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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.