Thomas Weyh

Targeted delivery of magnetic aerosol droplets to the lung

The inhalation of medical aerosols is widely used for the treatment of lung disorders such as asthma, chronic obstructive pulmonary disease1, cystic fibrosis2, respiratory infection3 and, more recently, lung cancer4. Targeted aerosol delivery to the affected lung tissue may improve therapeutic efficiency and minimize unwanted side effects. Despite enormous progress in optimizing aerosol delivery to the lung, targeted aerosol delivery to specific lung regions other than the airways or the lung periphery has not been adequately achieved to date5,6. Here, we show theoretically by computer-aided simulation, and for the first time experimentally in mice, that targeted aerosol delivery to the lung can be achieved with aerosol droplets comprising superparamagnetic iron oxide nanoparticles—so-called nanomagnetosols—in combination with a target-directed magnetic gradient field. We suggest that nanomagnetosols may be useful for treating localized lung disease, by targeting foci of bacterial infection or tumour nodules.

Design and Evaluation of Magnetic Fields for Nanoparticle Drug Targeting in Cancer

The retention of superparamagnetic nanoparticles under the influence of a high-gradient magnetic field was investigated. A simulation algorithm for prediction of the particles trajectories and, therefore, the total amount of adhered particles in an artificial vessel was developed. Comparisons between in vitro experiments and simulations showed that the required experimental magnetic moments were greater than the theoretically estimated magnetic moments. This paper presents a method for investigating magnetic fields and for determining the magnetic moment of particles by simulation of their trajectories. The detailed function of magnetic drug targeting is of great importance in animal studies and in human therapies

Analysis and Optimization of Pulse Dynamics for Magnetic Stimulation

Magnetic stimulation is a standard tool in brain research and has found important clinical applications in neurology, psychiatry, and rehabilitation. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received less attention. Typically, the magnetic field waveform is determined by available device circuit topologies rather than by consideration of what is optimal for neural stimulation. This paper analyzes and optimizes the waveform dynamics using a nonlinear model of a mammalian axon. The optimization objective was to minimize the pulse energy loss. The energy loss drives power consumption and heating, which are the dominating limitations of magnetic stimulation. The optimization approach is based on a hybrid global-local method. Different coordinate systems for describing the continuous waveforms in a limited parameter space are defined for numerical stability. The optimization results suggest that there are waveforms with substantially higher efficiency than that of traditional pulse shapes. One class of optimal pulses is analyzed further. Although the coil voltage profile of these waveforms is almost rectangular, the corresponding current shape presents distinctive characteristics, such as a slow low-amplitude first phase which precedes the main pulse and reduces the losses. Representatives of this class of waveforms corresponding to different maximum voltages are linked by a nonlinear transformation. The main phase, however, scales with time only. As with conventional magnetic stimulation pulses, briefer pulses result in lower energy loss but require higher coil voltage than longer pulses.

Marked differences in the thermal characteristics of figure-of-eight shaped coils used for repetitive transcranial magnetic stimulation.

OBJECTIVE To compare the heating behaviour of three figure-of-eight shaped coils during repetitive transcranial magnetic stimulation (rTMS). METHODS A custom-made coil (referred to as test coil) with a resistance-optimized conductor geometry was compared with two commercially available eight-shaped coils. Each coil was attached to the same energy source, which generated trains of 50 biphasic magnetic pulses every 20s. Coil temperature was continuously measured during nine rTMS protocols using various combinations of stimulus frequencies (5, 10 or 20Hz) and intensities (40, 50 or 60% of maximum stimulator output). A heating curve relating coil temperature and the number of applied stimuli was generated for each coil and rTMS condition. In eleven healthy volunteers, we evaluated the effectiveness of motor cortex stimulation. For each coil, we determined the motor threshold (MT) in the right first dorsal interosseus muscle. RESULTS The slope of the heating curves of the test coil was markedly flattened relative to the heating curves of the two standard coils. This allowed the application of at least twice as many stimuli until the temperature of the coil reached 40 degrees C. Based on these data, we showed that a one-mass model could be used to accurately describe the heating behaviour of each coil. MTs determined with the test coil were comparable to or lower than the MTs that were determined with the standard coils. CONCLUSIONS The efficacy of the test coil to stimulate the M1 was comparable to the efficacy of the two standard coils, yet thermal characteristics were markedly improved. SIGNIFICANCE Overheating of figure-of-eight shaped coils can be markedly delayed without reducing the efficacy of rTMS.

Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3‐D constructs for cartilage tissue engineering

Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production.

MEP latency shift after implantation of deep brain stimulation systems in the subthalamic nucleus in patients with advanced Parkinson's disease

Deep brain stimulation (DBS) into the subthalamic nucleus (STN) is a highly effective treatment for advanced Parkinsons disease (PD). The consequences of STN stimulation on intracortical and corticospinal excitability have been addressed in a few studies using transcranial magnetic stimulation (TMS). Although excitability measurements were compared between the STN stimulation OFF and ON condition, in these experiments, there are no longitudinal studies examining the impact of electrode implantation per se on motor excitability. Here, we explored the effects of STN electrode implantation on resting motor thresholds (RMT), motor evoked potential (MEP) recruitment curves, and MEP onset latencies on 2 consecutive days before and shortly after STN surgery with the stimulator switched off, thus avoiding the effects of chronic DBS on the motor system, in 8 PD patients not taking any dopaminergic medication. After surgery, RMT and MEP recruitment curves were unchanged. In contrast, MEP onset latencies were significantly shorter when examined in relaxed muscles but were unchanged under preactivation. We hypothesize that postoperatively TMS pulses induced small currents in scalp leads underneath the TMS coil connecting the external stimulator with STN electrodes leading to inadvertent stimulation of fast‐conducting descending neural elements in the vicinity of the STN, thereby producing submotor threshold descending volleys. These “conditioning” volleys probably preactivated spinal motor neurons leading to earlier suprathreshold activation by the multiple corticospinal volleys produced by TMS of the motor cortex. These TMS effects need to be considered when interpreting results of excitability measurements in PD patients after implantation of STN electrodes.

Circuit topology and control principle for a first magnetic stimulator with fully controllable waveform

Magnetic stimulation pulse sources are very inflexible high-power devices. The incorporated circuit topology is usually limited to a single pulse type. However, experimental and theoretical work shows that more freedom in choosing or even designing waveforms could notably enhance existing methods. Beyond that, it even allows entering new fields of application. We propose a technology that can solve the problem. Even in very high frequency ranges, the circuitry is very flexible and is able generate almost every waveform with unrivaled accuracy. This technology can dynamically change between different pulse shapes without any reconfiguration, recharging or other changes; thus the waveform can be modified also during a high-frequency repetitive pulse train. In addition to the option of online design and generation of still unknown waveforms, it amalgamates all existing device types with their specific pulse shapes, which have been leading an independent existence in the past years. These advantages were achieved by giving up the common basis of all magnetic stimulation devices so far, i.e., the high-voltage oscillator. Distributed electronics handle the high power dividing the high voltage and the required switching rate into small portions.

Muscle force development after low‐frequency magnetic burst stimulation in dogs

Magnetic stimulation allows for painless and non‐invasive extrinsic motor nerve stimulation. Despite several advantages, the limited coupling to the target reduces the application of magnetic pulses in rehabilitation. According to experience with electrical stimulation, magnetic bursts could remove this constraint.

Living Cells on Chip: Bioanalytical Applications

Cells are able to respond in an extremely sensitive way to changes in their environment. Electronic microstructures on sensor chips can be applied to analyse such responses by recording properties of cell metabolism and cell morphology. These parameters are linked intimately to the cellular signalling network and can thus be used as sensitive indicators for any perturbation of cellular physiology like toxic insults or receptor activation events. Sensor chips might be able to fill a gap by providing functional and dynamic assays related to cell metabolism and cell morphology. Arraying of sensor chips is a prerequisite in order to make such novel types of cell-based assays work efficiently. It depends on technological efforts in chip packaging and electrical connections, electronic sensor control and specific modes of automated liquid handling. A presentation of solutions developed in the authors’ laboratory is given but other approaches in the field of sensor-based cellular analysis will also be included.

A battery modular multilevel management system (BM3) for electric vehicles and stationary energy storage systems

The dependency of energy systems on battery storage systems is constantly increasing, but there are still several unsolved problems. Current battery systems are inflexible, only cells with the same electrical parameters can be combined, and cell defects cause a high reduction of the overall battery lifetime or even a system black out. In addition, the maximum usable capacity and the maximum charging current are limited by the weakest cell in the system. Current Battery Management Systems (BMS) can increase the usable battery capacity to some extend and are able to enlarge the maximum usable charging current. With the Battery Modular Multilevel Management System (BM3) presented in this paper, a very flexible, fault tolerant, and cost-efficient battery system can be implemented. With the system it is possible to establish either serial or parallel connections between neighboring cells or to bypass a cell. Thus the cells can be operated according to their needs and their state of charge (SOC). Separate balancing means for balancing the cells SOC, however, become obsolete.