Hepatic in vivo video microscopy for evaluating MR imaging agents

This paper reports on the hepatic effects of conventional and experimental MR imaging contrast agents that were compared by means of high-resolution in vivo video microscopy, which permits direct assessment of microvascular flow, sinusoidal cell morphology, endothelial activation, and Kupffer cell phagocytosis during and after administration of contrast agents. The left lateral liver lobe of Sprague-Dawley rats was exteriorized, transilluminated, and visualized with x10-x50 water-immersion objectives. Rats received either Gd-DTPA, paramagnetic iron oxide colloids AMI-25 or AG-USPIO or a perfluoro-carbon emulsion (FC-43) via the tail vein. Data were recorded onto video tape for 30 minutes prior to and for 1 hour after drug administration. Kupffer cell phagocytosis was measured with use of India ink. Kupffer cell phagocytosis was reduced in all rats receiving Gd-DTPA and FC-43. After administration of FC-43, microvascular flow abnormalities (intrahepatic shunting, Kupffer cell swelling, sinusoidal occlusion) were noted. Neutrophi endothelial adherence, indicating endothelial activation, was seen in three rates receiving AMI-25