Abstract
Effective transverse relaxivity of gadolinium-based contrast agents is often neglected in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we assess time and tissue dependence of R2* enhancement and its impact on pharmacokinetic parameter quantification and treatment monitoring. Multiecho DCE-MRI was performed at 7 T on mice bearing subcutaneous TOV-21G human ovarian cancer xenografts (n = 8) and on the transgenic adenocarcinoma of the mouse prostate (TRAMP) model (n = 7). Subsequently, the TOV-21G tumor-bearing mice were treated with bevacizumab and rescanned 2 days later. Pharmacokinetic analysis (extended Tofts model) was performed using either the first echo signal only (standard single-echo DCE-MRI) or the estimated signal at TE = 0 derived from exponential fitting of R2* relaxation (R2*-corrected). Neglecting R2* enhancement causes underestimation of Gd-DOTA concentration (peak enhancement underestimated by 9.4%–16% in TOV-21G tumors and 13%–20% in TRAMP prostates). Median Ktrans and ve were underestimated in every mouse (TOV-21G Ktrans: 11%–19%, TOV-21G ve: 5.3%–8.9%; TRAMP Ktrans: 8.6%–19%, TRAMP ve: 12%–21%). Bevacizumab treatment reduced Ktrans in all TOV-21G tumors after 48 hours. Treatment effect was significantly greater in all tumors after R2* correction (median change of −0.050 min−1 in R2*-corrected Ktrans vs. −0.037 min−1 in uncorrected Ktrans). R2* enhancement in DCE-MRI is both time- and tissue-dependent and may not be negligible at 7 T in tissue with high Ktrans. This has consequences for the use of Ktrans and other DCE-MRI parameters as biomarkers, because treatment effect size can be underestimated when R2* enhancement is neglected.
Highlights
Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is used to characterize tissue vascularization by tracking the distribution of an intravenously injected gadolinium (Gd)based contrast agent in tissue over the course of several minutes
Here, we showed that pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data is influenced by R2* relaxation, which is in agreement with previous studies [17, 19]
The transgenic adenocarcinoma of the mouse prostate (TRAMP) prostates required a higher number of echoes for accurate R2* computation than the human ovarian cancer xenograft model (TOV-21G) tumors
Summary
Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is used to characterize tissue vascularization by tracking the distribution of an intravenously injected gadolinium (Gd)based contrast agent in tissue over the course of several minutes. These paramagnetic contrast agents change the relaxation times of tissue water protons, thereby influencing the signal intensity in the images. As the net impact on signal intensity depends on the concentration of a contrast agent in a given volume, the serial magnetic resonance (MR) images provide qualitative or quantitative information on contrast agent pharmacokinetics. Several pharmacokinetic models have been developed to extract quantitative information on vascular structure and function [9]. The accelerating adoption of high field scanners, to the point where MRI is regularly performed at 3 T or even 7 T, has caused researchers to reassess how DCE-MRI data should be acquired and analyzed
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