Mouse muscle and skin permeability coefficients (Ps) to macromolecular contrast agent using magnetic resonance imaging (MRI)

Abstract

We evaluated the use of MRI to measure blood to tissue clearances of Gadomer (kindly provided by Bayer Schering Pharma), a gadolinium based contrast agent with an apparent MW of 35 kDa. C57 black mice (25–30 g) were anaesthetized (Isoflurane) and Gadomer was injected i.v. during scanning using a 7T Bruker Pharmascan. A T1‐weighted dynamic sequence (TR/TE= 11.1/2.5 ms, flip angle= 25°, time resolution 0.8 s, frames = 500) was used to measure signal intensity over time in selected Regions of Interest (ROI's) in the masseter muscle and head skin. Tracer concentration in blood vessels was also measured in small ROI's placed over arteries. Controlled bolus injection of 0.1 mmol Gd/kg BW caused an initial “step” increase in tracer intensity as the vascular volume was filled. Subsequent blood to tissue tracer exchange resulted in further (initially linear) increased (slope) in tracer intensity over periods of 100–300 seconds. Ps to Gadomer in tissue ROI's was calculated from the slope and step, assuming a microvessel volume to surface ratio of 2.5 microns (Curry et al, AJP245:H496, 1983). Average Ps values (X10‐7 cm/sec) were 2.9 ±1.0 (muscle) and 15±5 (skin). Corrections for the fall in plasma concentration increased estimates by 10–20%. The method enables repeated measurements Ps in organs of individual mouse of periods of days to weeks. Our research is supported by Research Council of Norway and University of Bergen.