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Khan, Asad; Antonakakis, Marios; Vogenauer, Nikolas; Haueisen, Jens; Wolters, Carsten H.
Individually optimized multi-channel tDCS for targeting somatosensory cortex. - In: Clinical neurophysiology, ISSN 1872-8952, Bd. 134 (2022), S. 9-26

Objective - Transcranial direct current stimulation (tDCS) is a non-invasive neuro-modulation technique that delivers current through the scalp by a pair of patch electrodes (2-Patch). This study proposes a new multi-channel tDCS (mc-tDCS) optimization method, the distributed constrained maximum intensity (D-CMI) approach. For targeting the P20/N20 somatosensory source at Brodmann area 3b, an integrated combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis is used with individualized skull conductivity calibrated realistic head modeling. - Methods - Simulated electric fields (EF) for our new D-CMI method and the already known maximum intensity (MI), alternating direction method of multipliers (ADMM) and 2-Patch methods were produced and compared for the individualized P20/N20 somatosensory target for 10 subjects. - Results - D-CMI and MI showed highest intensities parallel to the P20/N20 target compared to ADMM and 2-Patch, with ADMM achieving highest focality. D-CMI showed a slight reduction in intensity compared to MI while reducing side effects and skin level sensations by current distribution over multiple stimulation electrodes. - Conclusion - Individualized D-CMI montages are preferred for our follow up somatosensory experiment to provide a good balance between high current intensities at the target and reduced side effects and skin sensations. - Significance - An integrated combined MEG and EEG source analysis with D-CMI montages for mc-tDCS stimulation potentially can improve control, reproducibility and reduce sensitivity differences between sham and real stimulations.



https://doi.org/10.1016/j.clinph.2021.10.016
Schier, Peter; Liebl, Maik; Steinhoff, Uwe; Wiekhorst, Frank; Baumgarten, Daniel
Experimental demonstration of improved magnetorelaxometry imaging performance using optimized coil configurations. - In: Medical physics, ISSN 2473-4209, Bd. 49 (2022), 5, S. 3361-3374

Background: Magnetorelaxometry imaging is an experimental imaging technique capable of reconstructing magnetic nanoparticle distributions inside a volume noninvasively and with high specificity. Thus, magnetorelaxometry imaging is a promising candidate for monitoring a number of therapeutical approaches that employ magnetic nanoparticles, such as magnetic drug targeting and magnetic hyperthermia, to guarantee their safety and efficacy. Prior to a potential clinical application of this imaging modality, it is necessary to optimize magnetorelaxometry imaging systems to produce reliable imaging results and to maximize the reconstruction accuracy of the magnetic nanoparticle distributions. Multiple optimization approaches were already applied throughout a number of simulation studies, all of which yielded increased imaging qualities compared to intuitively designed measurement setups. Purpose: None of these simulative approaches was conducted in practice such that it still remains unclear if the theoretical results are achievable in an experimental setting. In this study, we demonstrate the technical feasibility and the increased reconstruction accuracy of optimized coil configurations in two distinct magnetorelaxometry setups. Methods: The electromagnetic coil positions and radii of a cuboidal as well as a cylindrical magnetorelaxometry imaging setup are optimized by minimizing the system matrix condition numbers of their corresponding linear forward models. The optimized coil configurations are manufactured alongside with two regular coil grids. Magnetorelaxometry measurements of three cuboidal and four cylindrical magnetic nanoparticle phantoms are conducted, and the resulting reconstruction qualities of the optimized and the regular coil configurations are compared. Results: The computed condition numbers of the optimized coil configurations are approximately one order of magnitude lower compared to the regular coil grids. The reconstruction results show that for both setups, every phantom is recovered more accurately by the optimized coil configurations compared to the regular coil grids. Additionally, the optimized coil configurations yield better signal qualities. Conclusions: The presented experimental study provides a proof of the practicality and the efficacy of optimizing magnetorelaxometry imaging systems with respect to the condition numbers of their system matrices, previously only demonstrated in simulations. From the promising results of our study, we infer that the minimization of the system matrix condition number will also enable the practical optimization of other design parameters of magnetorelaxometry imaging setups (e.g., sensor configuration, coil currents, etc.) in order to improve the achievable reconstruction qualities even further, eventually paving the way towards clinical application of this imaging modality.



https://doi.org/10.1002/mp.15594
Dölker, Eva-Maria; Lau, Stephan; Bernhard, Maria Anne; Haueisen, Jens
Perception thresholds and qualitative perceptions for electrocutaneous stimulation. - In: Scientific reports, ISSN 2045-2322, Bd. 12 (2022), 7335, S. 1-12

Our long-term goal is the development of a wearable warning system that uses electrocutaneous stimulation. To find appropriate stimulation parameters and electrode configurations, we investigate perception amplitude thresholds and qualitative perceptions of electrocutaneous stimulation for varying pulse widths, electrode sizes, and electrode positions. The upper right arm was stimulated in 81 healthy volunteers with biphasic rectangular current pulses varying between 20 and 2000 μs. We determined perception, attention, and intolerance thresholds and the corresponding qualitative perceptions for 8 electrode pairs distributed around the upper arm. For a pulse width of 150 μs, we find median values of 3.5, 6.9, and 13.8 mA for perception, attention, and intolerance thresholds, respectively. All thresholds decrease with increasing pulse width. Lateral electrode positions have higher intolerance thresholds than medial electrode positions, but perception and attention threshold are not significantly different across electrode positions. Electrode size between 15 × 15 mm2 and 40 × 40 mm2 has no significant influence on the thresholds. Knocking is the prevailing perception for perception and attention thresholds while mostly muscle twitching, pinching, and stinging are reported at the intolerance threshold. Biphasic stimulation pulse widths between 150 μs and 250 μs are suitable for electric warning wearables. Within the given practical limits at the upper arm, electrode size, inter-electrode distance, and electrode position are flexible parameters of electric warning wearables. Our investigations provide the basis for electric warning wearables.



https://doi.org/10.1038/s41598-022-10708-9
Simon, Rowena; Schwanengel, Linda; Klemm, Matthias; Meller, Daniel; Hammer, Martin
Spectral fundus autofluorescence peak emission wavelength in ageing and AMD. - In: Acta ophthalmologica, ISSN 1755-3768, Bd. 100 (2022), 6, S. e1223-e1231

Purpose To investigate the spectral characteristics of fundus autofluorescence (FAF) in AMD patients and controls. Methods Fundus autofluorescence spectral characteristics was described by the peak emission wavelength (PEW) of the spectra. Peak emission wavelength (PEW) was derived from the ratio of FAF recordings in two spectral channels at 500-560 nm and 560-720 nm by fluorescence lifetime imaging ophthalmoscopy. The ratio of FAF intensity in both channels was related to PEW by a calibration procedure. Peak emission wavelength (PEW) measurements were done in 44 young (mean age: 24.0 ± 3.8 years) and 18 elderly (mean age: 67.5 ± 10.2 years) healthy subjects as well as 63 patients with AMD (mean age: 74.0 ± 7.3 years) in each pixel of a 30˚ imaging field. The values were averaged over the central area, the inner and the outer ring of the ETDRS grid. Results There was no significant difference between PEW in young and elderly controls. However, PEW was significantly shorter in AMD patients (ETDRS grid centre: 571 ± 26 nm versus 599 ± 17 nm for elderly controls, inner ring: 596 ± 17 nm versus 611 ± 11 nm, outer ring: 602 ± 16 nm versus 614 ± 11 nm). After a mean follow-up time of 50.8 ± 10.8 months, the PEW in the patients decreased significantly by 9 ± 19 nm in the inner ring of the grid. Patients, showing progression to atrophic AMD in the follow up, had significantly (p ≤ 0.018) shorter PEW at baseline than non-progressing patients. Conclusions Peak emission wavelength (PEW) is related to AMD pathology and might be a diagnostic marker in AMD. Possibly, a short PEW can predict progression to retinal and/or pigment epithelium atrophy.



https://doi.org/https://doi.org/10.1111/aos.15070
Friedrich, Bernhard; Lyer, Stefan; Janko, Christina; Unterweger, Harald; Brox, Regine; Cunningham, Sarah; Dutz, Silvio; Taccardi, Nicola; Bikker, Floris J.; Hurle, Katrin; Sebald, Heidi; Lenz, Malte; Spiecker, Erdmann; Fester, Lars; Hackstein, Holger; Strauß, Richard; Boccaccini, Aldo R.; Bogdan, Christian; Alexiou, Christoph; Tietze, Rainer
Scavenging of bacteria or bacterial products by magnetic particles functionalized with a broad-spectrum pathogen recognition receptor motif offers diagnostic and therapeutic applications. - In: Acta biomaterialia, ISSN 1878-7568, Bd. 141 (2022), S. 418-428

Sepsis is a dysregulated host response of severe bloodstream infections, and given its frequency of occurrence and high mortality rate, therapeutic improvements are imperative. A reliable biomimetic strategy for the targeting and separation of bacterial pathogens in bloodstream infections involves the use of the broad-spectrum binding motif of human GP-340, a pattern-recognition receptor of the scavenger receptor cysteine rich (SRCR) superfamily that is expressed on epithelial surfaces but not found in blood. Here we show that these peptides, when conjugated to superparamagnetic iron oxide nanoparticles (SPIONs), can separate various bacterial endotoxins and intact microbes (E. coli, S. aureus, P. aeruginosa and S. marcescens) with high efficiency, especially at low and thus clinically relevant concentrations. This is accompanied by a subsequent strong depletion in cytokine release (TNF, IL-6, IL-1β, Il-10 and IFN-γ), which could have a direct therapeutic impact since escalating immune responses complicates severe bloodstream infections and sepsis courses. SPIONs are coated with aminoalkylsilane and capture peptides are orthogonally ligated to this surface. The particles behave fully cyto- and hemocompatible and do not interfere with host structures. Thus, this approach additionally aims to dramatically reduce diagnostic times for patients with suspected bloodstream infections and accelerate targeted antibiotic therapy. - Statement of significance - Sepsis is often associated with excessive release of cytokines. This aspect and slow diagnostic procedures are the major therapeutic obstacles. The use of magnetic particles conjugated with small peptides derived from the binding motif of a broad-spectrum mucosal pathogen recognition protein GP-340 provides a highly efficient scavenging platform. These peptides are not found in blood and therefore are not subject to inhibitory mechanisms like in other concepts (mannose binding lectine, aptamers, antibodies). In this work, data are shown on the broad bacterial binding spectrum, highly efficient toxin depletion, which directly reduces the release of cytokines. Host cells are not affected and antibiotics not adsorbed. The particle bound microbes can be recultured without restriction and thus be used directly for diagnostics.



https://doi.org/10.1016/j.actbio.2022.01.001
Simon, Rowena; Klemm, Matthias; Meller, Daniel; Hammer, Martin
Spectral calibration of fluorescence lifetime imaging ophthalmoscopy. - In: Acta ophthalmologica, ISSN 1755-3768, Bd. 100 (2022), 2, S. e612-e613

https://doi.org/10.1111/aos.14950
Fiedler, Patrique; Fonseca, Carlos; Supriyanto, Eko; Zanow, Frank; Haueisen, Jens
A high-density 256-channel cap for dry electroencephalography. - In: Human brain mapping, ISSN 1097-0193, Bd. 43 (2022), 4, S. 1295-1308

High-density electroencephalography (HD-EEG) is currently limited to laboratory environments since state-of-the-art electrode caps require skilled staff and extensive preparation. We propose and evaluate a 256-channel cap with dry multipin electrodes for HD-EEG. We describe the designs of the dry electrodes made from polyurethane and coated with Ag/AgCl. We compare in a study with 30 volunteers the novel dry HD-EEG cap to a conventional gel-based cap for electrode-skin impedances, resting state EEG, and visual evoked potentials (VEP). We perform wearing tests with eight electrodes mimicking cap applications on real human and artificial skin. Average impedances below 900 k[Ohm] for 252 out of 256 dry electrodes enables recording with state-of-the-art EEG amplifiers. For the dry EEG cap, we obtained a channel reliability of 84% and a reduction of the preparation time of 69%. After exclusion of an average of 16% (dry) and 3% (gel-based) bad channels, resting state EEG, alpha activity, and pattern reversal VEP can be recorded with less than 5% significant differences in all compared signal characteristics metrics. Volunteers reported wearing comfort of 3.6 ± 1.5 and 4.0 ± 1.8 for the dry and 2.5 ± 1.0 and 3.0 ± 1.1 for the gel-based cap prior and after the EEG recordings, respectively (scale 1-10). Wearing tests indicated that up to 3,200 applications are possible for the dry electrodes. The 256-channel HD-EEG dry electrode cap overcomes the principal limitations of HD-EEG regarding preparation complexity and allows rapid application by not medically trained persons, enabling new use cases for HD-EEG.



https://doi.org/10.1002/hbm.25721
Voss, Andreas; Schröder, Rico; Schulz, Steffen; Haueisen, Jens; Vogler, Stefanie; Horn, Paul; Stallmach, Andreas; Reuken, Philipp Alexander
Detection of liver dysfunction using a wearable electronic nose system based on semiconductor metal oxide sensors. - In: Biosensors, ISSN 2079-6374, Bd. 12 (2022), 2, 70, S. 1-15

https://doi.org/10.3390/bios12020070
Zahn, Diana; Landers, Joachim; Buchwald, Juliana; Diegel, Marco; Salamon, Soma; Müller, Robert; Köhler, Moritz; Ecke, Gernot; Wende, Heiko; Dutz, Silvio
Ferrimagnetic large single domain iron oxide nanoparticles for hyperthermia applications. - In: Nanomaterials, ISSN 2079-4991, Bd. 12 (2022), 3, 343, S. 1-12

This paper describes the preparation and obtained magnetic properties of large single domain iron oxide nanoparticles. Such ferrimagnetic particles are particularly interesting for diagnostic and therapeutic applications in medicine or (bio)technology. The particles were prepared by a modified oxidation method of non-magnetic precursors following the green rust synthesis and characterized regarding their structural and magnetic properties. For increasing preparation temperatures (5 to 85 ˚C), an increasing particle size in the range of 30 to 60 nm is observed. Magnetic measurements confirm a single domain ferrimagnetic behavior with a mean saturation magnetization of ca. 90 Am2/kg and a size-dependent coercivity in the range of 6 to 15 kA/m. The samples show a specific absorption rate (SAR) of up to 600 W/g, which is promising for magnetic hyperthermia application. For particle preparation temperatures above 45 ˚C, a non-magnetic impurity phase occurs besides the magnetic iron oxides that results in a reduced net saturation magnetization.



https://doi.org/10.3390/nano12030343
Shatooti, Sara; Mozaffari, Morteza; Reiter, Günter; Zahn, Diana; Dutz, Silvio
An investigation on the heat dissipation in Zn-substituted magnetite nanoparticles, coated with citric acid and pluronic F127 for hyperthermia application. - In: Physica, ISSN 1873-2135, Bd. 625 (2022), 413468

Zinc substituted spinel ferrite nanoparticles are appropriate for magnetic fluid hyperthermia. Stable suspensions of Zn2+ substituted magnetite (ZnxFe3-xO4, 0 ≤ x ≤ 0.20) nanoparticles in aqueous solutions (pH 5.5) were synthesized by means of co-precipitation approach, using citric acid (CA) and pluronic F127 as surfactants for hyperthermia application. The specimens were characterized by different methods. XRD patterns of the precipitates confirmed that all specimens have single phase cubic spinel structures and their lattice parameters increased as Zn2+ content increased. Mean crystallite sizes of the uncoated specimens were determined to be around 28 nm, using Scherrer's formula. By increasing the Zn2+ content, Curie temperature of the uncoated specimens reduced from 545 to 410 ˚C monotonically caused by reduction in super-exchange interactions. Room temperature saturation magnetizations of the uncoated specimens increased to 98.8 emu/g for x = 0.10 initially, and then decreased to 79.6 emu/g for x = 0.20. It is attributed to the replacement of paramagnetic Fe3+ ions by diamagnetic Zn2+ ones and spin canting. FTIR spectra reconfirmed formation of pure magnetite and Zn2+ substituted magnetite nanoparticles and also proved the presence of ligands on the surface of the nanoparticles. TEM investigation showed that mean particle sizes of the coated nanoparticles were in the range of 35-40 nm. The obtained ferrofluids showed a good stability in aqueous medium (pH 5.5) and according to the room temperature magnetic measurements, heating efficiency is scarcely released due to relaxation processes. Maximum obtained specific loss power (SLP) was 539 W/g and that of intrinsic loss power (ILP) was 7.26 nHm2/kg for x = 0.05 (f = 290 kHz, H = 16 kA/m) with a nanoparticle concentration as low as 1.2 mg/ml, which is a promising candidate for magnetic hyperthermia applications potentially.



https://doi.org/10.1016/j.physb.2021.413468