyond the micrometer scale. Angiogenic tumor spheroids promoted the growth of the vascular network, and the supportive vascular network, in turn, promoted the growth of co-cultivated tumor spheroids. The self-evolved vascular structure infiltrated the tumor spheroids, forming functional connections with the bioprinted endothelium, and proved perfusability to erythrocytes and 10 μm polystyrene μbeads. Additionally, our bioengineering approach proved suitable for the cultivation of patient-derived material, reflecting the phenotypic heterogeneity of human malignancies, similar to engraftment of cancer cells in mice.
Conclusion
Our novel 3D platform has the potential to enhance the predictive power of in vitro experimentation in basic cancer research and drug development, reducing the reliance on animal use.
Ms. Federica De Lorenzi
RWTH University Hospital Aachen
#Tissue Engineering
3
10:45 - 11:00
Introduction
Single-walled carbon nanotubes (SWCNTs) are an emerging material for chemical imaging, stand-off in-situ diagnostics, and process control. This is due to their near-infrared (NIR, 870 – 1700 nm) fluorescence emission, which offers extremely low background in biological samples. Chemical modification of the SWCNTs enables molecular recognition of target analytes with high sensitivity and selectivity by a fluorescence change upon analyte interaction. Powerful SWCNT-based sensors have been developed for bacterial motifs, signalling molecules like neurotransmitters or H2O2, lipids and proteins. However, so far, SWCNT sensors have mainly been processed from mixtures of different chiralities, because SWCNT growth cannot be adequately controlled during fabrication. Since the emission wavelength depends on the respective SWCNT chirality, this means a spectral overlap and congestion. At the same time, the emission in the NIR makes detection with typically used silicon-based cameras difficult due to decreasing sensitivity in the NIR (around 5% at 1000nm).Methods
Therefore, we developed an efficient separation approach to obtain (6,4)-SWCNT species (emission at 880 nm) from commercial SWCNT mixtures and tailored them exemplarily as sensors for the important neurotransmitter dopamine using specific DNA sequences.Results
It enabled us fast imaging (< 50 ms) with high-resolution standard cameras (> 50x more pixels compared to expensive InGaAs detectors actually designed for the NIR range and typically used). In addition, these sensors are 1.7-fold brighter and 7.5x more sensitive for dopamine. Furthermore, we show high-resolution imaging of dopamine release from cells.Conclusion
In conclusion, this approach provides fluorescent sensors that enable NIR biosensing and imaging of these nanomaterials in any conventional microscope or camera. Thus, the assembly of biosensors from (6,4)-SWCNTs combines the advantages of nanosensors working in the NIR with the sensitivity and low cost of standard cameras. This advance will make these powerful molecular sensors available to a broad community.Ms. Julia Ackermann
Fraunhofer-Institute for Microelectronic Circuits and Systems
Julia Ackermann received her M.Sc. in nanoengineering with a focus on nano-(opto)electronics at the university of Duisburg-Essen (Germany). Since 2020, she has been pursuing her Ph.D. at the Fraunhofer Institute for Microelectronic Circuits and Systems in Duisburg in the technology division of biomedical nanosensors. Her work focuses on improving the overall sensitivity and selectivity of carbon nanotube-based sensors by purification processes and pattern recognition.
#Sensor
4
11:00 - 11:15
Introduction
There is no clinically established prediction tool for the tumor accumulation of untargeted nanocarriers. While imaging of radioactively labeled nanocarriers is in principle an alternative, it is challenging to implement in daily clinical routine. As an applicable alternative, we here identified blood vessels and macrophages as histological biomarkers to differentiate between low- and high-accumulating tumors.
Methods
Tumor-bearing mice (A431, MLS or CT26) were injected with a fluorophore-labeled polymer (poly(HPMA), 10-20 nm) and the tumor accumulation was imaged via CT-FLT. Histological stainings of e.g. blood vessels, macrophages, smooth muscle actin, collagen or nuclei were used to screen for biomarkers correlating with the tumor accumulation of polymers. The whole set of biomarkers was further evaluated by gradient tree boosting identifying blood vessels and macrophages as predictive for tumor accumulation. In addition, resected patient tumors (head and neck, breast and lung) were histologically evaluated and compared with accumulation levels based on Harrington et al [PMID:11234875].
Results
Polymer accumulation varied between models (from 5 ID% for A431 up to 11 ID% for CT26) and several histological biomarkers correlated with tumor accumulation. Gradient tree boosting further confirmed the importance of blood vessels and macrophages (R² values of 0.5 for blood vessels and 0.8 for macrophages over all three models). Based on tumor accumulation values of doxorubicin-loaded liposomes in patients (head and neck, breast or lung, from Harrington et al.,) we could also show that it might be well possible to identify tumors that are highly unlikely to accumulate sufficient amounts of a nanocarrier using stainings of blood vessels and macrophages.
Conclusion
Using immunohistological stainings of blood vessels and macrophages, we were able to predict the nanocarrier accumulation of murine tumors. Our findings on human samples point towards a possible cost-efficient and broadly available measure to preselect patients in clinical trials.
Mr. Jan-Niklas May
RWTH Aachen University
#Nanomedicine #Patient Stratification #Biopsy #Gradient-Tree Boosting
5
11:15 - 11:30
Introduction
Sonoporation describes the creation of pores in cells as a consequence of nearby microbubble (MB) oscillation observed under ultrasound (US) exposure. Hard shell MB respond differently to US than soft shell MB which have been extensively analyzed in the past decade. This study evaluates suitable US parameters for the application of hard shell poly(n-butyl cyanoacrylate) (PBCA) MB to open cell membranes and cell-cell contacts.Methods
Epithelial cells were seeded on the bottom side of transwell inserts, brought into direct contact with the PBCA-MB which were treated with focused US at 1 MHz and five different acoustic pressures between 300-1500 kPa for 2 s. Cell membrane opening (n=9/ pressure) was investigated by propidium iodide (PI) uptake, the cytoplasm of intact cells was stained with fluorescein diacetate (FDA). Opening of cell-cell contacts (n=6/ pressure) was monitored by transepithelial electrical resistance (TEER) measurements using an EVOM2 device with a STX2 electrode before and after US application. Control groups were equally treated as the treatment groups, but without MB.Results
US-MB treated groups showed higher uptake of PI in comparison to the control groups (US only). PI uptake increased with US intensity. Independent of the US intensity, the TEER values decreased after US-MB and only US treatment. However, TEER drop in the US-MB treated groups was significant larger than in US only groups pointing to an opening of cell-cell-contacts mediated by MB-US interaction.Conclusion
Sonoporation with hard shell PBCA-MB induces pores in the cell membrane and disrupts intercellular contacts indicated by PI/ FDA uptake and change in TEER, respectively, already at low US intensities. As a next step, we will evaluate whether similar sonoporation effects can be induced by using soft shell MB with the same US settings.Ms. Julia Blöck
RWTH Aachen University
#Microbubbles #Sonoporation
6
11:30 - 11:45
Introduction
The tumor-microenvironment (TME) plays a key role in disease progression, thus emerging as a promising therapeutic target. For preclinical evaluation of TME-targeted therapies, we need models that (i) mimic the basic in vivo architectural features of solid malignancies (ii) are composed of distinct cell populations, and (iii) allow for longitudinal monitoring via imaging. Here, we utilized customized 2D co-cultures and 3D multicellular tumor spheroids to evaluate the efficacy of antifibrotics in combination with chemotherapeutics as a TME-targeted therapy.Methods
Ovarian cancer cells were co-cultured with fibroblasts to obtain customized 2D and 3D in vitro models. Different therapies such as (i) free-telmisartan, (ii) free-doxorubicin, and (iii) telmisartan-doxorubicin electrostatic pair (TelmiDOX) were applied to both the systems. 2D co-cultures were analyzed 24h and 48h post treatment whereas 3D spheroids, 2- and 5-days post treatment. The therapy outcome was analyzed via brightfield (BF) microscopy, western blotting, immunofluorescence (IF) and XTT to assess the ECM deposition and profile drug toxicity.Results
In 2D, quantification of IF images showed similar collagen deposition upon DOX and TelmiDOX treatment, suggesting the prevailing action of DOX over telmisartan. Spheroids showed reduction of diameter upon treatment with DOX and TelmiDOX. Similar cytotoxicity profiles for DOX and TelmiDOX indicated that electrostatic combination of doxorubicin with telmisartan did not alter the cytotoxic effect of DOX. The marginal differences between DOX and TelmiDOX allude to the insignificant / slow action of telmisartan and consideration of sequential administration in vivo.Conclusion
We demonstrated the use of 2D and 3D in vitro models for evaluating the effect of TME-targeted therapies. The multicellular spheroids displayed ECM deposition by stromal cells and were sensitive to drug treatment. The prevailing effect of DOX in the complex with Telmisartan, denotes that a sequential administration should be selected in an in vivo set-up, where a preceding administration of Telmisartan is selected.
Ms. Rasika Daware
Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University
#Combination therapy #Tumor microenvironment
7
11:45 - 12:00
Introduction
RNA therapeutics are a highly promising and emerging class of drugs for the treatment of various diseases in oncology and beyond. Their success rely on the use of drug delivery systems (DDS). Improving DDS-based RNA delivery requires implementation of superior imaging strategies. We herein show a multimodal and multiscale approach for monitoring the transfection, efficacy, biodistribution, and target site accumulation of RNA nanotherapeutics.Methods
RNA lipid nanoparticles (RNA-LNPs) with variable characteristics were manufactured using a T-junction or chaotic mixer microfluidic setup. The LNPs were assessed for their size, dispersity and zeta-potential via dynamic light scattering and electron microscopy. The particle uptake and transfection / knockdown efficacy were assessed via fluorescence microscopy and colorimetry. Therapeutic efficacy was assessed via life-cell imaging, visualizing changes in fluorescence life-times (FLIM) of NAD(P)H autofluorescence excited via two-photon microscopy. The biodistribution and target-site accumulation of a Cy7-labelled, firefly luciferase mRNA-loaded LNPs were assessed via hybrid µCT and fluorescence tomography (µCT-FLT).Results
Systematic screening of LNPs showed tuneable particle properties depending on the lipid composition or microfluidic settings. Functional screening in 4T1 and Hepa1-6 cancer cells demonstrated consistent differences in transfection/knock-down efficacy. FLIM data demonstrated quantifiable changes in redox-states of L929 fibroblasts before and after stimulation, and further visualised the metabolic and cell death response of Hepa1-6 after gene silencing using RNA-LNPs. Finally, µCT-FLT of 4T1 tumor-bearing mice showed distinct biodistributions of Cy7-mFLuc-LNPs upon different routes of administration, including tumor accumulation at 24h after i.m. injection.Conclusion
Using FLIM, we sucessfully evaluated cellular redox-state readouts for differentiating cell death pathways in treated cells. We further visualised and quantified particle uptake and RNA expression/knockdown in vitro and went on to track labelled particles with expresing mRNA in vivo.Mr. Jeffrey Momoh
Institute of Experimental Molecular Imaging, University hospital RWTH Aachen
#RNA delivery #lipid nanoparticles #Optical imaging #Microfluidics
Tue
26 Sep
10:15 - 11:45
BMT S-04
Magnetoelectric Sensor Systems for Biomedical Applications I
Room: Room 3 "Landschaftspark Duisburg-Nord" (Location: Meeting Room 3)
Chairs: Gerhard Schmidt and Eric ElzenheimerSubmissions:
1
10:15 - 10:30
Introduction
Surface acoustic wave (SAW) sensors are widely used in medical technology, e.g. for the analysis of microfluids. In recent years it has been shown that SAW sensors can also detect low magnetic fields [1]. They reach a limit of detection (LOD) below 100 pT/Hz for a frequency range between 1 Hz and 10 kHz. Therefore, they are promising for magnetic field assisted medical therapy such as deep brain stimulation.Methods
The SAW sensor excites an acoustic wave at interdigital transducers (IDT) on a piezoelectric substrate. A wave guiding layer confines the wave to the surface. The IDTs are arranged in a delay line, with a magnetostrictive sensing element located in between. A magnetic field generates a phase change in the SAW via the ΔE effect - change of elastic properties as a function of magnetization - in the sensing layer. For sensor fabrication, a ST-cut quartz substrate is coated with gold IDTs and amorphous SiO2 as a wave guiding layer. As a magnetic sensing layer amorphous FeCoSiB is sputtered by PVD on top. The sensitivity is determined by a Zurich Instruments UHFLI lock-in amplifier via a dynamic phase detection. Soft magnetic ribbons (Vitrovac 602SX) are used as flux concentrators, yielding a sensor size of 1.5 cm x 3.5 cm.Results
The state-of-the-art magnetic film deposition yielding in a high sensitivity is discussed. The dominant noise sources are found to be magnetically induced 1/f noise at lower frequencies and a constant thermal noise at higher frequencies. We show that flux concentrators can be used to increase the sensitivity to 7500°/mT at the expense of spatial resolution. The limit of detection is 15 pT/Hz at 10 Hz.Conclusion
The use of flux concentrators for magnetic sensing with SAW sensors results in 3 times greater sensitivity and 2 times smaller LOD.[1] A. Kittmann et al., Scientific Reports, vol. 8, no. 1, 278–287, 2018.
Mr. Felix Weisheit
Kiel University
#surface acoustic wave #magnetic field sensor
2
10:30 - 10:45
Introduction
The demand for magnetic field sensors has increased rapidly, driven not only by the need for systems with navigation, orientation, and motion tracking, but also by their growing use in the automotive sector and particularly in biomedical applications. The magnetosensitive material of the sensor presented here is a magnetostrictive polymer composite (MPC) composed of ferromagnetic particles embedded in a soft polymer matrix. The capacitive sensor includes an electret and is suited for biomedical applications due to its low resonance frequency of approximately 100 Hz.Methods
The sensor was characterized through three measurements. The AC resonance frequency of the sensor was determined through a frequency sweep, followed by a DC magnetic bias field measurement to identify the optimal working point. For the final measurement the sensor was operated at resonance frequency with the optimal bias field. The amplitude of the resonance frequency was decreased with each measurement to determine the minimum field that the sensor can measure.Results
The resonance frequency ranged from 50-150 Hz, which strongly depends on the geometry of the MPC. The sensor needs a bias field of several mT. This measurement also demonstrates that nothing within the sensor is remagnetized during the bias sweep. Even when not optimized, the sensor shows a linear behavior over 4 orders of magnitude and has a limit of detection of 9.6 nT.Conclusion
The sensor characterization of this novel sensor concept showed that it works in principle and that its magnetic properties are not changed when exposed to magnetic fields. It may provide insight into the limiting factor of all magnetic field sensors, which is noise. The mechanical properties of the sensor arise from the polymer matrix, while the magnetic properties are dominated by the particles. Both components can be changed independently.Mr. M. Sc. Lukas Zimoch
Christian-Albrechts-University of Kiel
#ME Sensor #Magnetostrictive Polymer Composite #Electret
3
10:45 - 11:00
Introduction
Accurate calibration is key for any reliable sensor system. Magnetoelectric (ME) sensors, in particular, are influenced in their operating point by external parameters such as the Earth’s magnetic field or the ambient temperature. We introduce a new planar coil design for the generation of a magnetic test field within the plane of the ME sensor. Furthermore, we implemented a method for measuring the sensor behaviour using a short-term magnetic noise signal. The combination of the printed circuit board (PCB) coil and the accelerated sensor characterization method allows the sensor system to be calibrated at the measurement site (in situ) without the need for laboratory equipment. We can show that the presented method for calibration achieves high-quality results in 10 seconds for a sensor affected by external interference fields.Methods
We experimentally compare the state-of-the-art method for determining sensor system characterisation and calibration with the newly implemented method using a PCB coil system. Both methods are used to approximate the sensor system with a filter.Results
The amplitude response of the sensor system can be determined equally with both measuring methods. Our new method is significantly faster than the state-of-the-art and robust against external parasitic magnetic fields.Conclusion
Based on visual inspection, the results obtained via the in situ measurement method are in high agreement with the results from a conventional characterisation. Both the measurement time and the measurement effort could be significantly reduced. It simplified filter design in comparison to discrete measurement points, which can, e.g., not anticipate slight changes in the resonance frequency due to interference fields.Mr. Henrik Wolframm
Kiel University
#IIR peak filter #Magnetoelectric sensors #noise signal #PCB coil #sensor system calibration
4
11:00 - 11:15
Introduction
This contribution presents a new motion tracking algorithm. Motion analysis is of great interest in virtual reality projects and medical diagnostic applications. In this case, the motion tracking application is to be used as a control interface for robotic surgery. To do this, the hand movement needs to be tracked in real time. We assume the hand as a kinematic chain model with magnetic sensors on every chain element. The commonly used localization algorithms are often computationally very intensive and are not suitable for an application with 30 or more sensors. Thus, a new and cheap iterative algorithm has been developed.Methods
This approach uses an iterative procedure to estimate the attitude of the hand. This is done by specifically designed magnetic exciation signals that allows to extract special features from the received sensor signals. These new features could be used to calculate the orientation for any position or the position for any orientation. These relations were combined with a priori knowledge oft he human anatomy to form an iterative algorithm.Results
The functionality of the algorithm was verified using a simulation. For this purpose, the algorithm was implemented in a real-time toolkit and individual movements were tested. A small prototype with a demo joint was built to test the algorithm in reality.Conclusion
In summary, a method for estimating hand posture has been developed. This method is characterized by a very low computational complexity. In the future it will be necessary to refine the utilized anatomical model and to improve the performance using a Kalman filter or other post-processing algorithms.Mr. Tobias Schmidt
Technische Fakultät Uni Kiel
#Magnetic localization #Motion tracking #kinematic chain
5
11:15 - 11:30
Introduction
Magnetic motion sensing enables non-contact tracking of relative position and orientation in 3D space. Recent advances in sensor and actuator technology, such as magnetoelectric (ME) sensors and permanent magnet cantilevers, are paving the way for novel applications in human movement analysis. However, establishing a setup from scratch in terms of hardware and software is challenging.Methods
We introduce a comprehensive simulation pipeline based on a digital twin concept. This includes a movement simulation based on kinematic chains and artificially generated movement sequences, which enables arbitrary placement of sensors and actuators. The resulting signals are forwarded to a kinematic processing stage and then fed into a magnetic sensor/actuator model with basic options for signal enhancement. At the system design stage, the idea is to transfer simulation results to a physical setup. Conversely, real-world measurements can be used to increase the simulation's realism. Validating motion sensing algorithms, such as Kalman filters or machine learning approaches, with simulated data accelerates the development cycle compared to real measurements. The digital twin offers a direct comparison between estimation results and the (simulated) ground truth.Results
Magnetic motion sensing plays out its benefits in specialized applications where other methods cause additional effort, are unavailable, or imprecise. We emphasize recent and prospective applications of our approach in terms of the physical and the corresponding digital twin. This includes step kinematics analysis, sensor glove tracking, swallow analysis, and magnetocardiography (MCG) in terms of heart localization.Conclusion
We described a real-time simulation pipeline for magnetic motion sensing that was applied in multiple exemplary applications. Regardless, some limitations regarding the definition of simplified artificial movements and sensor model details remain. Therefore, we consider the import of optical motion capturing data for reference purposes.Mr. Johannes Hoffmann
Kiel University
#Digital twin #Magnetic methods #Magnetoelectric sensors #Motion Sensing #Localization
6
11:30 - 11:45
Introduction
While mechanical tracking is commonly seen in robot-assisted surgery, contactless gesture control leads to a more intuitive approach. Magnetic localization systems might be able to provide an untethered access to the necessary hand movement data. A model-based system exploiting a priori knowledge to improve the accuracy and robustness can be beneficial in this context.Methods
We present a proof of concept, in which the index finger of a digital twin of a hand is tracked with three simulated sensors. To validate our tracking approach, the hand simulation is currently comprised of a cycle of a bending and corresponding unbending motion, as it might be used for pointing or - when used with multiple fingers - a gripping movement. Based on the physiological composition, the finger is modeled as a kinematic chain with rotational degrees of freedom between the segments according to the corresponding finger joints. In that, the range of motion of the individual joints is taken into account. We applied an extended Kalman filter using this description to enhance position and rotation estimates for the sensors on the finger segments.Results
As an evaluation reference, the preprocessed signals were filtered with a simple lowpass filter (Butterworth, 2nd order, \(5\,\mathrm{Hz}\)) which exhibits more erratic behaviour. With our method, we achieved mean absolute errors \(<1\,\mathrm{cm}\) for the positions and \(<10^\circ\) for the local rotations with first simulations of a bending motion.Conclusion
The local orientations of segments further along the chain suffer from potential error accumulation from the relative orientation computation during preprocessing, but the results are promising overall which motivates further research with several directions. The usage of the filter for multiple fingers would be of high interest. We also assume further modeling of inter-finger relations and adaptation of the covariance matrices at runtime to be beneficial.Mr. Moritz Boueke
Kiel University
#Extended Kalman filter #kinematic chain #pose estimation #robot-assisted surgery
Tue
26 Sep
10:15 - 11:45
BMT T-16
Model-based and Automated Medical Systems I
Room: Room 4 "Sportpark Duisburg" (Location: Meeting Room 4)
Chairs: Thomas Seel and Philipp RostalskiSubmissions:
1
10:15 - 10:30
Introduction
Staff shortage might affect the quality of medical treatment in the future. Physical stress and the unergonomic design of the equipment further decreases the attractivity of healthcare professions. The usage of medical devices which have a certain degree of autonomy for mechatronic movements might help.
However, to increase the market acceptance of these solutions, staff and patients must trust these mechatronic features.
Methods
Up to now, psychological aspects have only partially been considered during the development of mechatronic features for medical devices. Therefore, it is important to understand how trust is generated.
IEC/TR 60601-4-1 introduces levels of autonomy for medical devices. However, concentrating on mechatronic movements the presented 16 degrees are too complex. Thus, a simplified matrix for this use case was created.
Results
Over- and under-trust is one aspect which must be considered. Often misjudgment occur due to a different understanding of autonomy. The presented matrix can be used for communicating the degrees of autonomy of a certain mechatronic feature. Furthermore, it visualizes who is responsible for a certain task. At the same time, this information defines which safety requirements must be met by the developers.
It is important that the roles of the user and the machine are well-defined. During a certain workflow the responsibilities might change. For this reason, hand-over-points must be intuitive.
Finally, a roadmap for medical devices based on different levels of autonomy helps to generate trust and increase user acceptance.
Conclusion
Trust in autonomous medical devices is important for market acceptance. The definition and communication of autonomy levels reduces the risk of over- and under-trust. Furthermore, the matrix defines the roles between humans and machines. For the developer, the degrees of autonomy define the safety architecture of the mechatronic feature. Roadmaps can introduce autonomy to users gradually.
Ms. Dr. Verena Schmidt
Siemens Healthcare GmbH
#autonomous Medical Devices #Levels of Autonomy #appropriate Trust
2
10:30 - 10:45
Introduction
Current retinal implants stimulate all of the locally available Retinal Ganglion Cells (RGCs) indiscriminately, only linearly dependent on the respective pixel brightness. To mimic natural vision more closely, it is necessary to process the optical input of the implant in a way the underlying retinal network would do it, to receive cell-type selective activation functions.Methods
A widely used mathematical representation of RGC behaviour is the Difference of Gaussian (DoG) algorithm. For an ON-RGC, it can be described as\(DoG_{ON} (x,y,t) = I(x,y,t) * \Bigl( \frac{1}{2\pi \sigma^2_{c}} e^{-\frac{x^2-y^2}{2 \sigma^2_{c}}}-\frac{1}{2\pi \sigma^2_{s}} e^{-\frac{x^2-y^2}{2 \sigma^2_{s}}} \Bigl)\),
where \(I(x,y,t)\) represents the input frame, dependent on its x and y pixels and its timestep t. The size of the cell-type dependent receptive field (RF) is defined by the parameters \(\sigma_c\) and \(\sigma_s\). Together with other mathematical operators, this operation is to be realized in FPGA logic with minimum resource requirements.
Results
For an efficient implementation, it is not required to store an entire image frame into internal FPGA memory. Instead, the serial data output of a camera can be used to perform the image analysis sequentially, while only three first-in first-out (FIFO) registers are required to enable the analysis of RF sized structures, reducing the required parallel convonlution units to three. The correlation coefficient between the model output and natural RGC behaviour was 0.969 (ON-transient), 0.915 (ON-sustained), 0.986 (OFF-transient) and 0.83 (OFF-sustained).Conclusion
The shown implementation of the DoG-algorithm can differentiate between eight different RGC-subtypes extracted out of greyscale images. At a fixed frame rate, the maximum image size is dependent on the FPGA's master clock frequency. If a frequency of 200 MHz is used, the maximum image size is 5 megapixels, making this implementation superior to event cameras, that are also usable for this task. This implementation is thus very suitable for use in future retinal implants, as the algorithm's potential lies way above currently available stimulator resolutions.Mr. Philipp Löhler
University of Duisburg-Essen
#electrical stimulation #retinal ganglion cells #convolution #retinal implant
3
10:45 - 11:00
Introduction
The task of hematopoietic cell classification of image data obtained from microscopy images is essential in automatizing clinical workflows of medical experts in the field of hematology. Computed whole-slide image statistics can give quick indications for a multitude of different diseases. Several studies have proposed processing pipelines, nevertheless, evaluation methodology issues w.r.t. real-world applicability remain, e.g. dataset splitting, number of classes, used staining procedure, or microscope resolution.Methods
To ameliorate the effects of these issues we present a facility cross-validated evaluation of hematopoietic cell classifiers based on the DenseNet121 and ResNet152 architectures using four different datasets with different amounts of white and red blood cell classes. The datasets were extracted from bone marrow and peripheral blood and stained using the Pappenheim and faster Wright-Giemsa protocol. We analyze them for variability concerning H&E staining vectors and statistical criteria concerning color and cell size. Paired with cross-validation, we employ model ensembling, augmentation, and normalization to train domain-adapted models for each clinical site. We set our evaluations into practical context by performing an inter-rater analysis on a multi-labeled dataset of neutrophilic granulocytes and additionally evaluate using known metrics accounting for tolerable intra-lineage confusions.Results
We achieve accuracies of \(67.1\% \pm 0.622\%\) in 13-, 8-, and 5-class cross-validation setups, using different amounts of data each. Incorporating confusion tolerance yields accuracies of \(88.36\% \pm 6\%\), whilst ensembling site-specific classifiers increases scores in a similarly significant manner as training on larger combined datasets. Inter-rater agreement makes for accuracy of \(66.5\%\).Conclusion
Our study shows that models trained without appropriate color augmentations experience severe performance drops when evaluated on data from other sites. Especially brightness, contrast, hue, and saturation augmentations outperform staining augmentation and normalization approaches. Whilst our results show slightly better agreement with annotations compared to medical experts, careful analysis of the distribution of confusion remains essential to judge clinical applicability.Mr. Julian Thull
Institute for Experimental Molecular Imaging (ExMI), RWTH Aachen University, Aachen
#automatic blood cell classification #hematology
4
11:00 - 11:15
Introduction
Early detection of negative emotion can lead to timely intervention and effective treatment, thereby reducing the risk of long-term mental health problems such as chronic depression and anxiety disorders. In this study, we aim to develop an automated emotion detection system using electrodermal activity (EDA) signals.