First Superferromagnetic Remanence Characterization and Scan Optimization for Super-Resolution Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is a sensitive, high-contrast tracer modality that images superparamagnetic iron oxide nanoparticles, enabling radiation-free theranostic imaging. MPI resolution is currently limited by scanner and particle constraints. Recent tracers have experimentally shown 10× resolution and signal improvements with dramatically sharper M-H curves. Experiments show a dependence on interparticle interactions, conforming to literature definitions of superferromagnetism. We thus call our tracers superferromagnetic iron oxide nanoparticles (SFMIOs). While SFMIOs provide excellent signal and resolution, they exhibit hysteresis with non-negligible remanence and coercivity. We provide the first quantitative measurements of SFMIO remanence decay and reformation using a novel multiecho pulse sequence. We characterize MPI scanning with remanence decay and coercivity and describe an SNR-optimized pulse sequence for SFMIOs under human electromagnetic safety limitations. The resolution from SFMIOs could enable clinical MPI with 10× reduced scanner selection fields, reducing hardware costs by up to 100×.

Superferromagnetic Nanoparticles Enable Order-of-Magnitude Resolution & Sensitivity Gain in Magnetic Particle Imaging.

Magnetic nanoparticles have many advantages in medicine such as their use in non-invasive imaging as a Magnetic Particle Imaging (MPI) tracer or Magnetic Resonance Imaging contrast agent, the ability to be externally shifted or actuated and externally excited to generate heat or release drugs for therapy. Existing nanoparticles have a gentle sigmoidal magnetization response that limits resolution and sensitivity. Here it is shown that superferromagnetic iron oxide nanoparticle chains (SFMIOs) achieve an ideal step-like magnetization response to improve both image resolution & SNR by more than tenfold over conventional MPI. The underlying mechanism relies on dynamic magnetization with square-like hysteresis loops in response to 20 kHz, 15 kAm-1 MPI excitation, with nanoparticles assembling into a chain under an applied magnetic field. Experimental data shows a "1D avalanche" dipole reversal of every nanoparticle in the chain when the applied field overcomes the dynamic coercive threshold of dipole-dipole fields from adjacent nanoparticles in the chain. Intense inductive signal is produced from this event resulting in a sharp signal peak. Novel MPI imaging strategies are demonstrated to harness this behavior towards order-of-magnitude medical image improvements. SFMIOs can provide a breakthrough in noninvasive imaging of cancer, pulmonary embolism, gastrointestinal bleeds, stroke, and inflammation imaging.

Non-radioactive and sensitive tracking of neutrophils towards inflammation using antibody functionalized magnetic particle imaging tracers.

White blood cells (WBCs) are a key component of the mammalian immune system and play an essential role in surveillance, defense, and adaptation against foreign pathogens. Apart from their roles in the active combat of infection and the development of adaptive immunity, immune cells are also involved in tumor development and metastasis. Antibody-based therapeutics have been developed to regulate (i.e. selectively activate or inhibit immune function) and harness immune cells to fight malignancy. Alternatively, non-invasive tracking of WBC distribution can diagnose inflammation, infection, fevers of unknown origin (FUOs), and cancer. Magnetic Particle Imaging (MPI) is a non-invasive, non-radioactive, and sensitive medical imaging technique that uses safe superparamagnetic iron oxide nanoparticles (SPIOs) as tracers. MPI has previously been shown to track therapeutic stem cells for over 87 days with a ~200 cell detection limit. In the current work, we utilized antibody-conjugated SPIOs specific to neutrophils for in situ labeling, and non-invasive and radiation-free tracking of these inflammatory cells to sites of infection and inflammation in an in vivo murine model of lipopolysaccharide-induced myositis. MPI showed sensitive detection of inflammation with a contrast-to-noise ratio of ~8-13.

Combining magnetic particle imaging and magnetic fluid hyperthermia for localized and image-guided treatment.

Magnetic fluid hyperthermia (MFH) has been widely investigated as a treatment tool for cancer and other diseases. However, focusing traditional MFH to a tumor deep in the body is not feasible because the in vivo wavelength of 300 kHz very low frequency (VLF) excitation fields is longer than 100 m. Recently we demonstrated that millimeter-precision localized heating can be achieved by combining magnetic particle imaging (MPI) with MFH. In principle, real-time MPI imaging can also guide the location and dosing of MFH treatments. Hence, the combination of MPI imaging plus real time localized MPI-MFH could soon permit closed-loop high-resolution hyperthermia treatment. In this review, we will discuss the fundamentals of localized MFH (e.g. physics and biosafety limitations), hardware implementation, MPI real-time guidance, and new research directions on MPI-MFH. We will also discuss how the scale up to human-sized MPI-MFH scanners could proceed.

Monte Carlo simulation of polarization-sensitive second-harmonic generation and propagation in biological tissue.

Polarization-sensitive second harmonic generation (p-SHG) is a nonlinear optical microscopy technique that has shown great promise in biomedicine, such as in detecting changes in the collagen ultrastructure of the tumor microenvironment. However, the complex nature of light-tissue interactions and the heterogeneity of biological samples pose challenges in creating an analytical and experimental quantification platform for tissue characterization via p-SHG. We present a Monte Carlo (MC) p-SHG simulation model based on double Stokes-Mueller polarimetry for the investigation of nonlinear light-tissue interaction. The MC model predictions are compared with experimental measurements of second-order nonlinear susceptibility component ratio and degree of polarization (DOP) in rat-tail collagen. The observed trends in the behavior of these parameters as a function of tissue thickness, as well as the overall extent of agreement between MC and experimental results, are discussed. High sensitivities of the susceptibility ratio and DOP are observed for the varying tissue thickness on the incoming fundamental light propagation pathway.

A perspective on a rapid and radiation-free tracer imaging modality, magnetic particle imaging, with promise for clinical translation.

Magnetic particle imaging (MPI), introduced at the beginning of the twenty-first century, is emerging as a promising diagnostic tool in addition to the current repertoire of medical imaging modalities. Using superparamagnetic iron oxide nanoparticles (SPIOs), that are available for clinical use, MPI produces high contrast and highly sensitive tomographic images with absolute quantitation, no tissue attenuation at-depth, and there are no view limitations. The MPI signal is governed by the Brownian and Néel relaxation behavior of the particles. The relaxation time constants of these particles can be utilized to map information relating to the local microenvironment, such as viscosity and temperature. Proof-of-concept pre-clinical studies have shown favourable applications of MPI for better understanding the pathophysiology associated with vascular defects, tracking cell-based therapies and nanotheranostics. Functional imaging techniques using MPI will be useful for studying the pathology related to viscosity changes such as in vascular plaques and in determining cell viability of superparamagnetic iron oxide nanoparticle labeled cells. In this review article, an overview of MPI is provided with discussions mainly focusing on MPI tracers, applications of translational capabilities ranging from diagnostics to theranostics and finally outline a promising path towards clinical translation.