Page 55 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Introduction
Cell labeling with super paramagnetic iron oxide particles (SPIO) offers a promising method for in vivo human and animal model cell tracking by MRI. The low signal intensity (SI) on T2 or T2* weighted images reveals the presence of labeled cells (1–6). Depending on the location and the different mechanisms in tissue development, the labeled cells can be followed for as long as several weeks (7,8). Cell death, cell division, cell migration and iron re-uptake by surrounding cells or macrophages influence the detected signal intensity (9,10), and eventually may lead to misinterpretation of SI differences between labeled and nonlabeled regions. Longitudinal studies require assessment of these processes. However, detection of low-SI areas is an inadequate method.
The imaging setup parameters (such as coil and patient position), the artifacts (owing to motion and flow) and also technical imperfections (e.g. inhomogeneity in the coil sensitivity, transmit- ter and receiver decoupling problems) may compromise the reproducibility of SI values. These problems hamper quantification or reliable tracking during physiologically relevant processes.
Some studies have suggested R2 (1/T2) and R2* (1/T2*) parametric mapping to be a feasible and reproducible quantification method of SPIO or SPIO labeled cells per voxel (11–13). At sufficiently high imaging resolution, where the image distortions owing to the susceptibility inhomogeneities are negligible, the relaxation rates can be related to the imaged voxels (14,15).
Voxel-based relaxometry potentially allows assessment of iron concentration if a unique relationship can be established between relaxation rates and iron concentrations. As such, voxel-based relaxometry may establish a method of quantification for density of labeling particles and eventually for the number of labeled cells. Although many reports have demonstrated a linear (or at least monotonic) relationship between R2* or R2 values and iron concentration (3,16–18), there are other variables that may influence relaxation values, such as intravoxel distribution and compartmentalization of iron oxide particles (12,16,17). Additionally, the dependence of R2* or the R2-Fe concentration calibration curve on compartmentalization or on labeling particle size and
Quantification of iron labeled cell
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