Determination of macromolecular concentration following direct infusion into hydrogel using contrast-enhanced MRI

Direct tissue infusion has emerged as a promising drug delivery method for treating diseases of the nervous system because the blood-brain or blood-spinal cord barriers are circumvented. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment and optimizing infusion protocols. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers using contrast-enhanced MRI. An 11.1 T magnet system was used to image infusion of Gd-DTPA labeled albumin (Gd-albumin) into an agarose-based hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As an initial validation test, these concentration profiles were compared with distribution profiles predicted for porous media transport by convection and diffusion. Comparison of model results show good correlation between predicted distributions. In future studies, the presented methodology may be used to estimate the distribution of Gd-tracer following infusion directly into tissue.