Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection

Dynamic contrast-enhanced T1-weighted magnetic resonance imaging (DCE-MRI) is being increasingly used in various clinical trials involving brain tumors. It allows characterization of the vascular microenvironment in tumors by measurement of a range of parameters, such as Ktrans (forward transfer constant), kep (reverse transfer constant), ve (volume of the extravascular extracellular space), and vp (blood plasma volume) (1,2). These parameters reflect specific physiologic characteristics and hence relate to various aspects of tumor biology. One of the hurdles in obtaining these quantitative metrics is a lack of robust methods for approaching the problem of parametric estimation using multicompartmental pharmacokinetic models (3). Another issue is that current Food and Drug Administration (FDA)-approved extravascular contrast agents (CAs) used for the assessment of vascular parameters in solid tumors are relatively small (molecular weight