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

Abstract

Qingguo Wang, Kangan Li, Qimeng Quan, Guixiang ZhangDepartment of Radiology, Shanghai Jiaotong University Affiliated First People’s Hospital, Hongkou District, Shanghai, People’s Republic of ChinaObjective: 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 × 106 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.Keywords: EPC, magnetic resonance imaging, cell recruitment