Shiman Wu and Hua Zhang are dual first author. Both of them both have contributed equally to this work.Address reprint requests to: Z. Y., 12 Middle Urumqi Road, Jing'an District, Shanghai, 200040, China. E-mail: [email protected]Search for more papers by this author

Shiman Wu MD,

Shiman Wu MD

orcid.org/0000-0003-2222-6257

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Hua Zhang MD, PhD,

Hua Zhang MD, PhD

orcid.org/0000-0002-3635-9950

Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China

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Jing Wang MD,

Jing Wang MD

orcid.org/0000-0002-7689-8780

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Xiaoyan Li MD,

Xiaoyan Li MD

orcid.org/0000-0002-1243-3845

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China

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Xinyi Gao MD,

Xinyi Gao MD

orcid.org/0000-0002-3678-1182

Department of Radiology, Zhejiang Cancer Hospital, Hangzhou, China

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Ziwei Fang MD,

Ziwei Fang MD

orcid.org/0000-0002-1639-0176

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Jianxun Qu ME,

Jianxun Qu ME

orcid.org/0000-0003-4587-6439

GE Healthcare, MR research, Applied Science Lab, Shanghai, China

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Yue Wu MD, PhD,

Yue Wu MD, PhD

orcid.org/0000-0003-2893-0659

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Yan Ren MD, PhD,

Yan Ren MD, PhD

orcid.org/0000-0001-5993-9248

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Wenting Rui MD,

Wenting Rui MD

orcid.org/0000-0002-2241-0639

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Junhai Zhang MD, PhD,

Junhai Zhang MD, PhD

orcid.org/0000-0002-3514-0471

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

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Zhenwei Yao MD, PhD,

Corresponding Author

Zhenwei Yao MD, PhD

[email protected]

orcid.org/0000-0002-5681-4308

Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China

First published: 29 February 2020

https://doi.org/10.1002/jmri.27109

Citations: 4

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Abstract

Background

Despite the growing concern about the safety of gadolinium-based contrast agents (GBCAs), they are still the most commonly used. Ferumoxytol, as an off-label alternative MRI contrast agent, cannot be administered by a rapid bolus for dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI).

Purpose

To assess the feasibility of iron sucrose (IS) as a contrast agent for MR angiography (MRA) and DSC-PWI.

Study Type

Prospective animal model.

Animal Model

Thirty-six normal rats (16 for MRA, 20 for biocompability tests) and 36 occlusion of the middle cerebral artery (MCAO) model rats.

Field Strength/Sequence

3.0T; head and neck angiography, using a fast spoiled gradient-recalled-echo (FSPGR) sequence and DSC-MRI using echo planar imaging(EPI) sequence.

Assessment

MRA was performed on normal rats to examine the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different doses of IS. DSC-PWI was performed on MCAO rats at 0, 24, 48, and 72 hours postreperfusion to investigate the lesion detectability of IS. Arterial spin labeling (ASL) and DSC-PWI enhanced by GBCAs were conducted on MCAO rats as controls.

Statistical Tests

Kruskal–Wallis test was used to compare qualitative assessment. One-way analysis of variance (ANOVA) was used to compare the parametric data. Pearson's r values were evaluated between relative cerebral blood flow(rCBF)-ASL, rCBF-DSC_IS, and rCBF obtained from DSC-PWI enhanced by GBCA.

Results

The mean SNR and CNR of the common carotid artery at doses of 10 mg Fe/kg of IS were comparable with the standard dose of GBCAs (SNR: 68.04 ± 12.55 vs. 67.72 ± 14.66; CNR: 23.78 ± 7.21vs. 21.63 ± 6.83). In MCAO rat models, rCBF and relative cerebral blood volume (rCBV) of ipsilateral striatum declined (0.72 ± 0.14, 0.86 ± 0.11) with prolonged relative mean transit time (rMTT) and relative time-to-peak (rTTP) (1.27 ± 0.24, 1.07 ± 0.03) following occlusion. Hyperperfusion was observed in all rats at 48 and 72 hours postreperfusion, in 4/6 rats at 24 hours postreperfusion for IS-mediated DSC-PWI.

Data Conclusion

IS may be an effective contrast agent for both MRA and DSC-PWI in ischemic stroke models.

Level of Evidence

Technical Efficacy Stage

1 J. Magn. Reson. Imaging 2020;52:836–849.

Supporting Information

References

1McDonald RJ, McDonald JS, Kallmes DF, et al. Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology 2017; 285: 546-554.
10.1148/radiol.2017161595
PubMed Web of Science® Google Scholar
2Shen Z, Wu A, Chen X. Iron oxide nanoparticle based contrast agents for magnetic resonance imaging. Mol Pharm 2017; 14: 1352-1364.
10.1021/acs.molpharmaceut.6b00839
CAS PubMed Web of Science® Google Scholar
3Gale EM, Atanasova IP, Blasi F, Ay I, Caravan P. A manganese alternative to gadolinium for MRI contrast. J Am Chem Soc 2015; 137: 15548-15557.
10.1021/jacs.5b10748
CAS PubMed Web of Science® Google Scholar
4Bashir MR, Mody R, Neville A, et al. Retrospective assessment of the utility of an iron-based agent for contrast-enhanced magnetic resonance venography in patients with endstage renal diseases. J Magn Reson Imaging 2014; 40: 113-118.
10.1002/jmri.24330
PubMed Web of Science® Google Scholar
5Kim YK, Kim CS, Kwak HS, Lee JM. Three-dimensional dynamic liver MR imaging using sensitivity encoding for detection of hepatocellular carcinomas: Comparison with superparamagnetic iron oxide-enhanced MR imaging. J Magn Reson Imaging 2004; 20: 826-837.
10.1002/jmri.20188
CAS PubMed Web of Science® Google Scholar
6Melancon MP, Appleton Figueira T, Fuentes DT, et al. Development of an electroporation and nanoparticle-based therapeutic platform for bone metastases. Radiology 2017; 286: 149-157.
10.1148/radiol.2017161721
PubMed Web of Science® Google Scholar
7Mulvaney P, Jian J, Kadhiresan P, et al. Diverse applications of nanomedicine. ACS Nano 2017; 11: 2313-2381.
10.1021/acsnano.6b06040
PubMed Web of Science® Google Scholar
8Wang YXJ. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging. World J Gastroenterol 2015; 21: 13400-13402.
10.3748/wjg.v21.i47.13400
CAS PubMed Web of Science® Google Scholar
9Mukundan S, Steigner ML, Hsiao LL, et al. Ferumoxytol-enhanced magnetic resonance imaging in late-stage CKD. Am J Kidney Dis 2016; 67: 984-988.
10.1053/j.ajkd.2015.12.017
CAS PubMed Web of Science® Google Scholar
10Varallyay CG, Toth GB, Fu R, et al. What does the boxed warning tell us? Safe practice of using ferumoxytol as an MRI contrast agent. Am J Neuroradiol 2017; 38: 1297-1302.
10.3174/ajnr.A5188
CAS PubMed Web of Science® Google Scholar
11Charytan C, Levin N, Al-Saloum M, Hafeez T, Gagnon S, Van Wyck DB. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Am J Kidney Dis 2001; 37: 300-307.
10.1053/ajkd.2001.21293
CAS PubMed Web of Science® Google Scholar
12Span K, Pieters EHE, Hennink WE, et al. The use of magnetic resonance imaging for non-invasive assessment of Venofer® biodistribution in rats. Pharm Res 2018; 35: 88.
10.1007/s11095-018-2348-y
PubMed Web of Science® Google Scholar
13Goldstein LS, Morris DA, Warady B. Comparison of the safety and efficacy of 3 iron sucrose iron maintenance regimens in children, adolescents, and young adults with CKD: A randomized controlled trial. Am J Kidney Dis 2013; 61: 588-597.
10.1053/j.ajkd.2012.10.019
CAS PubMed Web of Science® Google Scholar
14Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2007; 22: 659-661.
10.1096/fj.07-9574LSF
CAS PubMed Web of Science® Google Scholar
15Longa Enrique Zea, Weinstein Philip R., Carlson Sara R, Cummins Robert. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20: 84-91.
10.1161/01.STR.20.1.84
CAS PubMed Web of Science® Google Scholar
16Zhu C, Haraldsson H, Kallianos K, et al. Gated thoracic magnetic resonance angiography at 3T: Noncontrast versus blood pool contrast. Int J Cardiovasc Imaging 2018; 34: 475-483.
10.1007/s10554-017-1242-8
PubMed Web of Science® Google Scholar
17Rojas S, Martín A, Justicia C, et al. Modest MRI signal intensity changes precede delayed cortical necrosis after transient focal ischemia in the rat. Stroke 2006; 37: 1525-1532.
10.1161/01.STR.0000221713.06148.16
PubMed Web of Science® Google Scholar
18Paxinos GT, Watson C. The rat brain in stereotaxic coordinates. Amsterdam: Elsevier; 1992.
Google Scholar
19Massicotte EM, Buist R, Del Bigio MR. Altered diffusion and perfusion in hydrocephalic rat brain: A magnetic resonance imaging analysis. Neurosurg Focus 2000; 92: 442-447.
CAS Google Scholar
20Tan J, Klabunde KJ, Sherwood PA. X-ray photoelectron spectroscopy studies of solvated metal atom dispersed catalysts. Monometallic iron and bimetallic iron-cobalt particles on alumina. Chem Mater 1990; 2: 186-191.
10.1021/cm00008a021
CAS Web of Science® Google Scholar
21Shen Q, Du F, Huang S, Duong TQ. Spatiotemporal characteristics of postischemic hyperperfusion with respect to changes in T1, T2, diffusion, angiography, and blood-brain barrier permeability. J Cereb Blood Flow Metab 2011; 31: 2076-2085.
10.1038/jcbfm.2011.64
PubMed Web of Science® Google Scholar
22Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA 2015; 314: 2062-2068.
10.1001/jama.2015.15572
CAS PubMed Web of Science® Google Scholar
23Bailie GR, Clark JA, Lane CE, Lane PL. Hypersensitivity reactions and deaths associated with intravenous iron preparations. Nephrol Dial Transplant 2005; 20: 1443-1449.
10.1093/ndt/gfh820
CAS PubMed Web of Science® Google Scholar
24Kanal E. Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of clinical experience. Magn Reson Imaging 2016; 34: 1341-1345.
10.1016/j.mri.2016.08.017
CAS PubMed Web of Science® Google Scholar
25Van Dorsten FA, Hata R, Maeda K, et al. Diffusion- and perfusion-weighted MR imaging of transient focal cerebral ischaemia in mice. NMR Biomed 1999; 12: 525-534.
10.1002/(SICI)1099-1492(199912)12:8<525::AID-NBM597>3.0.CO;2-F
CAS PubMed Web of Science® Google Scholar
26Naganawa S, Kawai H, Sone M, Nakashima T. Increased sensitivity to low concentration gadolinium contrast by optimized heavily T2-weighted 3D-FLAIR to visualize endolymphatic space. Magn Reson Med Sci 2010; 9: 73-80.
10.2463/mrms.9.73
PubMed Web of Science® Google Scholar
27Vinitski S, Thakur ML, Consigny PM, Mitchell DG, Mohamed FB, Ortega HV. Use of ferrum in MRI of lung parenchyma and pulmonary embolism. Magn Reson Imaging 1993; 11: 499-508.
10.1016/0730-725X(93)90469-T
CAS PubMed Web of Science® Google Scholar
28Wirestam R, Thilmann O, Knutsson L, Björkman-Burtscher IM, Larsson EM, Ståhlberg F. Comparison of quantitative dynamic susceptibility-contrast MRI perfusion estimates obtained using different contrast-agent administration schemes at 3 T. Eur J Radiol 2010; 75: e86-91.
10.1016/j.ejrad.2009.07.038
PubMed Web of Science® Google Scholar
29Tanaka Y, Nagaoka T, Nair G, Ohno K, Duong TQ. Arterial spin labeling and dynamic susceptibility contrast CBF MRI in postischemic hyperperfusion, hypercapnia, and after mannitol injection. J Cereb Blood Flow Metab 2011; 31: 1403-1411.
10.1038/jcbfm.2010.228
PubMed Web of Science® Google Scholar
30Welker K, Boxerman J, Kalnin A, Kaufmann T, Shiroishi M, Wintermark M. ASFNR recommendations for clinical performance of MR dynamic susceptibility contrast perfusion imaging of the brain. Am J Neuroradiol 2015; 36: E41-E51.
10.3174/ajnr.A4341
CAS PubMed Web of Science® Google Scholar
31Calamante F, Willats L, Gadian DG, Connelly A. Bolus delay and dispersion in perfusion MRI: Implications for tissue predictor models in stroke. Magn Reson Med 2006; 55: 1180-1185.
10.1002/mrm.20873
CAS PubMed Web of Science® Google Scholar
32Quarles CC, Bell LC, Stokes AM. Imaging vascular and hemodynamic features of the brain using dynamic susceptibility contrast and dynamic contrast enhanced MRI. Neuroimage 2019; 187(April 2018): 32-55.
10.1016/j.neuroimage.2018.04.069
PubMed Web of Science® Google Scholar
33Shen Q, Duong T. Magnetic resonance imaging of cerebral blood flow in animal stroke models. Brain Circ 2016; 2: 20-27.
10.4103/2394-8108.178544
PubMed Google Scholar
34Hara S, Tanaka Y, Ueda Y, et al. Noninvasive evaluation of CBF and perfusion delay of moyamoya disease using arterial spin-labeling MRI with multiple postlabeling delays: Comparison with 15O-gas PET and DSC-MRI. Am J Neuroradiol 2017; 38: 696-702.
10.3174/ajnr.A5068
CAS PubMed Web of Science® Google Scholar
35White CM, Pope WB, Zaw T, et al. Regional and voxel-wise comparisons of blood flow measurements between dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and arterial spin labeling (ASL) in brain tumors. J Neuroimaging 2014; 24: 23-30.
10.1111/j.1552-6569.2012.00703.x
PubMed Web of Science® Google Scholar
36Shen Q, Huang S, Duong TQ. Ultra-high spatial resolution basal and evoked cerebral blood flow MRI of the rat brain. Brain Res 2015; 1599: 126-136.
10.1016/j.brainres.2014.12.049
CAS PubMed Web of Science® Google Scholar
37Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A. The safety of intravenous iron preparations: Systematic review and meta-analysis. Mayo Clin Proc 2015; 90: 12-23.
10.1016/j.mayocp.2014.10.007
CAS PubMed Web of Science® Google Scholar
38Gómez-Ramírez S, Shander A, Spahn DR, et al. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfus 2019; 17: 137-145.
PubMed Web of Science® Google Scholar
39Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: A new paradigm. Hematology 2016; 2016: 57-66.
10.1182/asheducation-2016.1.57
PubMed Web of Science® Google Scholar
40Schubert T, Motosugi U, Kinner S, et al. Crossover comparison of ferumoxytol and gadobenate dimeglumine for abdominal MR-angiography at 3.0 Tesla: Effects of contrast bolus length and flip angle. J Magn Reson Imaging 2017; 45: 1617-1626.
10.1002/jmri.25513
PubMed Web of Science® Google Scholar

Citing Literature

Volume52, Issue3

September 2020

Pages 836-849

Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model

Abstract

Background

Purpose

Study Type

Animal Model

Field Strength/Sequence

Assessment

Statistical Tests

Results

Data Conclusion

Level of Evidence

Technical Efficacy Stage

Supporting Information

References

Citing Literature

References

Information

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Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model

Abstract

Background

Purpose

Study Type

Animal Model

Field Strength/Sequence

Assessment

Statistical Tests

Results

Data Conclusion

Level of Evidence

Technical Efficacy Stage

Supporting Information

References

Citing Literature

References

Related

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