1. ¹INSERM, U836, Grenoble, France
2. ²Université Joseph Fourier, Grenoble Institut des Neurosciences, UMR-S836, Grenoble, France
3. ³Oncodesign Inc., Dijon, France

Correspondence: Dr EL Barbier, Grenoble Institut des Neurosciences, INSERM U836/Equipe 5, Université Joseph Fourier, Site Santé à La Tronche, BP 170, 38042 Grenoble Cedex 9, France. E-mail: emmanuel.barbier@ujf-grenoble.fr

Received 10 December 2008; Revised 20 May 2009; Accepted 22 May 2009; Published online 8 July 2009.

Abstract

This study aimed at combining an iron-based, steady-state, vessel size index magnetic resonance imaging (VSI MRI) approach, and a gadolinium (Gd)-based, dynamic contrast-enhanced MRI approach (DCE MRI) to characterize tumoral microvasculature. Rats bearing an orthotopic glioma (C6, n=14 and RG2, n=6) underwent DCE MRI and combined VSI and DCE MRI 4 h later, at 2.35 T. Gd-DOTA (200 mol of Gd per kg) and ultrasmall superparamagnetic iron oxide (USPIO) (200 mol of iron per kg) were used for DCE and VSI MRI, respectively. C6 and RG2 gliomas were equally permeable to Gd-DOTA but presented different blood volume fractions and VSI, in good agreement with histologic data. The presence of USPIO yielded reduced K^trans values. The K^trans values obtained with Gd-DOTA in the absence and in the presence of USPIO were well correlated for the C6 glioma but not for the RG2 glioma. It was also observed that, within the time frame of DCE MRI, USPIO remained intravascular in the C6 glioma whereas it extravasated in the RG2 glioma. In conclusion, VSI and DCE MRI can be combined provided that USPIO does not extravasate with the time frame of the DCE MRI experiment. The mechanisms at the origin of USPIO extravasation remain to be elucidated.