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

doi:10.1148/radiol.2461070032

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

Molecular Imaging

Aortic Aneurysms in a Rat Model: In Vivo MR Imaging of Endovascular Cell Therapy¹

Jean-François Deux, MD, PhD, Jiangping Dai, MD, PhD, Charlotte Rivière, PhD, Florence Gazeau, PhD, Philippe Méric, PhD, Brigitte Gillet, PhD, Jacky Roger, MD, PhD, Jean-Noel Pons, PhD, Didier Letourneur, PhD, Frank P. Boudghène, MD, PhD, and Eric Allaire, MD, PhD

¹ From INSERM U 698, Bioengineering Department, University Paris 7-University Paris 13, X. Bichat Hospital, Paris, France (J.F.D., D.L.); Radiology Department (J.F.D.) and Centre National de la Recherche Scientifique, Unité Nixte de Recherche 7054 (J.D., E.A.), Assistance Publique-Hôpitaux de Paris, IFR de Médecine, University Paris 12, H. Mondor Hospital, Créteil, France; Laboratoire Matière et Systèmes Complexes, Paris, France (C.R., F.G.); Laboratoire de Resonance Magnetique Nucleaire Biologique-Institut de Chimie des Substances Naturelles, Gif sur Yvette, France (P.M., B.G.); Laboratoire des Liquides Ioniques et Interfaces Chargées, Paris, France (C.R., J.R., J.N.P.); and Radiology Department, Tenon Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France (F.P.B.). Received January 7, 2007; revision requested March 2; revision received April 16; accepted May 7; final version accepted June 18. Supported by the Centre National de la Recherche Scientifique (CNRS), the French Institut National de la Santé et de la Recherche Médicale (INSERM), the Ministère de l'Education Nationale de l'Enseignement Supérieur et de la Recherche (Action Concertée Incitative technologies pour la santé), Université Paris 13 (Bonus qualité recherche and Institut Federal de Recherche Paris-Nord Plaine de France), University Paris 12 Val de Marne, the Fondation Bettencourt-Schueller (Prix Coup d'Elan), and the Fondation de la Recherche Médicale. C.R. supported by the French Direction Générale de l'Armement (DGA doctorat fellowship). Address correspondence to J.F.D. (e-mail: jean-francois.deux{at}hmn.aphp.fr).

Purpose:To prospectively evaluate in rats whether magnetic cell labelingcan be used to noninvasively assess the technical success of endovascularcell therapy for abdominal aortic aneurysms (AAAs).

Materials and Methods:The study was approved by an institutionalanimal care and use committee. Vascular smooth muscle cells (VSMCs)labeled with iron oxide nanoparticles were seeded endovascularlyin already formed AAAs. T2*-weighted gradient-echo and T2-weightedspin-echo magnetic resonance (MR) imaging was performed in vivo at1.5 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-loadedcells, three were imaged on day 7 after cell delivery; three, onday 14; and four, on day 28; then they were euthanized. Ex vivo high-field-strengthMR 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 Wilcoxoncorrelation test.

Results:Magnetic cell labeling did not alter the capability of VSMCsto stabilize the diameter of the aneurysms. T2*-weighted gradient-echoimages showed areas of hypointense signal within the aortic wallimmediately and up to 1 month after cell therapy. The mean signalintensity decreased significantly after cell delivery (from 2362± 244 [standard deviation] before to 434 ± 275 afterdelivery, P < .001). Areas of hypointense signal and iron-loadedVSMCs were colocalized in the area of aortic wall reconstructionat both high-field-strength MR imaging and histologic analysis.