Magnetic Resonance Imaging of Carotid Atherosclerosis and the Risk of Stroke

Stroke attributable to carotid atherosclerosis is a leading cause of mortality and morbidity. The clinical management of carotid atherosclerosis presently relies on the degree of stenosis determined by angiography. Degree of stenosis is limited in stratifying patients’ risk of stroke. Advances in magnetic resonance imaging have resulted in the ability to directly assess atherosclerotic plaque components, morphology, and biomechanical stress levels. Components of atherosclerosis, including lipid-rich necrotic core, fibrous cap thickness/disruption, and intraplaque hemorrhage, are promising emerging indicators of stroke. Information beyond luminal stenosis from magnetic resonance imaging may allow for improved detection of patients at risk of stroke from carotid atherosclerosis. We review the recent literature on the relationship of magnetic resonance imaging detected plaque components and cerebrovascular events. Clinical applications of magnetic resonance imaging of carotid plaque components are discussed.     

3.0 T plaque imaging

OBJECTIVES: The aim of this article is to evaluate 3.0 T magnetic resonance imaging for characterization of vessel morphology and plaque composition. Emphasis is placed on early and moderate stages of carotid atherosclerosis, where increases in signal-to-noise (SNR) and contrast-to-noise (CNR) ratios compared with 1.5 T are sought. Comparison of in vivo 3.0 T imaging to histopathology is performed for validation. Parallel acceleration methods applied with an 8-channel carotid array are investigated as well as higher field ex vivo imaging to explore even further gains. The overall endeavor is to improve prospective assessment of atherosclerosis stage and stability for reduction of atherothrombotic event risk. METHODS: A total of 10 male and female subjects ranging in age from 22 to 72 years (5 healthy and 5 with cardiovascular disease) participated. Custom-built array coils were used with endogenous and exogenous multicontrast bright and black-blood protocols for 3.0 T carotid imaging. Comparisons were performed to 1.5 T, and ex vivo plaque was stained with hematoxylin and eosin for histology. Imaging (9.4 T) was also performed on intact specimens. RESULTS: The factor of 2 gain in signal-to-noise SNR is realized compared with 1.5 T along with improved wall-lumen and plaque component CNR. Post-contrast black-blood imaging within 5-10 minutes of gadolinium injection is optimal for detection of the necrotic lipid component. In a preliminary 18-month follow-up study, this method provided measurement of a 50% reduction in lipid content with minimal change in plaque size in a subject receiving aggressive statin therapy. Parallel imaging applied with signal averaging further improves 3.0 T black-blood vessel wall imaging. CONCLUSIONS: The use of 3.0 T for carotid plaque imaging has demonstrated increases in SNR and CNR compared with 1.5 T. Quantitative prospective studies of moderate and early plaques are feasible at 3.0 T. Continued improvements in coil arrays, 3-dimensional pulse sequences, and the use of novel molecular imaging agents implemented at high field will further improve magnetic resonance plaque characterization.     

Extracranial carotid MR imaging at 3T

Some controversy exists over the accuracy and optimal parameters for carotid CE MR angiography at 1.5T. Spatial resolution remains more important than does temporal resolution to address the key question of vessel stenosis, based upon a review of the available literature that compares CE MR angiography with DSA. Specifically, CE MR angiograms with 0.9- to 1.2-mm resolution in all three planes before interpolation have a high reported sensitivity and specificity compared with DSA. To achieve this type of spatial resolution, cover the entire course of the carotid arteries from the aortic arch through the skull base, and achieve an absence of venous signal usually requires an elliptic-centric phase encoding CE MR angiogram that lasts for 50 to 60 seconds without the use of parallel imaging techniques. This near-millimeter resolution requires an accurate timing of the gadolinium bolus arrival to maximize intra-arterial SNR and to minimize venous contamination. Parallel imaging techniques can decrease the imaging time, but at a cost of some SNR. Initial experience with eight-channel or higher neurovascular coils at 3T indicates an increase in SNR/CNR compared with 1.5T. This should allow more consistent submillimeter-resolution carotid CE MR angiography with adequate SNR to maintain good IQ in a wide variety of clinical patients. Although a definite, prospective comparison of various CE MR angiography techniques,including a 20- to 30-second scan with 1.2- to 1.4-mm(3) voxel resolution and 50- to 60-second scan with 0.9- to 1.1-mm(3) voxel resolution at 1.5T, as well as 0.5- to 0.6-mm(3) voxel resolution with scan time of 50 to 60 seconds at 3T versus rotational DSA does not exist, the expectation is that the higher resolution and increased SNR that has resulted from 3T carotid CE MR angiography will have high sensitivity and specificity in detecting severe carotid stenosis. The most exciting application of 3T for carotid artery imaging may not be the higher resolution CE MR angiogram, however. Early work has demonstrated the potential of 3T, combined with sensitive surface coils, to depict carotid plaque with sufficient SNR to identify important plaque components consistently in most patients. This could help move MR imaging of the carotid arteries away from a strict evaluation of luminal narrowing to a focused evaluation of plaque morphology. Much work needs to be done. Although there is a growing body of literature to support the contention that plaque morphology is a predictor of subsequent thrombo-embolic disease, the natural history of these various plaque components in a large number of patients needs to be elucidated. If plaque characterization proves to be an independent risk factor that predicts stroke, more aggressive clinical treatment option strategies may be devised for patients who are at the highest risk. Currently, plaque characterization at 3T requires a different set of coils compared with the global assessment of the entire course of the carotid arteries. Future generations of 16- to 32-channel carotid coils should be able to combine the best features of current 4- to 8-channel surface carotid coils and neurovascular coils. These will enable a comprehensive evaluation of the entire course of the carotid artery and detailed carotid bifurcation plaque characterization at 3T within a clinically acceptable 1-hour time frame. This comprehensive carotid artery evaluation with 3T MR imaging would be far superior to that which is possible with US or CT.     

磁共振评估冠状动脉粥样硬化斑块的研究进展

冠状动脉粥样硬化性心脏病(coronary atherosclerosis heart disease,CHD)是人类主要死亡原因之一,其中急性冠脉综合征(acute coronary syndromes,ACS)是导致患者预后不良和发生猝死的主要原因。尸检病理结果发现,ACS发病的主要原因为动脉粥样硬化易损斑块破裂或内皮表面糜烂导致冠脉内血栓形成。磁共振成像(magnetic resonance imaging,MRI)作为一种无创、可重复性强、组织分辨率高的检查方法,多对比成像序列经过20余年的研发在颈动脉粥样硬化斑块中的应用已得到广泛证实,并在临床上及病理对照上得到进一步的验证。但冠状动脉管壁成像由于成像技术复杂,目前尚处于研究阶段。本文就磁共振成像评估冠状动脉粥样硬化斑块的研究进展进行综述。     

Spiral computed tomographic imaging related to computerized ultrasonographic images of carotid plaque morphology and histology.

OBJECTIVE: Echolucency of carotid atherosclerotic plaques, as evaluated by computerized B-mode ultrasonographic images, has been associated with an increased incidence of brain infarcts on cerebral computed tomographic scans. We tested the hypotheses that characterization of carotid plaques on spiral computed tomographic images correlates with that on computerized B-mode ultrasonographic images and that spiral computed tomographic imaging predicts the histomorphometric plaque content. METHODS: The study included 38 patients with neurologic symptoms and at least 50% stenosis of the ipsilateral carotid artery. High-resolution B-mode ultrasonographic images and spiral computed tomographic images of carotid plaques were computer processed to yield a quantitative measure, the gray scale level of the plaque. RESULTS: The mean Hounsfield value for spiral computed tomographic images correlated with the gray scale median for B-mode ultrasonographic images (univariate linear regression analysis: r = 0.45; P = .01) and the histologic content of calcification in the plaque (r = 0.34; P = .04) but not with lipid, hemorrhage, or fibrous tissue in the plaque. CONCLUSIONS: Spiral computed tomographic imaging seems to correlate with B-mode ultrasonographic imaging for showing plaque characteristics. Spiral computed tomographic attenuation was also correlated with the amount of calcification noted on histologic examination but not with lipid and hemorrhage, the components thought to characterize vulnerable, rupture-prone plaques.     

MRI of atherosclerosis: diagnosis and monitoring therapy

Atherosclerosis is a prevalent disease affecting millions of Americans. Despite our advances in diagnosis and treatment, atherosclerosis is the leading cause of death in America. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading noninvasive imaging modality for atherosclerotic disease. Atherosclerosis of the arterial wall of the human carotid, aortic, peripheral and coronary arteries have all been successfully evaluated. In addition, the power of magnetic resonance imaging to differentiate the major components of atherosclerotic plaque has been validated. The ability to image the vessel wall and risk stratify atherosclerotic plaque will create management decisions not previously faced, and has the potential to change the way atherosclerosis is treated.     

MRI of atherosclerosis: diagnosis and monitoring therapy

Atherosclerosis is a prevalent disease affecting millions of Americans. Despite our advances in diagnosis and treatment, atherosclerosis is the leading cause of death in America. High-resolution magnetic resonance imaging has overcome the limitations of current angiographic techniques and has emerged as a leading noninvasive imaging modality for atherosclerotic disease. Atherosclerosis of the arterial wall of the human carotid, aortic, peripheral and coronary arteries have all been successfully evaluated. In addition, the power of magnetic resonance imaging to differentiate the major components of atherosclerotic plaque has been validated. The ability to image the vessel wall and risk stratify atherosclerotic plaque will create management decisions not previously faced, and has the potential to change the way atherosclerosis is treated.     

Three-dimensional volumetric analysis of atherosclerotic plaques: a magnetic resonance imaging-based study of patients with moderate stenosis carotid artery disease

Atherosclerotic plaque burden has a strong correlation with plaque vulnerability. Three-dimensional (3D) volumetric assessment of atherosclerotic plaques has been suggested as an accurate method of quantifying plaque burden but has not been performed. In this study we use high-resolution magnetic resonance (MR) imaging to compare 3D volume differences of asymptomatic and acutely symptomatic carotid plaques (i.e. had cerebrovascular ischaemic symptoms within the previous 72 h of MR imaging). One hundred patients (46 acutely symptomatic and 54 asymptomatic) with atherosclerotic carotid artery disease underwent carotid MR imaging. Manual segmentation of plaque components was done to delineate lipid, fibrous tissue and plaque haemorrhage (PH). 3D-volume reconstruction of plaque components was done and used for comparison. Acutely symptomatic plaques had a lower normalized wall index and normalized volume index than the asymptomatic group (P = 0.04 and 0.01 respectively). Median percentage lipid volume was higher for asymptomatic plaques (28 vs. 5%, P = 0.004). However, the median percentage volume and prevalence of PH was higher in the acutely symptomatic group (P = 0.01 and 0.02 respectively). Acutely symptomatic plaques have less lipid content immediately after the acute event than asymptomatic plaques. This is most likely because of the escape of lipid-rich atheromatous debris into the blood stream at the time of plaque rupture. Due to this paradox, “high” lipid content of a plaque may not be a reliable feature of estimating its vulnerability immediately following the acute event. PH, which is prevalent and consistent in such plaques, may be a better indicator of plaque vulnerability during that period.     

Advances in Molecular Imaging: Plaque Imaging

Recent advances in nuclear plaque imaging aim to achieve noninvasive identification of vulnerable atherosclerotic plaques using positron emission tomography (PET) with ¹⁸F-fluorodexoyglucose (FDG) and novel tracers targeting molecular markers of inflammation and other active metabolic processes. Nuclear imaging of atherosclerosis has been demonstrated in multiple vascular beds, including the carotid, aorta, peripheral and coronary arteries—but significant challenges remain, especially for coronary imaging. The advantage of PET over other molecular imaging modalities is its superior sensitivity, however, low spatial resolution means that images must be co-registered with computed tomography (CT) or magnetic resonance imaging (MRI) for precise anatomical localization of the PET signal. Such hybrid techniques provide the best hope for early detection of prospective culprit lesions—which may, in the coronary vasculature, appear falsely low-risk using conventional coronary angiography or stress imaging. Current hot topics in nuclear plaque imaging include the use of FDG-PET for therapeutic monitoring in drug development, identification of imaging biomarkers to evaluate cardiovascular risk, and the development of novel tracers against an array of biologically important markers of atherosclerosis. The purpose of this article is to review these recent advances in nuclear plaque imaging.     

颈动脉粥样硬化斑块的声学密度定量分析

目的：探讨声学密度技术对颈动脉粥样硬化斑块组织定征诊断价值及其对斑块危险性的评估价值。方法：使用Hpsonos5500型彩色多普勒超声仪,采用AD技术分析50例患者76块斑块的背向散射积分（IBS值）及IBS标化值（IBS%值）,了解不同类型斑块的声学密度情况;对比有无脑梗死患者斑块的IBS值、IBS%值及不同类型斑块的发生率。结果：不同类型颈动脉粥样硬化斑块的发生率依次为扁平斑38.11%、软斑27.63%、硬斑22.37%、溃疡斑11.84%;不同类型斑块IBS值不同：硬斑34.32±1.10dB,扁平斑表面20.12±1.07dB,软斑与扁平斑内部相同15.93±0.71dB,溃疡斑8.41±1.03dB;IBS%亦不同,各组间比较有统计学差异（P〈0.05）;脑梗死组斑块IBS值及IBS%值均低于非脑梗死组（P〈0.05）;脑梗死组软斑和溃疡斑的比例高于非脑梗死组（P〈0.05）。结论：声学密度定量技术可反映粥样硬化斑块不同的组织成分;声学密度定量技术可评价颈动脉粥样硬化斑块的危险性。     

In vivo detection of carotid plaque thrombus by ultrasonic tissue characterization

The purpose of the study was to determine whether ultrasonic tissue characterization could detect carotid plaque thrombus in vivo. Patients undergoing carotid endarterectomy were examined preoperatively and the ultrasonic tissue characterization findings were compared to those of optical microscopy of the removed plaque specimens. Ten of 15 patients studied had plaque thrombus. Ultra-ultrasonic tissue characterization entailed an analysis of parameters obtained from the power spectrum of backscattered ultrasound signals. Data were obtained with a nominal 10 MHz sector scanning transducer with an effective bandwidth of 3 to 13 MHz. The parameters were the slope and intercept derived from the linear regression of the normalized spectrum and total power (log of the integrated power of the normalized spectrum over the effective bandwidth). The combined effect of the three parameters was determined by discriminant function analysis and showed a significant difference (P < 0.05) between nonthrombus and plaque thrombus in a small sample of patients with advance carotid atherosclerosis. These parameters applied singly could not provide such a distinction. Correct classification of carotid plaque thrombus using the multiple-parameter analysis revealed a sensitivity of 90%, specificity of 80%, and accuracy of 86.7%. This study demonstrates that analysis utilizing a combination of multiple spectral parameters was able to detect carotid plaque thrombus in vivo.     

颈动脉易损斑块MRI表现与缺血性脑卒中的风险预测

目的应用磁共振高分辨率成像技术,探讨颈动脉易损斑块MR表现与缺血性脑卒中风险预测。材料与方法经B超检查筛选颈动脉斑块并行颈部血管磁共振检查的200例老年患者,颈动脉斑块分稳定斑块组和易损斑块组,分析两组斑块成分(脂质核团,脂质坏死核心,斑块内出血,钙化,纤维帽是否破裂)及管腔狭窄程度,随访60 d内发生缺血性脑卒中的患者。结果稳定斑块组112例,60 d内发生缺血性脑卒中的患者2例;易损斑块组88例,60 d内发生缺血性脑卒中26例。结论颈动脉易损斑块与60 d内发生缺血性脑卒中有显著相关性,可以作为颈动脉狭窄患者近期临床症状的预测指标。     

Characterization and molecular detection of atherothrombosis by magnetic resonance--potential tools for individual risk assessment and diagnostics

This review focuses on recent non-invasive or minimally invasive magnetic resonance (MR) approaches to study atherothrombosis. The potential benefits of combining diverse metabolic information obtained by the variety of MR techniques from tissues in vivo and ex vivo and from body fluids in vitro are also briefly discussed. A well established methodology is available for lipoprotein subclass quantification from plasma by 1H MR spectroscopy providing information for assessing the long-term risk of atherosclerosis. Multi-contrast MR imaging in vivo relying on endogenous contrast allows partial characterization of components in atherothrombotic plaques. The use of exogenous contrast agents in MR angiography enhances blood-tissue contrast and provides functional information on plaque metabolism, improving plaque characterization and assessment of plaque vulnerability by MR imaging. Recent applications of molecular targeted MR imaging have revealed novel opportunities for specific early detection of atherothrombotic processes, such as angiogenesis and accumulation of macrophages. Currently, MR imaging and spectroscopy can produce such metabolic in vivo and in vitro information that in combination could facilitate the screening, identification and follow-up of cardiovascularly vulnerable patients in research settings. The recent developments imply that in the near future MR techniques will be part of clinical protocols for individual diagnostics in atherothrombosis.     

高分辨磁共振成像对颈动脉粥样硬化斑块表面钙化与斑块稳定性关系研究

目的 通过高分辨磁共振成像(MRI)多序列扫描,分析颈动脉粥样硬化斑块的表面钙化的形状、位置与斑块稳定性的关系.方法 运用高分辨MRI多序列(3D-TOF、DIR T1WI、FSE T2WI、PDWI)对34例颈动脉斑块患者进行扫描,分析钙化类型和位置与斑块表面溃疡的关系.结果 87层表面钙化斑块,59层(67.8％)见斑块表面溃疡.按钙化类型和部位划分,64层为点状、弧形的不规则钙化,23层为大片状钙化;58层为边缘钙化,29层为中央钙化.不规则钙化组伴斑块表面溃疡的概率显著高于大片状钙化组;边缘钙化组较中央钙化组更易伴斑块表面溃疡.结论 表面钙化是斑块不稳定的重要因素之一,容易导致斑块表面溃疡形成;表面钙化的类型、部位对斑块的稳定性有重要影响.     

Non-Invasive Identification of Vulnerable Atherosclerotic Plaques Using Texture Analysis in Ultrasound Carotid Elastography: An In Vivo Feasibility Study Validated by Magnetic Resonance Imaging

The aims of this study were to quantify the textural information of strain rate images in ultrasound carotid elastography and evaluate the feasibility of using the textural features in discriminating stable and vulnerable plaques with magnetic resonance imaging as an in vivo reference. Ultrasound radiofrequency data were acquired in 80 carotid plaques from 52 patients, mainly in the longitudinal imaging view, and axial strain rate images were estimated with an ultrasound carotid elastography technique based on an optical flow algorithm. Four textural features of strain rate images—contrast, homogeneity, correlation and angular second moment—were derived based on the gray-level co-occurrence matrix in plaque regions to quantify the deformation distribution pattern. Conventional elastographic indices based on the magnitude of the absolute strain rate, such as the maximum, mean, median, standard deviation and 99th percentile of the axial strain rate, were also obtained for comparison. Composition measurement with magnetic resonance imaging identified 30 plaques as vulnerable and the other 50 as stable. The four textural features, as well as the magnitude of strain rate images, significantly differed between the two groups of plaques. The best performing features for plaque classification were found to be the contrast and 99th percentile of the absolute strain rate, with a comparative area under the receiver operating characteristic curve of 0.81; a slightly higher maximum accuracy of plaque classification can be achieved by the textural feature of contrast (83.8% vs. 81.3%). The results indicate that the use of texture analysis in plaque classification is feasible and that larger local deformations and higher level of complexity in deformation patterns (associated with the elastic or stiffness heterogeneity of plaque tissues) are more likely to occur in vulnerable plaques.     

Positron emission tomography of the vulnerable atherosclerotic plaque in man – a contemporary review

Atherosclerosis is the primary underlying cause of cardiovascular disease (CVD). It is the leading cause of morbidity and mortality in the Western world today and is set to become the prevailing disease and major cause of death worldwide by 2020. In the 1950s surgical intervention was introduced to treat symptomatic patients with high‐grade carotid artery stenosis due to atherosclerosis – a procedure known as carotid endarterectomy (CEA). By removing the atherosclerotic plaque from the affected carotid artery of these patients, CEA is beneficial by preventing subsequent ipsilateral ischemic stroke. However, it is known that patients with low to intermediate artery stenosis may still experience ischemic events, leading clinicians to consider plaque composition as an important feature of atherosclerosis. Today molecular imaging can be used for characterization, visualization and quantification of cellular and subcellular physiological processes as they take place in vivo; using this technology we can obtain valuable information on atherosclerostic plaque composition. Applying molecular imaging clinically to atherosclerotic disease therefore has the potential to identify atherosclerotic plaques vulnerable to rupture. This could prove to be an important tool for the selection of patients for CEA surgery in a health system increasingly focused on individualized treatment. This review focuses on current advances and future developments of in vivo atherosclerosis PET imaging in man.     

Intravascular magnetic resonance imaging

The purpose of this article is to review the current state of the art with respect to intravascular magnetic resonance imaging, including intravascular coils, their implementation for plaque identification and characterization, and strategies for future approaches to coronary imaging and other cardiovascular applications.     

Noninvasive imaging of atherosclerotic vessels by MRI for clinical assessment of the effectiveness of therapy

Atherosclerosis and its thrombotic complications are the major cause of morbidity and mortality in the industrialized countries. Despite advances in our understanding of the mechanisms of pathogenesis and new treatment modalities, the absence of an adequate noninvasive method for early detection limits prevention or treatment of patients with various degrees and localizations of atherothrombotic disease. The ideal clinical imaging modality for atherosclerosis should be safe, inexpensive, noninvasive or minimally invasive, accurate, and reproducible, thus allowing longitudinal studies in the same patients. Additionally, the results should correlate with the extent of atherosclerotic disease and have high predictive values for clinical events. In vivo, high-resolution magnetic resonance imaging (MRI) has recently emerged as one of the most promising techniques for the noninvasive study of atherothrombotic disease in several vascular beds such as the aorta, the carotid arteries, and the coronary arteries. Most importantly MRI can be used to characterize plaque composition as it allows the discrimination of lipid core, fibrosis, calcification, and intra-plaque hemorrhage deposits. MRI findings have been extensively validated against pathology in ex vivo studies of carotid, aortic, and coronary artery specimens obtained at autopsy and using experimental models of atherosclerosis. In vivo MRI of carotid arteries of patients referred for endarterectomy has shown a high correlation with pathology and with previous ex vivo results. A recent study in patients with plaques in the thoracic aorta showed that compared with transesophageal echocardiography plaque composition and size are more accurately characterized and measured using in vivo MRI. The composition of the plaque rather than the degree of stenosis determines the patient outcome. Therefore, a reliable noninvasive imaging tool able to detect early atherosclerotic disease in the various regions and identify the plaque composition is clinically desirable. MRI has potential in the detection arterial thrombi and in the definition of thrombus age. MRI has been used to monitor plaque progression and regression in several animal model of atherosclerosis and more recently in human. Advances in diagnosis prosper when they march hand-in-hand with advances in treatment. We stand at the threshold of accurate noninvasive assessment of atherosclerosis. Thus, MRI opens new strategies ranging from screening of high-risk patients for early detection and treatment as well as monitoring the target areas for pharmacological intervention.     

Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI,respectively, in the dal-PLAQUE study

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A₂, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.     

Characterization of carotid artery plaques with USPIO-enhanced MRI: assessment of inflammation and vascularity as in vivo imaging biomarkers for plaque vulnerability

To evaluate ultra small superparamagnetic iron oxide particles (USPIO) enhanced magnetic resonance (MR) imaging for characterization of atherosclerotic carotid plaques by assessing vascularity and plaque inflammation, besides contrast-enhanced MR angiography (CE-MRA) of the carotid artery stenosis. Twelve patients with severe carotid artery stenosis, scheduled for endarterectomy, underwent MRI of the carotid artery bifurcation using SHU 555 C at a dose of 40 μmol Fe/kg BW. The MR imaging protocol comprised pre- and post-contrast T2*-w, a first-pass CE-MRA and dynamic T1-w sequences. For quantitative data analysis, the signal intensities (SI) were measured and SNR-data (SNR = SI_{blood/plaque/bone marrow}/standard deviation_noise) as well as ΔSI-data (SNR_post–SNR_pre) were calculated. In addition, two radiologists rated the diagnostic performance of first-pass MRA according to a four level decision scale. Staining of anti-dextran (SHU 555 C) and anti-CD68 (macrophages) was performed for immunohistological confirmation. Plaque sections with a T2*-w signal decline (intracellular USPIO accumulation in macrophages) showed significantly changes (mean −14%, 95% CI, −5 to −20%; P < 0.01) and corresponding plaque regions had significantly higher (15.15 ± 1.76 vs. 5.22 ± 1.50; P < 0.01) T1-w enhancement data (global estimation of vascularity). The first-pass MRA of the supra-aortal vessels provided images of diagnostic quality. Representative immunohistology sections revealed colocalization of dextran- and CD68-immunoreactive cells. USPIO-enhanced MRI is feasible for in vivo assessment of vascularity and macrophage content in atherosclerotic carotid plaques, determining an association of these potential imaging biomarkers of plaque vulnerability. Diagnostic MRA of the supra-aortal vessels can be imaged additionally with a single administration of SHU 555 C.