MRI of Coronary Wall Remodeling in a Swine Model of Coronary Injury Using an Elastin-Binding Contrast Agent

Bary, Christian von; Makowski, Marcus R.; Preissel, Anne; Keithahn, Alexandra; Warley, Alice; Spuentrup, Elmar; Buecker, Arno; Lazewatsky, Joel; Cesati, Richard R.; Onthank, David; Schickl, Nikolaus; Schachoff, Sylvia; Hausleiter, Jörg; Schömig, Albert; Schwaiger, Markus; Robinson, Simonn; Botnar, René M.

doi:10.1161/circimaging.109.895607

Cited by 67 publications

(54 citation statements)

References 40 publications

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“…23 Gd-ESMA has been successfully applied to assess atherosclerotic plaque burden in a model of apolipoprotein E-deficient mice, 6 as well as to investigate arterial wall remodeling after stent placement in a swine model of coronary injury. 24 Preliminary data have also suggested that Gd-ESMA may be suitable for the quantification of elastin in liver fibrosis. 25 Although no specific toxicity studies for Gd-ESMA were performed yet, the previous reports published on Gd-ESMA, as well as our study, did not report any adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

Wildgruber

Bielicki

Aichler

et al. 2014

Circ: Cardiovascular Imaging

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Background-To prospectively evaluate an elastin-specific MR contrast agent (ESMA) for in vivo targeting of elastic fibers in myocardial infarction (MI) and postinfarction scar remodeling. Methods and Results-MI was induced in C57BL/6J mice (n=40) by permanent ligation of the left anterior descending coronary artery. MRI was performed at 7 and 21 days after MI. The merits of gadolinium-based ESMA (Gd-ESMA) were compared with gadopentetic acid (Gd-DTPA) for infarct size determination, contrast-to-noise ratio (CNR), and enhancement kinetics. Specific binding in vivo was evaluated by blocking the molecular target using nonparamagnetic lanthanum-ESMA. In vivo imaging results were confirmed by postmortem triphenyltetrazolium chloride staining, elastica van Gieson staining, and Western blotting. Delayed enhancement MRI revealed prolonged enhancement of Gd-ESMA in the postischemic scar compared with Gd-DTPA. Infarct size measurements showed good agreement between Gd-ESMA and Gd-DTPA and were confirmed by ex vivo triphenyltetrazolium chloride staining. Preinjection of the blocking lanthanum-ESMA resulted in significantly lower CNR of Gd-ESMA at the infarct site (P=0.0019). Although no significant differences in CNR were observed between delayed enhancement imaging and Gd-DTPA between days 7 and 21 (1.8± versus 3.8; P=ns), Gd-ESMA showed markedly higher CNR on day 21 after MI (14.1 versus 4.9; P=0.0032), which correlated with increased synthesis of tropoelastin detected by Western blot analysis and histology. Higher CNR values for Gd-ESMA further correlated with improved ejection fraction of the mice on day 21 after MI. Conclusions-Gd

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Section: Discussionmentioning

confidence: 99%

Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

Wildgruber

Bielicki

Aichler

et al. 2014

Circ: Cardiovascular Imaging

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“…In a study by von Bary et al, pigs with injury to the coronary wall by endothelial denudation or stent placement were imaged using a novel elastinbinding MR contrast agent, designated BMS-753951 (85). Delayed enhancement using BMS-753951 showed a 3-fold higher contrast-to-noise ratio in the stented coronary artery than in the balloon-injured or control (uninjured) artery, whereas gadolinium-DTPA showed only minor or no late enhancement.…”

Section: Advanced Molecular Imaging Applicationsmentioning

confidence: 99%

Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects

et al. 2013

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) advantages and shortcomings of hybrid PET/MR scanners with respect to cardiovascular applications (e.g. myocardial perfusion imaging and viability imaging), (2) additional value of the MR component in cardiac imaging, and (3) technical challenges and workflow considerations regarding hybrid PET/MR scanners in the field of cardiology (e.g. attenuation correction and cardiac/respiratory/patient motion).Financial Disclosure: Dr. Schwaiger is an investigator, meeting participant, and lecturer for Siemens Medical. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA Category 1 Credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, participants can access this activity through the SNMMI Web site (http:// www.snmmi.org/ce_online) through March 2016.PET/CT and other combined scanners have in the past decade rapidly emerged as important research tools and are proving to be invaluable for improved diagnostics in routine nuclear medicine. The design of hybrid PET/MR scanners presented a formidable technical challenge, and only recently were these instruments introduced to the market. Initial expectations of the performance of these scanners have been high, notably because of the potential for superior tissue contrast inherent in the MR modality, as well as the potential for multiparametric functional imaging in conjunction with PET. However, the additional value and potential clinical role that these new systems might bring to the cardiac field have yet to be documented. This review presents a comparative summary of the existing applications for PET and MR in the field of cardiology and suggests potential cardiac applications exploiting unique properties of the newly introduced combined instrumentation. The diverse range of imaging modalities for cardiology includes echocardiography, CT, MR imaging, SPECT, and PET, each of which offers distinct properties and advantages. The demand for combined PET/CT instrumentation in clinical nuclear medicine has grown remarkably, because of the notable advantages presented by hybrid imaging with respect to anatomic localization of lesions. Although these advantages were initially driven by the demands of oncology imaging, the resultant broader availability of PET/CT has provided the opportunity to use these scanners for indications beyond oncology, such as in the field of cardiac imaging (1). Furthermore, CT images are necessary for rapid attenuation correction, which is of particular importance for quantification in myocardial perfusion imaging. Through the use of suitable CT components a...

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“…Furthermore, the clearance of the contrast agent is comparable 27 to approved gadolinium-based MR contrast agents allowing for early imaging after injection with minimal background signal and thus maximal target to blood contrast to noise. The high-resolution DE-MRI and the T1 mapping sequences we developed and used are directly applicable to large animal models 42 and humans with an even higher expected accuracy and specificity due the ≈10 to 20 times greater arterial wall thickness and consequently higher elastin content.…”

Section: Translational Potential Of Esmamentioning

confidence: 99%

In Vivo Assessment of Aortic Aneurysm Wall Integrity Using Elastin-Specific Molecular Magnetic Resonance Imaging

Botnar

Wiethoff

Ebersberger

et al. 2014

Circ: Cardiovascular Imaging

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The extracellular matrix (ECM) of the tunica media is the most important structural component of the aortic wall. Elastin, as the most abundant protein in the tunica media, provides the tensile strength of the arterial wall, enabling it to sustain mechanical stress resulting from high intravascular pressure and arterial pulsation. 9 The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand the high intraluminal hemodynamic forces.10 Besides elastin, different forms of collagen play an important role in maintaining aortic Background-The incidence of abdominal aortic aneurysms (AAAs) has increased during the last decades. However, there is still controversy about the management of medium-sized AAAs. Therefore, novel biomarkers, besides aneurysmal diameter, are needed to assess aortic wall integrity and risk of rupture. Elastin is the key protein for maintaining aortic wall tensile strength and stability. The progressive breakdown of structural proteins, in particular, medial elastin, is responsible for the inability of the aortic wall to withstand intraluminal hemodynamic forces. Here, we evaluate the usefulness of elastin-specific molecular MRI for the in vivo characterization of AAAs. Methods and Results-To induce AAAs, ApoE -/-mice were infused with angiotensin-II. An elastin-specific magnetic resonance molecular imaging agent (ESMA) was administered after 1, 2, 3, and 4 weeks of angiotensin-II infusion to assess elastin composition of the aorta (n=8 per group). The high signal provided by ESMA allowed for imaging with high spatial resolution, resulting in an accurate assessment of ruptured elastic laminae and the compensatory expression of elastic fibers. In vivo contrast-to-noise ratios and R1-relaxation rates after ESMA administration were in good agreement with ex vivo histomorphometry (Elastica van Gieson stain) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy. Electron microscopy confirmed colocalization of ESMA with elastic fibers. Conclusions-Changes

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MRI of Coronary Wall Remodeling in a Swine Model of Coronary Injury Using an Elastin-Binding Contrast Agent

Cited by 67 publications

References 40 publications

Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects

In Vivo Assessment of Aortic Aneurysm Wall Integrity Using Elastin-Specific Molecular Magnetic Resonance Imaging

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