Progress in atherosclerotic plaque imaging

Cardiovascular diseases are the primary cause of mortality in the industrialized world,and arterial obstruction, triggered by rupture-prone atherosclerotic plaques,lead to myocardial infarction and cerebral stroke.Vulnerable plaques do not necessarily occur with flow-limiting stenosis,thus conventional luminographic assessment of the pathology fails to identify unstable lesions.In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging,computed tomography, nuclear imaging and their intravascular applications are illustrated,highlighting their specific diagnostic potential.Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation,concerning the specific invasiveness, accuracy and cost-effectiveness of these methods.     

MR imaging of atherosclerotic plaque

MRI is a powerful noninvasive imaging tool with high spatial resolution that continues to prove its value in determining atherosclerotic plaque size, volume, and tissue components. Multispectral MRI sequences have been validated to characterize atherosclerotic plaque components in animals; they have recently been applied to human aorta and carotid artery and are being used to identify the vulnerable plaque. The ability to measure wall thickness in human coronary artery wall has been realized. Future developments may allow plaque characterization in the coronary arteries with surface coil imaging, but intravascular MRI may play an important role in this regard. Novel contrast agents for identifying inflammation and thrombus within atherosclerotic plaque will aid in the identification of higher-risk atherosclerotic disease. Lastly, MRI has progressed to the point where it can be used in serial studies of atherosclerotic plaque progression and regression in the face of therapeutic intervention. MRI will continue to evolve an important role in imaging of atherosclerotic plaque.     

High-resolution, multicontrast three-dimensional-MRI characterizes atherosclerotic plaque composition in ApoE-/- mice ex vivo

PURPOSE: To systematically investigate intrinsic MR contrast mechanisms that would facilitate plaque characterization and quantification in the aortic root and brachiocephalic artery of ApoE-/- mice ex vivo. MATERIALS AND METHODS: To establish unambiguous MR parameters for routinely analyzing atherosclerotic plaque ex vivo at 11.7 T, relaxation times of plaque components were quantitatively assessed. Magnetization transfer and lipid-proton three-dimensional MR imaging was investigated for visualization of collagen- and lipid-rich plaque regions, respectively. A three-dimensional multiecho sequence with a spatial resolution of 47 x 47 x 63 microm was implemented providing a variable degree of T2-weighting. RESULTS: Relaxation time measurements showed clear tissue heterogeneity between atherosclerotic plaque components in the T2-values, but similar T1-values at 11.7 T (T1/T2 mean +/- SD; cellular plaque component: 1.2 +/- 0.3 seconds/26.3 +/- 0.4 msec; fibrofatty plaque component: 1.1 +/- 0.2 seconds/13.7 +/- 2.0 msec). The three-dimensional multiecho sequence allowed the calculation of the intrinsic proton density and T2-maps. The sum of the multiecho data provided strong T2-weighting that facilitated quantification of various components of atherosclerotic plaque in the mouse aortic root and correlated well with histology (P < 0.0001). CONCLUSION: High-resolution MRI allows for accurate classification and quantification of atherosclerotic plaque components in the aortic root of mice.     

颈动脉粥样硬化斑块的MR成像

目的：探讨MR成像技术在颈动脉粥样硬化斑块检测中的应用，及其对斑块内成份进行定性分析的可能性。方法：采用3D-TOF、Double-IR(DIR)T1WI、T2WI、PDWI序列对11位高度疑诊颈动脉粥样硬化的患者及9位健康志愿者进行颈动脉成像。部分患者行彩超对照。结果：11例患者中9例可见明显颈动脉粥样硬化改变。TOF上表现为管腔内高信号血流中见低信号充盈缺损。DIR T1WI、T2WI、PDWI表现为管壁增厚，斑块呈等、低均匀信号或等、低、高混杂信号。与多普勒彩超对比，MRI对颈动脉粥样硬化的检出准确率较高。结论：MRI对颈动脉粥样硬化可达到满意的诊断，并提示MRI能分析斑块内成份，分析斑块成份及性质为临床选择治疗方案及估计预后提供有力的帮助。     

冠状动脉粥样硬化斑块的影像学评价

冠状动脉硬化斑块易发和腐蚀和破裂,导致急性冠状动脉综合征,引起急性心肌梗塞.有效的评价斑块的结构及成分特点,监测其演变过程,对选择治疗时机和治疗方案有重要意义.本文综述了冠状动脉粥样硬化斑块的病理特点和演变规律,评价了各种影像技术包括血管内超声,多层螺旋CT和磁共振,冠状动脉造影对其诊断的价值以及应用的限度.     

High-resolution MRI with cardiac and respiratory gating allows for accurate in vivo atherosclerotic plaque visualization in the murine aortic arch.

Genetically engineered mouse models provide enormous potential for investigation of the underlying mechanisms of atherosclerotic disease, but noninvasive imaging methods for analysis of atherosclerosis in mice are currently limited. This study aimed to demonstrate the feasibility of MRI to noninvasively visualize atherosclerotic plaques in the thoracic aorta in mice deficient in apolipoprotein-E, who develop atherosclerotic lesions similar to those observed in humans. To freeze motion, MR data acquisition was both ECG- and respiratory-gated. T(1)-weighted MR images were acquired with TR/TE approximately 1000/10 ms. Spatial image resolution was 49 x 98 x 300 micro m(3). MRI revealed a detailed view of the lumen and the vessel wall of the entire thoracic aorta. Comparison of MRI with corresponding cross-sectional histopathology showed excellent agreement of aortic vessel wall area (r = 0.97). Hence, noninvasive MRI should allow new insights into the mechanisms involved in progression and regression of atherosclerotic disease.     

Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque.     

Techniques for high-resolution MR imaging of atherosclerotic plaque

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.     

动脉粥样硬化斑块显像研究进展

现有的一些用于动脉粥样硬化斑块诊断的检测方法如X线血管造影、血管内超声、光学相干体层扫描、B-型超声、电子束CT、核磁共振、拉曼光谱学检查和温度测量法等,在显示血管腔狭窄、管壁增厚、斑块体积以及斑块成分等方面各有其独特价值。但是,它们或因是创伤性检查、或因为检查本身的局限性(如只能显示钙化)、或不能早期发现以代谢紊乱为特征的病变,因而限制了它们在临床上的广泛应用。利用核素标记参与动脉粥样硬化的中间物质进行显像,可以精确、定量反映斑块成分和代谢情况,为无创伤性显示动脉粥样硬化斑块带来了希望,在疾病筛选、治疗决策、疗效观察以及随访研究上具有广阔的应用前景。     

Quantification of atherosclerotic plaque components using in vivo MRI and supervised classifiers.

In this work we aimed to study the possibility of using supervised classifiers to quantify the main components of carotid atherosclerotic plaque in vivo on the basis of multisequence MRI data. MRI data consisting of five MR weightings were obtained from 25 symptomatic subjects. Histological micrographs of endarterectomy specimens from the 25 carotids were used as a standard of reference for training and evaluation. The set of subjects was divided in a training set (12 subjects) and an evaluation set (13 subjects). Four different classifiers and two human MRI readers determined the percentages of calcified tissue, fibrous tissue, lipid core, and intraplaque hemorrhage on the subject level for all subjects in the evaluation set. Quantification of the relatively small amounts of calcium could not be done with statistical significance by either the classifiers or the MRI readers. For the other tissues a simple Bayesian classifier (Bayes) performed better than the other classifiers and the MRI readers. All classifiers performed better than the MRI readers in quantifying the sum of hemorrhage and lipid proportions. The MRI readers overestimated the hemorrhage proportions and tended to underestimate the lipid proportions. In conclusion, this pilot study demonstrates the benefits of algorithmic classifiers for quantifying plaque components.     

动脉粥样硬化斑块核素显像研究进展

核素显像是一种较为理想和具有广泛用途的无创伤性检查技术,是目前惟一能定性、定量反映器官组织血流、代谢及功能改变的影像学方法。利用放射性核素标记参与动脉粥样硬化的中间物质进行显像,可发现早期病变。     

Ex vivo coronary atherosclerotic plaque characterization with multi-detector-row CT

Multi-detector-row CT angiography (CTA) is a new technology that allows for non-invasive investigation of coronary atherosclerosis in patients. The relation between the morphology of atherosclerotic plaques assessed by CTA and histopathology is unknown. We investigated 11 human cadaver heart specimens. A mixture of methylcellulose and CT contrast media was injected into the coronary arteries to achieve in-vivo-like contrast enhancement within the coronary artery lumen. The morphologic pattern of atherosclerotic lesions found on CTA images and the tissue attenuation of non-calcified plaques were determined. After CTA imaging, atherosclerotic lesions in the coronary arteries were macroscopically identified and characterized histopathologically according to American Heart Association criteria. A total of 50 and 40 lesions were found macroscopically and by CTA, respectively. Thirty-three lesions could have been compared directly. The sensitivity of CTA compared with macroscopic detection of atheromas, fibroatheromas, fibrocalcified, and calcified lesions was 73, 70, 86, and 100%, respectively. The mean CT attenuation of predominantly lipid-rich and fibrous-rich plaques was significantly different (47±9 and 104±28 HU, respectively; p<0.01). Atherosclerotic coronary plaques detected by CTA may represent different stages of coronary atherosclerosis. The tissue attenuation of non-calcified plaques may allow for assessment of their predominant component.     

High-resolution three-dimensional magnetic resonance imaging of mouse lung in situ

OBJECTIVES: This study establishes a method for high-resolution isotropic magnetic resonance (MR) imaging of mouse lungs using tracheal liquid-instillation to remove MR susceptibility artifacts. METHODS: C57BL/6J mice were instilled sequentially with perfluorocarbon and phosphate-buffered saline to an airway pressure of 10, 20, or 30 cm H2O. Imaging was performed in a 7T MR scanner using a 2.5-cm Quadrature volume coil and a 3-dimensional (3D) FLASH imaging sequence. RESULTS: Liquid-instillation removed magnetic susceptibility artifacts and allowed lung structure to be viewed at an isotropic resolution of 78-90 microm. Instilled liquid and modeled lung volumes were well correlated (R = 0.92; P < 0.05) and differed by a constant tissue volume (220 +/- 92 microL). 3D image renderings allowed differences in structural dimensions (volumes and areas) to be accurately measured at each inflation pressure. CONCLUSION: These data demonstrate the efficacy of pulmonary liquid instillation for in situ high-resolution MR imaging of mouse lungs for accurate measurement of pulmonary airway, parenchymal, and vascular structures.     

Magnetic resonance chemical shift imaging and spectroscopy of atherosclerotic plaque

An in vivo magnetic resonance imaging (MRI) technique for identification and characterization of atherosclerotic plaque was assessed in animal and human models. Atherosclerosis was induced in the abdominal aorta of four rabbits by a combination of balloon denudation and a high cholesterol diet. In vivo conventional spin-echo and fat/water suppressed images of the rabbit aortae were obtained at 1.5 T. Chemical shift imaging (CSI) was achieved using a hybridization of selective excitation and modified Dixon techniques. These techniques were then used to obtain images of atherosclerotic lesions in the carotid arteries of four patients prior to endarterectomy. The MRI results were corroborated by histologic and high-resolution proton MR spectroscopic (8.5 T) analysis of rabbit aorta, human carotid endarterectomy, and six additional human superficial femoral and iliac atherectomy specimens. All animal and human lesions were classified as either fatty streaks or fibrotic plaque. When compared to conventional spin-echo images, fat suppression by CSI substantially improved the measured contrast-to-noise ratio between plaque and vessel lumen, and enhanced its discrimination from periadventitial fat. In contrast, water suppression eliminated visualization of plaque due to the negligible amount of isotropic (liquid-like) signal from the immobilized lesion lipids. Magnetic resonance spectroscopy corroborated the CSI results by demonstrating broad, ill-defined fat resonances characteristic of nonmobile lipids in both human and rabbit atherosclerotic lesions. These findings indicate that in vivo MRI of plaque is technically feasible and can be markedly improved using chemical shift imaging.     

Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study

PURPOSE: To prospectively evaluate if there is an association between plaque enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular risk factors and plaque content. MATERIALS AND METHODS: This study was performed with informed consent, HIPAA compliance, and institutional review board approval. Contrast agent dynamics within carotid plaques were measured in 30 patients (29 men, one woman; mean age, 67.7 years +/- 10.7 [standard deviation]) who were scheduled to undergo carotid endarterectomy. Measurements were based on kinetic modeling of images obtained at 15-second intervals during which a gadolinium-based contrast agent was injected. The time-varying signal intensities within the plaques were used to estimate the fractional plasma volume (vp) and transfer constant (Ktrans) of contrast material into the extracellular space. Pearson correlation coefficients were computed between blinded MR measurements and histologic measurements of plaque composition, including macrophages, neovasculature, necrotic core, calcification, loose matrix, and dense fibrous tissue. Correlation coefficients or mean differences were computed regarding clinical markers of cardiovascular risk. RESULTS: Analyzable MR images and histologic results were obtained in 27 patients. Measurements of Ktrans correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P < .001), and loose matrix (r = 0.50, P = .01) content. Measurements of v(p) correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P < .001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters, significant associations were correlated with Ktrans only, with decreased high-density lipoprotein levels (r = -0.66, P < .001) and elevated Ktrans measurements in smokers compared with nonsmokers (mean, 0.134 min(-1) vs 0.074 min(-1), respectively; P = .01). CONCLUSION: The correlations between Ktrans and histologic markers of inflammation suggest that Ktrans is a quantitative and noninvasive marker of plaque inflammation, which is further supported by the correlation of Ktrans with proinflammatory cardiovascular risk factors, decreased high-density lipoprotein levels, and smoking.     

High-resolution imaging of human atherosclerotic carotid plaques with micro<Superscript>18</Superscript>F-FDG PET scanning exploring plaque vulnerability

Aims  

FDG-PET can be used to identify vulnerable plaques in atherosclerotic disease. Clinical FDG-PET camera systems are restricted in terms of resolution for the visualization of detailed inflammation patterns in smaller vascular structures. The aim of the study is to evaluate the possible added value of a high-resolution microPET system in excised carotid plaques using FDG.     

High-resolution myocardial perfusion mapping in small animals in vivo by spin-labeling gradient-echo imaging.

An ECG and respiration-gated spin-labeling gradient-echo imaging technique is proposed for the quantitative and completely noninvasive measurement and mapping of myocardial perfusion in small animals in vivo. In contrast to snapshot FLASH imaging, the spatial resolution of the perfusion maps is not limited by the heart rate. A significant improvement in image quality is achieved by synchronizing the inversion pulse to the respiration movements of the animals, thereby allowing for spontaneous respiration. High-resolution myocardial perfusion maps (in-plane resolution=234 x 468 microm2) demonstrating the quality of the perfusion measurement were obtained at 4.7 T in a group of seven freely breathing Wistar-Kyoto rats under isoflurane anesthesia. The mean perfusion value (group average +/- SD) was 5.5 +/- 0.7 ml g(-1)min(-1). In four animals, myocardial perfusion was mapped and measured under cardiac dobutamine stress. Perfusion increased to 11.1 +/- 1.9 ml g(-1)min(-1). The proposed method is particularly useful for the study of small rodents at high fields.