R2* Relaxation Affects Pharmacokinetic Analysis of Dynamic Contrast-Enhanced MRI in Cancer and Underestimates Treatment Response at 7 T

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 TON-21G human ovarian cancer xenografts (n = 8) and on the tronsgenic adenocorcinomo of the mouse prostate (TRAMP) model (n = 7). Subsequently, the TOY-21G tumor-bearing mice were treated with bevacizumab and rescanned 2 days later, Pharmacokinetic analysis (extended Toffs 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 enhance meat underestimated by 9,4%-16% in TOV-21G tumors and 1 3%-20% in TRAMP prostates). Median K'r"' and v, were underestimated in every mouse (TOV-21G K-trans: 11%-19%, TOV-21G v(e): 5 3%-8.9%; TRAMP K-trans: 8.6%-19%, TRAMP v(e): 12%-21%). Bevacizumab treatment reduced K-trans 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 vs. 0.037 min(-1) in uncorrected K-trans). R2* enhancement in DOE-MRI is both time- and tissue-dependent and may not be negligible at 7 T in tissue with high. This has consequences for the use of K-trans and other DCE-MRI parameters as biomarkers, because treatment effect size can be underestimated when R2* enhancement is neglected.