|The Great Wall|
In Vivo MR Imaging of Endothelial VCAM-1
Expression in a Mouse Model of Both Stable and Vulnerable
Leonie Elisabeth Maria Paulis1, Glenda Sibylle van Bochove1, Dolf Segers2, Willem J. Mulder3, Grietje Molema4, Rob Krams5, Gustav J. Strijkers1, Klaas Nicolay1
1Eindhoven University of Technology, Eindhoven, Netherlands; 2Erasmus University Medical Center, Rotterdam, Netherlands; 3Mount Sinai School of Medicine, New York, USA; 4University Medical Center Groningen, Groningen, Netherlands; 5London Imperial College, London, UK
In this study the possibilities of MR-imaging to in vivo visualize the expression of VCAM-1 on vascular endothelium were explored in a mouse model where stable and vulnerable plaques are induced in the right carotid artery. This approach is challenging, because the contrast agents’ location will be restricted to one layer of cells. Paramagnetic anti-mouse VCAM-1 liposomes were designed that showed in vitro specificity for VCAM-1. Fluorescence microscopy showed in vivo targeting of endothelial VCAM-1 by anti-VCAM-1 liposomes. The strongest in vivo MRI signal enhancement by these liposomes was observed in stable plaques, but the effect did not reach significance.
Contrast-Enhanced MRI of Atherosclerosis with
Collagen Targeted CNA35-Micelles
Mariska de Smet1, Glenda S. van Bochove1, Honorius Sanders1, Francesca Arena2, Willem J. Mulder3, Rob Krams4, Maarten Merkx1, Gustav J. Strijkers1, Klaas Nicolay1
1Eindhoven University of Technology, Eindhoven, Netherlands; 2University of Turin, Turin, Italy; 3Mount Sinai School of Medicine, New York, New York, USA; 4Imperial College London, London, UK
Collagen plays an important role in the stabilization of atherosclerotic plaques. In this study, an MRI contrast agent based on paramagnetic micelles conjugated with collagen binding CNA35 protein, was characterized and tested in a mouse model of stable and vulnerable plaque. Because of their size, high relaxivity, stability in bloodserum and strong binding to collagen, these micelles can be suitable as MRI contrast agent for collagen imaging, for example in atherosclerotic plaques. Initial use of the contrast agent in the mouse model indeed showed that the region where stable (collagen-rich) plaques are expected showed the strongest contrast enhancement.
In Vivo Molecular MRI Using an
Elastin-Binding Contrast Agent Investigating Carotid Artery Injury in
Marcus Richard Makowski1, Ulrike Sausbier2, Yi Liu Liao2, Markus Schwaiger1, Winfried Neuhuber2, Peter Ruth2, Matthias Sausbier2, Rene M. Botnar1
1Technical University, Munich, Germany; 2Pharmacology, Tuebingen, Germany
Smooth-muscle-cell-proliferation and extracellular-matrix-turnover are thought to play an important role in vessel wall repair after vascular injury. Recently, we identified the cysteine-rich-protein-2 (CRP2) as novel molecular effector in vessel wall repair. We demonstrate the successful use of molecular MRI for the non-invasive assessment of alterations in the vessel wall after vascular injury in a mouse model of impaired smooth-muscle-cell-proliferation and ECM-formation (CRP2-/-). The differentiation of molecular alterations in the injured and non-injured vessel wall, as well as between wild type and CRP2-/- mice with regard to elastin formation after vascular injury could be made using CP1052.
MRI of Coronary Vessel Wall Injury in a Swine Model
of Coronary Intervention Using an Eletrostatically Stabilized VSOP
Christian von Bary1, Anne Preissel1, Susanne Wagner2, Marcus Richard Makowski1, Sylvia Schachoff1, Alexandra Keithahn1, Elmar Spuentrup3, Albert Schoemig1, Simon Robinson4, Joel Lazewatsky4, Markus Schwaiger1, Matthias Taupitz2, Rene Michael Botnar, 15
1Klinikum rechts der Isar, Munich, Germany; 2Charité, Berlin, Germany; 3University Hospital Cologne, Cologne, Germany; 4Bristol-Myers Squibb, North Billerica, USA; 5King's College London, London, UK
Abstract Summary We demonstrate the combined use of a matrix specific Gd-based contrast agent (BMS753951) together with an iron oxide nanoparticle for exclusive visualization of the pathologically altered coronary vessel wall.
Novel Nanomedicine for Anti-Inflammatory Therapy of
Atherosclerosis Monitored by Multimodality Imaging
Mark E. Lobatto1, Stephane Silvera1, Esad Vucic1, Venkatesh Mani1, Manuela Banciu2, Raymond M. Schiffelers2, Klaas Nicolay3, Gert Storm2, John T. Fallon1, James H. Rudd1, Valentin Fuster1, Edward A. Fisher4, Zahi A. Fayad1, Willem J. M. Mulder1
1Mount Sinai School of Medicine, New York, USA; 2Utrecht University, Utrecht, Netherlands; 3Eindhoven University of Technology, Eindhoven, Netherlands; 4New York University School of Medicine, New York, USA
We developed a novel theranostic targeted nanomedicine for the treatment of inflammation related to atherosclerosis. This agent was applied to atherosclerotic rabbits and we used clinical MRI to visualize their delivery and clinical FDG-PET/CT to quantify therapeutic efficacy. In addition, extensive immunohistochemistry and fluorescence microscopy was performed to confirm the in vivo findings.
|Detection of Atherosclerotic Plaque Progression:
Correlation of Contrast MRI with PET Using 64Cu-Labeled Natriuretic
Kyle S. McCommis1, Raffaella Rossin1, Dana R. Abenschein1, Beth Ochoa1, Geoff E. Woodard2, Michael J. Welch1, Pamela K. Woodard1, Jie Zheng1
1Washington University School of Medicine, St. Louis, Missouri, USA; 2National Institutes of Health, Bethesda, Maryland, USA
In this study, Gadofluorine M enhanced MRI was performed to image the femoral arteries of rabbits with the cholesterol-rich diet and double injury atherosclerotic plaque model. MicroPET imaging with a plaque targeted 64Cu-labeled natriuretic piptide was performed in the same day. Histological and immunohistochemistry images were also gathered. A correlation between enhanced MR signal intensity and SUV of PET images was observed and plaque progression was clearly demonstrated in both images. Further studies are needed to elucidate this correlation.
3D SPACE MR Imaging of Human
Atherosclerotic Femoral Artery at 3.0T
Zhuoli Zhang1, Zhaoyang Fan1, YiuCho Chung2, Peter Weale, 2, Timothy J. Carroll1, Ioannis Koktzoglou1, James Carr1, Renate Jerecic2, Mary McGrae McDermott1, Debiao Li1
1Northwestern University, Chicago, Illinois, USA; 2Siemens Medical Solutions, Chicago, Illinois, USA
Magnetic resonance imaging (MRI) could be used for the noninvasive assessment of atherosclerotic plaque burden in the peripheral circulation. Typically 2D dark blood turbo spin-echo (TSE) techniques are used for femoral arterial wall imaging. However, 2D techniques require prolonged imaging time to cover a large region of interest in the leg. Recently, variable-flip-angle 3D TSE T2-weighted (SPACE) has been introduced as a dark blood technique for fast imaging of vessel wall at 1.5T. The purpose of our study was to evaluate the potential of this technique for assessing atherosclerotic disease of the superficial femoral artery (SFA) at 3.0T.
Correlation of 3T-MRI Carotid Artery Wall Volume and
B-Mode Ultrasound Intima-Media Thickness Measurements
Raphael Duivenvoorden1, Eric de Groot1, John J.P. Kastelein1, J S. Lameris1, Aart J. Nederveen1
1Academic Medical Center, Amsterdam, New Hampshire, Netherlands
Cardiovascular MRI is a promising modality for the assessment of the atherosclerotic disease process. We compared 3T-MRI Arterial Wall Volume measurements with the widly used ultrasound Intima-Media Thickness measurements.
Spatial Heterogeneity of Carotid Artery Wall Strain
Using Displacement-Encoded MRI at 1.5T and 3.0T
Alexander Peter Lin1, 2, Lauren Wisk3, Eric Bennett2, Scott Fraser1, Han Wen2
1California Institute of Technology, Pasadena, California , USA; 2National Institutes of Health, Bethesda, Maryland, USA; 3University of California Los Angeles, Los Angeles, California , USA
The spatial distribution of carotid artery wall strain during systolic lumen expansion was measured with displacement-encoded MRI (DENSE). The results reveal spatial heterogeneity of the distribution of distension around the circumference of the artery in healthy volunteers. These results should motivate further investigation of a baseline pattern of the strain distribution in healthy humans and changes associated with vessel disease.
Flow-Sensitive 4D MRI for the Analysis of Aortic
Hemodynamics and Wall Shear Stress: Results Form Healthy Volunteers and
Follow-Up in Aortic Stenosis
Alex Frydrychowicz1, Maximilian F. Russe1, Aurélien F. Stalder1, Alexander Berger1, Andreas Harloff1, Raoul Arnold1, Mathias Langer1, Jürgen Hennig1, Michael Markl1
1University Hospital Freiburg, Freiburg, Germany
In light of the arterial remodeling attributed to factors such as the wall shear stress (WSS) and the oscillatory shear index (OSI) it was the aim of this study to exploit MR’s capability to directly measure blood flow and the option to calculate derived vessel wall parameters. Results in 11 young healthy volunteers were compared with findings in a 13 year-old boy with severe aortic coarctation before, and 5 and 9 month after therapy. Our data suggest that 4D MRI is capable of the detailed analysis of qualitative hemodynamics and derived vessel wall parameters, to show alterations even in areas not directly affected by a pathology, and that 4D MRI is suitable for follow-up examinations.