Background: Pharmacokinetic differences between hepatocyte-specific contrast agents and the non-linear response of magnetic resonance (MR) signal intensity (SI) to contrast concentration require a quantitative approach in the analysis of contrast uptake.
Purpose: To develop a procedure for quantifying the hepatocyte-specific uptake of Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist) and to investigate the correlation between the uptake estimates of these agents in healthy subjects.
Materials and Methods: Ten healthy volunteers were examined using Dynamic Contrast Enhanced MR-imaging (DCE-MRI) using 0.05 mmol/kg of Gd-BOPTA or 0.025 mmol/kg of Gd-EOB-DTPA on two separate occasions. The signal intensity (SI) of liver and spleen parenchyma, the common hepatic artery, the portal vein and the splenic vein was obtained before contrast agent administration, during the arterial and portal venous phases, and 10, 20, 30, and 40 min after intravenous contrast agent injection. Using twocompartment models of the liver and spleen, and contrast concentration estimates from relaxation rate values calculated from the SI measurements, a hepatic uptake rate estimate was derived. Pairwise correlation and linear regression were applied to compare the uptake rate with the quantitative SI-based liver-to-spleen ratio (Q-LSR). A Student’s ttest was used in comparisons of relaxation rate measures from the vessels and the spleen.
Results: A significant correlation was observed between the hepatobiliary Gd-EOBDTPA and Gd-BOPTA uptake, (rho=0.64; p<0.05). No significant correlation was observed for the SI-based Q-LSR values. A factor 11 higher hepatic uptake rate was determined using Gd-EOB-DTPA compared to Gd-BOPTA. Approximately 50% of the blood clearance of Gd-EOB-DTPA occurred during the early phases, compared to 25% for Gd-BOPTA, whereas there was little difference in blood clearance in later phases. A simulation of SI in the arterial and venous phase using double dose Gd-EOB-DTPA predicted improved vessel to liver contrast compared to the experiment using the clinically approved dose.
Conclusion: A novel signal rescaling procedure for correcting the non-linear SI response of T1-weighted images acquired using a standard clinical abdominal DCE-imaging protocol was demonstrated. By simple pharmacokinetic modeling, the hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was shown to be correlated in healthy subjects. The ratio of the hepatobiliary uptake using Gd-EOB-DTPA and Gd-BOPTA was in agreement with pre-clinical studies. Gd-BOPTA provided better vessel to liver contrast in the early time phases than Gd-EOB-DTPA at the clinically approved doses. Moreover, the low vessel to liver contrast during the early phases may be improved by doubling the dose of Gd-EOB-DTPA.