ECG Electrode Localization: 3D DS Camera System for Use in Diverse Clinical Environments.

Models of the human body representing digital twins of patients have attracted increasing interest in clinical research for the delivery of personalized diagnoses and treatments to patients. For example, noninvasive cardiac imaging models are used to localize the origin of cardiac arrhythmias and myocardial infarctions. The precise knowledge of a few hundred electrocardiogram (ECG) electrode positions is essential for their diagnostic value. Smaller positional errors are obtained when extracting the sensor positions, along with the anatomical information, for example, from X-ray Computed Tomography (CT) slices. Alternatively, the amount of ionizing radiation the patient is exposed to can be reduced by manually pointing a magnetic digitizer probe one by one to each sensor. An experienced user requires at least 15 min. to perform a precise measurement. Therefore, a 3D depth-sensing camera system was developed that can be operated under adverse lighting conditions and limited space, as encountered in clinical settings. The camera was used to record the positions of 67 electrodes attached to a patient's chest. These deviate, on average, by 2.0 mm ±1.5 mm from manually placed markers on the individual 3D views. This demonstrates that the system provides reasonable positional precision even when operated within clinical environments.

Hierarchical imaging and computational analysis of three-dimensional vascular network architecture in the entire postnatal and adult mouse brain.

The formation of new blood vessels and the establishment of vascular networks are crucial during brain development, in the adult healthy brain, as well as in various diseases of the central nervous system. Here, we describe a step-by-step protocol for our recently developed method that enables hierarchical imaging and computational analysis of vascular networks in postnatal and adult mouse brains. The different stages of the procedure include resin-based vascular corrosion casting, scanning electron microscopy, synchrotron radiation and desktop microcomputed tomography imaging, and computational network analysis. Combining these methods enables detailed visualization and quantification of the 3D brain vasculature. Network features such as vascular volume fraction, branch point density, vessel diameter, length, tortuosity and directionality as well as extravascular distance can be obtained at any developmental stage from the early postnatal to the adult brain. This approach can be used to provide a detailed morphological atlas of the entire mouse brain vasculature at both the postnatal and the adult stage of development. Our protocol allows the characterization of brain vascular networks separately for capillaries and noncapillaries. The entire protocol, from mouse perfusion to vessel network analysis, takes ~10 d.

Invariance and variability in interaction error-related potentials and their consequences for classification.

OBJECTIVE: This paper discusses the invariance and variability in interaction error-related potentials (ErrPs), where a special focus is laid upon the factors of (1) the human mental processing required to assess interface actions (2) time (3) subjects. APPROACH: Three different experiments were designed as to vary primarily with respect to the mental processes that are necessary to assess whether an interface error has occurred or not. The three experiments were carried out with 11 subjects in a repeated-measures experimental design. To study the effect of time, a subset of the recruited subjects additionally performed the same experiments on different days. MAIN RESULTS: The ErrP variability across the different experiments for the same subjects was found largely attributable to the different mental processing required to assess interface actions. Nonetheless, we found that interaction ErrPs are empirically invariant over time (for the same subject and same interface) and to a lesser extent across subjects (for the same interface). SIGNIFICANCE: The obtained results may be used to explain across-study variability of ErrPs, as well as to define guidelines for approaches to the ErrP classifier transferability problem.

A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes.

Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.

Nogo-A regulates vascular network architecture in the postnatal brain.

Recently, we discovered a new role for the well-known axonal growth inhibitory molecule Nogo-A as a negative regulator of angiogenesis in the developing central nervous system. However, how Nogo-A affected the three-dimensional (3D) central nervous system (CNS) vascular network architecture remained unknown. Here, using vascular corrosion casting, hierarchical, synchrotron radiation µCT-based network imaging and computer-aided network analysis, we found that genetic ablation of Nogo-A significantly increased the three-dimensional vascular volume fraction in the postnatal day 10 (P10) mouse brain. More detailed analysis of the cerebral cortex revealed that this effect was mainly due to an increased number of capillaries and capillary branchpoints. Interestingly, other vascular parameters such as vessel diameter, -length, -tortuosity, and -volume were comparable between both genotypes for non-capillary vessels and capillaries. Taken together, our three-dimensional data showing more vessel segments and branchpoints at unchanged vessel morphology suggest that stimulated angiogenesis upon Nogo-A gene deletion results in the insertion of complete capillary micro-networks and not just single vessels into existing vascular networks. These findings significantly enhance our understanding of how angiogenesis, vascular remodeling, and three-dimensional vessel network architecture are regulated during central nervous system development. Nogo-A may therefore be a potential novel target for angiogenesis-dependent central nervous system pathologies such as brain tumors or stroke.

Brain Computer Interface on Track to Home.

The novel BackHome system offers individuals with disabilities a range of useful services available via brain-computer interfaces (BCIs), to help restore their independence. This is the time such technology is ready to be deployed in the real world, that is, at the target end users' home. This has been achieved by the development of practical electrodes, easy to use software, and delivering telemonitoring and home support capabilities which have been conceived, implemented, and tested within a user-centred design approach. The final BackHome system is the result of a 3-year long process involving extensive user engagement to maximize effectiveness, reliability, robustness, and ease of use of a home based BCI system. The system is comprised of ergonomic and hassle-free BCI equipment; one-click software services for Smart Home control, cognitive stimulation, and web browsing; and remote telemonitoring and home support tools to enable independent home use for nonexpert caregivers and users. BackHome aims to successfully bring BCIs to the home of people with limited mobility to restore their independence and ultimately improve their quality of life.

Write, read and answer emails with a dry 'n' wireless brain-computer interface system.

Brain-computer interface (BCI) users can control very complex applications such as multimedia players or even web browsers. Therefore, different biosignal acquisition systems are available to noninvasively measure the electrical activity of the brain, the electroencephalogram (EEG). To make BCIs more practical, hardware and software are nowadays designed more user centered and user friendly. In this paper we evaluated one of the latest innovations in the area of BCI: A wireless EEG amplifier with dry electrode technology combined with a web browser which enables BCI users to use standard webmail. With this system ten volunteers performed a daily life task: Write, read and answer an email. Experimental results of this study demonstrate the power of the introduced BCI system.

How Many People Could Use an SSVEP BCI?

Brain-computer interfaces (BCI) are communication systems that allow people to send messages or commands without movement. BCIs rely on different types of signals in the electroencephalogram (EEG), typically P300s, steady-state visually evoked potentials (SSVEP), or event-related desynchronization. Early BCI systems were often evaluated with a selected group of subjects. Also, many articles do not mention data from subjects who performed poorly. These and other factors have made it difficult to estimate how many people could use different BCIs. The present study explored how many subjects could use an SSVEP BCI. We recorded data from 53 subjects while they participated in 1-4 runs that were each 4 min long. During these runs, the subjects focused on one of four LEDs that each flickered at a different frequency. The eight channel EEG data were analyzed with a minimum energy parameter estimation algorithm and classified with linear discriminant analysis into one of the four classes. Online results showed that SSVEP BCIs could provide effective communication for all 53 subjects, resulting in a grand average accuracy of 95.5%. About 96.2% of the subjects reached an accuracy above 80%, and nobody was below 60%. This study showed that SSVEP based BCI systems can reach very high accuracies after only a very short training period. The SSVEP approach worked for all participating subjects, who attained accuracy well above chance level. This is important because it shows that SSVEP BCIs could provide communication for some users when other approaches might not work for them.

High-throughput full-automatic synchrotron-based tomographic microscopy.

At the TOMCAT (TOmographic Microscopy and Coherent rAdiology experimenTs) beamline of the Swiss Light Source with an energy range of 8-45 keV and voxel size from 0.37 µm to 7.4 µm, full tomographic datasets are typically acquired in 5 to 10 min. To exploit the speed of the system and enable high-throughput studies to be performed in a fully automatic manner, a package of automation tools has been developed. The samples are automatically exchanged, aligned, moved to the correct region of interest, and scanned. This task is accomplished through the coordination of Python scripts, a robot-based sample-exchange system, sample positioning motors and a CCD camera. The tools are suited for any samples that can be mounted on a standard SEM stub, and require no specific environmental conditions. Up to 60 samples can be analyzed at a time without user intervention. The throughput of the system is dependent on resolution, energy and sample size, but rates of four samples per hour have been achieved with 0.74 µm voxel size at 17.5 keV. The maximum intervention-free scanning time is theoretically unlimited, and in practice experiments have been running unattended as long as 53 h (the average beam time allocation at TOMCAT is 48 h per user). The system is the first fully automated high-throughput tomography station: mounting samples, finding regions of interest, scanning and reconstructing can be performed without user intervention. The system also includes many features which accelerate and simplify the process of tomographic microscopy.

Radiation dose optimized lateral expansion of the field of view in synchrotron radiation X-ray tomographic microscopy.

Volumetric data at micrometer level resolution can be acquired within a few minutes using synchrotron-radiation-based tomographic microscopy. The field of view along the rotation axis of the sample can easily be increased by stacking several tomograms, allowing the investigation of long and thin objects at high resolution. On the contrary, an extension of the field of view in the perpendicular direction is non-trivial. This paper presents an acquisition protocol which increases the field of view of the tomographic dataset perpendicular to its rotation axis. The acquisition protocol can be tuned as a function of the reconstruction quality and scanning time. Since the scanning time is proportional to the radiation dose imparted to the sample, this method can be used to increase the field of view of tomographic microscopy instruments while optimizing the radiation dose for radiation-sensitive samples and keeping the quality of the tomographic dataset on the required level. This approach, dubbed wide-field synchrotron radiation tomographic microscopy, can increase the lateral field of view up to five times. The method has been successfully applied for the three-dimensional imaging of entire rat lung acini with a diameter of 4.1 mm at a voxel size of 1.48 microm.

Advanced phase-contrast imaging using a grating interferometer.

Phase-sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging, and therefore new and otherwise inaccessible information. Differential phase-contrast (DPC) imaging, which uses a grating interferometer and a phase-stepping technique, has been integrated into TOMCAT, a beamline dedicated to tomographic microscopy and coherent radiology experiments at the Swiss Light Source. Developments have been made focusing on the fast acquisition and post-processing of data to enable a high-throughput of samples, with obvious advantages, also through increasing the efficiency of the detecting system, of helping to reduce radiation dose imparted to the sample. A novel aquarium design allows a vertical rotation axis below the sample with measurements performed in aqueous environment. Optimization of the data acquisition procedure enables a full phase volume (1024 x 1024 pixels x 1000 projections x 9 phase steps, i.e. 9000 projections in total) to be acquired in 20 min (with a pixel size of 7.4 microm), and the subsequent post-processing has been integrated into the beamline pipeline for sinogram generation. Local DPC tomography allows one to focus with higher magnification on a particular region of interest of a sample without the presence of local tomography reconstruction artifacts. Furthermore, 'widefield' imaging is shown for DPC scans for the first time, enabling the field of view of the imaging system to be doubled for samples that are larger than the magnification allows. A case study is illustrated focusing on the visualization of soft tissue features, and particularly the substantia nigra of a rat brain. Darkfield images, based on local X-ray scattering, can also be extracted from a grating-based DPC scan: an example of the advantages of darkfield contrast is shown and the potential of darkfield X-ray tomography is discussed.

Sensitivity- and effort-gain analysis: multilead ECG electrode array selection for activation time imaging.

Methods for noninvasive imaging of electric function of the heart might become clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as an easy and fast application. In this paper, we propose a new electrode array which improves the resolution of methods for activation time imaging considering clinical constraints such as easy to apply and compatibility with routine leads. For identifying the body-surface regions where the body surface potential (BSP) is most sensitive to changes in transmembrane potential (TMP), a virtual array method was used to compute local linear dependency (LLD) maps. The virtual array method computes a measure for the LLD in every point on the body surface. The most suitable number and position of the electrodes within the sensitive body surface regions was selected by constructing effort gain (EG) plots. Such a plot depicts the relative attainable rank of the leadfield matrix in relation to the increase in number of electrodes required to build the electrode array. The attainable rank itself was computed by a detector criterion. Such a criterion estimates the maximum number of source space eigenvectors not covered by noise when being mapped to the electrode space by the leadfield matrix and recorded by a detector. From the sensitivity maps, we found that the BSP is most sensitive to changes in TMP on the upper left frontal and dorsal body surface. These sensitive regions are covered best by an electrode array consisting of two L-shaped parts of approximately 30 cm x 30 cm and approximately 20 cm x 20 cm. The EG analysis revealed that the array meeting clinical requirements best and improving the resolution of activation time imaging consists of 125 electrodes with a regular horizontal and vertical spacing of 2-3 cm.

Cardiac anisotropy: is it negligible regarding noninvasive activation time imaging?

The aim of this study was to quantify the effect of cardiac anisotropy in the activation-based inverse problem of electrocardiography. Differences of the patterns of simulated body surface potential maps for isotropic and anisotropic conditions were investigated with regard to activation time (AT) imaging of ventricular depolarization. AT maps were estimated by solving the nonlinear inverse ill-posed problem employing spatio-temporal regularization. Four different reference AT maps (sinus rhythm, right-ventricular and septal pacing, accessory pathway) were calculated with a bidomain theory based anisotropic finite-element heart model in combination with a cellular automaton. In this heart model a realistic fiber architecture and conduction system was implemented. Although the anisotropy has some effects on forward solutions, effects on inverse solutions are small indicating that cardiac anisotropy might be negligible for some clinical applications (e.g., imaging of focal events) of our AT imaging approach. The main characteristic events of the AT maps were estimated despite neglected electrical anisotropy in the inverse formulation. The worst correlation coefficient of the estimated AT maps was 0.810 in case of sinus rhythm. However, all characteristic events of the activation pattern were found. The results of this study confirm our clinical validation studies of noninvasive AT imaging in which cardiac anisotropy was neglected.

A model based approach for multi-lead ECG array layout selection.

In this study an approach for testing electrode array schemes with respect to their ability to improve the resolution of methods for activation time imaging is proposed. First local linear dependency maps are computed using a virtual array method. These maps depict the torso surface areas where the body surface potential is most sensitive to changes in the transmembrane potential. The optimal number and position of the electrodes within the sensitive body surface regions was selected by constructing effort gain (EG) plots. Such a plot depicts the relative attainable rank of the leadfield matrix in relation to the increase in number of electrodes required to build the electrode array. From the sensitivity maps it was found that the BSP is most sensitive to changes in TMP on the upper left frontal and dorsal body surface. The EG analysis revealed that the optimal array meeting clinical requirements and improving the resolution of activation time imaging consists of 125 electrodes.

Semiautomatic volume conductor modeling pipeline for imaging the cardiac electrophysiology noninvasively.

In this paper we present an approach for extracting patient individual volume conductor models (VCM) using volume data acquired from Magnetic Resonance Imaging (MRI) for computational biology of electrical excitation in the patient's heart. The VCM consists of the compartments chest surface, lung surfaces, the atrial and ventricular myocardium, and the blood masses. For each compartment a segmentation approach with no or little necessity of user interaction was implemented and integrated into a VCM segmentation pipeline to enable the inverse problem of electrocardiography to become clinical applicable. The segmentation pipeline was tested using volume data from ten patients with structurally normal hearts.

Rank Based Selection of Electrode Positions for a Multi-Lead ECG Electrode Array.

Methods for noninvasive imaging of electrical function of the heart seem to become a clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as easy and fast application. In this study we propose a new electrode array meeting clinical requirements such as easy to apply and compatibility with routine leads. Within body surface regions of high sensitivity, identified in a prior, information content based study, the number of required electrodes was optimized using effort-gain plots. These plots were generated by applying a so called type one detector criterion. The optimal array was selected from a set of 12 electrode arrays. Each of them consists of two L-shaped regular spaced parts. The optimal array was found by comparing several layouts and electrode densities to the electrode array we use for clinical studies. It consists of 125 electrodes with a regular spacing between 2cm and 3cm.

Simulation of atrial electrophysiology and body surface potentials for normal and abnormal rhythm.

The effect of different atrial electrical activation sequences (sinus rhythm and atrial flutter circling in the right atrium) on the body surface potentials is investigated in this study. A realistic volume conductor model consisting of atria, lungs, chest and blood masses is generated from image stacks recorded by magnetic resonance imaging. The electrical sources-the transmembrane potentials-within the atrial volumetric model are simulated for different atrial rhythms employing a cellular automaton capable of considering different parameters depending on the specific properties of the tissues. The potentials on the torso surface are computed applying the finite element method for solving the differential equations derived from the bidomain theory. Both the simulated atrial activation patterns and the computed torso potentials for atrial sinus rhythm and atrial flutter are in qualitatively and quantitatively good agreement with data measured in humans. The simulation of body surface potentials generated by different electrical activation sequences in the atria or ventricles allows testing and assessing noninvasive imaging of cardiac electrophysiology, as both the potentials on the body surface and the reference activation in the heart are available.

Multi-lead ECG electrode array for clinical application of electrocardiographic inverse problem.

Methods for noninvasive imaging of electric function of the heart might become clinical standard procedure the next years. Thus, the overall procedure has to meet clinical requirements as easy and fast application. In this study we propose a new electrode array which improves the information content in the ECG map, considering clinical constraints such as easy to apply and compatibility with routine leads. A major challenge is the development of an electrode array which yields a high information content even for a large interindividual variation in torso shape. For identifying regions of high information content we introduce the concept of a locally applied virtual electrode array. As a result of our analysis we constructed a new electrode array consisting of two L-shaped regular spaced parts and compared it to the electrode array we use for clinical studies upon activation time imaging. We assume that one side effect caused by the regular shape and spacing of the new array be that the reconstruction of electrodes placed on the patients back is simplified. It may be sufficient to record a few characteristic electrode positions and merge them with a model of the posterior array.