Volume 47, Issue 6 pp. 1589-1600

Original Research

Multiparametric characterization of response to anti-angiogenic therapy using USPIO contrast-enhanced MRI in combination with dynamic contrast-enhanced MRI

Jana Kim PhD,

Corresponding Author

Jana Kim PhD

[email protected]

orcid.org/0000-0003-4386-440X

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Address reprint requests to: J.K., Olav Kyrres gate 9, MTFS, 7030 Trondheim, Norway. E-mail:[email protected]Search for more papers by this author

Eugene Kim PhD,

Eugene Kim PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

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Leslie R. Euceda PhD,

Leslie R. Euceda PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

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Dan E. Meyer PhD,

Dan E. Meyer PhD

Biosciences Technology Organization, GE Global Research Center, Niskayuna, NY, United States

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Karina Langseth PhD,

Karina Langseth PhD

GE Healthcare AS, Oslo, Norway

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Tone F. Bathen PhD,

Tone F. Bathen PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

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Siver A. Moestue PhD,

Siver A. Moestue PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Laboratory Medicine, Women's and Children's Health, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

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Else Marie Huuse PhD,

Else Marie Huuse PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

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Jana Kim PhD,

Corresponding Author

Jana Kim PhD

[email protected]

orcid.org/0000-0003-4386-440X

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Address reprint requests to: J.K., Olav Kyrres gate 9, MTFS, 7030 Trondheim, Norway. E-mail:[email protected]Search for more papers by this author

Eugene Kim PhD,

Eugene Kim PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Search for more papers by this author

Leslie R. Euceda PhD,

Leslie R. Euceda PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Search for more papers by this author

Dan E. Meyer PhD,

Dan E. Meyer PhD

Biosciences Technology Organization, GE Global Research Center, Niskayuna, NY, United States

Search for more papers by this author

Karina Langseth PhD,

Karina Langseth PhD

GE Healthcare AS, Oslo, Norway

Search for more papers by this author

Tone F. Bathen PhD,

Tone F. Bathen PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Search for more papers by this author

Siver A. Moestue PhD,

Siver A. Moestue PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Laboratory Medicine, Women's and Children's Health, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Search for more papers by this author

Else Marie Huuse PhD,

Else Marie Huuse PhD

Department of Circulation and Medical Imaging, NTNU - Norwegian University of Science and Technology, Trondheim, Norway

Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

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First published: 04 December 2017

https://doi.org/10.1002/jmri.25898

Citations: 12

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Abstract

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 R₁-maps (RARE-sequence with variable TR), R₂-maps (multi-spin echo), and $urn:x-wiley:10531807:media:jmri25898:jmri25898-math-0001$ -maps (multi-gradient echo). Additionally, R₁ and R₂ maps were measured on the days after USPIO injection. For DCE-MRI with gadodiamide we acquired 200 T₁-weighted images (RARE-sequence).

Assessment

ΔR₁, ΔR₂, and $urn:x-wiley:10531807:media:jmri25898:jmri25898-math-0002$ 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, R₁ and R₂ values were lower in treated (R₁ = 0.49 ± 0.03s⁻¹, R₂ = 23.07 ± 1.49s⁻¹) compared with control tumors (R₁ = 0.52 ± 0.02s⁻¹, R₂ = 24.98 ± 1.01s⁻¹), indicating lower USPIO accumulation. Posttreatment SSC-MRI displayed significantly decreased tumor blood volume (change in ΔR₂ = -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.

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Citing Literature

Volume47, Issue6

June 2018

Pages 1589-1600