Cell quantification: evolution of compartmentalization and distribution of iron-oxide particles and labeled cells

The purpose of the study was to show the feasibility of quantification in the case of cell death, cell migration and cell division by parametric MRI. We identify limitations for quantitative cell tracking owing to mixed parallel processes. Various intravoxel SPIO-labeled cell, super paramagnetic iron oxide particles (SPIO) and micron-sized paramagnetic iron oxide (MPIO) particle distributions were prepared by methods mimicking biologically relevant processes (compartmentalization, migration, division and cell death). R(2)* and R(2) relaxometry measurements were performed at 3.0 T; iron concentration was measured by optical emission spectrometry. The effects of spatial distribution and compartmentalization of paramagnetic iron-oxide particles on relaxivity were analyzed. Assessment of R(2)' (R(2)*-R(2)) allowed differentiation between intracellular and extracellular SPIO only if no high-iron-content extracellular particles were present. Relaxivity was sensitive to variations in cell labeling. Samples of the same cell types embedded in the same suspension media at the same cell density produced different relaxivity values, depending on the preparation of the labeled cells. In the case of cell division, a unique relationship between relaxation rate and iron concentration was found, where the relaxivity proved to be independent of initial cell labeling. In case of cell mixing, the cell density could be derived from relaxation values, even if iron concentration was undetermined. We demonstrated that relaxometry does not allow labeled cell quantification when multiple physiological processes such as cell division and cell migration coexist. The measured transversal relaxation rates were sensitive to the labeling technique. However, under special circumstances, despite the numerous limiting factors, quantification of the number of labeled cells by relaxometry was feasible.