Response to 'Laurberg JM, Olsen AK, Hansen SB, et al. Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation' [Atherosclerosis 2006].
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Adipose Tissue, Brown↗
Biomedical subjects
Z A Fayad
Publications and source records attributed to Z A Fayad.
Characterization of aortic root atherosclerosis in ApoE knockout mice: high-resolution in vivo and ex vivo MRM with histological correlation.
In vivo, cardiac-gated, black-blood, and ex vivo magnetic resonance microscopy (MRM) images of the aortic root, and histopathology data were obtained from 12 transgenic and wild-type (WT) mice. MRM was performed using a black-blood imaging spin-echo sequence with upstream and downstream in-flow saturation pulses to obtain aortic root images in three contrast techniques: proton density-weighted (PDW), T(1)- (T(1)W), and T(2)-weighted (T(2)W). Aortic wall thickness and area were measured and correlated with histopathology data (R > 0.90). Ex vivo lesion components (lipid core, fibrous tissue, and cell tissue) were identified and characterized by differing image contrast in PDW, T(1)W, and T(2)W MRM, and by histopathology. The differences between WT and transgenic mice for maximal wall thickness and area were statistically significant (P < 0.05). This study demonstrates the feasibility of in vivo murine aortic root lesion assessment and ex vivo plaque characterization by MRM.
Animals↗
Integration of vascular biology and magnetic resonance imaging in the understanding of atherothrombosis and acute coronary syndromes.
The interaction between the vulnerable atherosclerotic plaque prone to disruption and thrombus formation is the cornerstone of acute coronary syndrome (ACS). Although distinct from one another, the atherosclerotic and thrombotic processes appear to be interdependent, hence the term atherothrombosis. Inflammation is a crucial common pathophysiological mechanism. Overall, the association of plaque vulnerability and ACS has been well documented. Given the multifactorial origin of atherothrombosis the best preventive approach should be aggressive management of all the risk factors. New interventions should be directed toward decreasing vulnerability of the lesions thereby decreasing the risk of ACS.
Animals↗
Molecular imaging for the diagnosis of high-risk plaque.
Despite advances in our understanding of the pathogenesis of atherosclerosis and new therapeutic modalities, the absence of an adequate method for early detection limits the prevention and treatment of the disease. High-resolution magnetic resonance has recently emerged as one of the most promising techniques for the non-invasive study of atherothrombotic disease, as it can characterize plaque composition and monitor progression. This review of plaque imaging focuses on the most recent technique: "molecular imaging", which uses specific contrast agents targeted to plaque components, and may allow for better stratification of "high-risk" plaque and "high-risk" patients.
Arteriosclerosis↗
Clinical imaging of the high-risk or vulnerable atherosclerotic plaque.
The study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of disease progression and regression and aid in selecting appropriate treatments. Several invasive and noninvasive imaging techniques are available to assess atherosclerotic vessels. Most of the standard techniques identify luminal diameter, stenosis, wall thickness, and plaque volume; however, none can characterize plaque composition and therefore identify the high-risk plaques. We will present the different imaging modalities that have been used for the direct assessment of the carotid, aortic, and coronary atherosclerotic plaques. We will review in detail the use of high-resolution, multicontrast magnetic resonance for the noninvasive imaging of vulnerable plaques and the characterization of plaques in terms of their various components (ie, lipid, fibrous, calcium, or thrombus).
Angioscopy↗
The human high-risk plaque and its detection by magnetic resonance imaging.
The study of atherosclerotic disease during its natural history and after therapeutic intervention will enhance our understanding of the progression and regression of this disease and will aid in selecting the appropriate treatments. Several invasive and noninvasive imaging techniques are available to assess vessels in atherosclerotic disease. Most of the standard techniques, however, identify luminal diameter or stenosis, wall thickness, or plaque volume. None of the standard techniques can characterize the composition of an atherosclerotic plaque and therefore are incapable of identifying the high-risk plaques. High-resolution, multicontrast, magnetic resonance imaging (MRI) can noninvasively image vulnerable plaques and characterize plaques in terms of their different components (ie, lipid, fibrous, calcium, or thrombus). Application of MRI opens up whole new areas for diagnosis, prevention, and treatment of atherosclerosis.
Aged↗
Effects of lipid-lowering by simvastatin on human atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging.
BACKGROUND: This study was designed to investigate the effects of lipid-lowering by simvastatin on human atherosclerotic lesions. METHODS AND RESULTS: Eighteen asymptomatic hypercholesterolemic patients with documented aortic and/or carotid atherosclerotic plaques were selected for the study. A total of 35 aortic and 25 carotid artery plaques were detected. Serial black-blood MRI of the aorta and carotid artery of the patients was performed at baseline and 6 and 12 months after lipid-lowering therapy with simvastatin. The effects of the treatment on atherosclerotic lesions were measured as changes in lumen area, vessel wall thickness, and vessel wall area, a surrogate of atherosclerotic burden. Simvastatin induced a significant (P<0.01) reduction in total and LDL cholesterol levels at 6 weeks that was maintained thereafter. At 6 months, no changes in lumen area, vessel wall thickness, or vessel wall area were observed. However, at 12 months, significant reductions in vessel wall thickness and vessel wall area, without changes in lumen area, were observed in both aortic and carotid arteries (P<0.001). CONCLUSIONS: This in vivo human study demonstrates that effective and maintained lipid-lowering therapy by simvastatin is associated with a significant regression of atherosclerotic lesions. Our observation suggests that statins induce vascular remodeling, as manifested by reduced atherosclerotic burden without changes in the lumen.
Aorta↗
Artery dissection and arterial thrombus aging: the role of noninvasive magnetic resonance imaging.
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Animals↗
Atherosclerotic aortic component quantification by noninvasive magnetic resonance imaging: an in vivo study in rabbits.
OBJECTIVES: We sought to demonstrate the ability that noninvasive in vivo magnetic resonance imaging (MRI) has to quantify the different components within atherosclerotic plaque. BACKGROUND: Atherosclerotic plaque composition plays a critical role in both lesion stability and subsequent thrombogenicity. Noninvasive MRI is a promising tool for the characterization of plaque composition. METHOD: Thoracic and abdominal aortic atherosclerotic lesions were induced in rabbits (n = 5). Nine months later, MRI was performed in a 1.5T system. Fast spin-echo sequences (proton density-weighted and T2-weighted [T2W] images) were obtained (in-plane resolution: 350 x 350 microns, slice thickness: 3 mm). Magnetic resonance images were correlated with matched histopathological sections (n = 108). RESULTS: A significant correlation (p < 0.001) was observed for mean wall thickness and vessel wall area between MRI and histopathology (r = 0.87 and r = 0.85, respectively). The correlation was also present on subanalysis of the thoracic and upper part of the abdominal aorta, susceptible to respiratory motion artifacts. There was a significant correlation for plaque composition (p < 0.05) between MRI and histopathology for the analysis of lipidic (low signal on T2W, r = 0.81) and fibrous (high signal on T2W, r = 0.86) areas with Oil Red O staining. T2-weighted images showed greater contrast than proton density-weighted between these different components of the plaques as assessed by signal intensity ratio analysis with the mean difference in signal ratios of 0.47 (S.E. 0.012, adjusted for clustering of observations within lesions) being significantly different from 0 (t1 = 39.1, p = 0.016). CONCLUSIONS: In vivo noninvasive high resolution MRI accurately quantifies fibrotic and lipidic components of atherosclerosis in this model. This may permit the serial analysis of therapeutic strategies on atherosclerotic plaque stabilization.
Animals↗
The assessment of the vulnerable atherosclerotic plaque using MR imaging: a brief review.
The study of atherosclerotic disease during its natural history and after therapeutic intervention may enhance our understanding of the progression and regression of this disease and will aid in selecting the appropriate medical treatments or surgical interventions. Several invasive and non-invasive imaging techniques are available to assess atherosclerotic disease vessels. Most of these techniques are strong in identifying the morphological features of the disease such as lumenal diameter and stenosis or wall thickness, and in some cases provide an assessment of the relative risk associated with the atherosclerotic disease. However, none of these techniques can fully characterize the composition of the atherosclerotic plaque in the vessel wall and therefore are incapable of identifying the vulnerable plaques. High-resolution, multi-contrast, magnetic resonance (MR) can non-invasively image vulnerable plaques and characterize plaques in terms of lipid and fibrous content and identify the presence of thrombus or calcium. Application of MR imaging opens up whole new areas for diagnosis, prevention, and treatment of atherosclerosis.
Animals↗
Cardiac gated breath-hold black blood MRI of the coronary artery wall: an in vivo and ex vivo comparison.
BACKGROUND: High resolution magnetic resonance (MR) imaging of the coronary artery wall in vivo has been limited by the cardiac and respiratory motion, flow artifacts as well as the relatively small size of the coronary arteries. We sought to validate in vivo black blood MR imaging of the coronary artery wall using a double inversion recovery fast spin echo MR imaging sequence with limited breath-holding and cardiac gating for suppression of motion artifacts by comparison with ex vivo MR imaging. METHODS: Yorkshire albino swine (n = 6) were used in this study and coronary lesions were induced with balloon angioplasty. Four weeks after balloon injury of the coronary arteries MR imaging of the coronary artery lesions was performed. High resolution in vivo and ex vivo images of the coronary artery wall and lesions were obtained using a double inversion recovery fast spin echo sequence in a 1.5 T MR system. There was a statistically significant agreement (p < 0.0001) between measurements of vessel wall area (r = 0.87, slope = 0.87) and maximal wall thickness (r = 0.84, slope = 0.88) from in vivo and ex vivo MR images of the coronary arteries. The mean differences between in vivo and ex vivo measurements were 0.56 +/- 1.98 mm2 for vessel wall area and 0.02 +/- 0.36 mm for maximal wall thickness. CONCLUSIONS: Using breathholding and cardiac gating, it is possible to perform high resolution MR imaging of the coronary artery wall in vivo with good suppression of motion artifacts with a double inversion recovery fast spin echo black blood imaging sequence.
Animals↗
Dramatic remodeling of advanced atherosclerotic plaques of the apolipoprotein E-deficient mouse in a novel transplantation model.
OBJECTIVE: Regression of atherosclerotic lesions is an important goal. No extensive experimental evidence shows that it can be achieved for advanced lesions. To study this, we developed a model to maintain a long-term change in the plasma lipoprotein environment of advanced arterial lesions of hyperlipidemic (apolipoprotein E [apoE]-deficient) mice. METHODS: The apoE-deficient mice (plasma total cholesterol of 1334 +/- 219 [+/- SEM] mg/dL) on a typical Western diet for 38 weeks had advanced atherosclerotic lesions (ie, beyond the macrophage foam cell stage) throughout the arterial tree. Lesion-containing thoracic aortas were transplanted (replacing a segment of abdominal aorta) into either apoE-deficient or wild-type (WT) (total cholesterol of 86 +/- 10 mg/dL) recipients. Grafts were harvested after 9 weeks. RESULTS: Compared with pretransplant lesions (area = 0.0892 +/- 0.0179 mm(2)), lesion size tended to increase in apoE-deficient to apoE-deficient grafts (0.2411 +/- 0.0636 mm(2); P =.06), whereas a significant reduction was seen in apoE-deficient to WT grafts (0.0214 +/- 0.0049 mm(2); P <.001). Also, foam cells were absent in apoE-deficient to WT grafts, but abundant in pretransplant lesions and apoE-deficient to apoE-deficient grafts. Grafts were evaluated noninvasively in vivo with magnetic resonance imaging, and wall thickening was detected in the apoE-deficient to apoE-deficient group. CONCLUSIONS: Nearly complete regression of advanced atherosclerotic lesions can be achieved with sustained normalization of the plasma lipoprotein profile. Syngeneic arterial transplantation in mice is a novel and valuable model system for atherosclerosis research; and magnetic resonance imaging can detect differences in characteristics in lesions undergoing regression.
Animals↗
New understanding of atherosclerosis (clinically and experimentally) with evolving MRI technology in vivo.
Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in industrialized countries. Despite advances in our understanding of the pathogenetic mechanisms and new treatment modalities, the absence of an adequate noninvasive method for early detection limits the prevention or treatment of patients with various degrees and localizations of atherothrombotic disease. High-resolution magnetic resonance (MR) has recently emerged as one of the most promising techniques for the noninvasive study of atherothrombotic disease. Most importantly, MR can be used to characterize plaque composition and monitor progression. Thus, MR opens new strategies, ranging from the screening of high-risk patients for early detection and treatment as well as the monitoring of target areas for pharmacological intervention.
Animals↗
Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging.
BACKGROUND: High-resolution MRI has the potential to noninvasively image the human coronary artery wall and define the degree and nature of coronary artery disease. Coronary artery imaging by MR has been limited by artifacts related to blood flow and motion and by low spatial resolution. METHODS AND RESULTS: We used a noninvasive black-blood (BB) MRI (BB-MR) method, free of motion and blood-flow artifacts, for high-resolution (down to 0.46 mm in-plane resolution and 3-mm slice thickness) imaging of the coronary artery lumen and wall. In vivo BB-MR of both normal and atherosclerotic human coronary arteries was performed in 13 subjects: 8 normal subjects and 5 patients with coronary artery disease. The average coronary wall thickness for each cross-sectional image was 0.75+/-0.17 mm (range, 0.55 to 1.0 mm) in the normal subjects. MR images of coronary arteries in patients with >/=40% stenosis as assessed by x-ray angiography showed localized wall thickness of 4.38+/-0.71 mm (range, 3.30 to 5.73 mm). The difference in maximum wall thickness between the normal subjects and patients was statistically significant (P<0.0001). CONCLUSIONS: In vivo high-spatial-resolution BB-MR provides a unique new method to noninvasively image and assess the morphological features of human coronary arteries. This may allow the identification of atherosclerotic disease before it is symptomatic. Further studies are necessary to identify the different plaque components and to assess lesions in asymptomatic patients and their outcomes.
Adult↗
Noninvasive in vivo magnetic resonance imaging of experimental coronary artery lesions in a porcine model.
BACKGROUND: The ability to characterize and quantify coronary artery atherosclerotic lesions accurately, reproducibly, and noninvasively may allow the stratification of risk for future acute coronary syndromes and help direct therapeutic management. MRI has been shown to accurately characterize and quantify atherosclerosis; however, because of the combination of cardiac and respiratory motion artifacts, nonlinear course, and relatively small size of the coronary arteries, these techniques have not been able to be translated to the coronary system in vivo. METHODS AND RESULTS: Coronary lesions were induced in Yorkshire albino swine (n=6) with balloon angioplasty, and 4 weeks later MRI of the coronary artery lesions was performed. High-resolution in vivo images of the coronary artery wall and lesions were obtained with a double-inversion-recovery fast-spin-echo sequence in a 1.5-T MR system. There was good agreement between measurements of vessel wall thickness and area from MR images of the coronary arteries and the matched histopathology sections (n=43). The mean difference (MRI minus histopathology +/- SD) for mean wall thickness was 0.26+/-0.18 mm, and for vessel wall area, 5.65+/-3.51 mm(2). MRI was also able to visualize intralesion hematoma (sensitivity 82%, specificity 84%). CONCLUSIONS: Using a clinical MR system, we were able to image coronary artery lesions in vivo in an experimental porcine model. Further studies are needed to assess the ability of MRI to characterize coronary atherosclerotic lesions in vivo.
Animals↗
Images in cardiovascular medicine. Magnetic resonance imaging and asymptomatic aortic dissection.
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Aortic Dissection↗
In vivo magnetic resonance evaluation of atherosclerotic plaques in the human thoracic aorta: a comparison with transesophageal echocardiography.
BACKGROUND: The structure and composition of aortic atherosclerotic plaques are associated with the risk of future cardiovascular events. Magnetic resonance (MR) imaging may allow accurate visualization and characterization of aortic plaques. METHODS AND RESULTS: We developed a noninvasive MR method, free of motion and blood flow artifacts, for submillimeter imaging of the thoracic aortic wall. MR imaging was performed on a clinical MR system in 10 patients with aortic plaques identified by transesophageal echocardiography (TEE). Plaque composition, extent, and size were assessed from T1-, proton density-, and T2- weighted images. Comparison of 25 matched MR and TEE cross-sectional aortic plaque images showed a strong correlation for plaque composition (chi(2) = 43.5, P<0.0001; 80% overall agreement; n = 25) and mean maximum plaque thickness (r = 0.88, n = 25; 4.56+/-0.21 mm by MR and 4.62+/-0.31 mm by TEE). Overall aortic plaque extent as assessed by TEE and MR was also statistically significant (chi(2) = 61.77, P<0.0001; 80% overall agreement; n = 30 regions). CONCLUSIONS: This study demonstrates that noninvasive MR evaluation of the aorta compares well with TEE imaging for the assessment of atherosclerotic plaque thickness, extent, and composition. This MR method may prove useful for the in vivo study of aortic atherosclerosis.
Adult↗
Serial in vivo MRI documents arterial remodeling in experimental atherosclerosis.
BACKGROUND: Arterial remodeling in response to atherosclerosis may be outward (positive) or inward (negative) and is an important mechanism in the clinical manifestations of atherosclerosis and restenosis after percutaneous coronary interventions. Postmortem and intravascular ultrasound studies of arterial remodeling do not allow serial and noninvasive data to be obtained. In a rabbit model of atherosclerosis, we sought to validate MRI as a new tool for documentation of arterial remodeling. METHODS AND RESULTS: Watanabe heritable hyperlipidemic rabbits underwent serial MRI at baseline and 6 months after aortic balloon denudation. The lumen area had a small but significant (P=0.006) increase, from 4.36+/-0.16 to 4. 89+/-0.12 mm(2). There was a large, significant (P<0.0001) increase in the outer wall area, from 7.96+/-0.19 to 10.46+/-0.19 mm(2). The vessel wall area (a marker of atherosclerotic burden) increased significantly (P<0.0001), from 3.61+/-0.07 to 5.57+/-0.09 mm(2). Thus, the increase in atherosclerotic burden over time was completely accounted for by positive arterial remodeling. The subgroup used for histopathological validation confirmed a significant (P<0.0001) agreement between histopathology and MRI for assessment of all 3 parameters. CONCLUSIONS: MRI can provide serial and noninvasive data about the arterial wall, allowing assessment of arterial remodeling in this rabbit model. Thus, MRI appears to be a useful tool for the investigation of arterial remodeling both in native atherosclerosis and after percutaneous coronary intervention.
Animals↗