Detection of viral antibodies in camel sera using magnetic particle spectroscopy.

Pandemics like SARS-Cov-2 very frequently have their origin in different animals and in particular herds of camels could be a source of zoonotic diseases. This study took advantage on a highly sensitive and adaptable method for the fast and reliable detection of viral antibodies in camels using low-cost equipment. Magnetic nanoparticles (MNP) have high variability in their functionalization with different peptides and proteins. We confirm that 3-aminopropyl triethoxysilane (APTES)-coated MNP could be functionalized with viral proteins. The protein loading could be confirmed by simple loading controls using FACS-analysis (p < 0.05). Complementary combination of antigen and antibody yields in a significant signal increase could be proven by both FACS and COMPASS. However, COMPASS needs only a few seconds for the measurement. In COMPASS, the phase φn on selected critical point of the fifth higher harmonic (n = 5th). Here, positive sera display highly significant signal increase over the control or negative sera. Furthermore, a clear distinction could be made in antibody detection as an immune response to closely related viruses (SARS-CoV2 and MERS). Using modified MNPs along with COMPASS offers a fast and reliable method that is less cost intensive than current technologies and offers the possibility to be quickly adapted in case of new occurring viral infections. KEY POINTS: • COMPASS (critical offset magnetic particle spectroscopy) allows the fast detection of antibodies. • Magnetic nanoparticles can be adapted by exchange of the linked bait molecule. • Antibodies could be detected in camel sera without washing steps within seconds.

Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics.

Magnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity.

Near real-time magnetic particle imaging for visual assessment of vascular stenosis in a phantom model.

PURPOSE: This study aimed to investigate the potential of magnetic particle imaging (MPI) to quantify artificial stenoses in vessel phantoms in near real-time. METHODS: Custom-made stenosis phantoms with different degrees of stenosis (0%, 25%, 50%, 75%, and 100%; length 40 mm, inner diameter 8 mm, Polyoxymethylene) were filled with diluted Ferucarbotran (superparamagnetic iron-oxide nanoparticle (SPION) tracer agent, 500 mmol (Fe)/l). A traveling wave MPI scanner (spatial resolution ~ 2 mm, gradient strength ~ 1.5 T/m, field of view: 65 mm length and 29 mm diameter, frequencies f1 = 1050 Hz and f2 = 12150 Hz) was used to acquire images of the phantoms (200 ms total acquisition time per image, 10 averages). Standardized grey scaling was used for comparability. All measured stenoses (n = 80) were graded manually using a dedicated software tool. RESULTS: MPI allowed for accurate visualization of stenoses at a frame rate of 5frames per second. Less severe stenoses were detected more precisely than higher-grade stenoses and came with smaller standard deviations. In particular, the 0%, 25%, 50%, 75%, and 100% stenosis phantom were measured as 3.7 ± 2.7% (mean ± standarddeviation), 18.6 ± 1.8%, 52.8 ± 3.7%, 77.8 ± 14.8% and 100 ± 0%. Geometrical distortions occurred around the center of the high-grade stenosis and led to higher standard deviations compared to lower grade stenoses. In the frame of this study the MPI signal depended linearly on the SPION concentration down to 0.05 mmol (Fe)/l. CONCLUSION: Near real-time MPI accurately visualized and quantified different stenosis grades in vascular phantoms.

Parallel magnetic particle imaging.

Magnetic Particle Imaging (MPI) is a promising tomographic method to visualize the distribution of superparamagnetic materials in three-dimensions. For encoding, a strong gradient represented by a field free point (FFP) or a field free line (FFL) is steered rapidly through the field of view (FOV), acquiring the signal successively. Conventional MPI scanners only provide a single FFP or FFL to sample the entire scan volume, which limits the size of the FOV and/or the temporal resolution. The alternative scanner concept of Traveling Wave MPI (TWMPI) uses a dynamic linear gradient array (dLGA) for dynamic FFP generation along the symmetry axis. The TWMPI scanner is capable of creating multiple FFPs simultaneously, and usually care is taken to locate only a single FFP in the desired FOV. In this manuscript, the concept of parallel MPI utilizing multiple FFPs simultaneously is introduced. For that, conceptual simulations are presented followed by reconstruction approaches for visualization of parallel MPI signals. In addition, an initial parallel MPI experiment with simultaneous acquisition of signals from two FFPs inside the FOV of the same scanner using two receive chains is demonstrated. This allows scanning a doubled FOV within the same acquisition time without sacrificing resolution compared to the standard TWMPI scanner.

Superspeed Bolus Visualization for Vascular Magnetic Particle Imaging.

Magnetic Particle Imaging (MPI) is a fast imaging technique to visualize the distribution of superparamagnetic iron-oxide nanoparticles (SPIONs). For spatial encoding, a field free area is moved rapidly through the field of view (FOV) generating localized signal. Fast moving samples, e.g., a bolus of SPIONs traveling through the large veins in the human body carried by blood flow with velocities in the order of ~45 cm/s, cause temporal blurring in MPI measurements using common sequences and reconstruction techniques. This hampers the evaluation of dynamics of fast moving samples. In this manuscript, a first study on fast moving samples visualized within an MPI scanner is demonstrated. By optimizing parameters for imaging and reconstruction, the dynamics of a fast moving bolus at different velocities can be visualized with high temporal resolution without blurring artifacts.

Magnetic Particle Imaging meets Computed Tomography: first simultaneous imaging.

Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented.

Magnetic Particle Imaging-Guided Stenting.

Purpose:To assess the feasibility of magnetic particle imaging (MPI) to guide stenting in a phantom model. Materials and Methods: MPI is a new tomographic imaging method based on the background-free magnetic field detection of a tracer agent composed of superparamagnetic iron oxide nanoparticles (SPIOs). All experiments were conducted on a custom-built MPI scanner (field of view: 29-mm diameter, 65-mm length; isotropic spatial resolution 1-1.5-mm). Stenosis phantoms (n=3) consisted of polyvinyl chloride (PVC) tubes (8-mm inner diameter) prepared with centrally aligned cable binders to form a ~50% stenosis. A dedicated image reconstruction algorithm allowed precise tracking of endovascular instruments at 8 frames/s with a latency time of ~115 ms. A custom-made MPI-visible lacquer was used to manually label conventional guidewires, balloon catheters, and stainless steel balloon-expandable stents. Vascular stenoses were visualized by injecting a diluted SPIO tracer (ferucarbotran, 10 mmol iron/L) into the vessel phantoms. Balloon angioplasty and stent placement were performed by inflating balloon catheters and stent delivery balloons with diluted ferucarbotran. Results: After deployment of the stent, the markers on its ends were clearly visible. The applied lacquer markers were thin enough to not relevantly alter gliding properties of the devices while withstanding friction during the experiments. Placing an optimized flexible lacquer formulation on the preexisting radiopaque stent markers provided enough stability to withstand stent expansion. Final MPA confirmed successful stenosis treatment, facilitated by the disappearance of the lacquer markers on the stent due to differences in SPIO concentration. Thus, the in-stent lumen could be visualized without interference by the signal from the markers. Conclusion: Near real-time visualization of MPI-guided stenting of stenoses in a phantom model is feasible. Optimized MPI-visible markers can withstand the expansion process of stents.

Magnetic Particle Imaging Guided Real-Time Percutaneous Transluminal Angioplasty in a Phantom Model.

PURPOSE: To investigate the potential of real-time magnetic particle imaging (MPI) to guide percutaneous transluminal angioplasty (PTA) of vascular stenoses in a phantom model. MATERIALS AND METHODS: Experiments were conducted on a custom-built MPI scanner. Vascular stenosis phantoms consisted of polyvinyl chloride tubes (inner diameter 8 mm) prepared with a centrally aligned cable tie to form ~ 50% stenoses. MPI angiography for visualization of stenoses was performed using the superparamagnetic iron oxide nanoparticle-based contrast agent Ferucarbotran (10 mmol (Fe)/l). Balloon catheters and guidewires for PTA were visualized using custom-made lacquer markers based on Ferucarbotran. Stenosis dilation (n = 3) was performed by manually inflating the PTA balloon with diluted Ferucarbotran. An online reconstruction framework was implemented for real-time imaging with very short latency time. RESULTS: Visualization of stenosis phantoms and guidance of interventional instruments in real-time (4 frames/s, ~ 100 ms latency time) was possible using an online reconstruction algorithm. Labeling of guidewires and balloon catheters allowed for precise visualization of instrument positions. CONCLUSION: Real-time MPI-guided PTA in a phantom model is feasible.

MRI Meets MPI: a bimodal MPI-MRI tomograph.

While magnetic particle imaging (MPI) constitutes a novel biomedical imaging technique for tracking superparamagnetic nanoparticles in vivo, unlike magnetic resonance imaging (MRI), it cannot provide anatomical background information. Until now these two modalities have been performed in separate scanners and image co-registration has been hampered by the need to reposition the sample in both systems as similarly as possible. This paper presents a bimodal MPI-MRI-tomograph that combines both modalities in a single system.MPI and MRI images can thus be acquired without moving the sample or replacing any parts in the setup. The images acquired with the presented setup show excellent agreement between the localization of the nanoparticles in MPI and the MRI background data. A combination of two highly complementary imaging modalities has been achieved.

Traveling wave magnetic particle imaging.

Most 3-D magnetic particle imaging (MPI) scanners currently use permanent magnets to create the strong gradient field required for high resolution MPI. However, using permanent magnets limits the field of view (FOV) due to the large amount of energy required to move the field free point (FFP) from the center of the scanner. To address this issue, an alternative approach called "Traveling Wave MPI" is here presented. This approach employs a novel gradient system, the dynamic linear gradient array, to cover a large FOV while dynamically creating a strong magnetic gradient. The proposed design also enables the use of a so-called line-scanning mode, which simplifies the FFP trajectory to a linear path through the 3-D volume. This results in simplified mathematics, which facilitates the image reconstruction.

Numerically efficient estimation of relaxation effects in magnetic particle imaging.

Current simulations of the signal in magnetic particle imaging (MPI) are either based on the Langevin function or on directly measuring the system function. The former completely ignores the influence of finite relaxation times of magnetic particles, and the latter requires time-consuming reference scans with an existing MPI scanner. Therefore, the resulting system function only applies for a given tracer type and the properties of the applied scanning trajectory. It requires separate reference scans for different trajectories and does not allow simulating theoretical magnetic particle suspensions. The most accessible and accurate way for including relaxation effects in the signal simulation would be using the Langevin equation. However, this is a very time-consuming approach because it calculates the stochastic dynamics of the individual particles and averages over large particle ensembles. In the current article, a numerically efficient way for approximating the averaged Langevin equation is proposed, which is much faster than the approach based on the Langevin equation because it is directly calculating the averaged time evolution of the magnetization. The proposed simulation yields promising results. Except for the case of small orthogonal offset fields, a high agreement with the full but significantly slower simulation could be shown.

Eating or meeting? Cluster analysis reveals intricacies of white shark (Carcharodon carcharias) migration and offshore behavior.

Elucidating how mobile ocean predators utilize the pelagic environment is vital to understanding the dynamics of oceanic species and ecosystems. Pop-up archival transmitting (PAT) tags have emerged as an important tool to describe animal migrations in oceanic environments where direct observation is not feasible. Available PAT tag data, however, are for the most part limited to geographic position, swimming depth and environmental temperature, making effective behavioral observation challenging. However, novel analysis approaches have the potential to extend the interpretive power of these limited observations. Here we developed an approach based on clustering analysis of PAT daily time-at-depth histogram records to distinguish behavioral modes in white sharks (Carcharodon carcharias). We found four dominant and distinctive behavioral clusters matching previously described behavioral patterns, including two distinctive offshore diving modes. Once validated, we mapped behavior mode occurrence in space and time. Our results demonstrate spatial, temporal and sex-based structure in the diving behavior of white sharks in the northeastern Pacific previously unrecognized including behavioral and migratory patterns resembling those of species with lek mating systems. We discuss our findings, in combination with available life history and environmental data, and propose specific testable hypotheses to distinguish between mating and foraging in northeastern Pacific white sharks that can provide a framework for future work. Our methodology can be applied to similar datasets from other species to further define behaviors during unobservable phases.