Aortic Aneurysms in a Rat Model: In Vivo MR Imaging of Endovascular Cell Therapy

Abstract

To prospectively evaluate in rats whether magnetic cell labeling can be used to noninvasively assess the technical success of endovascular cell therapy for abdominal aortic aneurysms (AAAs). The study was approved by an institutional animal care and use committee. Vascular smooth muscle cells (VSMCs) labeled with iron oxide nanoparticles were seeded endovascularly in already formed AAAs. T2*-weighted gradient-echo and T2-weighted spin-echo magnetic resonance (MR) imaging was performed in vivo at 1.5 T before and 30 minutes after the injection of iron-loaded VSMCs (14 rats), nonlabeled VSMCs (three rats), or iron-free particles (three rats). Ten rats were euthanized shortly after the injection (day 0). Of the 10 remaining rats, which were seeded with iron-loaded cells, three were imaged on day 7 after cell delivery; three, on day 14; and four, on day 28; then they were euthanized. Ex vivo high-field-strength MR imaging of two AAAs was performed 28 days after cell delivery. Histologic examination of cross sections of all AAAs was performed. Statistical evaluations were performed with a nonparametric Wilcoxon correlation test. Magnetic cell labeling did not alter the capability of VSMCs to stabilize the diameter of the aneurysms. T2*-weighted gradient-echo images showed areas of hypointense signal within the aortic wall immediately and up to 1 month after cell therapy. The mean signal intensity decreased significantly after cell delivery (from 2362 +/- 244 [standard deviation] before to 434 +/- 275 after delivery, P < .001). Areas of hypointense signal and iron-loaded VSMCs were colocalized in the area of aortic wall reconstruction at both high-field-strength MR imaging and histologic analysis. MR imaging with magnetic cell labeling can be used to document endovascular cell delivery in already formed AAAs in rats.