Unambiguous MRI Contrast with Magnetic Nanoparticles: "Color" Contrast at High Field and Positive Contrast at Low Field

Magnetic nanoparticles (MNPs) are typically thought of as negative contrast agents for magnetic resonance imaging (MRI). During an MRI scan, water protons situated nearby the strong magnetic field gradients of MNPs rapidly dephase, leading to decreased signal and dark contrast. Despite the loss in signal, MNP labels with negative contrast have been used for many applications, from clinical liver imaging to cellular MRI tracking. However, these methods have inherent ambiguity because negative contrast can be confused with magnetic susceptibility artifacts, such as air bubbles. MNPs are not strictly limited to negative contrast, though. In this talk, I will describe new pathways to realize unambiguous MNP labels using “color” contrast at high fields and positive contrast at low magnetic fields. First, I will describe how specially shaped MNP-polymer microparticles can be used as RF-addressable, “color” MRI contrast agents at high magnetic fields (9.4 T). These microparticles can generate a spectral shift 1000x larger than familiar NMR chemical shifts, providing an RF-identifier that is spectrally distinct from the environment. I will also show that the particles can be made of environmentally sensitive “smart” polymers for use as biosensors. Secondly, I will describe possibilities for using MNPs as positive contrast agents with low field MRI (LF-MRI). While MNPs can be used as positive contrast agents for clinical and high field MRI, the MNPs need to be specially synthesized with sizes of 3 nm or smaller. Here, I will discuss using FDA-approved contrast agents, like Ferumoxytol, as well as commercially available iron oxide MNPs with sizes of 5 nm – 16 nm for positive contrast at low field. LF-MRI scanners require less infrastructure than clinical MRI scanners and can be wheeled next to a patient’s bedside, creating revolutionary possibilities for point-of-care diagnostics. I will present experiments using an FDA-approved, 64 mT MRI scanner to evaluate the potential of MNPs as contrast agents for LF-MRI. At 64 mT, MNPs show enhanced longitudinal relaxivity (r₁) and reduced transverse relaxivity (r₂) compared to 3 T. Moreover, MNPs have a size-dependent r₁ that is up to 8x larger than a common Gd-based contrast agent (Gd-BOPTA), suggesting that MNPs may outperform traditional positive contrast agents at lower fields.