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Article

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

by
Jana Kim
1,2,
Siver A. Moestue
1,3,4,
Tone F. Bathen
1,2 and
Eugene Kim
1,5,*
1
Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU - Norwegian University of Science and Technology, Trondheim, Norway
2
St. Olavs Hospital, Trondheim, Norway
3
Department of Laboratory Medicine, Women’s and Children’s Health, NTNU - Norwegian University of Science and Technology, Trondheim, Norway
4
Department of Pharmacy, Faculty of Health Sciences, Nord University, Namsos, Norway
5
Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, England, UK
*
Author to whom correspondence should be addressed.
Tomography 2019, 5(3), 308-319; https://doi.org/10.18383/j.tom.2019.00015
Submission received: 6 June 2019 / Revised: 11 July 2019 / Accepted: 8 August 2019 / Published: 1 September 2019

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.
Keywords: DCE-MRI; r2* correction; transverse relaxation; multi-echo; treatment monitoring DCE-MRI; r2* correction; transverse relaxation; multi-echo; treatment monitoring

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MDPI and ACS Style

Kim, J.; Moestue, S.A.; Bathen, T.F.; Kim, E. R2* Relaxation Affects Pharmacokinetic Analysis of Dynamic Contrast-Enhanced MRI in Cancer and Underestimates Treatment Response at 7 T. Tomography 2019, 5, 308-319. https://doi.org/10.18383/j.tom.2019.00015

AMA Style

Kim J, Moestue SA, Bathen TF, Kim E. R2* Relaxation Affects Pharmacokinetic Analysis of Dynamic Contrast-Enhanced MRI in Cancer and Underestimates Treatment Response at 7 T. Tomography. 2019; 5(3):308-319. https://doi.org/10.18383/j.tom.2019.00015

Chicago/Turabian Style

Kim, Jana, Siver A. Moestue, Tone F. Bathen, and Eugene Kim. 2019. "R2* Relaxation Affects Pharmacokinetic Analysis of Dynamic Contrast-Enhanced MRI in Cancer and Underestimates Treatment Response at 7 T" Tomography 5, no. 3: 308-319. https://doi.org/10.18383/j.tom.2019.00015

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