Digital Simulation Assessments of the Sensitivity of Quantitative MRI for Detection of an Iron Oxide Nanoparticle Brain MRI Contrast Agent

There have been substantial efforts to develop targeted exogenous MRI contrast agents to assess specific brain pathologies. In parallel with other efforts, it is important to assess the sensitivity of candidate MRI methods for detection of contrast agents. Here, we propose a digital simulation approach, which includes MR relaxation (R1 and R2) mapping and image co-registration. We simulated the effects of 3 nm iron oxide nanoparticles (IONPs) as a model contrast agent. Two independent relaxation maps acquired from the brain of the same subject were co-registered. The baseline subtraction between the two relaxation maps showed good agreement, demonstrating the high reproducibility of the method. Next, the second relaxation map was digitally altered (“seeded”) to simulate additional MR relaxation values corresponding to several concentrations of 3 nm IONPs in various locations. The maps of absolute differences between the first relaxation map and the digitally altered second relaxation maps were assessed for conspicuity. Results based on living mouse and human brains scanned at 9.4 T and 3.0 T respectively both indicated reliable conspicuity for signal equivalent to 0.06 mM IONP or higher. Overall, the digital simulation approach is a useful method to improve the development of MRI contrast agents and accompanying MRI methodologies.