Magnetic Particle Imaging (MPI) is a non-ionizing tomographic technique capable of real-time 3D imaging with unmatched temporal resolution, reaching up to 46 vol/s. These features make MPI a promising tool for the monitoring of implantable resin composites, particularly in scenarios requiring frequent safe, and dynamic assessment. However, integrating magnetic responsiveness into medical materials without compromising their structural and biological integrity remains a challenge. In this study, it is presented the first strategy to enable MPI signal generation in a commercial implantable cement by depositing a continuous iron thin film onto its surface. This structured magnetic layer introduces directional magnetic anisotropy, resulting in an angle-dependent MPI signal. This directional dependence can be explored to noninvasively track for the position and orientation of the implant, potentially benefiting applications in confined anatomical regions. In vitro assays confirmed that the incorporation of the magnetic layer does not compromise cytocompatibility. Altogether, these findings demonstrate that magnetic thin films can serve as anisotropic contrast sources for MPI, expanding the range of new possibilities for imaging implantable materials with orientation-sensitive contrast and without ionizing radiation.
Magnetic particle imaging (MPI) is a tracer-based technique that directly detects the distribution of magnetic iron-oxide nanoparticles with millisecond temporal resolution and no tissue background. Despite extensive preclinical work, in-vivo application of MPI in humans has not previously been reported. Here, we report the first in-vivo human MPI angiography, visualizing venous perfusion of the upper extremity using a human-scale scanner and clinically approved ferucarbotran. Under identical procedural conditions, we performed X-ray digital subtraction angiography as the clinical gold standard. MPI visualized major superficial and deep veins, including inflow, branching, valve filling, and clearance dynamics in real time with 2 frames per second. These results establish magnetic particle imaging as a clinically translatable modality for radiation-free vascular imaging in humans and mark the transition of MPI from preclinical research to first clinical application.
Objectives:Magnetic particle imaging (MPI) is a tracer-based imaging modality enabling radiation-free visualization of superparamagnetic iron oxide nanoparticles with high temporal resolution. Despite extensive preclinical development, in-vivo application in humans has not previously been reported so far. This study aimed to demonstrate the feasibility of first-in-human MPI angiography and to compare it with conventional X-ray digital subtraction angiography (DSA). Materials and Methods:A first-in-human MPI angiography was performed in a healthy volunteer using a human-scale interventional MPI scanner and clinically approved ferucarbotran tracer. Imaging of the upper extremity veins was conducted under clinical angiography laboratory conditions with continuous physiological monitoring. Conventional DSA of the same region was performed under identical procedural conditions for direct comparison. MPI data were acquired in real time with 2 frames per second and co-registered with DSA images. Results:MPI successfully visualized major superficial and deep veins, including inflow, branching patterns, venous valve filling, collateral pathways, and tracer clearance dynamics. Spatial and temporal visualization was comparable to DSA for clinically relevant vascular structures. No adverse events occurred, and safety monitoring remained unremarkable throughout the procedure. Conclusions:This first in-vivo human demonstration shows that MPI enables real-time, radiation-free angiographic visualization of vascular structures with clinically relevant temporal resolution. MPI has potential as a novel imaging modality for selected vascular and interventional applications and represents an important step toward clinical translation. Key Points:· First in-human magnetic particle imaging angiography demonstrated feasibility. · Real-time vascular imaging without ionizing radiation achieved. · Comparable visualization to digital subtraction angiography. · Potential for interventional and vascular clinical applications. Citation Format:· Vogel P, Kampf T, Rückert MA et al. First In-vivo Human Magnetic Particle Imaging. Rofo 2026; DOI 10.1055/a-2856-9878.
BACKGROUND:Magnetic particle imaging (MPI) allows for radiation-free visualization of tracers without background signal. With the first human-sized interventional MPI scanner being recently developed, the aim of the present study was to test its performance for guiding of endovascular procedures in a realistic perfusion model. METHODS:Three fresh-frozen cadaveric legs were prepared to establish continuous circulation in the superficial femoral artery via introducer sheaths in the inguinal and infragenicular region. To facilitate vessel visualization, a mixture of a MPI tracer (Resotran® or Perimag®) and X-ray contrast agent was injected under continuous extracorporeal perfusion and imaged simultaneously with MPI angiography and digital subtraction angiography (DSA) as reference. RESULTS:The MPI scanner integrates seamlessly into the standard operating procedures in the angiography suite and simultaneous imaging with DSA and MPI is feasible. The MPI scanner detects a tracer bolus of 2 ml Perimag® or 1.5 ml Resotran®. Imaging results are consistent and reproducible in three cadaveric leg phantoms. CONCLUSION:This study demonstrates, that the recently developed human-sized MPI scanner facilitates reliable radiation-free image guidance for peripheral vascular interventions in the superficial femoral artery with a tracer approved for use in humans.
The application of a weak rotating magnetic field to magnetic particles, that show only Brownian dynamics and are suspended in a liquid leads to a nonlinear rotation if the magnetic field is not strong enough to overcome the rotational friction at the applied frequency. In this paper, the analytical solution to the equation of motion is derived for the case of negligible angular momentum and no random thermal interactions. The former is an accurate approximation in all typical applications such as magnetic particle imaging or magnetic particle based hyperthermia. Having a closed solution for the theoretical edge case, where random thermal interactions go to zero, can be used as a verification tool for more generalized particle simulations and it can also be used as a basis for constructing approximations for more general cases.
Magnetic Particle Imaging (MPI) is a preclinical imaging modality with potential for future clinical usage. The radiation-free guidance of endovascular interventions with MPI is especially promising. Here, we present a safety study on the heating of metallic medical implants during MPI measurements under realistic conditions in an extracorporeally-perfused cadaver model. The measurements were conducted by fiberoptic thermometers and showed no detectable heating of the tested endovascular devices in the cadaver model. A temperature increase of no more than 0.11 K was observed on the surface of the investigated proximal femoral nail. The in vitro testing of orthopedic prostheses (knee and hip) revealed a slight heating effect of 0.45 K. The dependence of heating on the applied excitation frequency was measured. Overall, the tested repertoire of implants did not heat by a clinically-relevant amount in a human-sized MPI-scanner under realistic conditions, indicating their safe usage in future clinical applications.
Objective.The availability of magnetic nanoparticles (MNPs) with medical approval for human intervention is fundamental to the clinical translation of magnetic particle imaging (MPI). In this work, we thoroughly evaluate and compare the magnetic properties of an magnetic resonance imaging (MRI) approved tracer to validate its performance for MPI in future human trials.Approach.We analyze whether the recently approved MRI tracer Resotran is suitable for MPI. In addition, we compare Resotran with the previously approved and extensively studied tracer Resovist, with Ferrotran, which is currently in a clinical phase III study, and with the tailored MPI tracer Perimag.Main results.Initial magnetic particle spectroscopy (MPS) measurements indicate that Resotran exhibits performance characteristics akin to Resovist, but below Perimag. We provide data on four different tracers using dynamic light scattering, transmission electron microscopy, vibrating sample magnetometry measurements, MPS to derive hysteresis, point spread functions, and a serial dilution, as well as system matrix based MPI measurements on a preclinical scanner (Bruker 25/20 FF), including reconstructed images.Significance.Numerous approved MNPs used as tracers in MRI lack the necessary magnetic properties essential for robust signal generation in MPI. The process of obtaining medical approval for dedicated MPI tracers optimized for signal performance is an arduous and costly endeavor, often only justifiable for companies with a well-defined clinical business case. Resotran is an approved tracer that has become available in Europe for MRI. In this work, we study the eligibility of Resotran for MPI in an effort to pave the way for human MPI trials.
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.
Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model.
Supporting files for manuscript: "iMPI – portable human-sized Magnetic Particle Imaging Scanner for real-time endovascular Interventions"
Abstract In the last decade Magnetic nanoparticles (MNPs) have gained an enormous interest in specialized areas such as medicine, cancer theranostics, biosensing, catalysis, agriculture, and the environmental protection. By controlled engineering of specific surface properties, named functionalization, MNPs are gaining special features for desired applications, e.g., bioassays for the detection of biomolecules or biomarkers such as antibodies. The characterization as well as a highly specific measurement of such binding states is of high interest and limited to highly sensitive techniques such as ELISA (Enzyme-linked Immunosorbent Assay) or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Novel upcoming methods, such as ACS (AC susceptometry) or MPS (Magnetic Particle Spectroscopy), exploit the magnetization response of functionalized MNP ensembles to assess specific information about the MNP mobility within their environment as well as the conjugations of chemical or biological compounds on their surface. Both methods have shown promising results reaching similar sensitivities within short measurement times but showing difficulties in data interpretation. Here, we report a novel method, COMPASS (Critical Offset Magnetic PArticle SpectroScopy), which is based on a critical offset magnetic field of MNPs, which enables 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 validated sensitivity of 0.85 fmole/50 µl sample volume ( ≙ 33 pM) SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is not only competitive with the sensitivity of commonly used ELISA or flow cytometry methods but provides more flexibility, robustness and rapid measurement withinwell below a minute per sample, including sample conjugation, mixing and incubation times. The underlying physical effect is based on an offset magnetic field induced suppression of a higher harmonic in the nonlinear magnetization response of the MNP to a time varying magnetic field resulting in a highly sensitive response of the signal phase to minimal changes in particle mobility. Since this effect is independent of MNP concentration, the sample handling is much simpler and robust. Our method thus may pave the way for deeper insights into complex and rapid binding dynamics of functionalization chemistry and can lead to a huge step forwards in point-of-care diagnostics as well as impacts other fields in research and industries.
Background To investigate the effects of B 1 -shimming and radiofrequency (RF) parallel transmission (pTX) on the visualization and quantification of the degree of stenosis in a coronary artery phantom using 7 Tesla (7 T) magnetic resonance imaging (MRI). Methods Stenosis phantoms with different grades of stenosis (0%, 20%, 40%, 60%, 80%, and 100%; 5 mm inner vessel diameter) were produced using 3D printing (clear resin). Phantoms were imaged with four different concentrations of diluted Gd-DOTA representing established arterial concentrations after intravenous injection in humans. Samples were centrally positioned in a thorax phantom of 30 cm diameter filled with a custom-made liquid featuring dielectric properties of muscle tissue. MRI was performed on a 7 T whole-body system. 2D-gradient-echo sequences were acquired with an 8-channel transmit 16-channel receive (8 Tx / 16 Rx) cardiac array prototype coil with and without pTX mode. Measurements were compared to those obtained with identical scan parameters using a commercially available 1 Tx / 16 Rx single transmit coil (sTX). To assess reproducibility, measurements ( n = 15) were repeated at different horizontal angles with respect to the B 0 -field. Results B 1 -shimming and pTX markedly improved flip angle homogeneity across the thorax phantom yielding a distinctly increased signal-to-noise ratio (SNR) averaged over a whole slice relative to non-manipulated RF fields. Images without B 1 -shimming showed shading artifacts due to local B 1 + -field inhomogeneities, which hampered stenosis quantification in severe cases. In contrast, B 1 -shimming and pTX provided superior image homogeneity. Compared with a conventional sTX coil higher grade stenoses (60% and 80%) were graded significantly (p<0.01) more precise. Mild to moderate grade stenoses did not show significant differences. Overall, SNR was distinctly higher with B 1 -shimming and pTX than with the conventional sTX coil (inside the stenosis phantoms 14%, outside the phantoms 32%). Both full and half concentration (10.2 mM and 5.1 mM) of a conventional Gd-DOTA dose for humans were equally suitable for stenosis evaluation in this phantom study. Conclusions B 1 -shimming and pTX at 7 T can distinctly improve image homogeneity and therefore provide considerably more accurate MR image analysis, which is beneficial for imaging of small vessel structures.
An accurate planar visualization (curved planar reformation - CPR) of intracranial arteries is mandatory for an improved luminal and mural assessment especially in low resolution Magnetic Resonance Imaging (MRI) data sets acquired in standard clinical settings. CPR visualization methods based on the centerline of the desired structure are fast and easy to implement but the accuracy strongly depends on the spatial resolution of the 3D data set and the size of the desired vessel. In the manuscript, a novel algorithm for fast and robust centerline calculation in multi-contrast 3D MRI data is presented. It considers the extracted surface of the vessel structure for a more accurate centerline prediction resulting in an enhanced CPR visualization of small vessels.
Simulations with high accuracy are an essential part of scientific research to accelerate the innovation process. They are especially useful for finding novel approaches or optimizing existing methods. Today, powerful software tools are available consisting of multiple packages with a wide variety of features, methods, and models meet the requirements for different questions in multiple fields of research. Unfortunately, the complexity and often inflexibility of such unspecific software tools can hinder an optimal workflow. Especially in the case of a novel research fields, e.g., Magnetic Particle Imaging (MPI), the requirements on a software tool are a high degree of flexibility paired with a manageable number of highly specific features to provide fast and easy access. Thus, often research sites generates their own software solution to address their specific demands. Until now, only few simulation frameworks are available, which partially fulfil most requirements of the young field of MPI. However, the coverage of the entire process of emulating a full MPI experiment from magnetic field and particle dynamic simulations, hardware and sequence programming over signal generation and data processing to final reconstruction and visualization combined with an easy-to-use graphical user interface (GUI) and without the need of complex combination of different software packages cannot be found in the literature or MPI community so far. With the presented modular simulation framework consisting of multiple interconnected software packages to specific purposes, all necessary simulation steps are provided. The high degree of flexibility and modularity allow the simulation and emulation of almost any kind of MPI scanners known in the MPI community. Furthermore, the modular framework allows an easy connection of third-party software using dedicated interfaces between important steps.
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 ( C ritical- O ffset- M agnetic- Pa rticle- S pectro S copy), 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.
Purpose: Magnetic Particle Imaging (MPI) is a new, background- and radiation-free tomographic imaging method that enables near real-time imaging of superparamagnetic iron-oxide nanoparticles (SPIONs) with high temporal and spatial resolution. This phantom study aims to investigate the potential of MPI for visualization of the stent lumen in intracranial flow diverters (FD). Methods: Nitinol FD of different dimensions (outer diameter: 3.5 mm, 4.0 mm, 5.5 mm; total length: 22-40 mm) were scanned in vascular phantoms in a custom-built MPI scanner (in-plane resolution: - 2 mm, field of view: 65 mm length, 29 mm diameter). Phantoms were filled with diluted (1:50) SPION tracer agent Ferucarbotran (10 mu mol (Fe)/ml; NaCL). Each phantom was measured in 32 different projections (overall acquisition time per image: 3200 ms, 5 averages). After image reconstruction from raw data, two radiologists assessed image quality using a 5-point Likert scale. The signal intensity profile was measured using a semi-automatic evaluation tool. Results: MPI visualized the lumen of all FD without relevant differences between the stented vessel phantom and the reference phantom. At 3.5 mm image quality was slightly inferior to the larger diameters. The FD themselves neither generated an MPI signal nor did they lead to relevant imaging artifacts. Ratings of both radiologists showed no significant difference, interrater reliability was good (ICC 0.84). A quantitative evaluation of the signal intensity profile did not reveal any significant differences (p > 0.05) either. Conclusion: MPI visualizes the lumen of nitinol FD stents in vessel phantoms without relevant stent-induced artifacts.
Vessel wall enhancement (VWE) may be commonly seen on MRI images of asymptomatic subjects. This study aimed to characterize the VWE of the proximal internal carotid (ICA) and vertebral arteries (VA) in a non-vasculitic elderly patient cohort. Cranial MRI scans at 3 Tesla were performed in 43 patients (aged ≥ 50 years) with known malignancy for exclusion of cerebral metastases. For vessel wall imaging (VWI), a high-resolution compressed-sensing black-blood 3D T1-weighted fast (turbo) spin echo sequence (T1 CS-SPACE prototype) was applied post gadolinium with an isotropic resolution of 0.55 mm. Bilateral proximal intradural ICA and VA segments were evaluated for presence, morphology, and longitudinal extension of VWE. Concentric VWE of the proximal intradural ICA was found in 13 (30%) patients, and of the proximal intradural VA in 39 (91%) patients. Mean longitudinal extension of VWE after dural entry was 13 mm in the VA and 2 mm in the ICA. In 14 of 39 patients (36%) with proximal intradural VWE, morphology of VWE was suggestive of the mere presence of vasa vasorum. In 25 patients (64 %), morphology indicated atherosclerotic lesions in addition to vasa vasorum. Vasa vasorum may account for concentric VWE within the proximal 2 mm of the ICA and 13 mm of the VA after dural entry in elderly subjects. Concentric VWE in these locations should not be confused with large artery vasculitis. Distal to these segments, VWE may be more likely related to pathologic conditions such as vasculitis. • Vasa vasorum may account for concentric VWE within the proximal 2 mm of the ICA and 13 mm of the VA after dural entry in non-vasculitic elderly people. • Concentric enhancement within the proximal 2 mm of the intradural ICA and within the proximal 13 mm of the intradural VA portions should not be misinterpreted as vasculitis. • Distal of this, VWE is likely related to pathologic conditions, in case of concentric VWE suggestive of vasculitis.
The success of tracer-based tomographic methods, such as Magnetic Particle Imaging (MPI), depends on two factors primarily: scanner hardware and tracer performance. Within the last years, several hardware improvements have been presented improving temporal and spatial resolution of MPI systems. However, there was still a lack of efficient commercially available tracers for MPI. Here we report on synomag® particles as a new tracer tailored for MPI, which shows almost four-times higher signal in a Traveling Wave MPI scanner than the established tracer Resovist®. Int. J. Mag. Part. Imag. 7(1), 2021, Article ID: 2103003, DOI: 10.18416/IJMPI.2021.2103003