Advances in MRI allow studies of physiological processes in time. Here we investigated vessel permeability (Ps) in mouse muscle to a macromolecular tracer using MRI. Gadomer (kindly provided by Bayer Schering Pharma, Germany), a gadolinium based contrast agent with an apparent MW of 35 kDa, was injected into the tail vein of C57 black mice (25–30 g) that were anaesthetized (Isoflurane, Isoba®vet, Schering-Plough, UK). The MR signal intensity (SI) was measured before, during and after injection of the tracer using a T1-weighted dynamic sequence (TR/TE= 11.1/2.5 ms, flip angle= 25°, time resolution 0.8 s, frames = 500). Regions of interests (ROIs) were placed over the masseter muscle and skin to obtain dynamic information. The arterial input to muscle tissue was estimated by placing small ROIs over supplying arteries to the tissue. The data analysis for quantification of the microvessel permeability was based on the time-course of the tracer concentration: 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) increase (slope) in tracer intensity over periods of 100–300 seconds. Ps to Gadomer in tissue ROIs was calculated from the slope and step, assuming a microvessel volume to surface ratio of 2.5 microns (Curry et al.1983). Average Ps values (× 10^-7 cm/sec) were 2.91.0 (muscle) and 155 (skin). Corrections for the fall in plasma concentration increased estimates by 10–20 %. The method enables non-invasive repeated measurements Ps in organs of individual mouse of periods of days to weeks.

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Curry F.E., Huxley V.H. & Adamson R.H. 1983. Am J Physiol, 245: 495–505.