The effects of intravoxel contrast agent diffusion on the analysis of DCE-MRI data in realistic tissue domains

Quantitative evaluation of dynamic contrast enhanced MRI (DCE-MRI) allows for estimating perfusion, vessel permeability, and tissue volume fractions by fitting signal intensity curves to pharmacokinetic models. These compart mental models assume rapid equilibration of contrast agent within each voxel. However, there is increasing evidence that this assumption is violated for small molecular weight gadolinium chelates. To evaluate the error introduced by this invalid assumption, we simulated DCE-MRI experiments with volume fractions computed from entire histological tumor cross-sections obtained from murine studies.

A 2D finite element model of a diffusion-compensated Tofts-Kety model was developed to simulate dynamic T₁ signal intensity data. Digitized histology slices were segmented into vascular (v_p ), cellular and extravascular extracellular (v_e ) volume fractions. Within this domain, K^trans (the volume transfer constant) was assigned values from 0 to 0.5 min^-1 . A representative signal enhancement curve was then calculated for each imaging voxel and the resulting simulated DCE-MRI data analyzed by the extended Tofts-Kety model.

Results indicated parameterization errors of -19.1% ± 10.6% in K^trans , -4.92% ± 3.86% in v_e , and 79.5% ± 16.8% in v_p for use of Gd-DTPA over 4 tumor domains.

These results indicate a need for revising the standard model of DCE-MRI to incorporate a correction for slow diffusion of contrast agent. Magn Reson Med 80:330-340, 2018. © 2017 International Society for Magnetic Resonance in Medicine.