Repeated Injection of Very Small Superparamagnetic Iron Oxide Particles (VSOPs) in Murine Atherosclerosis: A Safety Study.

Citrate-coated electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) have been successfully tested as magnetic resonance angiography (MRA) contrast agents and are promising tools for molecular imaging of atherosclerosis. Their repeated use in the background of pre-existing hyperlipidemia and atherosclerosis has not yet been studied. This study aimed to investigate the effect of multiple intravenous injections of VSOPs in atherosclerotic mice. Taurine-formulated VSOPs (VSOP-T) were repeatedly intravenously injected at 100 µmol Fe/kg in apolipoprotein E-deficient (ApoE KO) mice with diet-induced atherosclerosis. Angiographic imaging was carried out by in vivo MRI. Magnetic particle spectrometry was used to detect tissue VSOP content, and tissue iron content was quantified photometrically. Pathological changes in organs, atherosclerotic plaque development, and expression of hepatic iron-related proteins were evaluated. VSOP-T enabled the angiographic imaging of heart and blood vessels with a blood half-life of one hour. Repeated intravenous injection led to VSOP deposition and iron accumulation in the liver and spleen without affecting liver and spleen pathology, expression of hepatic iron metabolism proteins, serum lipids, or atherosclerotic lesion formation. Repeated injections of VSOP-T doses sufficient for MRA analyses had no significant effects on plaque burden, steatohepatitis, and iron homeostasis in atherosclerotic mice. These findings underscore the safety of VSOP-T and support its further development as a contrast agent and molecular imaging tool.

Counting cells in motion by quantitative real-time magnetic particle imaging.

Magnetic Particle Imaging (MPI) is an advanced and powerful imaging modality for visualization and quantitative real-time detection of magnetic nanoparticles (MNPs). This opens the possibility of tracking cells in vivo once they have been loaded by MNPs. Imaging modalities such as optical imaging, X-ray computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) face limitations, from depth of penetration and radiation exposure to resolution and quantification accuracy. MPI addresses these challenges, enabling radiation-free tracking of MNP-loaded cells with precise quantification. However, the real-time tracking of MNP-loaded cells with MPI has not been demonstrated yet. This study establishes real-time quantitative tracking of MNP-loaded cells. Therefore, THP-1 monocytes were loaded with three different MNP systems, including the MPI gold standard Resovist and Synomag. The real-time MPI experiments reveal different MPI resolution behaviors of the three MNP systems after cellular uptake. Real-time quantitative imaging was achieved by time-resolved cell number determination and comparison with the number of inserted cells. About 95% of the inserted cells were successfully tracked in a controlled phantom environment. These results underline the potential of MPI for real-time investigation of cell migration and interaction with tissue in vivo.

Nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles inside the gastrointestinal tract of Drosophila melanogaster.

Widefield magnetometry based on nitrogen-vacancy centers enables high spatial resolution imaging of magnetic field distributions without a need for spatial scanning. In this work, we show nitrogen-vacancy center magnetic imaging of Fe3O4 nanoparticles within the gastrointestinal tract of Drosophila melanogaster larvae. Vector magnetic field imaging based on optically detected magnetic resonance is carried out on dissected larvae intestine organs containing accumulations of externally loaded magnetic nanoparticles. The distribution of the magnetic nanoparticles within the tissue can be clearly deduced from the magnetic stray field measurements. Spatially resolved magnetic imaging requires the nitrogen-vacancy centers to be very close to the sample making the technique particularly interesting for thin tissue samples. This study is a proof of principle showing the capability of nitrogen-vacancy center magnetometry as a technique to detect magnetic nanoparticle distributions in Drosophila melanogaster larvae that can be extended to other biological systems.

Uremic Toxin-Induced Exosome-like Extracellular Vesicles Contain Enhanced Levels of Sulfated Glycosaminoglycans which Facilitate the Interaction with Very Small Superparamagnetic Iron Oxide Particles.

Uremic toxins exert pathophysiological effects on cells and tissues, such as the generation of a pro-calcifying subtype of exosome-like extracellular vesicles (EVs) in vascular cells. Little is known about the effects of the toxins on the surface structure of EVs. Thus, we studied the effects of uremic toxins on the abundance of sulfated glycosaminoglycans (GAGs) in EVs, and the implications for binding of ligands such as very small superparamagnetic iron oxide particles (VSOPs) which could be of relevance for radiological EV-imaging. Vascular cells were treated with the uremic toxins NaH2PO4 and a mixture of urea and indoxyl sulfate. Uremia in rats was induced by adenine feeding. EVs were isolated from culture supernatants and plasma of rats. By proton T1-relaxometry, magnetic particle spectroscopy, and analysis of genes, proteins, and GAG-contents, we analyzed the roles of GAGs in the ligand binding of EVs. By influencing GAG-associated genes in host cells, uremic toxins induced higher GAG contents in EVs, particularly of sulfated chondroitin sulfate and heparan sulfate chains. EVs with high GAG content interacted stronger with VSOPs compared to control ones. This was confirmed by experiments with GAG-depleted EVs from genetically modified CHO cells and with uremic rat-derived EVs. Mechanistically, uremic toxin-induced PI3K/AKT-signaling and expression of the sulfate transporter SLC26A2 in host cells contributed to high GAG contents in EVs. In conclusion, uremic conditions induce enhanced GAG contents in EVs, which entails a stronger interaction with VSOPs. VSOPs might be suitable for radiological imaging of EVs rich in GAGs.

Temperature dependent magnetorelaxometry of magnetic nanoparticle ensembles.

Magnetorelaxometry imaging (MRXI) is a non-invasive, quantitative imaging technique for magnetic nanoparticles (MNPs). The image resolution of this technique significantly depends on the relaxation amplitude (ΔB). For this work, we measured the room temperature (299 K) relaxation signals of eight commercial MNP sample systems with different magnetic properties, in both fluid and immobilized states, in order to select the most suitable sample for a particular MRXI setting. Additionally, the effect of elevated temperatures (up to hyperthermia temperature, 335 K) on the relaxation signals of four different MNP systems (Synomag, Perimag, BNF and Nanomag) in both states were investigated. The ΔBvalues of fluid samples significantly decreased with increasing temperature, and the behaviour for immobilized samples depended on their blocking temperature (TB). For samples withTB< 299 K, ΔBalso decreased with increasing temperature. Whereas for samples withTB> 299 K, the opposite behaviour was observed. These results are beneficial for improving the image resolution in MRXI and show, among the investigated systems, and for our setup, Synomag is the best candidate for futurein vitroandin vivostudies. This is due to its consistently high ΔBbetween 299 and 335 K in both states. Our findings demonstrate the feasibility of temperature imaging by MRXI.

Human-sized quantitative imaging of magnetic nanoparticles with nonlinear magnetorelaxometry.

Objective.Magnetorelaxomety imaging (MRXI) is a noninvasive imaging technique for quantitative detection of magnetic nanoparticles (MNPs). The qualitative and quantitative knowledge of the MNP distribution inside the body is a prerequisite for a number of arising biomedical applications, such as magnetic drug targeting and magnetic hyperthermia therapy. It was shown throughout numerous studies that MRXI is able to successfully localize and quantify MNP ensembles in volumes up to the size of a human head. However, deeper regions that lie far from the excitation coils and the magnetic sensors are harder to reconstruct due to the weaker signals from the MNPs in these areas. On the one hand, stronger magnetic fields need to be applied to produce measurable signals from such MNP distributions to further upscale MRXI, on the other hand, this invalidates the assumption of a linear relation between applied magnetic field and particle magnetization in the current MRXI forward model which is required for the imaging procedure.Approach.We tackle this problem by introducing a nonlinear MRXI forward model that is also valid for strong magnetic excitation fields.Main results.We demonstrate in our experimental feasibility study that scaling up the imaging region to the size of a human torso using nonlinear MRXI is possible. Despite the extreme simplicity of the imaging setup applied in this study, an immobilized MNP sample with 6.3 cm3and 12 mg Fe could be localized and quantified with an acceptable quality.Significance.A well-engineered MRXI setup could provide much better imaging qualities in shorter data acquisition times, making nonlinear MRXI a viable option for the supervision of MNP related therapies in all regions of the human body, specifically magnetic hyperthermia.

Determining the resolution of a tracer for magnetic particle imaging by means of magnetic particle spectroscopy.

Magnetic particle imaging (MPI) is an imaging modality to quantitatively determine the three-dimensional distribution of magnetic nanoparticles (MNPs) administered as a tracer into a biological system. Magnetic particle spectroscopy (MPS) is the zero-dimensional MPI counterpart without spatial coding but with much higher sensitivity. Generally, MPS is employed to qualitatively evaluate the MPI capability of tracer systems from the measured specific harmonic spectra. Here, we investigated the correlation of three characteristic MPS parameters with the achievable MPI resolution from a recently introduced procedure based on a two-voxel-analysis of data taken from the system function acquisition that is mandatory in Lissajous scanning MPI. We evaluated nine different tracer systems and determined their MPI capability and resolution from MPS measurements and compared the results with MPI phantom measurements.

Monitoring magnetic nanoparticle clustering and immobilization with thermal noise magnetometry using optically pumped magnetometers.

Thermal noise magnetometry (TNM) is a recently developed magnetic characterization technique where thermally induced fluctuations in magnetization are measured to gain insight into nanomagnetic structures like magnetic nanoparticles (MNPs). Due to the stochastic nature of the method, its signal amplitude scales with the square of the volume of the individual fluctuators, which makes the method therefore extra attractive to study MNP clustering and aggregation processes. Until now, TNM signals have exclusively been detected by using a superconducting quantum interference device (SQUID) sensor. In contrast, we present here a tabletop setup using optically pumped magnetometers (OPMs) in a compact magnetic shield, as a flexible alternative. The agreement between results obtained with both measurement systems is shown for different commercially available MNP samples. We argue that the OPM setup with low complexity complements the SQUID setup with high sensitivity and bandwidth. Furthermore, the OPM tabletop setup is well suited to monitor aggregation processes because of its excellent sensitivity in lower frequencies. As a proof of concept, we show the changes in the noise spectrum for three different MNP immobilization and clustering processes. From our results, we conclude that the tabletop setup offers a flexible and widely adoptable measurement unit to monitor the immobilization, aggregation, and clustering of MNPs for different applications, including interactions of the particles with biological systems and the long-term stability of magnetic samples.

Development of Phantoms for Multimodal Magnetic Resonance Imaging and Magnetic Particle Imaging.

Phantoms are crucial for the development of imaging techniques based on magnetic nanoparticles (MNP). They serve as test objects to simulate application scenarios but are also used for quality assurance and interlaboratory comparisons. Magnetic particle imaging (MPI) is excellent for specifically detecting magnetic nanoparticles (MNP) without any background signals. To obtain information about the surrounding soft tissue, MPI is often used in combination with magnetic resonance imaging (MRI). For such application scenarios, this poses a challenge for phantom fabrication, as they need to accommodate MNP as well as provide MR visibility. Recently, layer-by-layer fabrication of parts using Additive Manufacturing (AM) has emerged as a powerful tool for creating complex and patient-specific phantoms, but these are characterized by poor MR visibility of the AM material. We present the systematic screening of AM materials as candidates for multimodal MRI/MPI imaging. Of all investigated materials, silicone (Dreve, Biotec) exhibited the best properties with sufficient MR-signal performance and the lowest absorption of MNP at the interface of AM materials. With the help of AM and the selection of appropriate materials, we have been able to produce suitable MRI/MPI phantoms.

Developing magnetorelaxometry imaging for human applications.

Objective.Magnetic nanoparticles (MNPs) are a promising tool in biomedical applications such as cancer therapy and diagnosis, where localization and quantification of MNP distributions are often mandatory. This can be obtained by magnetorelaxometry imaging (MRXI).Approach.In this work, the capability of MRXI for quantitative imaging of MNP inside larger volumes such as a human head is investigated. We developed a human head phantom simulating a glioblastoma multiforme (GBM) tumor containing MNP for magnetic hyperthermia treatment. The sensitivity of our MRXI setup for detection of MNP concentrations in the range of 3-19 mg cm-3was studied.Main result.The results show the high capability of MRXI to detect MNPs in a human head sized volume. Superficial sources with a concentration larger than 12 mg cm-3could be reconstructed with a resulotion of about 1 cm-3.Significance.The reconstruction of the MNP distribution, mimicking a GBM tumor of 7 cm3volume with clinically relevant iron concentration, demonstrates thein vivofeasibility of MRXI in humans.

Quantitative imaging of magnetic nanoparticles in an unshielded environment using a large AC susceptibility array.

BACKGROUND: Non-invasive magnetic imaging techniques are necessary to assist magnetic nanoparticles in biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticle's magnetization response under an oscillating magnetic field, which is applied through an excitation coil, is detected with a balanced detection coil system. RESULTS: We built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticle distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a field of view of 14 × 14 cm2 with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coefficient between quantitative reconstructed and nominal magnetic nanoparticle distributions above 0.6 was found for all measurements. CONCLUSION: Besides other interesting features such as sufficient large field of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.

Cell Tracking by Magnetic Particle Imaging: Methodology for Labeling THP-1 Monocytes with Magnetic Nanoparticles for Cellular Imaging.

Magnetic particle imaging (MPI) is a noninvasive tomographic imaging modality for the quantitative visualization of magnetic nanoparticles (MNPs) with high temporal and spatial resolution. The general capability of MPI for cell tracking (e.g., monitoring living cells labeled with MNPs) has successfully been shown. MNPs in cell culture media are often subjected to structural and magnetic changes. In addition to the deteriorating reproducibility, this also complicates the systematic study of the relationship between the MNP properties and their cellular uptake for MPI. Here, we present a method for the preparation of magnetically labeled THP-1 (Tamm-Horsfall Protein-1) monocytes that are used in MPI cell tracking. The method development was performed using two different MPI tracers, which exhibited electrostatic and steric stabilizations, respectively. In the first step, the interaction between the MNPs and cell culture media was investigated and adjusted to ensure high structural and magnetic stability. Furthermore, the influences of the incubation time, MNP concentration used for cellular uptake, and individual preparation steps (e.g., the washing of cells) were systematically investigated. Finally, the success of the developed loading method was demonstrated by the MPI measurements. The presented systematic investigation of the factors that influence the MNP loading of cells will help to develop a reliable and reproducible method for MPI monocyte tracking for the early detection of inflammation in the future.

Experimental demonstration of improved magnetorelaxometry imaging performance using optimized coil configurations.

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.

2D Quantitative Imaging of Magnetic Nanoparticles by an AC Biosusceptometry Based Scanning Approach and Inverse Problem.

The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative knowledge of their quantitative distribution within the body. AC Biosusceptometry (ACB) is a biomagnetic technique recently employed to detect MNPs in vivo by measuring the MNPs response when exposed to an alternate magnetic field. The ACB technique presents some interesting characteristics: non-invasiveness, low operational cost, high portability, and no need for magnetic shielding. ACB conventional methods until now provided only qualitative information about the MNPs' mapping in small animals. We present a theoretical model and experimentally demonstrate the feasibility of ACB reconstructing 2D quantitative images of MNPs' distributions. We employed an ACB single-channel scanning approach, measuring at 361 sensor positions, to reconstruct MNPs' spatial distributions. For this, we established a discrete forward problem and solved the ACB system's inverse problem. Thus, we were able to determine the positions and quantities of MNPs in a field of view of 5×5×1 cm3 with good precision and accuracy. The results show the ACB system's capabilities to reconstruct the quantitative spatial distribution of MNPs with a spatial resolution better than 1 cm, and a sensitivity of 1.17 mg of MNPs fixed in gypsum. These results show the system's potential for biomedical application of MNPs in several studies, for example, electrochemical-functionalized MNPs for cancer cell targeting, quantitative sensing, and possibly in vivo imaging.

Advances in Magnetic Nanoparticles Engineering for Biomedical Applications-A Review.

Magnetic iron oxide nanoparticles (MNPs) have been developed and applied for a broad range of biomedical applications, such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery, gene therapy and tissue repair. As one key element, reproducible synthesis routes of MNPs are capable of controlling and adjusting structure, size, shape and magnetic properties are mandatory. In this review, we discuss advanced methods for engineering and utilizing MNPs, such as continuous synthesis approaches using microtechnologies and the biosynthesis of magnetosomes, biotechnological synthesized iron oxide nanoparticles from bacteria. We compare the technologies and resulting MNPs with conventional synthetic routes. Prominent biomedical applications of the MNPs such as diagnostic imaging, magnetic fluid hyperthermia, targeted drug delivery and magnetic actuation in micro/nanorobots will be presented.

Albumin-Coated Single-Core Iron Oxide Nanoparticles for Enhanced Molecular Magnetic Imaging (MRI/MPI).

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.

Tailored Magnetic Multicore Nanoparticles for Use as Blood Pool MPI Tracers.

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa. The resulting MCP-PEG variants with PEG-chain lengths of 10 kDa (MCP-PEG10K after one pegylation step and MCP-PEG10K2 after a second pegylation step) formed stable dispersions and showed strong evidence of a successful reaction of MCP and MCP-PEG10K with mPEG-amine with 10 kDa, while maintaining their magnetic properties. In rats, the mean blood half-lives, surprisingly, were 2 and 62 min, respectively, and therefore, for MCP-PEG10K2, dramatically extended compared to the parent MCP, presumably due to the higher PEG density on the particle surface, which may lead to a lower phagocytosis rate. Because of their significantly extended blood half-life, MCP-PEG10K2 are very promising as blood pool tracers for future in vivo cardiovascular MPI.

Nanomagnetic Actuation of Hybrid Stents for Hyperthermia Treatment of Hollow Organ Tumors.

This paper describes a magnetic nanotechnology that locally enables hyperthermia treatment of hollow organ tumors by using polymer hybrid stents with incorporated magnetic nanoparticles (MNP). The hybrid stents are implanted and activated in an alternating magnetic field to generate therapeutically effective heat, thereby destroying the tumor. Here, we demonstrate the feasibility of nanomagnetic actuation of three prototype hybrid stents for hyperthermia treatment of hollow organ tumors. The results show that the heating efficiency of stent filaments increases with frequency from approximately 60 W/gFe (95 kHz) to approximately 250 W/gFe (270 kHz). The same trend is observed for the variation of magnetic field amplitude; however, heating efficiency saturates at approximately 30 kA/m. MNP immobilization strongly influences heating efficiency showing a relative difference in heating output of up to 60% compared to that of freely dispersed MNP. The stents showed uniformly distributed heat on their surface reaching therapeutically effective temperatures of 43 °C and were tested in an explanted pig bile duct for their biological safety. Nanomagnetic actuation of hybrid stents opens new possibilities in cancer treatment of hollow organ tumors.

Whither Magnetic Hyperthermia? A Tentative Roadmap.

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy.

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.