Simultaneous evaluation of vascular morphology, blood volume and transvascular permeability using SPION-based, dual-contrast MRI: imaging optimization and feasibility test

Kwon, Heon‐Ju; Shim, Woo Hyun; Cho, Gyunggoo; Cho, Hyung Joon; Jung, Hoe Su; Lee, Chang Kyung; Lee, Yong Seok; Baek, Jin Hee; Kim, Sang Hyun; Suh, Ji-Yeon; Sung, Yu Sub; Woo, Dong‐Cheol; Kim, Young Ro; Kim, Jeong Kon

doi:10.1002/nbm.3293

Cited by 10 publications

(19 citation statements)

References 44 publications

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“…MR contrast enhancement simulations were conducted before and after SPION injections at various imaging parameters (TR, TE, and flip angle). The relationships of the signal enhancement with respect to the imaging parameters as function of SPION concentration (22,23) showed that SPION can act as positive and negative contrast agent. With a short TR, short TE, and large flip angle, the signal intensity increased with the increasing SPION concentration, denoting a T 1 -enhancement effect.…”

Section: Tablementioning

confidence: 99%

“…For example, Jung et al generated both negative and positive image contrasts by manipulating the pulse sequences together with the use of sizecontrolled SPIONs [22]. In another study, T 1 -weighted positive contrast obtained from SPIONs using ultrashort-echo-time was reported by Kwon et al [23]. In the clinic, Ferumoxytol (an ultrasmall SPION) can be utilized to obtain regional T 1 and T 2 ⁎ signal enhancement or loss with conventional pulse sequences [24].…”

Section: Introductionmentioning

confidence: 99%

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A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI

Alipour

Soran‐Erdem

Ütkür

et al. 2018

Magnetic Resonance Imaging

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Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as a robust negative contrast agent on conventional MRI. In this study, we (a) synthesized a new class of cubic SPIONs as a dual-mode contrast agent in MRI and (b) showed the in-vivo feasibility of these nanaoparticles as a simultaneous positive and negative contrast agent. Relaxation properties and contrast enhancement analysis of the synthesized SPIONs with two different shapes (cubic vs. spherical) and three different sizes 7nm, 11nm, and 14nm were investigated to evaluate contrast enhancement in-vitro. In-vivo MRI experiments were performed on a 3T MR scanner, where a healthy anesthetized rat was imaged before, and from 20 to 80min after intravenous injection of 1mg/kg of contrast agent. Representative transmission electron microscopy (TEM) images of the synthesized nanoparticles reveal that the particles are well dispersed in a solvent and do not aggregate. The in-vitro relaxivity and contrast enhancement analysis show that, among all six SPIONs tested, 11-nm cubic SPIONs possess optimal molar relaxivities and contrast enhancement values, which can shorten the spin-lattice and spin-spin relaxation times, simultaneously. No noticeable toxicity is observed during in-vitro cytotoxicity analysis. In-vivo T-and T-weighted acquisitions at 60-min post-injection of 11-nm cubic SPIONs result in 64% and 48% contrast enhancement on the T-and T-weighted images, respectively. By controlling the shape and size of SPIONs, we have introduced a new class of cubic SPIONs as a synergistic (dual-mode) MRI contrast agent. 11-nm cubic SPIONs with smaller size and high positive and negative contrast enhancements were selected as a promising candidate for dual-mode contrast agent. Our proof-of-concept MRI experiments on rat demonstrate the in-vivo dual-mode contrast enhancement feasibility of these nanoparticles.

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Section: Tablementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI

Alipour

Soran‐Erdem

Ütkür

et al. 2018

Magnetic Resonance Imaging

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“…However, attempts that visualize this with off-resonance imaging or imaging of local field inhomogeneities 155 were challenged by sensitivity and susceptibility artifacts. 156 …”

Section: Quantification With Iron Oxide Agentsmentioning

confidence: 99%

Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

Korchinski

Taha

Yang

et al. 2015

Magn Reson�Insights

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Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation.

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“…For measuring BV parameters (ie, ΔR 2 *and ΔR 2 ), SPION (30 mg Fe/kg bodyweight) was used as an intravascular susceptibility CA. The pharmacokinetic profile of SPION was detailed in a recent article 11. Before and after SPION injection, the R 2 value was measured using the multiecho spin‐echo sequence (TR, 3000 milliseconds; 15 TEs [10‐150 milliseconds; ΔTE, 10 milliseconds]; flip angle, 90°; slice thickness, 1 mm; number of slice, 12 or 13; FOV, 20 × 20 mm; matrix, 128 × 128), and the R 2 * was measured using the multiecho gradient‐echo sequence (TR, 1500 milliseconds; 12 TEs [5‐60 milliseconds; ΔTE, 5 milliseconds]; flip angle, 30°; slice thickness, 1 mm; number of slice, 12 or 13; FOV, 20 × 20 mm; matrix, 128 × 128), respectively.…”

Section: Methodsmentioning

confidence: 99%

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters

et al. 2018

Self Cite

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Tumor heterogeneity is an important concept when assessing intratumoral variety in vascular phenotypes and responses to antiangiogenic treatment. This study explored spatiotemporal heterogeneity of vascular alterations in C6 glioma mice during tumor growth and antiangiogenic treatment on serial MR examinations (days 0, 4, and 7 from initiation of vehicle or multireceptor tyrosine kinase inhibitor administration). Transvascular permeability (TP) was quantified on dynamic‐contrast‐enhanced MRI (DCE‐MRI) using extravascular extracellular agent (Gd‐DOTA); blood volume (BV) was estimated using intravascular T2 agent (SPION). With regard to region‐dependent variability in vascular phenotypes, the control group demonstrated higher TP in the tumor center than in the periphery, and greater BV in the tumor periphery than in the center. This distribution pattern became more apparent with tumor growth. Antiangiogenic treatment effect was regionally heterogeneous: in the tumor center, treatment significantly suppressed the increase in TP and decrease in BV (ie, typical temporal change in the control group); in the tumor periphery, treatment‐induced vascular alterations were insignificant and BV remained high. On histopathological examination, the control group showed greater CD31, VEGFR2, Ki67, and NG2 expression in the tumor periphery than in the center. After treatment, CD31 and Ki67 expression was significantly suppressed only in the tumor center, whereas VEGFR2 and α‐caspase 3 expression was decreased and NG2 expression was increased in the entire tumor. These results demonstrate that MRI can reliably depict spatial heterogeneity in tumor vascular phenotypes and antiangiogenic treatment effects. Preserved angiogenic activity (high BV on MRI and high CD31) and proliferation (high Ki67) in the tumor periphery after treatment may provide insights into the mechanism of tumor resistance to antiangiogenic treatment.

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Simultaneous evaluation of vascular morphology, blood volume and transvascular permeability using SPION-based, dual-contrast MRI: imaging optimization and feasibility test

Cited by 10 publications

References 44 publications

A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI

A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI

Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

Spatiotemporal heterogeneity of tumor vasculature during tumor growth and antiangiogenic treatment: MRI assessment using permeability and blood volume parameters

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