Positive contrast technique for the detection and quantification of superparamagnetic iron oxide nanoparticles in MRI

In vivo detection and quantification of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles has been attracting increasing attention. In particular, positive contrast methods, such as susceptibility gradient mapping (SGM) and phase gradient mapping (PGM), have been proposed for the improved detection of SPIO nanoparticles. In this study, a different implementation of the PGM method is introduced; it calculates the phase gradient in the image space using a fast Fourier transform without the need for phase unwrapping. We first compared positive contrast generation between the PGM and SGM methods, which estimates the susceptibility gradient in k space through echo shift measurements. Next, PGM was applied to quantify SPIO concentrations by fitting the resulting phase gradient maps to those of a theoretical model. MR experiments were conducted using a 3-T magnet scanner to acquire two datasets: the first was acquired from a gelatin phantom with three SPIO-doped vials of different concentrations, and the second was obtained in vivo from a nude rat with SPIO-labeled C6 glioma cells implanted in the flanks. The sensitivity of the PGM and SGM methods was compared using various factors, including different SPIO concentrations, TEs and signal-to-noise ratios. Based on the theoretical model of an infinite cylinder, the results demonstrated that, without loss of spatial resolution, the PGM method presents positive contrast maps with a higher sensitivity than SGM at medium and low SPIO concentrations, whereas SGM is more sensitive than PGM at longer TEs. The quantification of SPIO concentrations using the phantom dataset was also reported. On the basis of the same infinite cylinder model, it was shown that the PGM method provides an accurate estimation of SPIO concentration.