DCE-MRI in hepatocellular carcinoma-clinical and therapeutic image biomarker

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables tumor vascular physiology to be assessed. Within the tumor tissue, contrast agents (gadolinium chelates) extravasate from intravascular into the extravascular extracellular space (EES), which results in a signal increase on T1-weighted MRI. The rate of contrast agents extravasation to EES in the tumor tissue is determined by vessel leakiness and blood flow. Thus, the signal measured on DCE-MRI represents a combination of permeability and perfusion. The semi-quantitative analysis is based on the calculation of heuristic parameters that can be extracted from signal intensity-time curves. These enhancing curves can also be deconvoluted by mathematical modeling to extract quantitative parameters that may reflect tumor perfusion, vascular volume, vessel permeability and angiogenesis. Because hepatocellular carcinoma (HCC) is a hypervascular tumor, many emerging therapies focused on the inhibition of angiogenesis. DCE-MRI combined with a pharmacokinetic model allows us to produce highly reproducible and reliable parametric maps of quantitative parameters in HCC. Successful therapies change quantitative parameters of DCE-MRI, which may be used as early indicators of tumor response to anti-angiogenesis agents that modulate tumor vasculature. In the setting of clinical trials, DCE-MRI may provide relevant clinical information on the pharmacodynamic and biologic effects of novel drugs, monitor treatment response and predict survival outcome in HCC patients.