Carbon-Based Nanostructures as Advanced Contrast Agents for Magnetic Resonance Imaging

Superparamagnetic carbon-based nanostructures are presented as contrast agents (CAs) for advanced imaging applications such as cellular and molecular imaging using magnetic resonance imaging (MRI). Gadolinium-loaded, ultra-short single-walled carbon nanotubes (gadonanotubes; GNTs) are shown to have extremely high r1 relaxivities (contrast enhancement efficacy), especially at low-magnetic field strengths. The inherent lipophilicity of GNTs provides them the ability to image cells at low magnetic field strength.;A carboxylated dextran-coated GNT (GadoDex) has been synthesized and proposed as a new biocompatible high-performance MRI CA. The r1 relaxivity is ca. 20 times greater than for other paramagnetic Gd-based CAs. This enhanced relaxivity for GadoDex is due to the synergistic effects of an increased molecular tumbling time (tauR) and a faster proton exchange rate (taum).;GNTs also exhibit very large transverse relaxivities (r2) at high magnetic fields (≥ 3 T). The dependence of the transverse relaxation rates (especially R2*) of labeled cells on GNT concentration offers the possibility to quantify cell population in vivo using R2* mapping. The cell-labeling efficiency and high transverse relaxivities of GNTs has enabled the first non-iron oxide-based single-cell imaging using MRI.;The residual metal catalyst particles of SWNT materials also have transverse relaxation properties. All of the SWNT materials exhibit superior transverse relaxation properties. However, purified SWNTs and US-tubes with less residual metal content exhibit better transverse relaxivities (r2), demonstrating the importance of the SWNT structure for enhanced MRI CA performance.;A strategy to improve the r1 relaxivity of Gd-CAs by geometrically confining them within porous silicon particles (SiMPs) has been investigated. The enhancement in relaxivity is attributed to the slow diffusion of water molecules through the pores and the increase in the molecular tumbling time of the nanoconstruct. The universality of the strategy has been demonstrated for GNTs, gadofullerols and clinically-used MagnevistRTM.;In summary, primary nanoscale confinement of Gd3+ ions in US-tubes has resulted in a new class of CAs which could revitalize low-field contrast-enhanced MRI, while extending and complementing current high-field MRI technology, as well. The observed boost in relaxivity upon a secondary nanoscale confinement of Gd-CAs within SiMPs suggests that additional unforeseen nanoscale effects may have the potential to further boost performance of MRI CAs.