MRI cellular density quantification using balanced steady state free precession

Although magnetic resonance imaging (MRI) has a maximum resolution on the order of tens of micrometers, the development of superparamagnetic iron oxide (SPIO) nanoparticles enabled MR imaging of cells, which have diameters an order of magnitude less than the maximum MRI resolution. SPIO particles are an MR contrast agent and are taken up by cells through a variety of mechanisms, such as phagocytosis. Previous studies have confirmed a linear correlation between SPIO cellular loading and local magnetic dose (LMD), which is the main contributor to SPIO MR contrast. Thus, through pre-designed SPIO loading of macrophages and subsequent delivery to the body, it should be possible to quantify cellular density by analyzing MRI signal changes induced by SPIO. Nonetheless, no direct MRI imaging technique currently exists for true quantification of SPIO loaded cells. Gradient echo (GE) MRI sequences hold the distinct advantage of sensitivity to SPIO, while spin echo (SE) sequences are specific to magnetic field inhomogeneities induced by SPIO. Balanced steady state free precession (bSSFP) has recently emerged as an MRI pulse sequence with an enhanced SPIO sensitivity compared to SE, while retaining SE's SPIO specificity. The objective of the current work was to develop and validate a practical imaging technique for MRI cellular density quantification using bSSFP. Accordingly, the current work proposed and validated Inversion Recovery balanced Steady State Free Precession (IR bSSFP) as an SPIO cellular density quantification tool.;Using phantoms of micron-sized SPIO (MPIO) particles freely suspended in gelatin as models of SPIO loaded cells, the current work established that IR bSSFP has a relaxation rate enhancement, Delta RIR2b , that is linearly correlated with LMD. Additionally, Delta RIR2b has been shown to be 2.7 times more sensitive than SE's relaxation rate enhancement, Delta R2 , yet 4.3 times less sensitive than GE's relaxation rate enhancement, Delta R'2 , of SPIO loaded cells. Qualitative work comparing the relaxation rate enhancement mechanism in SE and IR bSSFP confirmed that the mechanism of relaxation rate enhancement in IR bSSFP is consistent with an enhancement caused by diffusion of protons through micro-field gradients created by SPIO.;Finally, MRI Bloch simulations of IR bSSFP revealed that IR bSSFP cellular density imaging is ideally suited for low cellular density applications, such as immunology and cancer metastasis.;In conclusion, the current work recommends the use of IR bSSFP for in vivo low density cellular quantification because of its excellent SPIO specificity compared to GE quantification and enhanced quantification sensitivity compared to SE quantification.