Page 71 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Cell division
The problem with quantifying the number of labeled cells in the case of cell division (passing SPIO content to daughter cells) was indicated in previous studies (24). Even in a simplified model of a cluster of dividing labeled cells, where cell density is kept constant, increasing heterogeneity is expected. Variations in cell doubling time and uneven distribution of SPIO to daughter cells lead to inhomogeneities in the spatial distribution of SPIOs. However, our results on cell division samples reveal a unique curve of the relaxation rate vs iron concentration (Fig. 7). Despite the differences in the initial iron content per cell, the samples could be characterized by the same relaxivity. We can conclude that in a volume where the cells are labeled and dividing, and also the cell density is constant (e.g. constant intracellular volume ratio and cell size can be assumed), the iron content can be determined. This iron content may serve as a basis for estimation of the number of labeled cells in the corresponding volume.
Mixed processes
Cell death, cell migration (or translocation), cell division, extracellular SPIO accumulation or dispersion can be modelled in vitro and a calibration on relaxivity can be established. We have demonstrated here that mixing, division and cellular load variations can exhibit different relaxivities. Unless there is only one, well-defined process going on in the volume of interest, neither the iron concentration nor the density of labeled cells can be determined by relaxation rate measurements only. Based on theoretical grounds, this finding would make cell quantification impossible for many in vivo situations. However, one can argue that, at sufficiently high imaging resolution, the coexistence of the different pathways in a single voxel is not probable. This biologically homogeneous compartment size could be determined for the investigated tissue type and assumed physiological processes, thus the imaging resolution could be chosen correspondingly. In this scenario, with the further assumption that the processes can be identified on a voxel level, we can conclude that iron quantification can be carried out by relaxometry.
Quantification of iron labeled cell
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