Measurement of subclinical atherosclerosis: beyond risk factor assessment

PURPOSE OF REVIEW: Assessment of subclinical atherosclerosis using the current available noninvasive imaging modalities holds promise for individual cardiovascular risk management and monitoring efficacy of therapeutic interventions (i.e. surrogate end-points). The present review addresses benefits and limitations of flow-mediated dilatation, intima-media thickness, electron-beam computed tomography and magnetic resonance coronary angiography. RECENT FINDINGS: Both carotid intima-media thickness and peripheral flow-mediated dilatation correlate inversely with cardiovascular risk factors and coronary artery disease. They have been shown to carry predictive value for future cardiovascular events, but clinical application of both intima-media thickness and flow-mediated dilatation demands further methodological maturation of these techniques. Intima thickening has been successfully targeted in numerous intervention trials, but determination of an explicit threshold value beyond which cardiovascular risk significantly increases will facilitate its utility as a routine clinical tool. Electron-beam computed tomography can accurately detect and quantify coronary artery calcification (an established marker of the total coronary plaque burden). However, lack of evidence of its additional predictive power for future coronary events warrants for further research. Finally, magnetic resonance coronary angiography appears to be a promising technique, integrating both functional and anatomical aspects of coronary artery disease. Properly designed studies are needed to determine its value in clinical practice. SUMMARY: Various noninvasive imaging techniques have recently emerged that may find applications in clinical research. However, before widespread clinical utilization, further technical refinement of all of the cited imaging modalities is mandatory. It will be a challenge over the coming few years to clarify whether improvements in surrogate end-points can directly be translated into improved outcomes.     

Thematic review series: patient-oriented research. Imaging atherosclerosis: state of the art

The ability to image obstructive arterial disease brought about a revolution in clinical cardiovascular care; the development of newer technologies that image arterial wall thicknesses, areas, volumes, and composition allows valid imaging of atherosclerosis for the first time. Development of noninvasive imaging of atherosclerosis has further led to a quantum shift in research in the field by enabling the study of asymptomatic populations and thus allowing investigators to focus on preclinical disease without the many biases associated with the study of symptomatic patients. These noninvasive investigations have broad implications for clinical care as well. Coronary angiography, computed tomographic (CT) imaging of coronary calcium, intravascular ultrasound, multidetector CT angiography, B mode ultrasound of the carotid arteries, and MRI of the carotid arteries all have unique strengths and weaknesses for imaging atherosclerosis. Certain of these techniques are extremely useful as outcome variables for clinical trials, and others are uniquely useful as predictors of the risk of cardiovascular disease. All are informative in one way or another with regard to the role of plaque remodeling and composition in disease causation. CT and MRI technology are advancing very rapidly, and research and clinical uses of these imaging modalities promise to further advance our understanding of atherosclerosis and its prevention.     

Progress in noninvasive coronary artery imaging using multislice CT

Conventional coronary angiography (CAG) has been the reference standard for the assessment of coronary artery disease since its introduction in 1958. However, several studies have shown that diagnostic CAG has an average morbidity of 2% and a mortality of approximately 0.1%.In the last decade, progress in medical imaging has opened the way to noninvasive assessment of the coronary arteries at lower cost and risk. Of the different modalities, multislice CT (MSCT) has made the biggest step forward. At the 2005 European Congress of Radiology (ECR), experiences with the latest developments in noninvasive coronary artery imaging were reported. This report summarises the advances in the use of MSCT in coronary stenosis detection, emergency decision-making, plaque imaging, and the analysis of cardiac function and late enhancement. Also, attention is paid to new strategies to reduce MSCT-related radiation exposure.     

Pericardial fat amount is an independent risk factor of coronary artery stenosis assessed by multidetector-row computed tomography: the Korean Atherosclerosis Study 2

Pericardial fat surrounding the heart and coronary arteries might aggravate vessel wall inflammation and stimulate the progression of coronary atherosclerosis. However, there has been little comprehensive evaluation of the effects of pericardial fat on coronary artery disease (CAD). We investigated the relationship between pericardial fat volume and the severity of coronary artery stenosis assessed by computed tomography and angiography among patients with suspected CAD. Participants from the cohort of the Korean Atherosclerosis Study 2 (n = 402, mean age of 54 years, 57.0% men) underwent 64-slice multidetector-row computed tomography (MDCT) to assess pericardial fat amount, coronary artery calcium score (CACS), severity of coronary artery stenosis, and plaque characteristics. Patients with atherosclerotic lesion had significantly larger volume of pericardial fat than patients without atherosclerosis (308 ± 96 cm(3) vs. 251 ± 93 cm(3); P < 0.01). In a multivariate regression analysis adjusting for age, gender and BMI, subjects with more pericardial fat had a higher risk for significant (>50%) stenosed coronary vessels (odds ratio (OR) = 1.012; 95% confidence interval (CI) 1.001-1.030; P = 0.017). This association remained after adjusting for hypertension, diabetes, smoking status, and lipid profiles (OR = 1.007; 95% CI 1.001-1.014; P = 0.042). In conclusion, an increased pericardial fat volume was an independent risk factor for stenotic CAD and could be helpful in assessing subclinical CADs.     

Atherosclerotic plaque imaging using phase-contrast X-ray computed tomography

Reliable, noninvasive imaging modalities to characterize plaque components are clinically desirable for detecting unstable coronary plaques, which cause acute coronary syndrome. Although recent clinical developments in computed tomography (CT) have enabled the visualization of luminal narrowing and calcified plaques in coronary arteries, the identification of noncalcified plaque components remains difficult. Phase-contrast X-ray CT imaging has great potentials to reveal the structures inside biological soft tissues, because its sensitivity to light elements is almost 1,000 times greater than that of absorption-contrast X-ray imaging. Moreover, a specific mass density of tissue can be estimated using phase-contrast X-ray CT. Ex vivo phase-contrast X-ray CT was performed using a synchrotron radiation source (SPring-8, Japan) to investigate atherosclerotic plaque components of apolipoprotein E-deficient mice. Samples were also histologically analyzed. Phase-contrast X-ray CT at a spatial resolution of 10-20 mum revealed atherosclerotic plaque components easily, and thin fibrous caps were detected. The specific mass densities of these plaque components were quantitatively estimated. The mass density of lipid area was significantly lower (1.011 +/- 0.001766 g/ml) than that of smooth muscle area or collagen area (1.057 +/- 0.001407 and 1.080 +/- 0.001794 g/ml, respectively). Moreover, the three-dimensional assessment of plaques could provide their anatomical information. Phase-contrast X-ray CT can estimate the tissue mass density of atherosclerotic plaques and detect lipid-rich areas. It can be a promising noninvasive technique for the investigation of plaque components and detection of unstable coronary plaques.     

Non-invasive measurement of coronary heart disease using electron beam computed tomography

PURPOSE OF REVIEW: Electron beam computed tomography is a non-invasive investigation that can quantify calcification within the walls of coronary arteries. Coronary arteries remodel to maintain luminal integrity, so that significant plaque may be present before the development of luminal stenoses. This has led to interest in techniques that assess the coronary artery wall, rather than the lumen. This review examines the power of coronary calcification detected by electron beam computed tomography to predict coronary heart disease events, and outlines recent studies in which it has been used as a surrogate marker for coronary heart disease. RECENT FINDINGS: The predictive power of coronary calcification has been shown to exceed that of traditional coronary heart disease risk factors and possibly also coronary angiography. This may justify the use of coronary calcification as a surrogate marker for coronary heart disease, and studies have thus examined cross-sectional associations between coronary calcification and potential risk factors in healthy individuals and patients with diabetes, end-stage renal failure and familial hypercholesterolaemia. Intervention studies can use the rate of change of coronary calcification detected by serial electron beam computed tomography imaging as an end-point, rather than relying on coronary heart disease events. As every participant reaches an end-point, sufficient power can be attained with smaller numbers at substantially less cost. SUMMARY: Coronary calcification detected by electron beam computed tomography may prove an invaluable tool in the selection of at-risk individuals suitable for primary prevention, and a useful surrogate marker for coronary heart disease in clinical trials.     

TEMP/TDM et TEP/TDM en cardiologie : quel avenir ?

Over the recent years, clinical cardiology has witnessed a rapid evolution of multi-slice computed tomography (CT), starting with 4-slice CT developing into the current state of the heart 64-slice CT technology. This technology permits non-invasive visualization of the coronaries with high precision. CT coronary angiography will likely play an important role in the diagnosis of coronary artery disease. Because not all coronary stenoses detected by CT angiography are flow limiting, the stress myocardial perfusion imaging data complement the CT information. The integration of nuclear imaging (SPECT or PET) and CT data provides a potential opportunity to delineate the anatomic extent and the physiologic severity of coronary artery disease. The objective of this article is to provide a critical view of the relative strengths and weaknesses of myocardial perfusion imaging and CT coronary angiography, which we hope will help elucidate the potential role of these modalities in the diagnosis and management algorithms of patients with known or suspected coronary artery disease.     

Cardiac PET-CT: advanced hybrid imaging for the detection of coronary artery disease

Hybrid imaging of positron emission tomography (PET) together with computed tomography (CT) is rapidly emerging. In cardiology, this new advanced hybrid imaging modality allows quantification of cardiac perfusion in combination with assessment of coronary anatomy within a single scanning session of less than 45 minutes. The near-simultaneous anatomical evaluation of coronary arteries using CT and corresponding functional status using PET provides a wealth of complementary information in patients who are being evaluated for (suspected) coronary artery disease, and could help guide clinical patient management in a novel manner. Clinical experience gained with this recently introduced advanced hybrid imaging tool, however, is still limited and its implementation into daily clinical practice remains largely unchartered territory. This review discusses principles of perfusion PET, its diagnostic accuracy, and potential clinical applications of cardiac PET-CT in patients with ischaemic heart disease. (Neth Heart J 2010;18:90–8.)     

Coronary artery anomalies detected by MSCT-coronary angiography in the adult

Background. Before coronary evaluation by modern imaging techniques was feasible, premorbid diagnoses of coronary artery anomalies (CAAs) were usually made fortuitously by invasive coronary angiography (ICA). However, this technique is limited by its invasive and projectional nature. Coronary magnetic resonance angiography (CMRA) and multi-slice computed tomography (MSCT) broadened clinical information by enabling visualisation of the coronary arteries in their anatomical environment. Methods. This case series visualises and reviews anomalous coronary artery from the opposite sinus (ACAOS) and coronary artery fistulae. All CAAs were detected by means of 64-slice dual source computed tomography after 1000 cardiac scans at the Erasmus MC, Rotterdam, the Netherlands. Results. Eight ACAOS cases, one anomalous left coronary artery from the pulmonary artery (ALCAPA) and one congenital aneurysm of an aortic sinus were found. Seven out often detected CAAs were considered malignant whereas three CAAs of the ACAOS type (retroaortic path) were considered benign. Significant coronary artery disease was found in three out of eight ACAOS cases. In one of the ACAOS cases complete evaluation of the anomalous coronary artery was limited by motion artifacts. All five cases of right ACAOS were referred for MSCT because the right coronary artery could not be located by invasive angiography. Conclusion. All CAAs were easy to diagnose because of 3D imaging and high temporal and spatial resolution. High resolution made it possible to not only depict coronary artery abnormalities, but also to quantify luminal and vessel properties such as stenosis grade, aspects of plaque, anomalous vessel length, luminal area ratio and the asymmetry ratio. Because of its comprehensiveness, MSCT can be an effective imaging modality in patients suspected of coronary artery abnormalities caused by coronary artery disease, CAAs, or a combination of both. (Neth Heart J 2008;16:369-75.)     

Nuclear cardiac imaging for the assessment of myocardial viability

An important aspect of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy is the assessment of myocardial viability. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischaemia but at the same time benefit most from revascularisation. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using ²⁰¹thallium, ^99mTc-sestamibi, or ^99mTc- tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management.Metabolic and perfusion imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularisation. New techniques in the nuclear cardiology field, such as attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and noninvasive coronary angiography to myocardial perfusion imaging and quantification.     

Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography

Sudden fibrous cap disruption of 'high-risk' atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary arteries, causing acute coronary syndromes. High-risk atherosclerotic plaques are characterized by their specific cellular and biological content (in particular, a high density of macrophages), rather than by their impact on the vessel lumen. Early identification of high-risk plaques may be useful for preventing ischemic events. One major hurdle in detecting high-risk atherosclerotic plaques in coronary arteries is the lack of an imaging modality that allows for the identification of atherosclerotic plaque composition with high spatial and temporal resolutions. Here we show that macrophages in atherosclerotic plaques of rabbits can be detected with a clinical X-ray computed tomography (CT) scanner after the intravenous injection of a contrast agent formed of iodinated nanoparticles dispersed with surfactant. This contrast agent may become an important adjunct to the clinical evaluation of coronary arteries with CT.     

Epicardial Adipose Tissue Thickness Correlates with the Presence and Severity of Angiographic Coronary Artery Disease in Stable Patients with Chest Pain

Objective

Epicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD).

Methods

We measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis.

Results

Of 970 patients (age 60.9 years, 71% male), 75% (n = 731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; p = 0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was OR = 1.46 [1.03–2.08], p = 0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (p = 0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76.

Conclusion

Although left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.     

Computed high concentrations of low-density lipoprotein correlate with plaque locations in human coronary arteries

Subendothelial accumulation of low-density lipoprotein (LDL) in arterial walls is an initiator of atherosclerotic plaque formation. We report here on the correlation between healthy state subendothelial LDL concentration distribution and sites of subsequent plaque formation in coronary arteries of patients with coronary artery disease (CAD). We acquired left (LCA) and right coronary artery (RCA) and atherosclerotic plaque geometries of 60 patients with CAD using dual-source computed tomography angiography. After virtually removing all plaques to obtain an approximation of the arteries' healthy state, we calculated LDL concentration in the artery walls as a function of local lumen-side shear stress. We found that maximum subendothelial LDL concentrations at plaque locations were, on average, 45% (RCA) and 187% (LCA) higher than the respective average subendothelial concentration. Our results demonstrate that locally elevated subendothelial LDL concentration correlates with subsequent plaque formation at the same location.     

缺血性心肌病的多模态心血管影像学方法进展

近年来,超声(ultrasound, US)、CT冠状动脉造影(CT coronary angiography, CCTA)、血管内超声(intravenous ultrasound,IVUS)、光学相干断层成像(optical coherence tomography, OCT)、多层螺旋CT成像(multi-slice computed tomography, MSCT)、单光子发射计算机断层成像(single-photon emission computed tomography, SPECT)、正电子发射计算机断层成像(positron emission computed tomography, PET)及心脏磁共振(cardiac magnetic resonance, CMR)等多种心血管成像技术能够提供与冠脉病变及心肌形态和功能相关的解剖学、血流动力学、细胞生物学及病理生理学等方面的重要信息,在缺血性心肌病的临床诊疗及预后评估中发挥着日益重要的作用。然而,如何恰当选择的多模态心血管影像技术是临床医师面临的一大难题。因此,本文在归纳总结主要心血管成像技术临床应用进展的基础上,对多模态心血管影像学在缺血性心肌病相关的冠脉解剖与斑块成像、心肌功能、心肌灌注及心肌活性显像中的临床应用价值进行综述。旨在帮助临床医师客观认识各种成像技术的优势与不足,从而制定最优化的选择方案。     

Quantification of atherosclerotic plaque activity and vascular inflammation using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC) and carotid intimal medial thickness (C-IMT) provide information about the burden of disease. However, despite multiple validation studies of CAC, and C-IMT, these modalities do not accurately assess plaque characteristics, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events. [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity, an important source of cellular inflammation in vessel walls. More recently, we and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors and is also highly associated with overall burden of atherosclerosis. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy as well as longer term therapeutic lifestyle changes (16 months). The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications.     

Techniques d’imagerie de la cardiopathie ischémique : le point de vue du clinicien

Coronary angiography often remains an unavoidable gold standard in cardiology practice for determining the severity, extent and prognosis of coronary artery disease and for therapeutic decision making, although established non-invasive testing – such as myocardial perfusion imaging or stress echocardiography – have demonstrated their diagnostic value and their incremental pronostic value over coronary angiography. Newer noninvasive techniques, such as multidetector computed tomography and magnetic resonance imaging, are currently being validated and will very soon be considered as alternatives to these imaging modalities in clinical practice. Facing this wide choice of tests, the cardiology community has the difficult task to determine the role and place of these various investigating techniques and to evaluate their resource implications, in other words, to optimize the cost-efficacy and ratios in the management of coronary artery disease.     

Performances diagnostiques actuelles du coroscanner dans la détection de la maladie coronaire

Recent advances in multislice computed tomography (MSCT), which might represent a minimally invasive alternative to coronary angiography (CA), have allowed the ability to analyze coronary arteries. In this review, we present the current diagnostic performance of MSCT, as compared with the reference standard (CA), for the assessment of native coronary arteries, coronary in-stent restenosis and coronary artery bypass graft.     

Recommendations of the Spanish Societies of Radiation Oncology (SEOR), Nuclear Medicine & Molecular Imaging (SEMNiM), and Medical Physics (SEFM) on 18F-FDG PET-CT for radiotherapy treatment planning

Positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (FDG) is a valuable tool for diagnosing and staging malignant lesions. The fusion of PET and computed tomography (CT) yields images that contain both metabolic and morphological information, which, taken together, have improved the diagnostic precision of PET in oncology. The main imaging modality for planning radiotherapy treatment is CT. However, PET-CT is an emerging modality for use in planning treatments because it allows for more accurate treatment volume definition. The use of PET-CT for treatment planning is highly complex, and protocols and standards for its use are still being developed. It seems probable that PET-CT will eventually replace current CT-based planning methods, but this will require a full understanding of the relevant technical aspects of PET-CT planning. The aim of the present document is to review these technical aspects and to provide recommendations for clinical use of this imaging modality in the radiotherapy planning process.     

大咯血介入治疗失败的罕见原因：腹腔动脉系统参与供血（附2例报告及文献复习）

目的：咯血的主要责任血管是支气管动脉,非支气管性体动脉参与供血是大咯血介入治疗失败的重要原因,腹腔动脉系统分支动脉参与供血更为罕见。本文通过收集相关病例,结合国内外相关研究,提高对腹腔动脉系统分支动脉为咯血责任动脉的认识,探讨其可能的病理机制、危险因素。方法：回顾分析2例腹腔动脉系统分支（胃左动脉、肝左动脉）参与大咯血供血动脉的临床及影像学资料,并报道介入栓塞治疗的效果。结果：2例患者均为支气管动脉栓塞后再发大咯血,再次血管造影显示1例肝左动脉参与供血,1例胃左动脉参与供血。栓塞上述血管后,患者止血成功。病变位于下肺、伴有胸膜增厚,提示有腹腔动脉系统分支动脉参与供血的可能。术前仔细阅读患者影像学资料,术前行主动脉分支动脉CT血管成像,可减少对责任性非支气管性体动脉的遗漏。结论：腹腔动脉系统参与供血是介入栓塞治疗后咯血复发的少见原因,了解其病理机制、危险因素,及时进行栓塞,可以降低咯血的复发率。     

Construction of healthy arteries using computed tomography and virtual histology intravascular ultrasound

Vessel geometry for numerical analysis is generally obtained by computed tomography (CT) or magnetic resonance imaging (MRI) and intravascular ultrasound (IVUS). Most medical imaging is obtained from patients for hemodynamic analysis due to the properties of vascular disease and the difficulties in angiography. To predict the site where plaque occurs and understand the progression of the lesion, however, it is necessary to take into consideration not only the diseased artery, but also the blood flow characteristics of healthy artery. In order to simulate healthy vessels prior to lesion formation, we performed CT and virtual histology intravascular ultrasound (VH-IVUS) on three actual patients and this data was used to develop criteria for healthy vessel construction, a method that virtually removes all intravascular plaque. The lumen of a vessel generated by CT and the lumen from VH-IVUS were compared, and the cross-sectional areas of plaque components (fibrous, fibrofatty, dense calcium, and necrotic) and the lumen from VH-IVUS were analyzed. Geometric differences in the healthy vessel and diseased vessel were analyzed, and flow characteristics of the healthy vessel and diseased vessel were compared through computational fluid dynamics simulation. Low average wall shear stress (AWSS) was distributed in the site where plaque was removed from the healthy vessel, and a high oscillatory shear index (OSI) was observed in the region proximal to the site where plaque previously existed. Low AWSS and high OSI are widely accepted indicators of plaque formation or the direction of plaque progression. A numerical model that effectively predicts lesion forming sites was also generated based on the healthy vessel construction method presented in this study.