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Multiparametric characterization of response to anti‐angiogenic therapy using USPIO contrast‐enhanced MRI in combination with dynamic contrast‐enhanced MRI
Author(s) -
Kim Jana,
Kim Eugene,
Euceda Leslie R.,
Meyer Dan E.,
Langseth Karina,
Bathen Tone F.,
Moestue Siver A.,
Huuse Else Marie
Publication year - 2018
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.25898
Subject(s) - medicine , nuclear medicine , magnetic resonance imaging , gadodiamide , gradient echo , gadolinium , dynamic contrast enhanced mri , radiology , materials science , metallurgy
Background Steady state susceptibility contrast (SSC)‐MRI provides information on vascular morphology but is a rarely used method. Purpose To investigate the utility of the ultrasmall superparamagnetic iron oxide particles (USPIOs) GEH121333 for measuring tumor response to bevacizumab and compare this with gadolinium‐based DCE‐MRI. Study Type Prospective preclinical animal model study. ANIMAL MODEL Mice bearing subcutaneous TOV‐21G human ovarian cancer xenografts treated with bevacizumab (n = 9) or saline (n = 9). Field Strength/Sequence Imaging was performed on a 7T Bruker Biospec. For SSC‐MRI with GEH121333 we acquired R 1 ‐maps (RARE‐sequence with variable TR), R 2 ‐maps (multi‐spin echo), andR 2 * ‐maps (multi‐gradient echo). Additionally, R 1 and R 2 maps were measured on the days after USPIO injection. For DCE‐MRI with gadodiamide we acquired 200 T 1 ‐weighted images (RARE‐sequence). Assessment ΔR 1 , ΔR 2 , and Δ R 2 *maps were computed from SSC‐MRI. DCE‐MRI was analysed using the extended Tofts model. Statistical Tests Results from pre‐ and 3 days posttreatment SSC‐MRI were compared using paired‐sample t‐tests. Treatment and control groups were compared using independent sample t‐tests. Performance of SSC‐ and DCE‐MRI was compared using multivariate partial least squares discriminant analysis. Results Already one day after treatment and USPIO injection, R 1 and R 2 values were lower in treated (R 1 = 0.49 ± 0.03s −1 , R 2 = 23.07 ± 1.49s −1 ) compared with control tumors (R 1 = 0.52 ± 0.02s −1 , R 2 = 24.98 ± 1.01s −1 ), indicating lower USPIO accumulation. Posttreatment SSC‐MRI displayed significantly decreased tumor blood volume (change in ΔR 2 = ‐0.43 ± 0.26s −1 , P = 0.001) and vessel density (change in Q = ‐0.032 ± 0.020s −1/3 , P = 0.002). DCE‐MRI showed among others lower K trans in treated tumors (control = 0.064 ± 0.011min −1 , tx = 0.046 ± 0.008min −1 , P = 0.002). Multivariate analysis suggests that SSC‐MRI was slightly inferior to DCE‐MRI in distinguishing treated from control tumors (accuracy = 75%, P = 0.058 versus 80%, P = 0.028), but a combination of both was best (accuracy = 85%; P = 0.003). Data Conclusion SSC‐MRI with GEH121333 is sensitive to early (<24 h) and late changes in tumor vasculature. SSC‐MRI and DCE‐MRI provide complementary information and can be used to assess different aspects of vascular responses to anti‐angiogenic therapies. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1589–1600.