RunDAE model: Running denoising autoencoder models for denoising ECG signals.

BACKGROUND: The denoising autoencoder (DAE) is commonly used to denoise bio-signals such as electrocardiogram (ECG) signals through dimensional reduction. Typically, the DAE model needs to be trained using correlated input segments such as QRS-aligned segments or long ECG segments. However, using long ECG segments as an input can result in a complex deep DAE model that requires many hidden layers to achieve a low-dimensional representation, which is a major drawback. METHODS: This work proposes a novel DAE model, called running DAE (RunDAE), for denoising short ECG segments without relying on the R-peak detection algorithm for alignment. The proposed RunDAE model employs a sample-by-sample processing approach, considering the correlation between consecutive, overlapped ECG segments. The performance of both the classical DAE and RunDAE models with convolutional and dense layers, respectively, is evaluated using corrupted QRS-aligned and non-aligned ECG segments with physical noise such as motion artifacts, electrode movement, baseline wander, and simulated noise such as Gaussian white noise. RESULTS: The simulation results indicate that 1. QRS-aligned segments are preferable to non-aligned segments, 2. the RunDAE model outperforms the classical DAE model in denoising ECG signals, especially when using dense layers and QRS-aligned segments, 3. training the RunDAE models with normal and arrhythmic ECG signals enhance model's properties/capabilities, and 4. the RunDAE is a multistage, non-causal, nonlinear adaptive filter. CONCLUSION: A shallow learning model, which consists of a couple of hidden layers, could achieve outstanding denoising performance using only the correlation among neighboring samples.

Multiple ECG segments denoising autoencoder model.

OBJECTIVES: Denoising autoencoder (DAE) with a single hidden layer of neurons can recode a signal, i.e., converting the original signal into a noise-reduced signal. The DAE approach has shown a good performance in denoising bio-signals, like electrocardiograms (ECG). In this paper, we study the effect of correlated, uncorrelated and jittered datasets on the performance of the DAE model. METHODS: Vectors of multiple concatenated ECG segments of simultaneously recorded Einthoven recordings I, II, III are considered to establish the following dataset cases: (1) correlated, (2) uncorrelated, and (3) jittered. We consider our previous work in finding the optimal number of hidden neurons receiving the input signal with respect to signal quality and computational burden by applying Akaike's information criterion. To evaluate DAE, these datasets are corrupted with six types of noise, namely mix noise (MX), motion artifact noise (MA), electrode movement (EM), baseline wander (BW), Gaussian white noise (GWN) and high-frequency noise (HFN), to simulate real case scenario. Spectral analysis is used to study the effects of noise whose power spectrum may overlap with the power spectrum of the wanted signal on DAE performance. RESULTS: The simulation results show (a) that the number of hidden neurons to denoise multiple correlated ECG is much lower than for jittered signals, (b) QRS-complex based ECG alignment preferable, (c) noises with slightly overlapping power spectrum, like BW and HFN, can be easily removed with sufficient number of neurons, while the noise with completely overlapping spectrum, like GWN, requires a very low-dimensional and thus coarser reduction to recover the signal. CONCLUSIONS: The performance of DAE model in terms of signal-to-noise ratio improvement and the required number of hidden neurons can be improved by utilizing the correlation among simultaneous Einthoven I, II, III records.

[The G-BA innovation fund's project "Avenue-Pal" - analysis and improvement of cross-sectoral and cross-departmental interface and relocation management in palliative care]. / Das G-BA-Innovationsfonds-Projekt "Avenue-Pal" : Analyse und Verbesserung des sektor- und bereichsübergreifenden Schnittstellen- und Verlegungsmanagements in der Palliativversorgung.

BACKGROUND: About 80% of all people in Germany die in inpatient care. Around every fifth person in inpatient care is relocated to another care area in the last phase of their life. That is more than 150,000 people being relocated, often without indication. 13 risk factors were identified for these non-indicated relocations. METHOD: With the support of the AWMF, two regionally effective guidelines were developed and implemented in a maximum care hospital and a care facility. A palliative consultation service has been established in the university hospital. Comprehensive personnel and organizational development was carried out in the care facility. Different collaborations with relevant regional partners of both model institutions were systematically expanded. RESULTS AND CONCLUSIONS: The relocations could be significantly reduced despite the short duration of the project. This was also possible through the establishment of decision-making aids and digital implementation support. The results of the accompanying ethical and social research justify the procedure: There is an increase in the satisfaction of relatives and employees.

High speed external cavity diode laser concept based on a resonantly driven MEMS scanner for the mid-infrared region.

The rapid detection of trace gases is of great relevance for various spectroscopy applications. In this regard, the technology of external cavity diode lasers (ECDLs) has firmly established itself due to its excellent properties. Outside of the laboratory environment, however, these still have some restrictions, especially with regard to high acquisition rates for sensitive spectroscopy applications and mode-hop-free tuning. In this article, we present our innovative GaSb-based ECDL concept, in which a resonantly driven microelectromechanical system actuator is used. With this, a defined frequency range can be tuned extremely fast and without mode hops. Results of the characterization and its use for the rapid detection of trace gases are presented.

Fractal Characterization of Subviral Particle Motion: On the Influence of Spatio-Temporal Interpolation Methods.

Due to the rapid globalization there is an increasing danger for pandemic outbreaks. The high death toll of fast spreading diseases like the Ebola infection demand the fast development of new medicines. Thus, the automation of pharmaceutical processes is an indispensable but challenging task. In cooperation with the Institute for Virology, Philipps-University, Marburg, Germany, recently, algorithms to detect and evaluate subviral particle tracks in live-cell fluorescence image sequences were developed. In steady interdisciplinary exchange between pharmacists and engineers it turned out that new measures to identify and classify subviral particle motion are required. This article focuses on the evaluation and optimization of a new method to classify subviral particle motion using fractal dimension estimation. The influence of global and local interpolation methods on fractal dimension estimation is investigated. The methods are tested on simulated data and applied to real image sequences. The results prospect a high benefit of using the presented methods for an effective classification of subviral particle behavior.

An optically powered single-channel stimulation implant as test system for chronic biocompatibility and biostability of miniaturized retinal vision prostheses.

A microsystem based microimplant with an optically powered single-channel stimulator was designed and developed as test system for an epi-retinal vision implant. Biostability of the hybrid assembly and the encapsulation materials were evaluated in pilot experiments in chronic implantations in a cat animal model. The implant was fabricated on a flexible polyimide substrate with integrated platinum electrode, interconnection lines, and contact pads for hybrid integration of electronic components. The receiver part was realized with four photodiodes connected in series. A parylene C coating was deposited on the electronic components as insulation layer. Silicone rubber was used to encapsulate the electronics in the shape of an artificial intraocular lens to allow proper implantation in the eye. Pilot experiments showed the biostability of the encapsulation approach and full electric functionality of the microimplant to generate stimulation currents over the implantation period of three months in two cats. In one cat, electrical stimulation of the retina evoked neuronal responses in the visual cortex and indicated the feasibility of the system approach for chronic use.

Intraocular fluid-air exchange reduces retinal ganglion cell activity.

AIM: To demonstrate the influence of intraocular fluid-air exchange on retinal ganglion cell activity. METHODS: In two cats lensectomy and vitrectomy were performed in a two-step approach 2 weeks prior to recording experiments. To measure retinal activity, up to two fiber microelectrodes were inserted via a scleral port. Precise micromanipulator positioning of the electrodes' tips onto the inner retinal surface were verified by ophthalmoscopy and simultaneous electrical recording. Neuronal activity of the retina was continuously recorded with or without visual stimulation. We maintained the intraocular pressure constant at 29 mm Hg. Fluid-air exchange and fluid refill were performed with an infusion tube integrated in the manipulator and slowly to avoid direct mechanical/stream-based damage of the retina. RESULTS: We found that fluid-air exchange leads to a rapid reduction of spontaneous as well as visually evoked retinal ganglion cell activity. The activity started to diminish within few minutes, and then it halved approximately every 3 min. Even 1 h after eye fluid refill, the retinal activity recovered only partially. CONCLUSION: Decrease in retinal activity after fluid-air exchange can be explained by mechanical stress-induced drying of the inner retinal surface and by potential changes of extracellular ion concentration. Since even moderate airstream-based fluid-air exchanges can lead to retinal damage, the surgeon should minimize the quantity of air passing open sclerotomy sites until a better understanding of the retinal effects of this essential technique in modern vitrectomy is available.

Visualization of the visual cortex in minipigs using fMRI.

Minipigs are widely used to examine physiologic mechanisms under experimental settings. The purpose of our study was to localize the visual cortex of minipigs using visual stimulation in functional magnetic resonance imaging (fMRI). Five male Göttinger minipigs were studied with fMRI during visual stimulation with series of light impulses conducted into the MR cabin via fibre optical wave guides (EPI sequences, block design, 1.5 T clinical routine MR-scanner). Statistics were performed using SPM'99. All minipigs showed activation of the visual cortex due to light stimulation. The activation could be superimposed to T2-weighted structural images with good spatial resolution revealing the exact location of the visual cortex. We were able to localize the visual cortex in minipigs for the first time utilizing fMRI on a routine scanner. However, this may be useful for precise positioning of electrodes or implants or be used as a further uncomplicated non-invasive method in physiologic experiments.

Visual resolution with retinal implants estimated from recordings in cat visual cortex.

We investigated cortical responses to electrical stimulation of the retina using epi- and sub-retinal electrodes of 20-100 microm diameter. Temporal and spatial resolutions were assessed by recordings from the visual cortex with arrays of microelectrodes and optical imaging. The estimated resolutions were approximately 40 ms and approximately 1 degrees of visual angle. This temporal resolution of 25 frames per second and spatial resolution of about 0.8 cm at about 1m and correspondingly 8 cm at 10 m distance seems sufficient for useful object recognition and visuo-motor behavior in many in- and out-door situations of daily life.

Implantation and testing of subretinal film electrodes in domestic pigs.

By definition, an electronic subretinal visual prosthesis requires the implantation of stimulation electrodes in the subretinal space of the eye. Polyimide film electrodes with flat contacts were implanted subretinally and used for electrical stimulation in acute experiments in anaesthetised domestic pigs. In two pigs, the film electrode was inserted through a sclerostomy into the vitreous cavity and, subsequently, via a retinotomy into the subretinal space around the posterior pole (ab interno approach). In three other pigs the sclera and pigment epithelium were opened for combined ab interno and transscleral positioning of the subretinal electrode. In all cases, perfluorocarbon liquid (PFCL) was used to establish a close contact between the film electrode and the outer retina. After cranial preparations of three pigs for epidural recording of visual cortex responses, retinal stimulation was performed in one pig with a film electrode implanted ab interno and in two pigs with film electrodes implanted by the ab interno and transscleral procedure. The five subretinal implantations were carried out successfully and each polyimide film electrode tip was positioned beneath the outer retina of the posterior pole. The retina was attached to the stimulation electrode in all cases. Epidural cortical responses to light and electrical stimulation were recorded in three experiments. Initial cortical responses to Ganzfeld light and to electrical stimuli occurred about 40 and 20 ms, respectively, after stimulation onset. The stimulation threshold was approximately 100 microA and, like the cortical response amplitudes, depended both on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. Our results in a domestic pig model demonstrate that polyimide film electrodes can be implanted subretinally and tested by recording cortical responses to electrical stimulation. These findings suggest that the domestic pig could be an appropriate animal model for basic testing of subretinal implants.

Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development.

Loss of photoreceptor function is responsible for a variety of blinding diseases, including retinitis pigmentosa. Advances in microtechnology have led to the development of electronic visual prostheses which are currently under investigation for the treatment of human blindness. The design of a subretinal prosthesis requires that the stimulation device should be implantable in the subretinal space of the eye. Current limitations in eye surgery have to be overcome to demonstrate the feasibility of this approach and to determine basic stimulation parameters. Therefore, polyimide film-bound electrodes were implanted in the subretinal space in anaesthetized domestic pigs as a prelude to electrical stimulation in acute experiments. Eight eyes underwent surgery to demonstrate the transscleral implantability of the device. Four of the eight eyes were stimulated electrically. In these four animals the cranium was prepared for epidural recording of evoked visual cortex responses, and stimulation was performed with sequences of current impulses. All eight subretinal implantation procedures were carried out successfully with polyimide film electrodes and each electrode was implanted beneath the outer retina of the posterior pole of the operated eyes. Four eyes were used for neurophysiological testing, involving recordings of epidural cortical responses to light and electrical stimulation. A light stimulus response, which occurred 40 ms after stimulation, proved the integrity of the operated eye. The electrical stimuli occurred about 20 ms after the onset of stimulation. The stimulation threshold was approximately 100 microA. Both the threshold and the cortical responses depended on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. The subretinal implantation of complex stimulation devices using the transscleral procedure with consecutive subretinal stimulation is feasible in acute experiments in an animal model approximating to the situation in humans. The domestic pig is an appropriate animal model for basic testing of subretinal implants. Animal experiments with chronically implanted devices and long-term stimulation are advisable to prepare the field for successful human experiments.

Retino-cortical information transmission achievable with a retina implant.

Blind subjects with photoreceptor degeneration perceive phosphenes when their intact retinal ganglion cells are stimulated electrically. Is this approach suitable for transmitting enough information to the visual cortex for partially restoring vision? We stimulated the retina of anesthetized cats electrically and visually while recording the responses in the visual cortex. Transmission of retino-cortical information T was quantified by information theory. T was 20-160 bit/s (per stimulation and recording site) with random electrical or visual impulse stimulation at rates between 20 and 40 s-1. While increasing spatial density of independent electrical stimulation channels T did not saturate with 7 electrodes/mm2 retina. With seven electrodes up to 500 bit/s was transmitted to 15 cortical recording sites. Electrical stimulation basically employs temporal stimulus patterns. They are intimately linked with intensity/contrast information coded by the spike density of retinal ganglion cells. From the cortical information spread we estimated the spatial resolution as 0.5mm cortex corresponding to 0.5-1.0 degrees visual angle. If the human cortex can receive and decode the information transmitted by a retina implant, our quantitative results measured in cats suggest that visuo-motor coordination and object recognition in many in- and out-door situations will be possible.

Subretinal implantation and testing of polyimide film electrodes in cats.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site. RESULTS: All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.

Implantes eletrônicos para restabelecimento da visão em cegos / Electronic implants to restore vision in blind patients

O sucesso recente no desenvolvimento de uma prótese eletrônica coclear para surdos estimulou vários grupos de cientistas ao desenvolvimento de próteses visuais. A maioria dos protótipos de próteses visuais está baseada em estimulação elétrica neuronal em diferentes localizações do sistema visual até o sistema nervoso central. Atualmente os esforços estão concentrados em três localizações de implantes visuais: retina, nervo óptico e córtex. Implantes de retina e do nervo óptico têm o potencial de restabelecer a visão em pacientes com degenerações retinianas progressivas por meio de estimulação elétrica de neurônios do sistema visual. Próteses corticais podem beneficiar um número maior de pacientes cegos devido à sua localização mais posterior no sistema visual. Apesar dos grandes avanços, torna-se ainda necessária a elucidação de questões importantes na avaliação do funcionamento, em longo prazo, dos vários implantes eletrônicos para cegos, em estudo. Neste artigo analisamos os motivos que justificam o início dos experimentos nas três posições mencionadas e os desafios advindos de tal decisão.

Chronically implanted epidural electrodes in Göttinger minipigs allow function tests of epiretinal implants.

BACKGROUND: To test the function of implantable devices for electrical stimulation of the retina, long-term registration tests of cortical-evoked potentials are required. Skin electrodes are not appropriate to provide representative recordings, due to the voluminous pneumatic frontal sinus of minipigs. Therefore, epidural electrodes were permanently implanted in minipigs and tested with visual and electrical retinal stimulation. The present study describes long-term recordings of electrically evoked cortical potentials in minipigs. METHODS: Three-channel silver-silver chloride electrodes were fixed on the epidura dorsal to the primary visual cortex of one hemisphere in Göttinger minipigs. Repeated light stimulation was performed and platinum-polyimide film multielectrode arrays were implanted on the retina for electrical stimulation and were later removed. Cortical potentials were recorded after stimulation with short biphasic charge-balanced currents. RESULTS: For up to 18 months, the implanted epidural electrodes allowed recording of visual cortex potentials evoked by visual or electrical retina stimulation. Small changes of response amplitudes in subsequent experiments indicated a stable location and recording properties of the cortex electrodes. Visual stimulation often yielded stronger responses for the contralateral eye. Superthreshold electrical retina stimulation evoked cortical responses with less delay compared to visual stimulation. We found threshold currents of 50 microA for charge-balanced biphasic trains of current impulses. Postoperative examination showed an attached and unchanged retina. CONCLUSIONS: The minipig model is appropriate for the implantation of epiretinal stimulation electrodes and for the long-term tests of retinal implants by recording of cortical responses with chronically implanted epidural electrodes.

Towards the cortical representation of form and motion stimuli generated by a retina implant.

BACKGROUND: A retina implant for restoring basic visual perception in patients who are blind due to photoreceptor loss should not only evoke focal phosphenes at high resolution, but should also generate cortical representations of form and motion. We are currently exploring these potential capabilities in anaesthetised cats. METHODS: Fibre electrodes were inserted through a small scleral incision onto the retinal surface for stimulation. For the recording of cortical population activities we placed up to 16 fibre electrodes in areas 17 and/or 18. Retinal and cortical electrodes were adjusted to corresponding sites, i.e., overlapping receptive fields. Electrical stimuli were charge-balanced impulses (200 micros, 10-100 microA). Basic form stimuli were generated by the selective and synchronous activation of some of the seven retinal stimulation electrodes. Movement stimuli were generated by spatio-temporal shifting of form stimuli. From multiple microelectrode recordings we computed stimulus-related spatio-temporal cortical activation profiles. We used these profiles to estimate the relations between stimulation distance and spatial resolution (form) and between stimulus velocity and spatio-temporal resolution (movement). Influences by the retino-cortical pathway were assessed by comparing cortical activations evoked by true form or motion stimuli with synthetic responses composed by superpositioning of responses to appropriate subsets of form and motion stimuli. In addition, we compared cortical responses to form and motion stimuli by a receptive-field-based backprojection of cortical activities. RESULTS: We confirmed our previous finding that electrical retina stimulation may yield a spatial resolution of 1-5 degrees visual angle and a temporal resolution of about 20 ms. We found that the spatio-temporal cortical activation profiles are commonly related to retinal form and motion stimuli. Cortical activity analyses showed that for two-point form stimuli the neuronal interaction depends on the stimulation electrodes' distance and that local cortical group activities can exhibit some tuning to the directions or the velocities of moving electrical bars'. Projections of cortical activations to visual space were consistent with electrical form and motion stimulation of the retina. CONCLUSIONS: Our data indicate that retinal stimulation with electrical form and motion stimuli can lead to spatio-temporally related cortical activations. However, the selective activation of single cortical neurones with specific visual tuning properties by electrical retina stimulation and the potential adaptation of the visual system to long-term stimulation with retina implants should be addressed in future work.

Visual resolution with epi-retinal electrical stimulation estimated from activation profiles in cat visual cortex.

Blinds with receptor degeneration can perceive localized phosphenes in response to focal electrical epi-retinal stimuli. To avoid extensive basic stimulation tests in human patients, we developed techniques for estimating visual spatial resolution in anesthetized cats. Electrical epi-retinal and visual stimulation was combined with multiple-site retinal and cortical microelectrode recordings of local field potentials (LFPs) from visual areas 17 and 18. Classical visual receptive fields were characterized for retinal and cortical recording sites using multifocal visual stimulation combined with stimulus-response cross-correlation. We estimated visual spatial resolution from the size of the cortical activation profiles in response to single focal stimuli. For comparison, we determined activation profiles in response to visual stimuli at the same retinal location. Activation profiles were single peaked or multipeaked. In multipeaked profiles, the peak locations coincided with discontinuities in cortical retinotopy. Location and width of cortical activation profiles were distinct for retinal stimulation sites. On average, the activation profiles had a size of 1.28 +/- 0.03 mm cortex. Projected to visual space this corresponds to a spatial resolution of 1.49 deg +/- 0.04 deg visual angle. Best resolutions were 0.5 deg at low and medium stimulation currents corresponding to a visus of 1/30. Higher stimulation currents caused lower spatial, but higher temporal resolution (up to 70 stimuli/s). In analogy to the receptive-field concept in visual space, we defined and characterized electrical receptive fields. As our estimates of visual resolutions are conservative, we assume that a visual prosthesis will induce phosphenes at least at this resolution. This would enable visuomotor coordinations and object recognition in many indoor and outdoor situations of daily life.

Activation zones in cat visual cortex evoked by electrical retina stimulation.

BACKGROUND: A retina implant for restoring simple basic visual perception in patients who are blind due to photoreceptor loss requires optimisation of stimulation parameters for obtaining high spatio-temporal resolution. We developed effective low-power epi-retinal stimulation and intracortical recording in semichronically prepared cats. METHODS: Individually driveable fibre electrodes were inserted through a small scleral incision and positioned at the area centralis. Polyimide-platinum film electrodes were inserted via a corneal incision and fixed by instillation of perfluorocarbon liquid on the internal limiting membrane. For electrical stimulation we used short charge-balanced current impulses of 100-400 micro s duration and amplitudes ranging from 1 to 100 micro A. During stimulation we recorded multiple single-cell and population activities from areas 17 and 18. Recordings were stored digitally. Stimulus-response relations including response strength, cortical activation zones, information transmission, and electrical receptive fields were analysed off-line. RESULTS: We found low-threshold activations with fibre electrodes and polyimide-platinum film electrodes in close mechanical contact to the retina. Retinal stimulation with bipolar charge-balanced impulses resulted in cortical activation zones corresponding to 1-5 degrees visual angle at paracentral locations dependent on the eccentricity of the retinal stimulation point. Retino-cortical transinformation analysis revealed 20-30 bits/s per electrode, corresponding to 10-15 four-level pictures/s. Electrical receptive fields had sizes of 1-3 degrees visual angle. CONCLUSIONS: Coarse visuomotor coordination and navigation seems possible with retina implants.

Classification of neural signals by a generalized correlation classifier based on radial basis functions.

A common problem in neuroscience is to identify the features by which a set of measurements can be segregated into different classes, for example into different responses to sensory stimuli. A main difficulty is that the derived distributions are often high-dimensional and complex. Many multivariate analysis techniques, therefore, aim to find a simpler low-dimensional representation. Most of them either involve huge efforts in implementation and data handling or ignore important structures and relationships within the original data. We developed a dimension reduction method by means of radial basis functions (RBF), where only a system of linear equations has to be solved. We show that this approach can be regarded as an extension of a linear correlation-based classifier. The validity and reliability of this technique is demonstrated on artificial data sets. Its practical relevance is further confirmed by discriminating recordings from monkey visual cortex evoked by different stimuli.