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Hide Applications Cited by (38) Imaging the vulnerable plaqueJournal of the American College of Cardiology
Focus on the research utility of intravascular ultrasound - Comparison with other invasive modalitiesCardiovascular Ultrasound, Volume 9, Issue 1, 2011
Abstract
Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques. © 2011 Bourantas et al; licensee BioMed Central Ltd.
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Journal of the American College of CardiologyVolume 47, Issue 8, Supplement 1, 18 April 2006, Pages C48-C56
Detection of Vulnerable Plaques
doi:10.1016/j.jacc.2005.11.048 | How to Cite or Link Using DOI Permissions & Reprints Viewpoint
Role of Magnetic Resonance and Intravascular Magnetic Resonance in the Detection of Vulnerable PlaquesRobert L. Wilensky MD
, a, 
, 
, Hee Kwon Song PhD† and Victor A. Ferrari MD, †, b
Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
†Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
Received 16 June 2005; revised 8 November 2005; accepted 12 November 2005. Available online 20 April 2006.Noninvasive magnetic resonance imaging (MRI) has been used to determine vascular three-dimensional structure, detect the presence of subclinical atherosclerotic disease in high-risk patient subgroups, and optimize and follow therapy in individual patients. The outstanding soft-tissue–characterizing capabilities of MRI permit depiction of various components of atherothrombotic plaque, including lipid, fibrous tissue, calcium, and thrombus formation. However, noninvasive MRI visualization of coronary arteries is currently limited by the small size of the coronary arteries, the deep arterial location, and arterial motion. The combination of MR imaging and molecular probes offers exciting possibilities of direct visualization of biologic processes within atherosclerotic tissue. The self-contained intravascular MRI probe appears to hold promise in the identification of high-risk coronary atherosclerotic lesions with increased superficial lipid content.
Role of Magnetic Resonance and Intravascular Magnetic Resonance in the Detection of Vulnerable Plaques
Robert L. Wilensky, Hee Kwon Song, Victor A. Ferrari
The outstanding soft-tissue-characterizing capabilities of magnetic resonance imaging (MRI) permit depiction of various components of atherothrombotic plaque, including lipid, fibrous tissue, calcium, and thrombus formation. This review discusses the current state of research in noninvasive MRI, the combination of MRI and contrast agents, and the self-contained intravascular MRI catheter.
Abbreviations: HDL, high-density lipoprotein; IVMRI, intravascular magnetic resonance imaging; LDL, low-density lipoprotein; MRI, magnetic resonance imaging; PD, proton density; RF, radiofrequency; SNR, signal-to-noise ratio; TE-MRI, transesophageal magnetic resonance imaging; TOF, time of flight; USPIO, ultra-small particles of iron oxide
Article Outline
- MRI techniques
- Limitations of MRI for coronary artery imaging
- Multiple contrast MRI for plaque characterization
- Intravascular coils
- Use of MRI to evaluate atherosclerosis progression and regression and changes in plaque composition
- Molecular and targeted contrast imaging
- Self-contained intravascular MRI
- Technical properties of the IVMRI catheter
- References
Magnetic resonance imaging (MRI) is being increasingly recognized as a potential approach for the quantitation of vascular plaque burden and assessment of lesion composition (1). An advantage of such noninvasive strategies is the inherently lower risk afforded by avoidance of catheter manipulation, systemic effects of contrast agents, and unnecessary X-ray exposure. Although angiography is an excellent tool to determine the degree and extent of luminal narrowing, it cannot detect early lesion development when luminal area is maintained by positive vascular remodeling. This is an important limitation of angiography in that high-grade coronary stenoses are more likely to produce stable ischemia, but lesions with positive remodeling are often the lesions that cause unstable disease, such as myocardial infarction or death. Magnetic resonance imaging, on the other hand, allows for three-dimensional evaluation of vascular structures and outstanding depiction of various components of the atherothrombotic plaque, including lipid, fibrous tissue, calcium, and thrombus formation (2). Finally, combining MRI with cellular and molecular targeting may provide important data on the biological activity of potentially vulnerable lesions (i.e., cap thickness, lipid content, and the presence of activated macrophages, tissue factor, or integrins).
Currently, the feasibility of external field MRI to diagnose vulnerable plaques in coronary arteries has not been demonstrated, given limitations of the technique. However, MRI has been used to determine plaque size and composition in aortae and carotid arteries, and MRI-guided coronary catheterization has been performed in experimental models (3). Accordingly, this review will describe and highlight the role of conventional and intravascular MRI methods in the assessment of morphology and plaque vulnerability and describe the potential for novel cellular and molecular imaging techniques to contribute additive in vivo information on coronary artery plaque biology.
MRI techniques
Magnetic resonance imaging essentially evaluates the differential biophysical response of the interrogated tissue to an electromagnetic radiofrequency (RF) pulse application within a strong, static magnetic field. Application of a magnetic field to biologic tissues leads to a net alignment of the proton spins within the body along the direction of the magnetic field. These protons absorb energy when a short RF pulse is applied. The RF energy is subsequently released as the excited protons return to their original equilibrium state. The rate of energy release is determined by the spin-lattice relaxation time, called T1. In addition, the spins dephase at a specific rate determined by the spin-spin relaxation time, measured as T2. Both the T1 and the T2 relaxation times are dependent on tissue composition and the local spin environment. The relative contribution of T1 and T2 in the reconstructed image can be controlled with sequence repetition time or echo time imaging parameters. In addition, a proton-density (PD)-weighted image can be obtained by adjusting imaging parameters to reduce the T1 and T2 contributions, leaving only the differences in water or lipid PDs. These three different imaging contrasts (T1, T2, and PD), along with a time-of-flight (TOF) scan, are used to determine plaque composition. The TOF scan exploits the principle of moving blood (protons) that causes a detectable flow disturbance—even in areas of very slow flow—and produces a three-dimensional image limited to moving blood within vessels in an image plane.
A major challenge in high-resolution, in vivo imaging is the achievable signal-to-noise ratio (SNR). Recent advances in hardware, pulse sequences, and imaging approaches for plaque evaluation have improved the SNR, allowing the assessment of the morphology and composition of vascular plaques. Novel techniques, such as the black-blood pulse sequence and the use of phased-array receiver coils, have been developed to improve the arterial lumen-vascular wall contrast critical for lesion delineation. Black-blood pulse sequence refers to suppression of the blood signal to provide high contrast between the lumen and the vessel wall. Placement of multiple receiver coils circumferentially aligned in close proximity to the artery (phased-array receiver coils) increases the overall detection sensitivity and, ultimately, the image SNR. With such coil arrays, high-resolution images of the carotid arteries (<400 μm and 2- to 3-mm slice thickness) are now routinely obtained, and multiple scans with different contrast weightings can be achieved with sufficient image quality.
Limitations of MRI for coronary artery imaging
The MRI evaluation of coronary vessels is considerably more difficult than imaging either carotid arteries or the aorta. As distance between the MRI coil and the interrogated structure increases, the SNR decreases, resulting in a reduction in the image quality. The deep intrathoracic position of the coronary arteries (4 to 10 cm from the surface) and the difficulty with optimal receiver coil placement makes attaining sufficient SNR a major challenge. Geometric considerations, including the smaller dimensions of the coronary arterial wall and the tortuous and irregular course of the vessels, further exacerbate the problem, since higher spatial resolution is required for accurate plaque volume quantification and classification. Partial volume effects from relatively thick slices or large in-plane pixel widths can cause an overestimation of the wall thickness and lesion size. Most importantly, motion effects due to cardiac and diaphragmatic motion limit the success of multi-slice reconstruction techniques, and so both respiratory and cardiac gating are necessary to prevent motion artifacts. Acquiring the image during one or more breath-holds can reduce this limitation, although whole-heart, single breath-hold techniques have not been optimized. However, prospective diaphragmatic navigator gating and real-time imaging (4 and 5) have resulted in more rapid image acquisition.
Double-inversion black-blood techniques have also been used for imaging coronary arteries. With dedicated phased-array cardiac receiver coils and further optimization of black-blood pulse sequences, high-resolution imaging of coronary lesions may be possible (6). Higher field strength afforded by a new generation of whole-body scanners (≥3-T) increases the SNR and can be utilized to achieve higher spatial resolution for improved measurement accuracy, detection sensitivity, or reduced scan time. An SNR improvement of 2, for example, could potentially be used to lower the scan time by a factor of 4 or increase the in-plane resolution by a factor of √2. Botnar et al. (7) demonstrated high-quality images of the human coronaries and vessel wall pathology at 3-T, while Ruff et al. (8) have imaged mouse coronary arteries using a 7-T magnet. Nonetheless, current techniques are limited primarily to the major epicardial coronary arteries, and additional studies are needed to validate the accuracy of the current strategies. In addition, new challenges to image quality exist at high fields, such as susceptibility artifacts, that ultimately limit the practicality of moving to larger field systems.
Multiple contrast MRI for plaque characterization
The possible role of MRI for noninvasive assessment of plaque morphology and content has been demonstrated in several investigations (9, 10, 11, 12 and 13). Martin et al. (9) showed that the transverse relaxation time T2 can be used to discriminate between medial and adventitial layers of the arterial wall, as well as to detect intimal thickening at early stages of the atherosclerotic process. Toussaint et al. (10) found that T2-weighted imaging could discriminate between the collagenous cap and lipid core of atherosclerotic lesions. For plaque tissue characterization, a combination of TOF, PD, and T1- and T2-weighted scans can help determine the presence of calcifications, necrotic cores, and recent hemorrhage in carotid arteries (11 and 12) (Table 1). Figure 1 shows in vivo images of the carotid arteries with different contrast weightings, including TOF and T1-, T2-, and PD-weighted black-blood images, permitting discrimination of plaque components in various stages of lesion development.
Table 1. Plaque Characterization of the Carotid Artery Based on Multiple Contrast Weightings PD = proton density; TOF = time of flight.
Intensities are relative to that of the sternocleidomastoid muscle. Modified, with permission, from Saam T, et al. Quantitative evaluation of carotid plaque composition by in vivo MRI. Arterioscler Thromb Vasc Biol 2005;25:1–6. View Within Article
Figure 1. (A) A small eccentric plaque within the carotid thought to be composed of fibrous tissue (FT) (dark in time of flight [TOF], moderate/high in both T1- and proton density (PD)-weighted images) indicates a type III plaque. (B) A carotid plaque consisting of both lipid and fibrous tissue, with a region of calcium deposits (Ca) indicative of a type IV to V plaque. (C) A carotid lesion with recent intraplaque hemorrhage (arrows) demonstrating high signal intensity on all sequences, and no evidence of plaque rupture with a thick fibrous cap surrounding the lumen (arrowhead). Figure 1C reproduced, with permission, from Kampschulte et al. (12).
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Intravascular coils
One approach to interrogate deeper-lying arteries, such as coronary arteries, is placement of an intravascular coil. Using a custom intravascular coil, Correia et al. (13) demonstrated that MRI results correlated well with histology and luminal area from isolated human thoracic aortic segments. Fibrous cap recognition was observed in 20 of 24 plaques, and a necrotic core in 23 of 24. In human carotid plaques, signal property differences between fibrous cap, lipid, and calcium has been shown ex vivo with an intravascular coil (14). Currently the use of intravascular coils is limited by the invasive nature of the diagnostic approach, the size of the catheter, and the time-consuming imaging protocols. Also, an important safety issue is the potential for local vessel wall heating using in vivo coils, particularly at high field strengths. While moving blood may dissipate some heating effects, small vessels such as the coronary arteries may be more susceptible to temperature rises under the intense RF administration needed for full tissue characterization and anatomic depiction. Hence, before these techniques are adopted, a lack of significant vessel wall heating must be demonstrated.
Use of MRI to evaluate atherosclerosis progression and regression and changes in plaque composition
Magnetic resonance imaging has been used to diagnose and follow the development of in vivo atherosclerotic lesions. In rabbits, T2-weighted MRI documented aortic lesion regression and a decrease in the atherosclerotic plaque lipid components after withdrawal of the atherosclerotic diet. In animals continued on a high-cholesterol diet, progression of disease and increased lipid deposition has been observed (15 and 16). Regression in vessel wall thickness in an atherosclerotic rabbit model treated with a peroxisomal proliferator-activated receptor-gamma agonist and simvastatin has also been shown (17).
Clinically, MRI can quantify and serially follow arterial remodeling and the diffuse thickening of the coronary arterial wall (18 and 19) (Fig. 2). Corti et al. (20) demonstrated a decrease in plaque size in atherosclerotic segments of the aorta and carotid artery in asymptomatic patients treated with a statin. An increase in lumen area was seen at 18 and 24 months after therapy, secondary to decreased plaque size and vascular remodeling (21). Zhao et al. (22) used MRI in a case-control study of carotid disease to demonstrate that patients treated with intensive lipid-lowering therapy and experiencing resulting lower low-density lipoprotein (LDL) and higher high-density lipoprotein (HDL) levels, had decreased plaque lipid content and a smaller lipid core area. Decreased lipid plaque content has been associated with more stable atherosclerotic lesions. Lima et al. (23) recently demonstrated the utility of combined surface and transesophageal magnetic resonance imaging (TE-MRI) in the assessment of aortic plaque regression after six months of simvastatin therapy. A 12% reduction in both plaque volume and plaque area was observed, associated with a reduction in mean LDL levels.
Figure 2. Double-inversion fast spin echo black-blood images of the right coronary artery (arrow) in a normal subject. (A) Without fat suppression; (B) with fat saturation applied (inset: magnified). The vessel wall is more clearly visible in the fat-saturated images. Each image was acquired during a single 20-s breath-hold scan using a single 3-inch surface receiver coil.
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Molecular and targeted contrast imaging
An exciting area of MRI research has been the use of noninvasive MRI techniques for molecular and targeted contrast imaging. These methods permit the detection of specific molecular markers or substances commonly found in vulnerable plaques. Conventional (non-targeted) gadolinium-containing intravenous contrast agents can improve detection of intravascular plaque (24 and 25), identify plaques with increased vascularity (26), and identify the fibrous cap in aortic plaques (27). Gadolinium-based moieties remain the only clinically approved contrast agents, although several new derivatives are proving useful for targeted plaque imaging. Gadofluorine M (Gad M) appears to have strong uptake and retention in the extracellular matrix of plaques (28) and has been shown to produce enhancement in the aortic wall of hyperlipidemic rabbits (29), a marker of lipid-rich plaque (30) (Fig. 3).
Figure 3. Magnetic resonance images of a diseased rabbit abdominal aorta in the sagittal (A) and transverse (B) planes and corresponding histopathology. Panel A demonstrates diffuse and heterogeneous aortic plaque enhancement longitudinally from the renal artery to the distal segment 24 h after gadofluorine injection. Three slice locations (1, 2, 3) were used for transverse magnetic resonance images (B) and H&E staining (C). (B) Differences in signal intensity vary with slice location, and reflect differing plaque composition, with greater enhancement in sections with larger lipid content. (D) Corresponding histopathological sections, and plaque composition. In slice 2, a large lipid core corresponds to greatest plaque enhancement. Plaque at level 3 has a large lipid content with corresponding well with the greatest plaque enhancement. Ad = adventitia; F = loose fibrous tissue; FC = fibrous cap; L = lumen; LC = lipid core; M = macrophages. Reproduced, with permission, from Sirol et al. (30).
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In order to image the often very small amount of plaque-related substances, contrast agents must carry a large number of imageable material combined with antibodies or peptides that can bind to the target region. A number of novel targeted agents have been recently produced for imaging of plaque components associated with vulnerable lesions. Ultra-small particles of iron oxide (USPIOs) administered intravenously are retained in intraplaque macrophages (31 and 32). In vivo plaque imaging using these nanoparticles in humans has shown diffuse involvement within the aorta (33), with USPIO uptake present in 75% of ruptured or vulnerable plaques but in only 7% of stable plaques. Recently, Li et al. (34) reported on a dual-labeled contrast agent (PTIR267) with fluorescent and gadolinium-based components that provided in vivo detection of LDL receptors. Using labeled LDL, normal livers showed significant contrast enhancement, while LDL receptor gene knockout mice demonstrated markedly reduced enhancement effect. Current studies are ongoing to evaluate whether such an approach can be used to determine the presence of vascular lesions with increased LDL concentration or as a “Trojan horse” for treatment of vulnerable plaques. Recombinant gadolinium-labeled human HDL nanoparticles as an endogenous contrast agent are a novel approach to atherosclerosis imaging. Since HDL can enter atherosclerotic plaques, no additional targeting mechanisms are necessary. Peak contrast effect—reflecting accumulation in the intimal layer—occurred 24 h after intravenous injection in apoE-knockout mice, and the mean enhancement of vessel plaque was 35% greater than surrounding muscle (35). Enhancement was also related to underlying plaque composition, with greater enhancement in more cellular lesions. Thus, these new particles may permit use of endogenous biological transport systems to enhance plaque lipids, and perhaps to deliver therapeutic agents in the future.
Several tissue-specific agents are in development for MRI-based applications in vulnerable plaque assessment. Tissue factor expression has been imaged using a specific magnetic resonance contrast agent (36). Tissue factor is normally present in the subendothelial space, but in atherosclerosis, tissue factor has been demonstrated in virtually all cell types within an atheroma as well as circulating leucocytes. Hence, a more quantitative approach to determine pathologic tissue factor expression levels within higher risk lesions will be necessary. Another novel set of nanoparticle agents target the αvβ3 integrin (Fig. 4) in order to assess angiogenesis within plaques exhibiting neovascularization (37 and 38). Plaque-affected walls showed significantly greater enhancement using targeted versus non-targeted nanoparticles, and enhancement has correlated well with histological demonstration of the presence of greater αvβ3 integrin concentration. Endothelial vascular cell adhesion molecule-1 expression has also been imaged with MRI (39).
Figure 4. (Top) A set of in vivo spin echo images was reformatted to display a long-axis view of a diseased aorta from a hypercholesterolemic rabbit model. Orientation is from renal artery level (left) to diaphragm (right) and at single transverse slices (bottom) before (pre) and 120 min after (post) infusion of αvβ3-integrin targeted gadolinium-carrying perfluorocarbon nanoparticles. Semiautomated segmentation (segmented, grayish ring, panel 3) and color-coded signal enhancement (enhancement) above baseline (in percent) are shown. Reprinted, with permission, from Winter et al. (37).
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Given the important role of intravascular thrombus formation in acute vascular disease, a number of MR contrast agents have been developed specifically to detect substances associated with the coagulation cascade. Botnar et al. (40) showed that molecular imaging using a fibrin-specific binding contrast agent detected acute and subacute thrombi in a rabbit atherosclerotic model. Winter et al. (41) developed a fibrin-targeted, lipid-encapsulated perfluorocarbon nanoparticle linked to gadolinium that binds vigorously to thrombus and may be useful as a clinical agent, if demonstrated in vivo. Activated platelets have been imaged using a USPIO agent targeted to the αIIbβ3 receptor, and Factor XIIIa has been detected using custom iron oxide particles. While these latter two agents can only bind to the surface of thrombi, and therefore only create a modest contrast effect, a newer peptide that can infiltrate thrombus has been developed, improving potential clinical applications (42).
Self-contained intravascular MRI
One approach to take advantage of MRI’s ability to differentiate various tissue characteristics while bypassing limitations inherent in external coil MRI is a self-contained MRI probe. Previous studies using MR have demonstrated differential water diffusion coefficients within the atherosclerotic plaque lipid core compared to the collageneous cap and medial smooth-muscle layers (43). Intravascular MRI (IVMRI) makes use of these differences to determine the extent and location of increased vascular lipid infiltration (Fig. 5). Thin fibrous cap atheromas, considered vulnerable lesions, are thought to contain a high lipid content within the superficial areas of the arterial wall (<250 μm), indicating little presence of smooth-muscle cells or extracellular matrix within the cap. Conversely, the presence of either high extracellular matrix content or smooth-muscle-cell rich tissue is thought to indicate the presence of a stable, non-vulnerable lesion. This catheter offers superior spatial resolution compared to conventional MRI. Whereas the conventional MRI can obtain images of the coronary artery in a rectangular grid with an approximate 0.46-mm planar resolution and 2- to 5-mm slice thickness, the IVMRI obtains an image in a cylindrical-type grid with z resolution of approximately 1.5 mm and an angular resolution of 60° (44). The IVMRI probe provides a radial resolution of 250 μm.
Figure 5. Apparent diffusion constants obtained by magnetic resonance from human aortic samples containing normal fibrous tissue, fatty streaks, and complex lipid-laden lesions are seen in photomicrographs. The apparent diffusion constant shows clear difference between the fibrous and lipid-rich tissue, with overlap noted between lipid-rich and fatty streak tissue (studies performed in collaboration with Dr. Renu Virmani).
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Technical properties of the IVMRI catheter
The system consists of a catheter containing an integrated MRI probe containing the magnets, RF coil, and electronics at its tip, connected to a portable control unit. Since it has no external magnets or coils, the system is transportable and studies can be performed in the cardiac catheterization laboratory. In order to eliminate motion artifacts, a balloon, placed opposite the RF coil, is inflated to juxtaposition the probe over the arterial segment in question. Two bands are obtained simultaneously, a shallow luminal band 0 to 100 μm and a deeper band 100 to 250 μm in depth (Fig. 6). Preliminary experiments with the MRI probe in carotid endarterectomy plaques demonstrated that lipid-rich tissue could be differentiated from fibrous tissue with a sensitivity of 90% (J. Schneiderman, MD, unpublished results, 2001).
Figure 6. Intravascular magnetic resonance imaging (IVMRI) results in ex vivo human coronary arteries. Intermediate lesions on coronary angiography underwent interrogation with the IVMRI probe. Top row shows the lesions on postmortem angiography. The arrows point (left to right) to lesions in the intermediate, right coronary, and left anterior descending arteries. The middle row shows the histology of these lesions, indicating a stable plaque on the left, a stable plaque with a deep necrotic core (+) in the middle, and a thin fibrous-cap atheroma (TFCA) on the right (necrotic core, *). The bottom row is the corresponding IVMRI results, indicating (left to right) no substantial lipid deposition, lipid deposit/necrotic core deep within the arterial cross-section, and a TFCA with increased lipid deposition noted in three of four deep bands (yellow) and two of four superficial bands. Adapted from Schneiderman et al. (45).
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Proof of concept of the IVMRI catheter to analyze vascular composition in human vascular tissues has been shown in studies of fresh postmortem human aortas and coronary arteries of patients dying of presumed vascular causes (45). There was a strong correlation of the MRI data with histology (ulcerated plaques, thin fibrous cap atheromas, thick fibrous cap atheromas, intimal xanthomas, and adaptive intimal thickening), with a resulting 95% sensitivity and 100% specificity. Further studies were performed in ex vivo hearts with in situ coronary arteries and demonstrated a strong correlation of the IVMRI with histology in intermediate arteries.
Clinical studies with the IVMRI unit have been initiated in patients with intermediate lesions during angiographic assessment or concomitant percutaneous coronary intervention (Fig. 7). Early results indicate that clinical evaluation of coronary artery lipid content is feasible and safe. Future developments may make use of molecular and targeted contrast imaging combined with IVMRI to locate the presence of an increased concentration of macrophages and/or thrombus.
Figure 7. Left anterior descending artery angiogram (A) and intravascular magnetic resonance imaging (IVMRI) (B) of a 77-year old man with unstable angina pectoris. Arrow shows location of the IVMRI interrogation. The IVMRI cross-sectional view demonstrates increased lipid content (yellow) in all three quadrants and both bands (0 to 100 μm and 100 to 250 μm).
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Currently, the evaluation of the safety and potential clinical role of the IVMRI probe is being evaluated in a phase II international, multi-center trial. The combination of MRI and molecular probes is being evaluated clinically, as well. Noninvasive MRI for the evaluation of high-risk thin fibrous cap atheromas in coronary vasculature is still in development.
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Dr. William A. Zoghbi acted as guest editor.
Reprint requests and correspondence: Dr. Robert L. Wilensky, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Gates, Philadelphia, Pennsylvania 19104.a Dr. Wilensky’s potential conflicts of interest are as follows: Scientific Advisory Board member for Topspin Medical (maker of the intravascular MRI device), Medeikon, and Boston Scientific Corp.; stock options in Topspin Medical and Medeikon; equity interest in Johnson & Johnson Company; research grants from Boston Scientific Corporation, GlaxoSmithKline Inc., and Medeikon; Speaker’s Bureau for Pfizer Corp.
b Dr. Ferrari has grant support from Novartis Inc. and Glaxo SmithKline Inc. Copyright © 2006 American College of Cardiology Foundation Published by Elsevier Inc.
Journal of the American College of Cardiology
Volume 47, Issue 8, Supplement 1, 18 April 2006, Pages C48-C56
Detection of Vulnerable Plaques
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