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

Kim, Jana; Kim, Eugene; Euceda, Leslie R.; Meyer, Dan E.; Langseth, Karina; Bathen, Tone Frost; Moestue, Siver Andreas; Huuse, Else Marie

doi:10.1002/jmri.25898

Cited by 11 publications

(13 citation statements)

References 45 publications

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“…Posttreatment scans using the same protocol were performed 2 days later. In a previous study, we showed that this regimen significantly reduced the blood volume, vascular density, and K trans of TOV-21G tumors (26).…”

Section: Methodsmentioning

confidence: 80%

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

et al. 2019

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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.

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Section: Methodsmentioning

confidence: 80%

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

et al. 2019

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“…This would limit the quantitative reliability of T1 weighted imaging for IONPs in vivo. Considering the potential benefits of longitudinal studies, there have been efforts to utilize quantitative T1 mapping of the effects of IONPs in rodent studies 41,42 . The T1 (or R1) mapping provided objective quantification of IONPs induced R1 (= 1/T1) enhancement.…”

Section: Discussionmentioning

confidence: 99%

Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration

Kim

Dodd

et al. 2021

Sci Rep

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Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo. In this study, an optimized Magnetization Prepared—RApid Gradient Echo (MP-RAGE) with 2 inversion times called MP2RAGE combined with advanced image co-registration is presented as an effective non-invasive methodology to quantitatively detect T1 MR contrast agents. The optimized MP2RAGE produced high quality in vivo mouse brain T1 (or R1 = 1/T1) map with high spatial resolution, 160 × 160 × 160 µm3 voxel at 9.4 T. Test–retest signal to noise was > 20 for most voxels. Extremely small iron oxide nanoparticles (ESIONPs) having 3 nm core size and 11 nm hydrodynamic radius after polyethylene glycol (PEG) coating were intracranially injected into mouse brain and detected as a proof-of-concept. Two independent MP2RAGE MR scans were performed pre- and post-injection of ESIONPs followed by advanced image co-registration. The comparison of two T1 (or R1) maps after image co-registration provided precise and quantitative assessment of the effects of the injected ESIONPs at each voxel. The proposed MR protocol has potential for future use in the detection of T1 molecular contrast agents.

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“…Ultrasmall superparamagnetic iron oxides (USPIOs) are high-contrast MRI contrast agents which are very small and are useful in assessment of the blood pool. Currently, they are more frequently utilized in research settings but are helpful in evaluating vessel characteristics, such as size or density [27] (Figure 5). discontinued gadofosveset trisodium, extravasates at sites of angiogenesis, but also can leak from normal blood vessels.…”

Section: Invasive and Non-invasive Imaging Methodsmentioning

confidence: 99%

Current Concepts in Multi-Modality Imaging of Solid Tumor Angiogenesis

Soliman

Guccione

Reiter

et al. 2020

Cancers

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There have been rapid advancements in cancer treatment in recent years, including targeted molecular therapy and the emergence of anti-angiogenic agents, which necessitate the need to quickly and accurately assess treatment response. The ideal tool is robust and non-invasive so that the treatment can be rapidly adjusted or discontinued based on efficacy. Since targeted therapies primarily affect tumor angiogenesis, morphological assessment based on tumor size alone may be insufficient, and other imaging modalities and features may be more helpful in assessing response. This review aims to discuss the biological principles of tumor angiogenesis and the multi-modality imaging evaluation of anti-angiogenic therapeutic responses.

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

Abstract: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1589-1600.

Cited by 11 publications

References 45 publications

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

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

Sensitive detection of extremely small iron oxide nanoparticles in living mice using MP2RAGE with advanced image co-registration

Current Concepts in Multi-Modality Imaging of Solid Tumor Angiogenesis

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