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...

Experimental results are presented demonstrating how temperature can influence the dynamics of magnetic nanoparticles (MNPs) in liquid suspension, when exposed to alternating magnetic fields in the kilohertz frequency range. The measurements used to probe the nanoparticle systems are directly linked to both the emerging biomedical technique of magnetic particle imaging (MPI), and to the recently proposed concept of remote nanoscale thermometry using MNPs under AC field excitation. Here, we report measurements on three common types of MNPs, two of which are currently leading candidates for use as tracers in MPI. Using highly-sensitive magnetic particle spectroscopy (MPS), we demonstrate significant and divergent thermal dependences in several key measures used in the evaluation of MNP dynamics for use in MPI and other applications. The temperature range studied was between 296 and 318 Kelvin, making our findings of particular importance for MPI and other biomedical technologies. Furthermore, we report the detection of the same temperature dependences in measurements conducted using the detection coils within an operational preclinical MPI scanner. This clearly shows the importance of considering temperature during MPI development, and the potential for temperature-resolved MPI using this system. We propose possible physical explanations for the differences in the behaviors observed between the different particle types, and discuss our results in terms of the opportunities and concerns they raise for MPI and other MNP based technologies.

Magnetic particle imaging (MPI) is an imaging modality capable of quantitatively determining the 3D distribution of a magnetic nanoparticle (MNP) ensemble. In this work, we present a method for reducing the MNP limit of detection by employing a new receive-only coil (Rx-coil) for signal acquisition. The new signal detector is designed to improve the sensitivity and thus quality of reconstructed images. We present characterization measurements conducted with the prototype Rx-coil installed in a preclinical MPI scanner. The gradiometric design of the Rx-coil attenuates the unwanted signal contributions arising from the excitation field, leading to a 17 dB lower background level compared to the conventional dual-purpose coil (TxRx-coil), which is crucial for detecting low amounts of MNP. Network analyzer measurements of the frequency-dependent coil sensitivity, as well as spectral analysis of recorded MPI data demonstrate an overall increase of the coil sensitivity of about  +12 dB for the Rx-coil. Comparisons of the sensitivity distributions revealed no significant degradations in terms of homogeneity for the Rx-coil compared to the TxRx-coil in an imaging volume of 6  ×  3  ×  3 cm. Finally, the limit of detection was determined experimentally for each coil type using a serial dilution of MNPs, resulting in values of 133 ng of iron for the conventional TxRx-coil and 20 ng for the new Rx-coil, using an acquisition time of 2 s. A linear relationship between the reconstructed signal intensities and the iron mass in the samples was observed with coefficients of determination (R) of above 99% in the range of the limit of detection to 3 10ng(Fe). These results open the way for improved image quality and faster acquisition time in pre-clinical MPI scanners.

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