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Dutz, Silvio; Weidner, Andreas; Lühe, Moritz von der; Gräfe, Christine; Biehl, Philip; Demut, Johanna; Warncke, Paul; Jungmann, Sandra; Fischer, Dagmar; Schacher, Felix; Clement, Joachim H.
Hybrid nanomaterials of biomolecule corona coated magnetic nanoparticles and their interaction with biological systems. - In: Physical sciences reviews, ISSN 2365-659X, Bd. 7 (2022), 11, S. 1311-1344

Magnetic nanoparticles (MNPs) are interesting for various applications in medicine. If administered to a biological system like the human body, a so-called biomolecule corona is formed on the surface of the particles, which highly determines the biological fate of the particles. To elucidate whether a preconditioning of the MNPs by incubation with biomolecules influences biocompatibility and bioavailability, the formation of such a corona was investigated in more detail. For this, the influence of particle characteristics, e.g., surface charge, as well as various incubation parameters on the resulting corona was investigated. It was found that the biomolecule corona is formed immediately after bringing together the particles with the biomolecule source. By variation of the biomolecule content of the incubation medium, the size of the corona can be modulated. Regarding the interaction of the nanoparticles with cells, it was shown that the presence of a biomolecule corona reduces the interaction and that a more pronounced biomolecule corona leads to a reduced uptake of the magnetic nanohybrids into the cells. Cell viability tests confirmed biocompatibility of the biomolecule-coated particles. A more pronounced corona promotes a higher cell viability. By using a shell-less hen's egg model, no or reduced adverse effects of all biomolecule-coated MNP for this in vivo test were found. Resulting from these investigations, we were able to demonstrate that our newly developed nanohybrids significantly reduce in vivo toxicity compared to uncoated MNPs.



https://doi.org/10.1515/psr-2019-0110
Gräfe, Christine; Müller, Elena; Gresing, Lennart; Weidner, Andreas; Radon, Patricia; Friedrich, Ralf P.; Alexiou, Christoph; Wiekhorst, Frank; Dutz, Silvio; Clement, Joachim
Magnetic hybrid materials interact with biological matrices. - In: Physical sciences reviews, ISSN 2365-659X, Bd. 7 (2022), 12, S. 1443-1500

Magnetic hybrid materials are a promising group of substances. Their interaction with matrices is challenging with regard to the underlying physical and chemical mechanisms. But thinking matrices as biological membranes or even structured cell layers they become interesting with regard to potential biomedical applications. Therefore, we established in vitro blood-organ barrier models to study the interaction and processing of superparamagnetic iron oxide nanoparticles (SPIONs) with these cellular structures in the presence of a magnetic field gradient. A one-cell-type-based blood-brain barrier model was used to investigate the attachment and uptake mechanisms of differentially charged magnetic hybrid materials. Inhibition of clathrin-dependent endocytosis and F-actin depolymerization led to a dramatic reduction of cellular uptake. Furthermore, the subsequent transportation of SPIONs through the barrier and the ability to detect these particles was of interest. Negatively charged SPIONs could be detected behind the barrier as well as in a reporter cell line. These observations could be confirmed with a two-cell-type-based blood-placenta barrier model. While positively charged SPIONs heavily interact with the apical cell layer, neutrally charged SPIONs showed a retarded interaction behavior. Behind the blood-placenta barrier, negatively charged SPIONs could be clearly detected. Finally, the transfer of the in vitro blood-placenta model in a microfluidic biochip allows the integration of shear stress into the system. Even without particle accumulation in a magnetic field gradient, the negatively charged SPIONs were detectable behind the barrier. In conclusion, in vitro blood-organ barrier models allow the broad investigation of magnetic hybrid materials with regard to biocompatibility, cell interaction, and transfer through cell layers on their way to biomedical application.



https://doi.org/10.1515/psr-2019-0114
Fröhlich, Thomas; Sindram, Johannes; Haueisen, Jens; Hunold, Alexander
Kraftmessung von Elektroden an einem menschlichen Kopfmodell :
Force measurement of electrodes on a human head model. - In: Technisches Messen, ISSN 2196-7113, Bd. 88 (2021), 11, S. 724-730

Electroencephalography (EEG) and transcranial electric stimulation (TES) require caps for holding the respective electrodes in place. To support the optimal design of such caps, knowledge of the force-displacement curves for each electrode position is desirable. We propose a calibrated setup to traceably measure force-displacement curves which consists of a human head model, a force sensor, a linear guide, a stepper motor, and a multiplexing multimeter. Repeated measures of a textile EEG-cap and a TES-cap show significant non-linearity and hysteresis effects for the force-displacement curves. Our setup will allow for the assessment of the fit of EEG and TES-caps for various head shapes and sizes.



https://doi.org/10.1515/teme-2021-0082
Schramm, Stefan; Dietzel, Alexander; Link, Dietmar; Blum, Maren-Christina; Klee, Sascha
3D retinal imaging and measurement using light field technology. - In: Journal of biomedical optics, ISSN 1560-2281, Bd. 26 (2021), 12, S. 126002-1-126002-19

Significance: Light-field fundus photography has the potential to be a new milestone in ophthalmology. Up-to-date publications show only unsatisfactory image quality, preventing the use of depth measurements. We show that good image quality and, consequently, reliable depth measurements are possible, and we investigate the current challenges of this novel technology. Aim: We investigated whether light field (LF) imaging of the retina provides depth information, on which structures the depth is estimated, which illumination wavelength should be used, whether deeper layers are measurable, and what kinds of artifacts occur. Approach: The technical setup, a mydriatic fundus camera with an LF imager, and depth estimation were validated by an eye model and in vivo measurements of three healthy subjects and three subjects with suspected glaucoma. Comparisons between subjects and the corresponding optical coherence tomography (OCT) measurements were used for verification of the depth estimation. Results: This LF setup allowed for three-dimensional one-shot imaging and depth estimation of the optic disc with green light. In addition, a linear relationship was found between the depth estimates of the OCT and those of the setup developed here. This result is supported by the eye model study. Deeper layers were not measurable. Conclusions: If image artifacts can be handled, LF technology has the potential to help diagnose and monitor glaucoma risk at an early stage through a rapid, cost-effective one-shot technology.



https://doi.org/10.1117/1.JBO.26.12.126002
Lopes, Cláudia; Fiedler, Patrique; Rodrigues, Marco Sampaio; Borges, Joel; Bertollo, Maurizio; Alves, Eduardo; Barradas, Nuno Pessoa; Comani, Silvia; Haueisen, Jens; Vaz, Filipe
Me-doped Ti-Me intermetallic thin films used for dry biopotential electrodes: a comparative case study. - In: Sensors, ISSN 1424-8220, Bd. 21 (2021), 23, 8143, S. 1-17

In a new era for digital health, dry electrodes for biopotential measurement enable the monitoring of essential vital functions outside of specialized healthcare centers. In this paper, a new type of nanostructured titanium-based thin film is proposed, revealing improved biopotential sensing performance and overcoming several of the limitations of conventional gel-based electrodes such as reusability, durability, biocompatibility, and comfort. The thin films were deposited on stainless steel (SS) discs and polyurethane (PU) substrates to be used as dry electrodes, for non-invasive monitoring of body surface biopotentials. Four different Ti-Me (Me = Al, Cu, Ag, or Au) metallic binary systems were prepared by magnetron sputtering. The morphology of the resulting Ti-Me systems was found to be dependent on the chemical composition of the films, specifically on the type and amount of Me. The existence of crystalline intermetallic phases or glassy amorphous structures also revealed a strong influence on the morphological features developed by the different systems. The electrodes were tested in an in-vivo study on 20 volunteers during sports activity, allowing study of the application-specific characteristics of the dry electrodes, based on Ti-Me intermetallic thin films, and evaluation of the impact of the electrode-skin impedance on biopotential sensing. The electrode-skin impedance results support the reusability and the high degree of reliability of the Ti-Me dry electrodes. The Ti-Al films revealed the least performance as biopotential electrodes, while the Ti-Au system provided excellent results very close to the Ag/AgCl reference electrodes.



https://doi.org/10.3390/s21238143
Comani, Silvia; Bertollo, Maurizio; Haueisen, Jens
Editorial: Dry electroencephalography for brain monitoring in sports and movement science. - In: Frontiers in neuroscience, ISSN 1662-453X, Bd. 15 (2021), 809227, S. 1-2

https://doi.org/10.3389/fnins.2021.809227
Kutschka, Hermann; Doeller, Christian F.; Haueisen, Jens; Maess, Burkhard
Magnetic field compensation coil design for magnetoencephalography. - In: Scientific reports, ISSN 2045-2322, Bd. 11 (2021), 22650, S. 1-12

While optically pumped magnetometers (OPMs) can be attached to the head of a person and allow for highly sensitive recordings of the human magnetoencephalogram (MEG), they are mostly limited to an operational range of approximately 5 nT. Consequently, even inside a magnetically shielded room (MSR), movements in the remnant magnetic field disable the OPMs. Active suppression of the remnant field utilizing compensation coils is therefore essential. We propose 8 compensation coils on 5 sides of a cube with a side length of approximately 2 m which were optimized for operation inside an MSR. Compared to previously built bi-planar compensation coils, the coils proposed in this report are more complex in geometry and achieved smaller errors for simulated compensation fields. The proposed coils will allow for larger head movements or smaller movement artifacts in future MEG experiments compared to existing coils.



https://doi.org/10.1038/s41598-021-01894-z
Krauß, Benedikt; Link, Dietmar; Stodtmeister, Richard; Nagel, Edgar; Vilser, Walthard; Klee, Sascha
Modulation of human intraocular pressure using a pneumatic system. - In: Translational Vision Science & Technology, ISSN 2164-2591, Bd. 10 (2021), 14, 4, S. 1-9

https://doi.org/10.1167/tvst.10.14.4
Gast, Richard; Knösche, Thomas R.; Schmidt, Helmut
Mean-field approximations of networks of spiking neurons with short-term synaptic plasticity. - In: Physical review, ISSN 2470-0053, Bd. 104 (2021), 4, 044310, insges. 15 S.

Low-dimensional descriptions of spiking neural network dynamics are an effective tool for bridging different scales of organization of brain structure and function. Recent advances in deriving mean-field descriptions for networks of coupled oscillators have sparked the development of a new generation of neural mass models. Of notable interest are mean-field descriptions of all-to-all coupled quadratic integrate-and-fire (QIF) neurons, which have already seen numerous extensions and applications. These extensions include different forms of short-term adaptation considered to play an important role in generating and sustaining dynamic regimes of interest in the brain. It is an open question, however, whether the incorporation of presynaptic forms of synaptic plasticity driven by single neuron activity would still permit the derivation of mean-field equations using the same method. Here we discuss this problem using an established model of short-term synaptic plasticity at the single neuron level, for which we present two different approaches for the derivation of the mean-field equations. We compare these models with a recently proposed mean-field approximation that assumes stochastic spike timings. In general, the latter fails to accurately reproduce the macroscopic activity in networks of deterministic QIF neurons with distributed parameters. We show that the mean-field models we propose provide a more accurate description of the network dynamics, although they are mathematically more involved. Using bifurcation analysis, we find that QIF networks with presynaptic short-term plasticity can express regimes of periodic bursting activity as well as bistable regimes. Together, we provide novel insight into the macroscopic effects of short-term synaptic plasticity in spiking neural networks, as well as two different mean-field descriptions for future investigations of such networks.



https://doi.org/10.1103/PhysRevE.104.044310
Numssen, Ole; Zier, Anna-Leah; Thielscher, Axel; Hartwigsen, Gesa; Knösche, Thomas R.; Weise, Konstantin
Efficient high-resolution TMS mapping of the human motor cortex by nonlinear regression. - In: NeuroImage, ISSN 1095-9572, Bd. 245 (2021), 118654, insges. 11 S.

Transcranial magnetic stimulation (TMS) is a powerful tool to investigate causal structure-function relationships in the human brain. However, a precise delineation of the effectively stimulated neuronal populations is notoriously impeded by the widespread and complex distribution of the induced electric field. Here, we propose a method that allows rapid and feasible cortical localization at the individual subject level. The functional relationship between electric field and behavioral effect is quantified by combining experimental data with numerically modeled fields to identify the cortical origin of the modulated effect. Motor evoked potentials (MEPs) from three finger muscles were recorded for a set of random stimulations around the primary motor area. All induced electric fields were nonlinearly regressed against the elicited MEPs to identify their cortical origin. We could distinguish cortical muscle representation with high spatial resolution and localized them primarily on the crowns and rims of the precentral gyrus. A post-hoc analysis revealed exponential convergence of the method with the number of stimulations, yielding a minimum of about 180 random stimulations to obtain stable results. Establishing a functional link between the modulated effect and the underlying mode of action, the induced electric field, is a fundamental step to fully exploit the potential of TMS. In contrast to previous approaches, the presented protocol is particularly easy to implement, fast to apply, and very robust due to the random coil positioning and therefore is suitable for practical and clinical applications.



https://doi.org/10.1016/j.neuroimage.2021.118654