Post-synthesis Oxidation of Superparamagnetic Iron Oxide Nanoparticles to Enhance Magnetic Particle Imaging Performance.

This study investigates the impact of post-synthesis oxidation on the performance of superparamagnetic iron oxide nanoparticles (SPIONs) in magnetic particle imaging (MPI), an emerging technology with applications in diagnostic imaging and theranostics. SPIONs synthesized from iron oleate were subjected to a post-synthesis oxidation treatment with a 1% Oxygen in Argon mixture. MPI performance, gauged via signal intensity and resolution using a MOMENTUM™ scanner, was correlated to the nanoparticles' physical and magnetic properties. Post-synthesis oxidation did not alter physical attributes like size and shape, but significantly enhanced magnetic properties. Saturation magnetization increased from 52% to 93% of the bulk value for magnetite, leading to better MPI performance in terms of signal intensity and resolution. However, the observed MPI performance did not fully align with predictions based on the ideal Langevin model, indicating the need for considering factors like relaxation and shape anisotropy. The findings underscore the potential of post-synthesis oxidation as a method to fine-tune magnetic properties of SPIONs and improve MPI performance, and the need for reproducible synthesis methods that afford finely tuned control of nanoparticle size, shape, and magnetic properties.

Magnetic Cellular Backpacks for Spatial Targeting, Imaging, and Immunotherapy.

Adoptive cell transfer (ACT) therapies are growing in popularity due to their ability to interact with diseased tissues in a specific manner. Disc-shaped particles, or "backpacks", that bind to cellular surfaces show promise for augmenting the therapeutic potential of adoptively transferred cells by resisting phagocytosis and locally releasing drugs to maintain cellular activity over time. However, many ACTs suffer from limited tumor infiltration and retention and lack a method for real-time spatial analysis. Therefore, we have designed biodegradable backpacks loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to improve upon current ACT strategies by (i) controlling the localization of cell-backpack complexes using gradient magnetic fields and (ii) enabling magnetic particle imaging (MPI) to track complexes after injection. We show that magnetic backpacks bound to macrophages and loaded with a proinflammatory drug, resiquimod, maintain anticancer phenotypes of carrier macrophages for 5 days and create cytokine "factories" that continuously release IL-12. Furthermore, we establish that forces generated by gradient magnet fields are sufficient to displace cell-backpack complexes in physiological settings. Finally, we demonstrate that MPI can be used to visualize cell-backpack complexes in mouse tumors, enabling a potential strategy to track the biodistribution of ACTs in real time.

Inter-user Comparison for Quantification of Superparamagnetic Iron Oxides with Magnetic Particle Imaging Across Two Institutions Highlights a Need for Standardized Approaches.

PURPOSE: Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, a few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. PROCEDURES: Six users (3 from each institute) imaged a known amount of Vivotrax + (10 µg Fe), diluted in a small (10 µL) or large (500 µL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users × triplicate samples × 2 sample volumes × 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax + quantification, and ROI selection were compared across users, within and across institutions. RESULTS: MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax + . Overall quantification yielded measurements that were within [Formula: see text] 20% from ground truth; however, SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. CONCLUSIONS: This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental setup, image acquisition parameters, and ROI selection analysis.

Inter-user comparison for quantification of superparamagnetic iron oxides with magnetic particle imaging across two institutions highlights a need for standardized approaches.

Purpose: Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. Procedures: Six users (3 from each institute) imaged a known amount of Vivotrax+ (10 µg Fe), diluted in a small (10 µL) or large (500 µL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users x triplicate samples x 2 sample volumes x 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax+ quantification, and ROI selection was compared across users, within and across institutions. Results: MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax+. Overall quantification yielded measurements that were within ± 20% from ground truth, however SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. Conclusions: This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental set up, image acquisition parameters, and ROI selection analysis.

An anatomically correct 3D-printed mouse phantom for magnetic particle imaging studies.

We report anatomically correct 3D-printed mouse phantoms that can be used to plan experiments and evaluate analysis protocols for magnetic particle imaging (MPI) studies. The 3D-printed phantoms were based on the Digimouse 3D whole body mouse atlas and incorporate cavities representative of a liver, brain tumor, and orthotopic breast cancer tumor placed in anatomically correct locations, allowing evaluation of the effect of precise doses of MPI tracer. To illustrate their use, a constant tracer iron mass was present in the liver for the breast (200 µgFe) and brain tumor (10 µgFe) model, respectively, while a series of decreasing tracer iron mass was placed in the tumor region. MPI scans were acquired in 2D and 3D high sensitivity and high sensitivity/high resolution (HSHR) modes using a MOMENTUM imager. A thresholding algorithm was used to define regions of interest (ROIs) in the scans and the tracer mass in the liver and tumors was calculated by comparison of the signal in their respective ROI against that of known mass fiducials that were included in each scan. The results demonstrate that this approach to image analysis provides accurate estimates of tracer mass. Additionally, the results show how the limit of detection in MPI is sensitive to the details of tracer distribution in the subject, as we found that a greater tracer mass in the liver cavity resulted in poorer sensitivity in tumor regions. These experiments illustrate the utility of the reported 3D-printed anatomically correct mouse phantoms in evaluating methods to analyze MPI scans and plan in vivo experiments.