Intraindividual in vivo comparison of gadolinium contrast agents for pharmacokinetic analysis using dynamic contrast enhanced magnetic resonance imaging

Abstract

Purpose: To compare the intraindividual differences of dynamic signal characteristics for 3 gadolinium chelates (gadopentetate dimeglumine [Gd-DTPA], gadodiamide [Gd-DTPA-BMA], and gadobenate dimeglumine [Gd-BOPTA]) using dynamic contrast enhanced magnetic resonance (MR) imaging (DCE-MRI) with a preclinical beagle model at 7 Tesla.

Method and materials: Seven beagles were scanned 3 times each with a 7-day interval between the scans on a 7T whole body MRI system (Achieva, Philips) using a T/R head coil. Three different Gd contrast agents including Gd-DTPA, Gd-DTPABMA, and Gd-BOPTA were injected in a randomized order with a power injector (Spectris, MedRad, Indianola, PA) using dose of 0.1 mmol/kg body weight and flow rate of 0.06 mL/s. During image acquisition and data analysis, the identity of the specific contrast agent used for each examination was blinded. A 3D RF-spoiled fast field echo sequence was used for dynamic scans with in-plane spatial resolution 0.47 x 0.47 mm(2), temporal resolution of 9.5 seconds, and a total of 60 time points. Regions of interest were drawn within the carotid arteries and muscle tissue to determine semiquantitative parameters including maximum enhancement ratio, area under the signal enhancement curve over 90 seconds after contrast injection (AUC_90), time to maximum signal enhancement (T(max)), and washout_score. Additionally, quantitative pharmacokinetic parameters were measured in muscle tissues by applying 3 separate 2-compartment models; (1) artery input function (AIF) based Tofts model, (2) Brix model without AIF, and (3) AIF decomposed refined Brix model.

Results: Gd-BOPTA produced higher signal to noise ratio on postcontrast T1- weighted images than the other 2 Gd based contrast agents at 7T. Quantitatively, Gd-BOPTA provided a significantly higher maximum enhancement ratio (P < 0.01), AUC_90 (P < 0.01) and washout_score (P < 0.01) in beagle musculature and cranial vasculature compared with both Gd-DTPA and Gd-DTPA-BMA. Among all the quantitative pharmacokinetic parameters, only the exchange rate constants (kep) calculated from these 3 models did not show a significant difference among the various contrast agents.

Conclusions: Gd chelate containing MR contrast agents can be used at 7T for DCEMRI. Gd-BOPTA demonstrates stronger signal enhancement than standard Gd chelates, in concordance with the results of studies at lower fields. The observed enhancement characteristics for the 3 contrast agents demonstrate that the pharmacokinetic parameter kep is more robust in various models using DCE-MRI than the other pharmacokinetic parameters. This information is important relative to multisite clinical trials and long-term clinical studies that often use several different contrast agents and different models.