Large T₁ contrast enhancement using superparamagnetic nanoparticles in ultra-low field MRI

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely investigated and utilized as magnetic resonance imaging (MRI) contrast and therapy agents due to their large magnetic moments. Local field inhomogeneities caused by these high magnetic moments are used to generate T₂ contrast in clinical high-field MRI, resulting in signal loss (darker contrast). Here we present strong T₁ contrast enhancement (brighter contrast) from SPIONs (diameters from 11 nm to 22 nm) as observed in the ultra-low field (ULF) MRI at 0.13 mT. We have achieved a high longitudinal relaxivity for 18 nm SPION solutions, r₁ = 615 s^-1 mM^-1, which is two orders of magnitude larger than typical commercial Gd-based T₁ contrast agents operating at high fields (1.5 T and 3 T). The significantly enhanced r₁ value at ultra-low fields is attributed to the coupling of proton spins with SPION magnetic fluctuations (Brownian and Néel) associated with a low frequency peak in the imaginary part of AC susceptibility (χ"). SPION-based T₁-weighted ULF MRI has the advantages of enhanced signal, shorter imaging times, and iron-oxide-based nontoxic biocompatible agents. This approach shows promise to become a functional imaging technique, similar to PET, where low spatial resolution is compensated for by important functional information.