Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI

Abstract

Convection-enhanced delivery (CED), i.e., direct tissue infusion, has emerged as a promising local drug delivery method for treating diseases of the nervous system. Determination of the spatial distribution of therapeutic agents after infusion is important in evaluating the efficacy of treatment, optimizing infusion protocols, and improving the understanding of drug pharmacokinetics. In this study, we provide a methodology to determine the concentration distribution of Gd-labeled tracers during infusion using contrast-enhanced MR imaging. To the best of our knowledge, MR studies that quantify concentration profiles for CED have not been previously reported. The methodology utilizes intrinsic material properties (T 1 and R 1 ) and reduces the effect of instrumental factors (e.g., inhomogeneity of MR detection field). As a methodology investigation, this study used an agarose hydrogel phantom as a tissue substitute for infusion. An 11.1 T magnet system was used to image infusion of Gd-DTPA labeled albumin (Gd-albumin) into the hydrogel. By using data from preliminary scans, Gd-albumin distribution was determined from the signal intensity of the MR images. As a validation test, MR-derived concentration profiles were found comparable to both results measured directly using quantitative optical imaging and results from a computational transport model in porous media. In future studies, the developed methodology will be used to quantitatively monitor the distribution of Gd-tracer following infusion directly into tissues.

Influence of Needle Insertion Speed on Backflow for Convection-Enhanced Delivery

“…Due to continuity, Po is equal to p at this interface. A value of 0.6 was taken for the porosity based on our previous hydrogel studies [13]. The flow through the hemisphere {Q¡) at the tip of the carmula was taken to be half that for spherical cavity whose radius is equal to the radius of the needle.…”

“…Substituting Eq. (12) into (11) and integrating, the pressure distribution was obtained (13) where C/ and C2 are integration constants. To evaluate these constants, the pressure at the interior surface was considered equal to the infusion pressure (PQ).…”

Evaluation of a Voxelized Model Based on DCE-MRI for Tracer Transport in Tumor

“…Serial DCE-MR images consisting of a T 1 -weighted spinecho sequence were acquired before and after administration of the tracer. The MRI measured Gd-DTPA concentration in the tissue was then calculated based on the MR signal enhancement due to the contrast agent using the standard spin-echo signal equation [33]. The measured tracer concentration in the tissue at early time points (%20 min) was fitted to a two-compartment model [34] to obtain the K trans maps and the / maps.…”

Role of convection and diffusion on DCE-MRI parameters in low leakiness KHT sarcomas

“…K trans maps were created by fitting the first 15 min of Gd-DTPA concentration in tissue, C t , data using a standard two-compartment (Tofts and Kermode, 1991). Experimental C t was estimated by the method described by Chen et al (Chen et al, 2008) with a longitudinal relativity, R 1 , of 2.7 s −1 mM −1 based on rat muscle at 6.7 T (Rozijn et al, 1999). The filtration rate of plasma fluid per unit volume (J V /V) across the vessel wall is described by the Starling equation: J V /V = L p S/V(p e − p).…”