Low threshold detection of USPIO concentrations in different environments simulating tissue diversity

Introduction: Ultra-small Super-Paramagnetic Iron Oxide (USPIO) is commonly used as an MRI labeling agent to track cell migration. Different methods exist for USPIO detection, including gradient-based methods (1), and RF-based methods (2,3). Among the latter, IRON relies on suppression of on-resonant spins using a conventional water saturation pre-pulse, and results in positive contrast in a bloom pattern surrounding dense USPIO clusters (2). On the other hand, Off-Resonance Saturation (ORS) uses a prepulse to saturate off-resonant spins, resulting in negative contrast within the locus of the particles, and was found to be sensitive to low concentrations of USPIO in water solution (3). Zurkiya et al. examined USPIO detection with varying diffusion properties to simulate the diverse environments in living organisms, but only at higher USPIO concentrations (3), while in physiological applications, much lower detection levels may be necessary. The aim of the present study was to examine the detection threshold of USPIO concentrations in different environments simulating tissue diversity. Therefore, we extended the investigation of Zurkiya et al. to a range of low USPIO concentrations in solutions with varying polyethylene glycol 400 (PEG 400) fractions, which modulates the diffusion coefficient of the solution. Firstly, we examined the detection effectiveness of a variety of ORS pre-pulses. Secondly, having chosen an appropriate pre-pulse, we noted the USPIO detection threshold of the ORS method.