Atherosclerosis: Contrast-enhanced MR Imaging of Vessel Wall in Rabbit Model—Comparison of Gadofosveset and Gadopentetate Dimeglumine

Lobbes, Marc; Miserus, Robbert-Jan J.H.M.; Heeneman, Sylvia; Passos, Valéria Lima; Mutsaers, P.H.A.; Debernardi, N.; Misselwitz, Bernd; Post, Mark J.; Daemen, Mat J.A.P.; Engelshoven, Jos M. A. van; Leiner, Tim; Kooi, M. Eline

doi:10.1148/radiol.2503080875

Cited by 36 publications

(35 citation statements)

References 27 publications

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“…Indeed, extravascular albumin has been detected in both human and mouse atherosclerotic lesions. 38,39 Here, we extend these findings, demonstrating an apparent size limit for endothelial leakage in vasa vasorum of 70 to 150 kDa in vivo in aged ApoE −/− mice. The origin of the microvascular hyperpermeability remains to be further elucidated.…”

Section: Discussionsupporting

confidence: 69%

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

Rademakers

Douma

Hackeng

et al. 2013

ATVB

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Objective-Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization, although its functional implications are yet unresolved. Here, we aimed to elucidate functional and morphological properties of plaque microvessels in mice in vivo. Methods and Results-Atherosclerotic carotid arteries from aged (>40 weeks) apolipoprotein E-deficient mice were imaged in vivo using multiphoton laser scanning microscopy. Two distinct groups of vasa vasorum microvessels were observed at sites of atherosclerosis development (median diameters of 18.5 and 5.9 μm, respectively), whereas microvessels within the plaque could only rarely be found. In vivo imaging showed ongoing angiogenic activity and injection of fluorescein isothiocyanate-dextran confirmed active perfusion. Plaque vasa vasorum showed increased microvascular leakage, combined with a loss of endothelial glycocalyx. Mean blood flow velocity in plaque-associated vasa vasorum was reduced by ±50% compared with diameter-matched control capillaries, whereas mean blood flow was reduced 8-fold. Leukocyte adhesion and extravasation were increased 6-fold in vasa vasorum versus control capillaries. Conclusion-Using a novel in vivo functional imaging strategy, we showed that plaque-associated vasa vasorum were angiogenically active and, albeit poorly, perfused. Moreover, plaque-associated vasa vasorum showed increased permeability, reduced blood flow, and increased leukocyte adhesion and extravasation (ie, characteristics that could contribute to plaque progression and destabilization). Key Words: angiogenesis ◼ atherosclerosis ◼ in vivo imaging ◼ microcirculation ◼ multiphoton laser scanning microscopy

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Section: Discussionsupporting

confidence: 69%

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

Rademakers

Douma

Hackeng

et al. 2013

ATVB

Self Cite

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“…Previous studies suggested that extravasation of gadofosveset in experimental 32 and human atherosclerosis 33 occurs through leaky microvessels. However, in these studies, a detailed analysis of the endothelium was not performed.…”

Section: Discussionmentioning

confidence: 97%

“…[27][28][29] Gadofosveset is a clinically approved gadolinium-based contrast agent that reversibly binds to serum albumin, resulting in a prolonged vascular presence and a 5-to 10-fold increase in relaxivity (r 1 ). 30,31 Gadofosveset is predominantly present within the vessel lumen but may enter the vessel wall through leaky neovessels 32,33 and mechanically damaged endothelium. 34 Although it has long been known that endothelial dysfunction is the primary event in atherogenesis, noninvasive assessment of endothelial permeability has not yet been established in vivo.…”

Section: Clinical Perspective On P 719mentioning

confidence: 99%

Noninvasive Magnetic Resonance Imaging Evaluation of Endothelial Permeability in Murine Atherosclerosis Using an Albumin-Binding Contrast Agent

et al. 2012

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Background-Endothelial dysfunction promotes atherosclerosis and precedes acute cardiovascular events. We investigated whether in vivo magnetic resonance imaging with the use of an albumin-binding contrast agent, gadofosveset, could detect endothelial damage associated with atherosclerosis in apolipoprotein E-deficient (ApoE Ϫ/Ϫ ) mice. Furthermore, we tested whether magnetic resonance imaging could noninvasively assess endothelial function by measuring the endothelial-dependent vasodilation in response to acetylcholine. Methods and Results-ApoEϪ/Ϫ mice were imaged at 4, 8, and 12 weeks after commencement of a high-fat diet. Statin-treated ApoE Ϫ/Ϫ mice were scanned after 12 weeks of a high-fat diet. Wild-type mice were imaged before and 48 hours after injection of Russell's viper venom, an endothelial toxin. Delayed enhancement magnetic resonance imaging and T1 mapping of the brachiocephalic artery, 30 minutes after injection of gadofosveset, showed increased vessel wall enhancement and relaxation rate (R 1 ) with progression of atherosclerosis in ApoE (R 1 ϭ3.0Ϯ0.65) mice showed less enhancement. Uptake of gadofosveset correlated with Evans blue staining, morphological changes of endothelial cells, and widening of the cell-cell junctions, suggesting that uptake occurs in regions of increased vascular permeability. Endothelial-dependent vasomotor responses showed vasoconstriction of the arteries of the ApoE Ϫ/Ϫ (Ϫ22.22Ϯ7.95%) and Russell's viper venom-injected (Ϫ10.37Ϯ17.60%) mice compared with wild-type mice (32.45Ϯ12.35%). Statin treatment improved endothelium morphology and function (Ϫ8.12Ϯ8.22%). Conclusions-We demonstrate the noninvasive assessment of endothelial permeability and function with the use of an albumin-binding magnetic resonance contrast agent. Blood albumin leakage could be a surrogate marker for the in vivo evaluation of interventions that aim to restore the endothelium. (Circulation. 2012;126:707-719.)Key Words: atherosclerosis Ⅲ endothelial dysfunction Ⅲ gadofosveset Ⅲ magnetic resonance imaging Ⅲ permeability A therosclerosis is a chronic disease of the vessels and a major cause of death in Western societies. Dysfunction of the vascular endothelium triggers leukocyte transmigration, platelet activation, smooth muscle cell proliferation, and vasoconstriction, which collectively promote the development of atherosclerosis. 1 Additionally, damaged endothelium can precipitate the complications of atherosclerosis through vasospasm and thrombosis, causing life-threatening cardiovascular events. Clinical Perspective on p 719Transport across the normal endothelium occurs between endothelial cells (ECs) (intercellular pathway) and/or through the ECs (transcytosis). Intercellular junctions with a diameter of Ϸ2 nm allow transport of small water-soluble molecules up to that diameter, 2 whereas breaks in the tight junctions with a diameter of Ϸ20 nm 3,4 accommodate the influx of albumin (diameter of Ϸ6 nm) and Evans blue dye (EBD). At the molecular level, oxidized low-density lipoprotein (1) decreases...

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“…Studies using clinically approved extracellular contrast agents showed that uptake in the coronary artery wall is non-specific and could be associated with both atherosclerotic plaque composition and inflammation in patients with stable CAD or acute coronary syndrome [80,81]. Enhancement with newly developed albumin binding and iron oxide-based contrast agents is associated with increased endothelial permeability and thus can be used for coronary wall imaging [82][83][84][85].…”

Section: Coronary Artery Wall Imagingmentioning

confidence: 99%

Cardiac MR Assessment of Coronary Arteries

Hamdy

Ishida

Sakuma

2017

Cardiovasc Imaging Asia

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Imaging of coronary arteries with magnetic resonance has undergone undeniable progress during the past two decades. Although coronary computed tomography angiography detects coronary artery disease (CAD) with excellent diagnostic accuracy, the inevitable exposure to ionizing radiation and iodinated contrast administration make it less appealing in certain patient populations. Coronary magnetic resonance angiography (MRA) is now performed mostly as a whole heart, free breathing, three-dimensional study. Several factors influence quality and speed of the scan, including use of the appropriate pulse sequence according to the strength of the magnetic field, cardiac and respiratory gating, preparation pulses, multi-channel cardiac coils, parallel imaging, and contrast material injection. The use of coronary MRA is well established in coronary artery anomalies and aneurysms. While diagnostic performance has also improved markedly for the detection of CAD, coronary MRA is not yet a routine clinical study. However, coronary MRA is expected to be play a major role in the near future due to continuous research and technical achievements.

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Atherosclerosis: Contrast-enhanced MR Imaging of Vessel Wall in Rabbit Model—Comparison of Gadofosveset and Gadopentetate Dimeglumine

Abstract: http://radiology.rsnajnls.org/cgi/content/full/250/3/682/DC1.

Cited by 36 publications

References 27 publications

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo

Noninvasive Magnetic Resonance Imaging Evaluation of Endothelial Permeability in Murine Atherosclerosis Using an Albumin-Binding Contrast Agent

Cardiac MR Assessment of Coronary Arteries

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