Magnetic particle imaging (Mpi) is a non-invasive, non-ionizing imaging technique for the visualization and quantification of magnetic nanoparticles (MNPs). The technique is especially suitable for cell imaging as it offers zero background contribution from the surrounding tissue, high sensitivity, and good spatial and temporal resolutions. Previous studies have demonstrated that the dynamic magnetic behaviour of MNPs changes during cellular binding and internalization. In this study, we demonstrate how this information is encoded in the Mpi imaging signal. through Mpi imaging we are able to discriminate between free and cell-bound MNPs in reconstructed images. This technique was used to image and quantify the changes that occur in-vitro when free Mnps come into contact with cells and undergo cellular-uptake over time. The quantitative MPI results were verified by colorimetric measurements of the iron content. The results showed a mean relative difference between the MPI results and the reference method of 23.8% for the quantification of cell-bound MNPs. With this technique, the uptake of MNPs in cells can be imaged and quantified directly from the first MNP cell contact, providing information on the dynamics of cellular uptake. Magnetic particle imaging (MPI) is a non-invasive technique capable of determining the spatial distribution of magnetic nanoparticles (MNPs) both in-vivo and in-vitro 1. MPI achieves imaging and quantification detecting the non-linear dynamic magnetic response of MNPs exposed to multiple superimposed static and dynamic magnetic fields with a submillimetre spatial resolution. No background signals are generated by bone or tissue. The technique uses non-ionizing radiation and non-toxic nanoparticles to prevent tissue damage. MPI shows great potential for different biomedical applications, such as angiography, stem cell tracking, diagnosis of inflammatory diseases and cancer 2-11. In inflammation-associated diseases, including cancer, MNPs accumulate preferentially in diseased tissue as a result of leaky vasculature thereby enabling imaging with MRI and MPI 12-16. In diseased tissue, MNPs accumulate mainly in macrophages 17,18. These phagocytic cells are a hallmark of tissue inflammation and their quantity is considered a marker of the severity of the disease 19-21. The magnetic response generated by MNPs is severely influenced by their local environment. In this respect, the changing magnetic properties of MNPs induced by their interaction with cells are a relevant factor for MPI. Previous studies using magnetic particle spectroscopy (MPS), have described and quantified the changes that occur in the dynamic magnetization of certain MNP systems upon interaction with living cells 22-26. These effects may be caused by a variety of factors including the aggregation of particles in the surrounding solution, within the extra-cellular matrix or within various intracellular compartments. "Size-filtering" during cellular uptake and an increase in dipole-dipole interactions caused by a lower separati...

Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP) and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP) designed by our department for magnetic particle imaging (MPI) with discontinued Resovist ® regarding their suitability for detection of single mesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of >10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist ® in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP-uptake-dependent biocompatibility studies and cell detection by MRI and future MPI. Additionally, using a 7 T MR imager equipped with a cryocoil resulted in approximately two times higher detection. In conclusion, we established labeling conditions for new high-relaxivity MCP, VSOP, and Resovist ® for improved MRI of MSC with single-cell sensitivity.

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Magnetic particle imaging (MPI) is a novel technology, which opens new possibilities for promising biomedical applications. MPI uses magnetic fields to generate a specific response from magnetic nanoparticles (MNPs), to determine their spatial location non-invasively and without using ionizing radiation. One open challenge of MPI is to achieve further improvements in terms of sensitivity to translate the currently preclinical performed research into clinical applications. In this work, we study the noise and background signals of our preclinical MPI system, to identify and characterize disturbing signal contributions. The current limit of detection achieved with our device was determined previously to be 20 ng of iron. Based on the results presented in this work, we describe possible hardware and software improvements and estimate that the limit of detection could be lowered to about 1–2 ng. Additionally, a long-term analysis of the scanner performance over the last 3 years is presented, which proved to be an easy and effective way to monitor possible changes or damage of hardware components. All the presented results were obtained by analysing empty scanner measurements and the presented methodology can easily be adapted for different scanner types, to compare their performances.

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