Quantitative X-Ray Imaging of Intraplaque Hemorrhage in Aortas of ApoE−/−/LDL−/− Double Knockout Mice

Objectives:To determine if hemorrhage into an arterial wall can be detected in CT images by virtue of the iron content. Materials and Methods:Aortas from male apoE−/−/LDL−/− mice (n = 31) were infused in situ with contrast agent, for micro-CT scanning and histology. Roentgen-opacities within the aortic walls were identified by histology and micro-x-ray fluorescence to be iron or calcium. Dual-energy scanning was performed at 2 energy levels using synchrotron-based micro-CT [(2 &mgr;m)3 voxels, 16 and 20 keV] and 64-slice CT (0.4 × 0.4 × 0.6 mm voxels, 80 and 120 kVp). Results:Opacities were identified as hemorrhage-related clusters of multiple punctate deposits, containing both Fe (0.48 × 10−12 g/voxel) and Ca (3.18 × 10−2 g/voxel), or as isolated confluent accumulations of exclusively calcium. Subtraction of the dual-energy CT scans discriminated iron from calcium deposits. Conclusion:Detection and quantification of iron deposits in hemorrhaged atherosclerotic lesions is feasible by dual-energy CT imaging.

[1]  J. Burda,et al.  Iron Deposition after Transient Forebrain Ischemia in Rat Brain , 2002, Neurochemical Research.

[2]  A Macovski,et al.  An Implementation of Dual Energy CT Scanning , 1984, Journal of computer assisted tomography.

[3]  Erik L Ritman,et al.  Correlation of Vasa Vasorum Neovascularization and Plaque Progression in Aortas of Apolipoprotein E−/−/Low-Density Lipoprotein−/− Double Knockout Mice , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[4]  P. Serruys,et al.  Usefulness of multislice computed tomography for detecting obstructive coronary artery disease. , 2002, The American journal of cardiology.

[5]  R. Günther,et al.  Coronary Calcium Scoring Using 16-Row Multislice Computed Tomography: Nonenhanced Versus Contrast-Enhanced Studies In Vitro and In Vivo , 2005, Investigative radiology.

[6]  W D Wagner,et al.  A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[7]  Erik L Ritman,et al.  Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE-/-/LDL-/- double knockout mice. , 2007, Atherosclerosis.

[8]  J. Jukema,et al.  Lesional Overexpression of Matrix Metalloproteinase-9 Promotes Intraplaque Hemorrhage in Advanced Lesions But Not at Earlier Stages of Atherogenesis , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[9]  K. Stierstorfer,et al.  First performance evaluation of a dual-source CT (DSCT) system , 2006, European Radiology.

[10]  C Georg,et al.  Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography. , 2001, Journal of the American College of Cardiology.

[11]  Aloke V. Finn,et al.  Atherosclerotic Plaque Progression and Vulnerability to Rupture: Angiogenesis as a Source of Intraplaque Hemorrhage , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[12]  Naoyuki Yokoyama,et al.  Accuracy of Attenuation Measurement of Vascular Wall In Vitro on Computed Tomography Angiography: Effect of Wall Thickness, Density of Contrast Medium, and Measurement Point , 2006, Investigative radiology.

[13]  Pedro A. Lemos,et al.  Reliable Noninvasive Coronary Angiography With Fast Submillimeter Multislice Spiral Computed Tomography , 2002, Circulation.

[14]  Gieri Cathomas,et al.  Arterial Neovascularization and Inflammation in Vulnerable Patients: Early and Late Signs of Symptomatic Atherosclerosis , 2004, Circulation.

[15]  A. Barger,et al.  Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. , 1984, The New England journal of medicine.

[16]  S. Achenbach,et al.  Computed tomography of the coronary arteries: more than meets the (angiographic) eye. , 2005, Journal of the American College of Cardiology.

[17]  Richard D. White,et al.  Noninvasive imaging of coronary arteries: current and future role of multi-detector row CT. , 2004, Radiology.

[18]  Stefan Vogt,et al.  Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. , 2005, Journal of the National Cancer Institute.

[19]  Paul J. Thomas,et al.  Synchrotron-based micro-CT of in-situ biological basic functional units and their integration , 1997, Optics & Photonics.

[20]  Renu Virmani,et al.  Intraplaque hemorrhage and progression of coronary atheroma. , 2003, The New England journal of medicine.

[21]  Noninvasive quantitation of liver iron in dogs with hemochromatosis using dual-energy CT scanning. , 1982, Investigative radiology.

[22]  D. Woolley,et al.  Local neovascularization and cellular composition within vulnerable regions of atherosclerotic plaques of human carotid arteries , 1999, The Journal of pathology.

[23]  Konstantin Nikolaou,et al.  Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound. , 2006, Journal of the American College of Cardiology.

[24]  Wei Li,et al.  Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis. , 1996, Atherosclerosis.

[25]  D. Blanchard,et al.  Fine Characterization of a Series of New Monoclonal Antibodies Directed against Glycophorin A , 1997, Vox sanguinis.

[26]  D. Woolley,et al.  Neovascularization in early atherosclerotic lesions of human carotid arteries: its potential contribution to plaque development. , 1999, Human pathology.

[27]  Renu Virmani,et al.  Pathology of the vulnerable plaque. , 2007, Journal of the American College of Cardiology.

[28]  C. Becker.  Noninvasive assessment of coronary atherosclerosis by multidetector-row computed tomography , 2004, Expert Review of Cardiovascular Therapy.

[29]  S. Achenbach,et al.  Noncalcified and calcified coronary plaque detection by contrast-enhanced multi-detector computed tomography: a study of interobserver agreement. , 2006, Journal of the American College of Cardiology.

[30]  W. Bautz,et al.  Detection of Coronary Artery Stenoses With Thin-Slice Multi-Detector Row Spiral Computed Tomography and Multiplanar Reconstruction , 2003, Circulation.

[31]  R. Bohle,et al.  Atherosclerotic lesions at micro CT: feasibility for analysis of coronary artery wall in autopsy specimens. , 2004, Radiology.

[32]  S. Achenbach,et al.  Relation between coronary calcium and 10-year risk scores in primary prevention patients. , 2003, The American journal of cardiology.

[33]  Tzong-Shyuan Lee,et al.  Erythrophagocytosis and iron deposition in atherosclerotic lesions. , 1999, The Chinese journal of physiology.

[34]  K. Stierstorfer,et al.  Image reconstruction and image quality evaluation for a 64-slice CT scanner with z-flying focal spot. , 2005, Medical physics.

[35]  M. Ono,et al.  Severe Hypercholesterolemia, Impaired Fat Tolerance, and Advanced Atherosclerosis in Mice Lacking Both Low Density Lipoprotein Receptor-related Protein 5 and Apolipoprotein E* , 2003, The Journal of Biological Chemistry.

[36]  Udo Hoffmann,et al.  Quantitative parameters of image quality in 64-slice computed tomography angiography of the coronary arteries. , 2006, European journal of radiology.