This study was designed in 2 stages as single- and multidose experiments. In both stages, a linear contrast agent (gadodiamide) was administered intravenously through the tail vein at a dose of 0.3, 0.6, and 1.2 mmol/kg. A dose of 0.6 mmol/kg corresponds to 0.1 mmol/kg in humans after adjusting for body surface area according to the U.S. Food and Drug Administration guidelines.18 This dose was halved (lower dose) and doubled (higher dose) to assess dose-dependent retention. Group allocation and study algorithm are summarized in Figure 1. The animals were sacrificed 3 hours after MRI examinations in all groups.
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