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MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging
- Robin P. Choudhury,
- Valentin Fuster,
- Juan J. Badimon,
- Edward A. Fisher and
- Zahi A. Fayad
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 22, Issue 71 July 2002

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Noninvasive high-resolution magnetic resonance has the potential to image atherosclerotic plaque and to determine its composition and microanatomy. This review summarizes the rationale for plaque imaging and describes the characteristics of plaque by use of existing MRI techniques. The use of MRI in human disease and in animal models, particularly in rabbits and mice, is presented. Present and future applications of MRI, including real-time vascular intervention, new contrast agents, and molecular imaging, are also discussed.
Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage
- Luigi Sironi,
- Mauro Cimino,
- Uliano Guerrini,
- Anna Maria Calvio,
- Barbara Lodetti,
- Maria Asdente,
- Walter Balduini,
- Rodolfo Paoletti and
- Elena Tremoli
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 23, Issue 21 February 2003

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Objective— In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat.Methods and Results— Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats.Conclusions— Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.
Soluble CD40 Ligand Levels Indicate Lipid Accumulation in Carotid Atheroma: An In Vivo Study With High-Resolution MRI
- Gavin J. Blake,
- Robert J. Ostfeld,
- E. Kent Yucel,
- Nerea Varo,
- Uwe Schönbeck,
- Michael A. Blake,
- Marie Gerhard,
- Paul M. Ridker,
- Peter Libby and
- Richard T. Lee
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 23, Issue 11 January 2003

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Objective— The CD40/CD40 ligand pathway mediates inflammatory processes important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that plasma levels of soluble CD40 ligand are elevated in patients with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI) of carotid stenoses.Methods and Results— We recruited 49 patients with evidence of carotid atherosclerosis on ultrasonography; 3 patients could not undergo carotid MRI because of claustrophobia. The remaining 46 patients underwent high-resolution MRI of the carotid arteries. Two radiologists blinded to all other data determined the presence or absence of an intraplaque lipid pool based on the loss of signal between the 20-ms echo time (TE20) and the fat-suppressed TE55 fast spin-echo images. Plasma levels of soluble CD40 ligand were determined by ELISA. Baseline levels of soluble CD40 ligand were higher among patients with evidence of intraplaque lipid (n=14) than among those without it (n=32; median, 2.54 ng/mL; interquartile range [IQR], 1.85 to 3.52 vs median, 1.58 ng/mL; IQR, 1.21 to 2.39; P=0.02). In contrast, soluble CD40 ligand levels were not correlated with percent diameter stenosis (r=−0.19; P=0.21). The relative risk for intraplaque lipid associated with soluble CD40 ligand levels above the median was 6.0 (95% confidence interval, 1.15 to 31.23; P=0.03). The magnitude of this predictive effect did not substantially change after adjustment for traditional cardiovascular risk factors (relative risk, 5.12; 95% confidence interval, 0.78 to 33.73; P=0.09).Conclusions— Plasma levels of soluble CD40 ligand may predict patients with features of high-risk atherosclerotic lesions. These data provide novel insight into the mechanism through which elevated levels of soluble CD40 ligand may reflect cardiovascular risk in humans and illustrate the potential value of interfacing high-resolution MRI with studies of vascular inflammation.
A Novel Nonobstructive Intravascular MRI Coil: In Vivo Imaging of Experimental Atherosclerosis
- Stephen G. Worthley,
- Gérard Helft,
- Valentin Fuster,
- Zahi A. Fayad,
- Meir Shinnar,
- Lawrence A. Minkoff,
- Clyde Schechter,
- John T. Fallon and
- Juan J. Badimon
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 23, Issue 21 February 2003

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Objective— MRI is being used to characterize the composition of atherosclerotic plaques. However, the resolution achievable using surface radiofrequency coils is limited by the signal to noise ratio. We studied the utility of a new intravascular (IV) MRI probe for high-resolution in vivo imaging of atherosclerotic lesions.Methods and Results— Balloon-injured Watanabe heritable hyperlipidemic rabbits served as the experimental model of atherosclerosis. The newly developed IV MRI probe is 1.3 mm in diameter and can be positioned over a guidewire. MRI was performed with both an external phased-array coil and the IV MR coil. MR observations were correlated with histopathology. After MRI, the animals were killed and analysis of agreement between MR and histopathology was performed. The IV MR coil allows aortic images to be obtained with 156×156 μm² in-plane resolution versus 352×352 μm² when used with the external phased-array coil. No significant motion artifacts were noted, despite the continuation of arterial blood flow during image acquisition around the IV probe. The different components of the atherosclerotic lesions (lipid core and fibrous cap) were easily identified. There was an excellent agreement between MRI with the IV coil and histopathology by simple linear regression for both the mean wall thickness (r=0.88, slope 0.82, P<0.0001) and vessel wall area (r=0.86, slope 1.08, P<0.0001).Conclusions— The new nonobstructive design for this intravascular coil provides great promise for additional work in high-resolution MRI characterization of atherosclerotic plaques in vivo. The ability to position the probe with a guidewire allows its placement under fluoroscopic or MRI guidance, whereas its size is compatible with human coronary arteries.
Quantification and 3D Reconstruction of Atherosclerotic Plaque Components in Apolipoprotein E Knockout Mice Using Ex Vivo High-Resolution MRI
- Martina A. McAteer,
- Jürgen E. Schneider,
- Kieran Clarke,
- Stefan Neubauer,
- Keith M. Channon and
- Robin P. Choudhury
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 24, Issue 121 December 2004

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Objective— To investigate the ability of high-resolution MRI to determine composition and microanatomy of atherosclerosis in mouse aortic root and brachiocephalic artery.Methods and Results— Aortic root and brachiocephalic arteries of apolipoprotein E knockout (apoE−/−) mice fed Western diet for 10, 20, or 30 weeks were imaged ex vivo (11.7 T; 3D multiecho sequence; resolution 47×47×62.5 μm). Using semiautomated histogram-based methods, MRI accurately quantified lipid-rich/necrotic areas in the aortic root (r²=0.84; P<0.001) and brachiocephalic artery (r²=0.90; P<0.001) compared with histology. Similarly, cell-rich caps in aortic roots, quantified by MRI and histology, correlated closely (r²=0.74; P<0.001). Reconstruction of segmented brachiocephalic arteries in 3D provided unique insights into plaque microanatomy and enabled volumetric quantification of plaque and lipid-rich/necrotic core. Between 10 and 30 weeks, 3D measurement identified an 11.6-fold increase in plaque volume (versus 4.1-fold for 2D) and a 21.3-fold increase in plaque lipid-rich/necrotic core volume (versus 6.4-fold for 2D), indicating superior power of 3D quantification.Conclusions— Ex-vivo high-resolution 3D MRI accurately quantified lipid-rich/necrotic core and cell-rich cap areas in atherosclerotic lesions in apoE−/− mice. Reconstruction and volumetric quantification of segmented brachiocephalic arteries demonstrated greater sensitivity in detecting changes in plaque size and lipid composition over time than 2D analysis.We tested the ability of high-resolution MRI to quantify mouse atherosclerotic plaque components ex vivo. MRI accurately quantified lipid-rich/necrotic core and cell-rich cap components, as confirmed by histopathology. Three-dimensional reconstruction of brachiocephalic arteries enabled more sensitive volumetric quantification of differences in plaque and lipid-rich/necrotic cores than 2D analysis.
Carotid Plaque Composition Differs Between Ethno-Racial Groups: An MRI Pilot Study Comparing Mainland Chinese and American Caucasian Patients
- T. Saam,
- J.M. Cai,
- Y.Q. Cai,
- N.Y. An,
- A. Kampschulte,
- D. Xu,
- W.S. Kerwin,
- N. Takaya,
- N.L. Polissar,
- T.S. Hatsukami and
- C. Yuan
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 25, Issue 31 March 2005

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Objective— Ethnicity-based research may identify new clues to the pathogenesis of atherosclerotic disease. Therefore, we sought to determine whether carotid lesions differ between 20 Chinese and 20 Caucasian Americans by MRI.Methods and Results— Inclusion criteria were >50% stenosis as measured by duplex ultrasound and recent symptoms attributed to carotid artery disease. The patients were imaged in 2 centers (Beijing, China and Seattle, Wash) using a standardized protocol. Both carotid arteries were reviewed quantitatively (lumen, wall, outer wall, tissue components) and morphologically (lesion types, fibrous cap status). Significant differences between the Chinese and Americans were found for the mean size of the lipid/necrotic core (13.6 versus 7.8 mm²; P=0.002), percentage of slices with calcified type VII lesions (1.6 versus 12.4%; P=0.03), and percentage of slices with early type III lesions (19.3 versus 9.3%; P=0.02). Furthermore, the mean outer wall area in the common carotid artery was larger in the Chinese population (P=0.007).Conclusions— This pilot study suggests that composition and morphology of atherosclerotic lesions in symptomatic carotid disease differ between ethno-racial groups. Quantitative MRI-based review of carotid atherosclerosis comparing plaque morphology and composition between ethno-racial groups is feasible, and future MRI studies may improve our understanding of the pathophysiology of this disease.Twenty Chinese patients and 20 American Caucasian patients, all recently symptomatic, were imaged by MRI. Carotid lesions were bilaterally evaluated for plaque composition and plaque morphology. Plaque composition and morphology differed significantly between the ethno-racial groups. MRI is a promising tool to noninvasively study differences in atherosclerotic lesions across distinctive populations.
Coronary Artery Atherosclerosis Is Related to Reduced Regional Left Ventricular Function in Individuals Without History of Clinical Cardiovascular Disease: The Multiethnic Study of Atherosclerosis
- Thor Edvardsen,
- Robert Detrano,
- Boaz D. Rosen,
- J. Jeffrey Carr,
- Kiang Liu,
- Shenghan Lai,
- Steven Shea,
- Li Pan,
- David A. Bluemke and
- João A.C. Lima
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 11 January 2006

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Objective— We investigated whether regional coronary calcium score by computed tomography is related to regional left ventricular systolic function measured by MRI tagging in participants of the Multiethnic Study of Atherosclerosis.Methods and Results— The Multiethnic Study of Atherosclerosis is a prospective observational study of men and women without a history of previous heart disease from 4 ethnic groups. Calcium scores were measured separately for the left anterior descendent (LAD), left circumflex (LCX), and right (RCA) coronary arteries. Left ventricular strain and strain rate were determined by tagged MRI in the corresponding vascular territories of the coronary vessels in 509 participants. Greater coronary calcification in the LAD, LCX, and right RCA coronary arteries were related to worse function in their respective perfusion. Anterior wall strain rate was −1.37±0.41 when LAD calcium was zero versus −1.17±0.24 1/s in the highest quartile of calcium score (P<0.001). Similar relationships were evident in the LCX and RCA regions. Participants with 1- and 2-vessel coronary artery calcium had better myocardial function in the remote area compared with the territory supplied by the diseased artery.Conclusions— High-local calcium score is related to regional dysfunction in the corresponding coronary territory among individuals without a history of previous heart disease. These results indicate a link between atherosclerosis and subclinical regional left ventricular dysfunction.Participants of the Multiethnic Study of Atherosclerosis without history of previous heart disease were studied by MRI tagging and computed tomography. Greater coronary calcification in all coronary arteries were related to worse function in their respective perfusion territories. These results indicate a link between atherosclerosis and subclinical regional left ventricular dysfunction.
Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta: Relationship Between Signal Loss and Macrophage Infiltration
- Fabien Hyafil,
- Jean-Pierre Laissy,
- Mikael Mazighi,
- Didier Tchétché,
- Liliane Louedec,
- Homa Adle-Biassette,
- Sylvie Chillon,
- Dominique Henin,
- Marie-Paule Jacob,
- Didier Letourneur and
- Laurent J. Feldman
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 11 January 2006

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Objective— Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10–enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits.Methods and Results— Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10–induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r=0.82; P<0.05).Conclusion— Ferumoxtran-10–enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.We evaluated the ability of ferumoxtran-10–enhanced MRI to quantify macrophage infiltration in the aortic wall of hypercholesterolemic rabbits. Ferumoxtran-10–induced magnetic susceptibility artifacts were detected by in vivo MRI only in macrophage–rich aortic segments. Magnetic susceptibility artifact–related luminal narrowing on MRI correlated with macrophage infiltration on corresponding aortic cross-sections.
A Possible Association Between Coronary Plaque Instability and Complex Plaques in Abdominal Aorta
- Yukihiko Momiyama,
- Ryuichi Kato,
- Zahi A. Fayad,
- Nobukiyo Tanaka,
- Hiroaki Taniguchi,
- Reiko Ohmori,
- Teruyoshi Kihara,
- Akira Kameyama,
- Koji Miyazaki,
- Kazuo Kimura,
- Koh Arakawa,
- Masatoshi Kusuhara,
- Masayoshi Nagata,
- Haruo Nakamura and
- Fumitaka Ohsuzu
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 41 April 2006

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Objective— Coronary plaque instability causes myocardial infarction (MI). Angiographic lesions with such instability are complex lesions. Complex carotid plaques were reported to be prevalent in unstable angina. We investigated associations between coronary plaque instability, such as MI and angiographic complex coronary lesions, and aortic plaques.Methods and Results— Aortic MRI was performed in 146 patients undergoing coronary angiography, of whom 108 had coronary artery disease (CAD) and 44 also had MI. Prevalence of plaques in thoracic and abdominal aortas was higher in patients with than without CAD (73% and 94% versus 32% and 79%), but it was similar in CAD patients with and without MI. Notably, complex plaques in abdominal aorta were more prevalent in CAD patients with than without MI (36% versus 14%; P<0.025). In multivariate analysis, abdominal complex plaques were associated with MI (odds ratio [OR], 4.5; 95% CI, 1.5 to 13.8). Among patients without MI, thoracic and abdominal complex plaques were more prevalent in patients with than without complex coronary lesions (22% and 33% versus 2% and 7%; P<0.05). Abdominal complex plaques were also associated with complex coronary lesions (OR, 9.8; 95% CI, 1.1 to 85.9).Conclusion— Complex plaques in abdominal aorta were associated with MI and complex coronary lesions, suggesting a link between coronary and aortic plaque instability.To elucidate the association between coronary and aortic plaque instability, aortic MRI was performed in 146 patients undergoing coronary angiography. Complex plaques in abdominal aorta were associated with myocardial infarction and complex coronary lesions, suggesting a link between coronary and aortic plaque instability.
Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages
- Rikin A. Trivedi,
- Chinthake Mallawarachi,
- Jean-Marie U-King-Im,
- Martin J. Graves,
- Jo Horsley,
- Martin J. Goddard,
- Andrew Brown,
- Liqun Wang,
- Peter J. Kirkpatrick,
- John Brown and
- Jonathan H. Gillard
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 71 July 2006

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Background— Inflammation within atherosclerotic lesions contributes to plaque instability and vulnerability to rupture. We set out to evaluate the use of a macrophage labeling agent to identify carotid plaque inflammation by in vivo magnetic resonance imaging (MRI).Methods and Results— Thirty patients with symptomatic severe carotid stenosis scheduled for carotid endarterectomy underwent multi-sequence MRI of the carotid bifurcation before and after injection of ultrasmall superparamagnetic particles of iron oxide (USPIOs). USPIO particles accumulated in macrophages in 24 of 30 plaques (80%). Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in 24 of 27 (89%) patients, with an average reduction in signal intensity induced by the USPIO particles of 24% (range, 3.1% to 60.8%).Conclusions— USPIO-enhanced MRI can identify plaque inflammation in vivo by accumulation of USPIO within macrophages in carotid plaques.The in vivo detection of plaque inflammation was evaluated using a macrophage labeling MRI contrast agent. Areas of focal signal loss on MRI corresponded to macrophage populations, thereby identifying inflamed plaques in 24 of 27 symptomatic individuals with severe ICA stenosis were detected and confirmed histologically.
Quantitation and Localization of Matrix Metalloproteinases and Their Inhibitors in Human Carotid Endarterectomy Tissues
- Salman Choudhary,
- Catherine L. Higgins,
- Iou Yih Chen,
- Michael Reardon,
- Gerald Lawrie,
- G. Wesley Vick,
- Christof Karmonik,
- David P. Via and
- Joel D. Morrisett
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 26, Issue 101 October 2006

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Background— Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a central role in arterial wall remodeling, affecting stability of fibrous caps covering atherosclerotic plaques. The objective of this study was to determine the spatial distribution of TIMP mass and MMP mass and activity of carotid endarterectomy (CEA) tissues and relate it to the distribution of atherosclerotic lesions.Methods and Results— Fresh CEA tissues were imaged by multicontrast MRI to generate 3D reconstructions. Tissue segments were cut transversely from the common, bifurcation, internal, and external regions. Segments were subjected to total protein extractions and analyzed by ELISA for MMP-2 and -9 and TIMP-1 and -2 mass and by zymography for gelatinase activity. Segments at or near the bifurcation with highly calcified lesions contained higher MMP levels and activity than segments distant from the bifurcation; highly fibrotic or necrotic plaque contained lower MMP levels and activity and higher TIMP levels. Fatty streak, fibroatheroma with hemorrhage and calcification, and fully occluded lesions were enriched in MMP-2, MMP-9, and TIMP-1 and TIMP-2, respectively.Conclusion— The spatial distribution of MMPs and TIMPs in carotid atherosclerotic lesions is highly heterogeneous, reflecting lesion location, size, and composition. This study provides the first semi-quantitative maps of differential distribution of MMPs and TIMPs over atherosclerotic plaques.Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a central role in arterial wall remodeling. Their spatial distribution in carotid atherosclerotic lesions is highly heterogeneous, reflecting lesion location, size, and composition. This study provides the first semiquantitative maps of differential distribution of MMPs and TIMPs over atherosclerotic plaques.
The Prevalence and Quantification of Atherosclerosis in an Elderly Population Assessed by Whole-Body Magnetic Resonance Angiography
- T. Hansen,
- J. Wikström,
- L.O. Johansson,
- L. Lind and
- H. Ahlström
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 27, Issue 31 March 2007

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Objective— The principal aim of the present study was to explore the feasibility of using whole-body magnetic resonance angiography to assess atherosclerosis in different vascular territories in a cohort of elderly.Methods and Results— Three hundred six 70-year-old subjects (145 women, 161 men) recruited from a population-based cohort study (Prospective Investigation of the Vasculature in Uppsala Seniors, ie, the PIVUS study) underwent 1.5-T whole-body magnetic resonance angiography with gadodiamide. The arteries were divided into 26 segments. In total, 7956 vessel segments were evaluated with 7900 segments (99.3%) possible to evaluate. Of these, 7186 segments (91%) were normal. Luminal narrowing of ≥50% was observed in 9 (1.5%) of the renal arteries, 12 (1.8%) of the carotid arteries, in 31 segments (1.1%) of the pelvic/upper leg territories, and in 136 segments (6.2%) of territories in the lower leg. Approximately one-third of the sample had no vascular abnormalities, one-third had stenoses of <50%, and the remainder had stenoses ≥50% or occlusions. Six subjects (2%) had aortic aneurysms. In subjects without evident vascular disease, 26% had significant vascular abnormalities.Conclusions— Whole-body magnetic resonance angiography performed with a clinical scanner can be used for quantifying atherosclerosis in different vascular territories in a single examination in an elderly population.Whole-body MRA, a minimally invasive, nonradiation technique, was used in a large cohort of elderly citizens and could be used in an epidemiological setting for quantifying atherosclerosis in different vascular territories, excluding the coronary arteries, in a single examination.
The Diagnostic Accuracy of Ex Vivo MRI for Human Atherosclerotic Plaque Characterization
- Meir Shinnar,
- John T. Fallon,
- Suzanne Wehrli,
- Michael Levin,
- Dolcine Dalmacy,
- Zahi A. Fayad,
- Juan J. Badimon,
- Martin Harrington,
- Elizabeth Harrington and
- Valentin Fuster
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 19, Issue 111 November 1999

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Abstract—Recent evidence indicates that the type of atherosclerotic plaque, rather than the degree of obstruction to flow, is an important determinant of the risk of cardiovascular complications. In previous work, the feasibility of using MRI for the characterization of plaque components was shown. This study extends the previous work to all the plaque components and shows the accuracy of this method. Twenty-two human carotid endarterectomy specimens underwent ex vivo MRI and histopathological examination. Sixty-six cross sections were matched between MRI and histopathology. In each cross section, the presence or absence of plaque components were prospectively identified on the MRI images. The overall sensitivity and specificity for each tissue component were very high. Calcification and fibrocellular tissue were readily identified. Lipid core was also identifiable. However, thrombus was the plaque component for which MRI had the lowest sensitivity. A semiautomated algorithm was created to identify all major atherosclerotic plaque components. MRI can characterize carotid artery plaques with a high level of sensitivity and specificity. Application of these results in the clinical setting may be feasible in the near future.
MRI of Rabbit Atherosclerosis in Response to Dietary Cholesterol Lowering
- Michael V. McConnell,
- Masanori Aikawa,
- Stephan E. Maier,
- Peter Ganz,
- Peter Libby and
- Richard T. Lee
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 19, Issue 81 August 1999

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Abstract—Direct imaging of the atherosclerotic plaque, rather than the angiographic lumen, may provide greater insight into the response of atherosclerosis to cholesterol-lowering therapy. Aortic plaque was studied in vivo by MRI in rabbits undergoing dietary cholesterol intervention. Thirty-one rabbits underwent aortic balloon injury and high-cholesterol diet for 4 months and then were assigned to low-cholesterol versus continued high-cholesterol diet for up to an additional 16 months. High-resolution (310 μm) fast spin-echo MRI of the abdominal aorta was performed at 4, 12, and 20 months and compared with histology. MRI demonstrated a significant reduction in % area stenosis in rabbits placed on low-cholesterol diet (44.6±2.1% at 20 months versus 55.8±1.5% at 4 months, P=0.0002). In contrast, % area stenosis increased in rabbits maintained on high-cholesterol diet (69.8±3.8% at 20 months versus 55.8±1.5% at 4 months, P=0.001). Similarly, plaque thickness decreased significantly in the low-cholesterol group (0.60±0.05 mm at 20 months versus 0.85±0.06 mm at 4 months, P=0.006), with a trend toward increase in the high-cholesterol group (1.02±0.08 mm at 20 months versus 0.85±0.06 mm at 4 months, P=0.1). Thus, in rabbits undergoing dietary cholesterol lowering, MRI detected regression of aortic atherosclerotic plaque in vivo. Plaque progression was seen with maintenance of high-cholesterol diet. MRI is a promising noninvasive technology for directly imaging atherosclerosis and its response to therapeutic interventions.
Characterization of Signal Properties in Atherosclerotic Plaque Components by Intravascular MRI
- Walter J. Rogers,
- Jeffrey W. Prichard,
- Yong-Lin Hu,
- Peter R. Olson,
- Daniel H. Benckart,
- Christopher M. Kramer,
- Diane A. Vido and
- Nathaniel Reichek
Arteriosclerosis, Thrombosis, and Vascular Biology Volume 20, Issue 71 July 2000

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Abstract—Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter–based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37°C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156×250 μm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo–to–spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Masson’s trichrome, Kossa, oil red O, and Gomori’s iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62±13) than in all other components (P<0.05) The inversion ratio was greater in lipid (0.91±0.09) than all other components (P<0.05). Calcium was best distinguished by using the gradient echo–to–spin echo ratio, which was lower in calcium (0.36±0.2) than in all plaque components, except for the organizing thrombus (P<0.04). Absolute T1 (range 300±140 ms for lipid to 630±321 ms for calcium) and T2 (range 40±12 ms for fresh thrombus to 59±21 ms for smooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium. Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque components associated with plaque stability by use of existing whole-body scanners.
Role of Computed Tomography and Magnetic Resonance Imaging for Deep Venous Thrombosis and Pulmonary Embolism
- Jeffrey P. Kanne and
- Tasneem A. Lalani
Circulation Volume 109, Issue 12_suppl_130 March 2004

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During the 1990s, computed tomography (CT) and magnetic resonance (MR) imaging underwent extensive technological advancement and expanded clinical use in patients with venous thromboembolic disease, particularly with regard to evaluation of the pulmonary vasculature. In many institutions, helical (spiral) CT pulmonary angiography has become the initial imaging study of choice to evaluate patients with suspected pulmonary embolism, supplanting ventilation/perfusion scintigraphy. In addition, CT venography of the pelvis and lower extremities is often incorporated into the CT angiography protocol to identify or exclude concurrent deep venous thrombosis. MR pulmonary angiography and MR venography are second-line diagnostic tools because of their higher cost, limited availability, and other logistical constraints. As the technology improves and becomes more widely available, MR imaging may play a greater role in the evaluation of patients with venous thromboembolic disease.
Nitric Oxide Mediates Benefits of Angiotensin II Type 2 Receptor Overexpression During Post-Infarct Remodeling
- Christina M. Bove,
- Zequan Yang,
- Wesley D. Gilson,
- Frederick H. Epstein,
- Brent A. French,
- Stuart S. Berr,
- Sanford P. Bishop,
- Hiroaki Matsubara,
- Robert M. Carey and
- Christopher M. Kramer
Hypertension Volume 43, Issue 31 March 2004

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We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT₂-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT₂-R overexpression were studied by cardiac magnetic resonance imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior descending artery occlusion and reperfusion. Sixteen TG mice were treated from day 1 through 28 post-MI with the NO synthase inhibitor N^G-nitro-l-arginine methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI), wall thickness, percent thickening, and ejection fraction (EF) were measured. Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen was quantified in noninfarcted regions. At baseline, heart rate (HR), blood pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41±0.18 μL/g versus 2.53±0.14 μL/g in WT; 2.17±0.14 μL/g in TG-Rx; P<0.008 for both). At day 28, EF was higher in TG (46.3%±2.9%) compared with WT and TG-Rx (32.7±2.3% and 33.7±2.3, respectively; P<0.003 for both). Wall thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and TG-Rx. Noninfarcted region interstitial collagen was similar between groups. Thus, the NO pathway may mediate much of the benefits of cardiac AT₂-R overexpression during post-MI remodeling.
Physiological Basis for Potassium (³⁹K) Magnetic Resonance Imaging of the Heart
- David S. Fieno,
- Raymond J. Kim,
- Wolfgang G. Rehwald and
- Robert M. Judd
Circulation Research Volume 84, Issue 830 April 1999

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Abstract—The potassium cation (K⁺) is fundamentally involved in myocyte metabolism. To explore the potential utility of direct MRI of the most abundant natural isotope of potassium, ³⁹K, we compared ³⁹K magnetic resonance (MR) image intensity with regional myocardial K⁺ concentrations after irreversible injury. Rabbits were subjected either to 40 minutes of in situ coronary artery occlusion and 1 hour of reperfusion (n=26) or to 24 hours of permanent occlusion (n=4). The hearts were then isolated and imaged by ³⁹K MRI (n=10), or tissue samples were analyzed for regional ³⁹K content by MR spectroscopy (n=9), K⁺ and Na⁺ concentrations by atomic emission spectroscopy (inductively coupled plasma atomic emission spectroscopy; n=5), or intracellular K⁺ content by electron probe x-ray microanalysis (n=6). Three-dimensional ³⁹K MR images of the isolated hearts were acquired in 44 minutes with 3×3×3–mm resolution. ³⁹K MR image intensity was reduced in infarcted regions (51.7±4.8% of remote; P<0.001). The circumferential extent and location of regions of reduced ³⁹K image intensity were correlated with those of infarcted regions defined histologically (r=0.97 and r=0.98, respectively). Compared with remote regions, tissue analysis revealed that infarcted regions had reduced ³⁹K concentration (by MR spectroscopy, 40.5±9.3% of remote; P<0.001), reduced potassium-to-sodium ratio (by inductively coupled plasma atomic emission spectroscopy, 20.7±2.1% of remote; P<0.01), and reduced intracellular potassium (by electron probe x-ray microanalysis, K⁺ peak-to-background ratio 0.95±0.32 versus 2.86±1.10, respectively; P<0.01). We acquired the first ³⁹K MR images of hearts subjected to infarction. In the pathophysiologies examined, potassium (³⁹K) MR image intensity primarily reflects regional intracellular K⁺ concentrations.
Dobutamine-Stress Magnetic Resonance Microimaging in Mice : Acute Changes of Cardiac Geometry and Function in Normal and Failing Murine Hearts
- Frank Wiesmann,
- Jan Ruff,
- Stefan Engelhardt,
- Lutz Hein,
- Charlotte Dienesch,
- Andrea Leupold,
- Ralf Illinger,
- Alex Frydrychowicz,
- Karl-Heinz Hiller,
- Eberhard Rommel,
- Axel Haase,
- Martin J. Lohse and
- Stefan Neubauer
Circulation Research Volume 88, Issue 630 March 2001

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Abstract— The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 μg/g IP dobutamine. There was a significant increase of heart rate, cardiac output, and ejection fraction and significant decrease of end-diastolic and end-systolic left ventricular (LV) volumes (P<0.01 each) in normal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatation. There was a significant decrease of LV ejection fraction in infarcted mice (29%) versus sham mice (58%). Mice with MI showed a significantly reduced maximum LV ejection rate (P<0.001) and LV filling rate (P<0.01) and no increase of LV dynamics during dobutamine action, indicating loss of contractile and relaxation reserve. In 4-month-old transgenic mice with cardiospecific overexpression of the β₁-adrenergic receptor, which at this early stage do not show abnormalities of resting cardiac function, LV filling rate failed to increase after dobutamine stress (transgenic, 0.19±0.03 μL/ms; wild type, 0.36±0.01 μL/ms; P<0.01). Thus, MRI unmasked diastolic dysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasive assessment of systolic and diastolic components of heart failure. This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.
Interaction Between Hypertension, apoE, and Cerebral White Matter Lesions
- Frank-Erik de Leeuw,
- Florence Richard,
- Jan Cees de Groot,
- Cornelia M. van Duijn,
- Albert Hofman,
- Jan van Gijn and
- Monique M.B. Breteler
Stroke Volume 35, Issue 51 May 2004

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Background and Purpose— Cerebral white matter lesions (WMLs) are frequently found on magnetic resonance imaging scans in both cognitively intact and demented elderly persons. Vascular risk factors, especially hypertension, are related to their presence. However, not every person with vascular risk factors has WMLs, which suggests interaction with other determinants, eg, genetic factors. The ε4 allele of the apolipoprotein E gene (apoE) may be a candidate because this allele is associated with both the vascular risk factors and the consequences (cognitive impairment, dementia) of WMLs.Methods— We investigated apoE genotype, blood pressure levels, and their interaction in relation to subcortical and periventricular WMLs in 971 participants in the Rotterdam Scan Study.Results— ApoE ε4 carriers had a significantly higher subcortical WML volume than did apoE ε3ε3 carriers (adjusted mean difference, 0.5; 95% confidence interval, 0.2 to 0.8), irrespective of hypertension. This was not found for periventricular WMLs. Participants with both hypertension and at least 1 apoE ε4 allele had the highest degree of both types of WML; the interaction was statistically significant for subcortical WMLs (P=0.016).Conclusions— apoE ε4 carriers are at increased risk for WMLs if they suffer from hypertension as well. This may reflect a diminished capacity for neuronal repair in apoE ε4 carriers.

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