R2* and R2 mapping for quantifying recruitment of superparamagnetic iron oxide-tagged endothelial progenitor cells to injured liver: tracking in vitro and in vivo

OBJECTIVE To evaluate clinical 3.0T magnetic resonance for tracking and quantifying superparamagnetic iron oxide (SPIO)-labeled endothelial progenitor cells (EPCs) in vitro and homing to liver with acute injury in vivo. METHODS The bone marrow-derived EPCs were isolated and cultured for 4 days and examined in vitro for lineage markers. Then the cultured cells were labeled with a ferumoxides-protamine sulfate complex. Iron uptake was analyzed with an electron microscope and Prussian blue staining. Agarose gel phantoms containing different amounts of EPCs (0-2.5 × 10(6) cells per milliliter of 1.0% agarose gel) were analyzed with 3.0T R2 and R2* relaxometry. For in vivo tracking, liver injury was induced in healthy C57 mice (female, 6 weeks old, weight 19-20 g) by administration of carbon tetrachloride by single intraperitoneal injection. The R2* and R2 mapping of injured and normal livers of C57 mice were conducted by using 3.0T magnetic resonance on Days 0, 1, 4, and 8 after intravenous SPIO-tagged cells transplantation. RESULTS Electron microscope and Perls Prussian blue stain revealed the efficiency of SPIO particles uptake was more than 95% and no structural changes of labeled cells were found compared with control group. R2 and R2* values were linearly correlated with the number of iron-loaded cells in the agarose gel phantoms, and R2* values were significantly greater than R2 (P<0.01). R2* values in all groups were obviously greater than R2 (P<0.01). The R2* values of the injured livers were greater than normal on Days 1 and 4 (P<0.01). No significant difference of R2 values could be found among the three groups. CONCLUSION Quantitative R2* mapping provides a useful method for quantifying intravascular administered SPIO-tagged EPCs homing to injured livers.