Page 69 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Another possible explanation of the differences in relaxivities (Fig. 4) may be that the magnetization of the labeled cells is not proportional to the number of incorporated SPIOs (a hypothesized saturation effect). In this case, the samples where SPIOs are concentrated in fewer cells would lead to lower cellular magnetization and LMD value, and thus lower R2', according to SD model. However, this hypothesis would contradict the previous findings reported by Bowen et al. [(16), table 3], where the LMD and iron content of SPIO labeled cells were found proportional.
According to SD theory predictions, the relaxation rate is proportional to the internal magnetization of the magnetic disturbers relative to the magnetization of the surrounding medium R2' ≈(M - M0). The R2' values of the labeled cell suspensions are reduced by the presence of SPIOs in the suspension medium. This prediction is in good agreement with our findings (Fig. 5a). Irrespective to the validity of SD, it can be assumed that R2' is a monotonic function of M - M0.
The behavior of R2' relaxation illustrated in Fig. 6(a and b) is surprising, especially in comparison with the SD predictions. SD regime assumption with the further assumption that the intracellular magnetization is proportional to the SPIO content per cell predicts that R2' is determined by the iron concentration. The findings illustrated by Fig. 6 contradict this prediction. It can be hypothesized that at increasing volume fraction of the magnetic disturbers (moving away from the dilute SD regime), the cellular magnetization plays a lesser role and the number of disturbers (volume fraction) becomes more important.
Extra-cellular/intra-cellular differentiation
Numerous studies have suggested that the r2* and r2 relaxivities depend on compartmentalization of iron particles. The r2' relaxivity is negligible for free, equally distributed SPIO. As was previously suggested (12), R2' values can be used to determine labeled cell number per voxel. R2' is a valid measure of the number of labeled cells, assuming a simple scenario for cell death, where SPIO is transferred from the intracellular space to the extracellular space and evenly distributed. Our results confirm this assumption. However, they also suggest that extracellular iron may give a nonzero contribution to R2'. In case of extreme iron deposits (see MPIO on Fig. 3), extracellular iron produces
Quantification of iron labeled cell
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