Magnetic particle imaging: tracer development and the biomedical applications of a radiation-free, sensitive, and quantitative imaging modality

Magnetic particle imaging (MPI) is an emerging tracer-based modality that enables real-time three-dimensional imaging of the non-linear magnetisation produced by superparamagnetic iron oxide nanoparticles (SPIONs), in the presence of an...

Sensitive and Specific Detection of Breast Cancer Lymph Node Metastasis Through Dual-Modality Magnetic Particle Imaging and Fluorescence Molecular Imaging: a Preclinical Evaluation

Purpose: A sensitive and specific imaging method to detect metastatic cancer cells in lymph nodes (LNs) to detect the early-stage breast cancer is urgently needed. The purpose of this study was to investigate a novel breast cancer-targeting and tumour microenvironment ATP-responsive superparamagnetic iron oxide (SPIOs) imaging probe that was developed to detect lymph node metastasis (LNMs) through fluorescence molecular imaging (FMI) and magnetic particle imaging (MPI). The imaging nanoprobe comprised of SPIOs conjugated with breast cancer-targeting peptides (CREKA) and an ATP-responsive DNA aptamer (dsDNA-Cy5.5), abbreviated as SPIOs@A-T. Methods: SPIOs@A-T was synthesised and characterized for its imaging properties, targeting ability and toxicity in vitro. Mice with metastatic lymph node (MLN) of breast cancer were established to evaluate the FMI and MPI imaging strategy in vivo. Healthy mice with normal lymph node (NLN) were used as control group. Histological examination and biosafety evaluation were performed for further assessment. Results: After injection with SPIO@A-T, the obvious high fluorescent intensity and MPI signal were observed in MLN group than those in NLN group. MPI could also complement the limitation of imaging depth from FMI, thus could detect MLN more sensitively. The combination of the imaging strengths of FMI and MPI ensured the detection of breast cancer metastases with high sensitivity and specificity, thereby facilitating the precision differentiation of malignant from benign LNs. Besides, the biosafety evaluation results showed SPIO@A-T had good biocompatibility. Conclusion: Due to the superior properties of tumour-targeting, detection specificity, and biosafety, the SPIOs@A-T imaging probe in combination with FMI and MPI can provide a promising novel method for the early and precise detection of LNMs in clinical practice.

Modelling of Dynamic Behaviour in Magnetic Nanoparticles

The efficient development and utilisation of magnetic nanoparticles (MNPs) for applications in enhanced biosensing relies on the use of magnetisation dynamics, which are primarily governed by the time-dependent motion of the magnetisation due to externally applied magnetic fields. An accurate description of the physics involved is complex and not yet fully understood, especially in the frequency range where Néel and Brownian relaxation processes compete. However, even though it is well known that non-zero, non-static local fields significantly influence these magnetisation dynamics, the modelling of magnetic dynamics for MNPs often uses zero-field dynamics or a static Langevin approach. In this paper, we developed an approximation to model and evaluate its performance for MNPs exposed to a magnetic field with varying amplitude and frequency. This model was initially developed to predict superparamagnetic nanoparticle behaviour in differential magnetometry applications but it can also be applied to similar techniques such as magnetic particle imaging and frequency mixing. Our model was based upon the Fokker–Planck equations for the two relaxation mechanisms. The equations were solved through numerical approximation and they were then combined, while taking into account the particle size distribution and the respective anisotropy distribution. Our model was evaluated for Synomag®-D70, Synomag®-D50 and SHP-15, which resulted in an overall good agreement between measurement and simulation.

Magnetic particle imaging of magnetotactic bacteria as living contrast agents is improved by altering magnetosome structures

ABSTRACTIron nanoparticles used as imaging contrast agents can help differentiate between normal and diseased tissue, or track cell movement and localize pathologies. Magnetic particle imaging (MPI) is an imaging modality that uses the magnetic properties of iron nanoparticles to provide specific, quantitative and sensitive imaging data. MPI signals depend on the size, structure and composition of the nanoparticles; MPI-tailored nanoparticles have been developed by modifying these properties. Magnetotactic bacteria produce magnetosomes which mimic synthetic nanoparticles, and thus comprise a living contrast agent in which nanoparticle formation can be modified by mutating genes. Specifically, genes that encode proteins critical to magnetosome formation and regulation, such as mamJ which helps with filament turnover. Deletion of mamJ in Magnetospirillum gryphiswaldense, MSR-1 led to clustered magnetosomes instead of the typical linear chains. Here we examined the effects of this magnetosome structure and revealed improved MPI signal and resolution from clustered magnetosomes compared to linear chains. Bioluminescent MSR-1 with the mamJ deletion were injected intravenously into tumor-bearing and healthy mice and imaged using both in vivo bioluminescence imaging (BLI) and MPI. BLI revealed the location and viability of bacteria which was used to validate localization of MPI signals. BLI identified the viability of MSR-1 for 24 hours and MPI detected iron in the liver and in multiple tumors. Development of living contrast agents offers new opportunities for imaging and therapy by using multimodality imaging to track the location and viability of the therapy and the resulting biological effects.

The sensitivity of magnetic particle imaging and fluorine-19 magnetic resonance imaging for cell tracking

Magnetic particle imaging (MPI) and fluorine-19 (19F) MRI produce images which allow for quantification of labeled cells. MPI is an emerging instrument for cell tracking, which is expected to have superior sensitivity compared to 19F MRI. Our objective is to assess the cellular sensitivity of MPI and 19F MRI for detection of mesenchymal stem cells (MSC) and breast cancer cells. Cells were labeled with ferucarbotran or perfluoropolyether, for imaging on a preclinical MPI system or 3 Tesla clinical MRI, respectively. Using the same imaging time, as few as 4000 MSC (76 ng iron) and 8000 breast cancer cells (74 ng iron) were reliably detected with MPI, and 256,000 MSC (9.01 × 1016 19F atoms) were detected with 19F MRI, with SNR > 5. MPI has the potential to be more sensitive than 19F MRI for cell tracking. In vivo sensitivity with MPI and 19F MRI was evaluated by imaging MSC that were administered by different routes. In vivo imaging revealed reduced sensitivity compared to ex vivo cell pellets of the same cell number. We attribute reduced MPI and 19F MRI cell detection in vivo to the effect of cell dispersion among other factors, which are described.

Particle interactions and their effect on magnetic particle imaging and spectroscopy

Tracer and thus signal stability is crucial for an accurate diagnosis via magnetic particle imaging (MPI). However, MPI-tracer nanoparticles frequently agglomerate during their in vivo applications leading to particle interactions. Here, we investigate the influence of such magnetic coupling phenomena on the MPI signal. We prepared and characterized Zn0.4Fe2.6O4 nanoparticles and controlled their interparticle distance by varying SiO2 coating thickness. The silica shell affected the magnetic properties indicating stronger particle interactions for a smaller interparticle distance. The SiO2-coated Zn0.4Fe2.6O4 outperformed the bare sample in magnetic particle spectroscopy (MPS) in terms of signal/noise, however, the shell thickness itself only weakly influenced the MPS signal. To investigate the importance of magnetic coupling effects in more detail, we benchmarked the MPS signal of the bare and SiO2-coated Zn-ferrites against commercially available PVP-coated Fe3O4 nanoparticles in water and PBS. PBS is known to destabilize nano-particles mimicking an agglomeration in vivo. The bare and coated Zn-ferrites showed excellent signal stability, despite their agglomeration in PBS. We attribute this to their aggregated morphology formed during their flame-synthesis. On the other hand, the MPS signal of commercial PVP-coated Fe3O4 strongly decreased in PBS compared to water, indicating strongly changed particle interactions. The relevance of this effect was further investigated in a mammalian cell model. For PVP-coated Fe3O4, we could detect a strong discrepancy between the particle concentration obtained from the MPS signal and the actual concentration determined via ICP-MS. The same trend was observed during their MPI analysis; while SiO2-coated Zn-ferrites could be precisely located in water and PBS, PVP-coated Fe3O4 could not be detected in PBS at all. This drastically limits the sensitivity and also general applicability of MPI using such standard commercial tracers and highlights the advantages of our flame-made Zn-ferrites concerning signal stability and ultimately diagnostic accuracy.