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Updated: Jun 8, 2026
In Vivo Quantitative Assessment of Myocardial Structure, Function, Perfusion and Viability Using Cardiac Micro-computed Tomography
Published on: February 16, 2016
Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of
Glenda S van Bochove1, Leonie E M Paulis, Dolf Segers
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, The Netherlands.
Abstract:
Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A tapered cast was implanted around the right carotid artery of apoE(-/-) mice to induce two different plaque phenotypes: a thin cap fibroatheroma (TCFA) and a non-TCFA lesion. Both plaques were allowed to develop over 6 and 9 weeks, leading to an intermediate and advanced lesion, respectively. Signal enhancement in the carotid artery wall, following intravenous injection of Gd-HP-DO3A as well as paramagnetic micelles and liposomes was evaluated. In vivo T(1) -weighted MRI plaque enhancement characteristics were complemented by fluorescence microscopy and correlated to lesion phenotype. The two smallest contrast agents, i.e. Gd-HP-DO3A and micelles, were found to enhance contrast in T(1) -weighted MR images of all investigated plaque phenotypes. Maximum contrast enhancement ranged between 53 and 70% at 6 min after injection of Gd-HP-DO3A with highest enhancement and longest retention in the non-TCFA lesion. Twenty-four hours after injection of micelles maximum contrast enhancement ranged between 24 and 35% in all plaque phenotypes. Administration of the larger liposomes did not cause significant contrast enhancement in the atherosclerotic plaques. Confocal fluorescence microscopy confirmed the MRI-based differences in plaque permeation between micelles and liposomes. Plaque permeation of contrast agents was strongly dependent on size. Our results implicate that, when equipped with targeting ligands, liposomes are most suitable for the imaging of plaque-associated endothelial markers due to low background enhancement, whereas micelles, which accumulate extravascularly on a long timescale, are suited for imaging of less abundant markers inside plaques. Low molecular weight compounds may be employed for target-specific imaging of highly abundant extravascular plaque-associated targets.
Insights
Contrast-enhanced MRI using gadolinium-based agents effectively characterizes atherosclerotic plaques. Smaller agents like Gd-HP-DO3A and micelles show plaque enhancement, while larger liposomes do not, indicating size-dependent permeation for targeted plaque imaging.
Area of Science:
- Biomedical Imaging
- Cardiovascular Research
- Nanotechnology in Medicine
Background:
- Contrast-enhanced magnetic resonance imaging (MRI) is crucial for in vivo characterization of atherosclerotic plaques.
- Gadolinium-based contrast agents (GBCAs) vary in size and properties, influencing their ability to permeate biological barriers.
Purpose of the Study:
- To evaluate the intrinsic ability of three differently sized GBCAs to permeate distinct mouse plaque phenotypes using MRI.
- To correlate MRI findings with fluorescence microscopy for a comprehensive understanding of contrast agent behavior.
Main Methods:
- Induction of thin cap fibroatheroma (TCFA) and non-TCFA lesions in apoE(-/-) mice carotid arteries via cast implantation.
- Intravenous injection of Gd-HP-DO3A, paramagnetic micelles, and liposomes, followed by T(1)-weighted MRI.
- Complementary analysis using confocal fluorescence microscopy to confirm plaque permeation differences.
Main Results:
- Gd-HP-DO3A and micelles enhanced T(1)-weighted MR images across all plaque phenotypes.
- Gd-HP-DO3A showed maximum enhancement (53-70%) with longest retention in non-TCFA lesions.
- Micelles exhibited lower enhancement (24-35%) over 24 hours, while liposomes caused no significant enhancement, confirming size-dependent permeation.
Conclusions:
- Contrast agent size is a critical determinant of plaque permeation in MRI.
- Liposomes are suitable for imaging plaque-associated endothelial markers due to low background enhancement.
- Micelles are effective for imaging less abundant plaque markers, and low molecular weight agents for abundant extravascular targets.
