MNP-Enhanced Microwave Medical Imaging by Means of Pseudo-Noise Sensing.

Magnetic nanoparticles have been investigated for microwave imaging over the last decade. The use of functionalized magnetic nanoparticles, which are able to accumulate selectively within tumorous tissue, can increase the diagnostic reliability. This paper deals with the detecting and imaging of magnetic nanoparticles by means of ultra-wideband microwave sensing via pseudo-noise technology. The investigations were based on phantom measurements. In the first experiment, we analyzed the detectability of magnetic nanoparticles depending on the magnetic field intensity of the polarizing magnetic field, as well as the viscosity of the target and the surrounding medium in which the particles were embedded, respectively. The results show a nonlinear behavior of the magnetic nanoparticle response depending on the magnetic field intensity for magnetic nanoparticles diluted in distilled water and for magnetic nanoparticles embedded in a solid medium. Furthermore, the maximum amplitude of the magnetic nanoparticles responses varies for the different surrounding materials of the magnetic nanoparticles. In the second experiment, we investigated the influence of the target position on the three-dimensional imaging of the magnetic nanoparticles in a realistic measurement setup for breast cancer imaging. The results show that the magnetic nanoparticles can be detected successfully. However, the intensity of the particles in the image depends on its position due to the path-dependent attenuation, the inhomogeneous microwave illumination of the breast, and the inhomogeneity of the magnetic field. Regarding the last point, we present an approach to compensate for the inhomogeneity of the magnetic field by computing a position-dependent correction factor based on the measured magnetic field intensity and the magnetic susceptibility of the magnetic particles. Moreover, the results indicate an influence of the polarizing magnetic field on the measured ultra-wideband signals even without magnetic nanoparticles. Such a disturbing influence of the polarizing magnetic field on the measurements should be reduced for a robust magnetic nanoparticles detection. Therefore, we analyzed the two-state (ON/OFF) and the sinusoidal modulation of the external magnetic field concerning the detectability of the magnetic nanoparticles with respect to these spurious effects, as well as their practical application.

Comparison between Intramuscular Multichannel Electrodes and Supramysial Multichannel Electrodes via EMG Measurements for Potential Use as Larynx Stimulation Electrodes: In Vivo Animal Analysis.

One of the most common causes for larynx paralysis is the injury of the recurrent laryngeal nerve which, among others, causes the paralysis of the posterior cricoarytenoideus muscle (PCA). Electrical stimulation of PCA offers an approach to retaining the function of the paralyzed larynx muscle. The study aim was to test the applicability of an intramuscular multichannel array electrode as a measuring electrode for myoelectrical potentials and as a possible electrode for stimulation, e.g., posterior cricoarytenoideus muscle stimulation. For this purpose, two different kinds of electrodes were compared. 42 intramuscular multichannel array electrodes and 11 supramysial multichannel electrodes were implanted into the triceps brachii muscle of rats. The triceps brachii muscle of rats is suitable to serve as a substitute muscle for the human PCA muscle in an in vivo animal model. It has the same striated muscle cells, is of comparable size, and fundamentally serves a similar function to the human PCA muscle during normal respiration. Walking and breathing are circular functions that cause minimal muscle fatigue when carried out steadily. In total, the myoelectrical activity of 6703 steps could be recorded, allowing a comparison and statistical analysis of the EMG amplitudes and EMG activation patterns. Small differences can be detected between the EMG signals of both electrode types which, however, can be explained physiologically. Both electrode types reveal the basic characteristics of the triceps brachii muscle activity, namely the muscle contraction strength and the coordination pattern. This indicates that the intramuscular electrode may be applied for a detailed analysis of the human larynx.

Method to test the long-term stability of functional electrical stimulation via multichannel electrodes (e.g., applicable for laryngeal pacing) and to define best points for stimulation: in vivo animal analysis.

The study aim was to identify and analyze intramuscular electrically sensitive points. Electrically sensitive points are herein defined as positions, which allow muscles stimulation with a minimum possible fatigue for a maximum amount of time. A multichannel array electrode was used which could be interesting to retain the function of larynx muscle after paralysis. Eight array electrodes were implanted in the triceps brachii muscle of four rats. While being under anesthesia, the animals were intramuscularly stimulated at 16 different positions. Sihler's staining technique was used to make visible the nerves routes and the intramuscular position of the individual electrode plate. The positions of the motor end plates were determined by means of multichannel-electromyography. The positions that allow longest stimulation periods are located close to the points where the nerves enter the muscle. Stimulation at the position of the motor end plates does not result in stimulation periods above average. Locations initially causing strong muscle contractions are not necessarily identical to the ones allowing long stimulation periods. The animal model identified the stimulation points for minimal possible muscle fatigue stimulation as being located close to the points of entrance of the nerve into the muscle. Stimulation causing an initially strong contraction response is no indication of optimal location of the stimulation electrode in terms of chronic stimulation. The array electrode of this study could be interesting as a stimulation electrode for a larynx pacemaker.

Local Magnetic Hyperthermia and Systemic Gemcitabine/Paclitaxel Chemotherapy Triggers Neo-Angiogenesis in Orthotopic Pancreatic Tumors without Involvement of Auto/Paracrine Tumor Cell VEGF Signaling and Hypoxia.

There is a growing interest in exploring the therapeutically mediated modulation of tumor vascularization of pancreatic cancer, which is known for its poorly perfused tumor microenvironment limiting the delivery of therapeutic agents to the tumor site. Here, we assessed how magnetic hyperthermia in combination with chemotherapy selectively affects growth, the vascular compartment of tumors, and the presence of tumor cells expressing key regulators of angiogenesis. To that purpose, a orthotopic PANC-1 (fluorescent human pancreatic adenocarcinoma) mouse tumor model (Rj:Athym-Foxn1nu/nu) was used. Magnetic hyperthermia was applied alone or in combination with systemic chemotherapy (gemcitabine 50 mg per kg body weight, nab-pacitaxel 30 mg/kg body weight) on days 1 and 7 following magnetic nanoparticle application (dose: 1 mg per 100 mm3 of tumor). We used ultrasound imaging, immunohistochemistry, multi-spectral optoacoustic tomography (MSOT), and hematology to assess the biological parameters mentioned above. We found that magnetic hyperthermia in combination with gemcitabine/paclitaxel chemotherapy was able to impact tumor growth (decreased volumes and Ki67 expression) and to trigger neo-angiogenesis (increased small vessel diameter) as a result of the therapeutically mediated cell damages/stress in tumors. The applied stressors activated specific pro-angiogenic mechanisms, which differed from those seen in hypoxic conditions involving HIF-1α, since (a) treated tumors showed a significant decrease of cells expressing VEGF, CD31, HIF-1α, and neuropilin-1; and (b) the relative tumor blood volume and oxygen level remained unchanged. Neo-angiogenesis seems to be the result of the activation of cell stress pathways, like MAPK pathways (high number of pERK-expressing tumor cells). In the long term, the combination of magnetic hyperthermia and chemotherapy could potentially be applied to transiently modulate tumor angiogenesis and to improve drug accessibility during oncologic therapies of pancreatic cancer.

Drug loss from Paclitaxel-Coated Balloons During Preparation, Insertion and Inflation for Angioplasty: A Laboratory Investigation.

PURPOSE: To investigate drug contamination of the working environment with paclitaxel drug-coated balloon (DCB) angioplasty due to loss of paclitaxel containing particles from the coating during DCB preparation, insertion, and inflation. MATERIAL AND METHODS: In an experimetal laboratory setting, drug loss during removal of the protective cover and insertion of the DCB through the hemostatic valve of the introducer sheath and after inflation was examined. In seven DCB types of different manufacturers, semi-quantitative image analysis was performed during five standardized tests cycles. Additionally, every DCB type passed one cycle of a wipe test and one cycle of air sampling. RESULTS: By removing the protective cover, the paclitaxel-covered balloon surface was significantly reduced in 3 out of 7 products (P = 0.043). Overall, extend of decline ranged from 0.4 to 12%. In 6 of 7 products, powdered paclitaxel clusters dropped down upon removal of the protective cover (0.099 ng/cm2 up to approx. 22 ng/cm2). Contamination of the air was detected in none of the DCB types. When pushed through the vascular sheath, none of the investigated DCB types showed a significant loss of paclitaxel from the coated balloon surface. After balloon inflation, the paclitaxel-coated surface area varied between manufacturers ranging from 25.9 to 97.8%. CONCLUSION: In some DCB types, the removal of the protective cover already leads to a significant loss of paclitaxel and paclitaxel-coated surfaces. As a result, there will be a contamination of the workplace and a reduction in the therapeutic dose. LEVEL OF EVIDENCE: No level of evidence.

Kinematic and electromyographic tools for characterizing movement disorders in mice.

Increasing interest in rodent models for movement disorders has led to an increasing need for more accurate and precise methods for both delineating the nature of abnormal movements and measuring their severity. These studies describe application of simultaneous high-speed video kinematics with multichannel electromyography (EMG) to characterize the movement disorder exhibited by tottering mutant mice. These mice provide a uniquely valuable model, because they exhibit paroxysmal dystonia superimposed on mild baseline ataxia, permitting the examination of these two different problems within the same animals. At baseline with mild ataxia, the mutants exhibited poorly coordinated movements with increased variation of stance and swing times, and slower spontaneous walking velocities. The corresponding EMG showed reduced mean amplitudes of biceps femoris and vastus lateralis, and poorly modulated EMG activities during the step cycle. Attacks of paroxysmal dystonia were preceded by trains of EMG bursts with doublets and triplets simultaneously in the biceps femoris and vastus lateralis followed by more sustained coactivation. These EMG characteristics are consistent with the clinical phenomenology of the motor phenotype of tottering mice as a baseline of mild ataxia with intermittent attacks of paroxysmal dystonia. The EMG characteristics of ataxia and dystonia in the tottering mice also are consistent with EMG studies of other ataxic or dystonic animals and humans. These studies provide insights into how these methods can be used for delineating movement disorders in mice and for how they may be compared with similar disorders of humans.

MNP Enhanced Microwave Imaging by Means of Pseudo-Noise Sensing with Different External Magnetic Field Modulations.

This contribution deals with the detection and imaging of magnetic modulated nanoparticles by means of ultra-wideband sensing. We performed phantom measurements in a practical measurement setup where the magnetic nanoparticles are modulated by a static and a low periodic changing external magnetic field. We investigated the influence of the modulation type of the polarizing magnetic field on both, detectability and imaging of magnetic nanoparticles. We can conclude that both modulations generate a sufficient contrast in order that the nanoparticles were detected at the correct position in a three-dimensional volume. The imaging results, including 32 channels, indicate that the two state (ON/OFF) modulation of the magnetic field under constant environmental conditions shows better results compared to a sinusoidal excitation of the magnetic field.

EMG analysis of the thenar muscles as a model for EMG-triggered larynx stimulation.

Paralysis of one or both sides of the larynx musculature compromises breathing and speech function. Currently there is no surgical remedy to restore adequate function of the larynx. A plausible alternative solution is triggered electrical stimulation of the paralysed larynx site using a laryngeal pacemaker. Triggering of the pacemaker succeeds via constant EMG measurement of the muscle activity of the healthy larynx side. The EMG data analysis described in this work is one possible approach for regulating pacemaker triggering. In this study we used EMG data from the thenar muscles as a model to calculate a trigger point.

Development of a novel larynx pacemaker multichannel array electrode: In vivo animal analysis.

OBJECTIVES/HYPOTHESIS: Electrical stimulation of posterior cricoarytenoid muscle offers a physiological approach to retain the function of the paralyzed larynx muscle after paralysis. The aim of this study was to develop and evaluate a durable, biocompatible, and atraumatic array electrode for inclusion in a larynx pacemaker. In addition to developing the electrode array, an evaluation methodology using in vivo multichannel electromyography was assessed. STUDY DESIGN: In vivo test procedures for material evaluation: an animal model. METHODS: Over the research period, 42 array electrodes representing nine different prototypes were implanted in the triceps brachii muscle of 21 rats. Biocompatibility and atraumatic functions were evaluated via observation. Electrode function and durability were determined by comparison of daily electromyographic measurements of the muscle activity of the front leg (triceps brachii muscle) during locomotion. RESULTS: The used animal model demonstrated electrode material problems that could not be material evaluation from in vitro tests alone. Through use of this in vivo method, it was found that an array tip that is durable, biocompatible, and atraumatic should consist of many small electrode plates cast in flexible silicone. The connecting wires to the individual electrode plates should be Litz wire, which consists of multiple strands. CONCLUSIONS: The here demonstrated in vivo test method was a suitable animal model for designing and evaluating electrodes to be further developed for inclusion in human implants. LEVEL OF EVIDENCE: N/A.

Re-evaluation of the amplitude-force relationship of trunk muscles.

Amplitude-force relationships of major trunk muscles are established in terms of curve characteristics, but up to now were not normalized with respect to maximum voluntary contraction (MVC) force levels. The study therefore aims at a re-evaluation of trunk muscle amplitude-force relationship data according to MVC. Surface EMG of five major trunk muscles was taken from 50 healthy subjects of both sexes (age 20-40 years). All tasks were performed in a device where submaximal loads on the trunk were applied by gradually tilting the subjects in sagittal plane to horizontal position. MVC flexion and extension forces were determined in upright position using an additional harness over the subject's shoulders. Furthermore, the subject's upper body mass (UBM) was obtained during forward tilt to horizontal. MVC to UBM ratio was calculated, corrected by the actual tilt angle, and these linearly estimated values compared with the measured relative values according to MVC. All abdominal muscles confirmed the known non-linear amplitude-force relationship. At low load levels the linearly estimated values overestimated the measured ones and, at higher load levels, underestimated the true stress levels considerably. Back muscles confirmed the known linear curve shape, but for the longissimus muscle at L1 level measured data was always below estimated values. With increasing load, muscular stress of abdominal muscles changes from overestimated towards considerably underestimated values if expected stress levels are based on linear interpolation. Major back muscles' activation levels are nearly linear, but the amplitude-force relationship values seem overestimated for longissimus.

Alteration of Surface EMG amplitude levels of five major trunk muscles by defined electrode location displacement.

Exact electrode positioning is vital for obtaining reliable results in Surface EMG. This study aimed at systematically assessing the influence of defined electrode shifts on measured Surface EMG amplitudes of trunk muscles in a group of 15 middle aged healthy male subjects. The following leftsided muscles were investigated: rectus abdominis muscle, internal and external oblique abdominal muscles, lumbar multifidus muscle, and longissimus muscle. In addition to the recommended electrode positions, extra electrodes were placed parallel to these and along muscle fiber direction. Measurements were performed under isometric conditions in upright body position. Gradually changing, but defined loads were applied considering subject's upper body weight. For the abdominal muscles amplitude differences varied considerably depending on load level, magnitude, and direction. For both back muscles amplitudes dropped consistently but rather little for parallel electrode displacements. However, for the longissimus muscle a caudal electrode shift resulted in an amplitude increase of similar extent and independent from load level. Influence of electrode position variations can be proven for all trunk muscles but are more evident in abdominal than back muscles. Those muscle-specific effects confirm the necessity for an exact definition of electrode positioning to allow comparisons between individual subjects, groups of subjects, and studies.