The overall goal of this study is to perform a pilot study in healthy volunteers to compare the hepatobiliary gadolinium based contrast agent, gadoxetic acid, alone and in combination with an intravascular gadolinium based contrast agent, gadofosveset trisodium, for improved detection of metastatic disease to the liver. The data generated from this small pilot will lay the foundation for a larger clinical study in patients with known or suspected metastatic liver disease.
Modern gadolinium based contrast agents (GBCA) for liver imaging, such as gadoxetic acid, have a specific hepatocellular uptake in healthy hepatocytes. Liver lesions without hepatocytes such as malignancies experience no selective uptake. Detection of hypointense lesions on hepatobiliary phase imaging using gadoxetic acid is an excellent method to detect and characterize focal liver lesions, particularly metastatic disease to the liver. However, two major challenges remain. First, vessels and lesions both appear dark and can be difficult to distinguish from one another. Second, benign cavernous hemangiomas are very common benign lesions that also appear dark on delayed hepatobiliary images. Hence, while it is widely believed that the sensitivity of detection of metastatic disease with hepatobiliary gadoxetic acid is high, the specificity, while not fully understood, is generally considered to be low.
The purpose of this work is to improve the diagnostic ability of the hepatobiliary phase for detection and characterization of metastatic disease by using an intravascular gadolinium based contrast agent, gadofosveset trisodium in combination with gadoxetic acid. Gadofosveset trisodium is a recently FDA-approved GBCA that persists in the blood, enhancing blood vessels and vascular lesions such as hemangiomas. We hypothesize that the enhancement of blood vessels and hemangiomas from gadofosveset after the injection of gadoxetic acid will improve detection and characterization of focal liver lesions â€“ metastases will appear dark with no or very little contrast enhancement, while blood vessels and hemangiomas will be appear very bright.
In this study, we propose to image twelve healthy volunteers who will undergo dynamic contrast enhanced MR imaging of the liver on a clinical 3T MRI system (GE Healthcare, Waukesha, WI) using a 32-channel phased array body coil (Neocoil, Pewaukee, WI). First, gadoxetic acid will be injected and images will be acquired during pre-contrast phase, dynamic contrast phases and hepatobiliary phase using a standard breathheld T1-weighted 3D spoiled gradient echo sequence, and a navigator based T1 weighted high resolution acquisition that has been optimized for maximum contrast between liver and non-hepatocyte lesions. Second, gadofosveset will be injected intravenously and images using the above mentioned sequences will be acquired during dynamic contrast phases and equilibrium phase of gadofosveset (>2 minutes after injection).