Bio-Medical Materials and Engineering 18 (2008) 261–272 261 DOI 10.3233/BME-2008-0535 IOS Press Quantitative dynamic contrast enhanced MRI of experimental synovitis in the rabbit knee: Comparison of macromolecular blood pool agents vs. Gadolinium-DOTA Astrid Watrin-Pinzano a , Damien Loeuille a , Jean-Christophe Goebel a , Françoise Lapicque a , Fredéric Walter b , Philippe Robert c , Patrick Netter a , Claire Corot c , Pierre Gillet a, and Alain Blum a,b a Faculté de Médecine de Nancy, UMR 7561 CNRS – Nancy Université, France b Service de Radiologie Guilloz, Hôpital Central, CHU Nancy, France c Guerbet Research, Roissy CDG, France Abstract. The purpose of this study was to assess 2 Gd-based macromolecular intravascular contrast agents (P792, rapid clearance blood pool agent (rBPA) and P717, slow clearance blood pool agent (sBPA)) compared to Gd-DOTA (representative extracellular non specific agent) in MR imaging of knee rabbit experimental synovitis. Quantitative dynamic contrast enhanced MRI (qDCE-MRI) after intravascular injection of a low molecular weight contrast agent of 0.56 kDa (Gd-DOTA) and 2 high- molecular-weight contrast agents of 6.47 kDa (P792) and 52 kDa (P717) was performed in rabbits with carrageenan-induced synovitis of the right knee. P792 and P717 provided a progressive and persistent enhancement of arthritic synovial tissue while Gd-DOTA provided an early and rapidly declining enhancement with a concomitant diffusion in synovial fluid, thus limitating delineation of synovial pannus. P792 allowed acquisition of high-quality MR arthrograms, due to both a better diffusion in synovial pannus (vs. P717) and a concomitant restricted diffusion into the synovial fluid (vs. Gd-DOTA). In fact, experimental rabbit synovitis represent a specific entity that favors the T1 effect of high-molecular-weight agents, and especially rBPA P792, entrapped in synovial pannus, without diffusion in the synovial fluid. Due to this lack of arthrographic effect, P792 accumulation could be specifically sequentially analyzed by qDCE-MRI for detecting, characterizing and monitoring synovial vascular permeability changes during mono- or polysynovitis. Keywords: Inflammation, experimental synovitis, contrast medium, MRI 1. Introduction In certain rheumatologic situations, the synovial membrane, as lining of the joints, may become thick- ened and inflamed. Normally consisting in only a few cell layers thick, the synovium can become swollen, more cellular, and engorged with fluid in an archetypal condition called synovitis. Most com- monly seen in arthritic conditions, and most pronounced in rheumatoid arthritis (RA), synovitis can cause pain and inflammation within the affected joint, and progressively leading to erosive osteochon- dral damages [29]. Radiography is the traditional method used for diagnosing, staging, and following * Address for correspondence: Pr. Pierre Gillet, MD, PhD, Laboratoire de Pharmacologie, UMR 7561 CNRS-UHP, Faculté de Medecine, Avenue Foret de haye, BP 184, 54505 Vandoeuvre lès Nancy, France. E-mail: p.gillet@chu-nancy.fr. 0959-2989/08/$17.00 2008 – IOS Press and the authors. All rights reserved