Review“In vivo” imaging of atherosclerosis
Introduction
The enormous progress in our understanding of atherosclerosis during the last two decades and the rapid translational of research and technology from bench to bedside have allowed to open the way to explore – in vivo‖ atherosclerosis for both clinical and investigational applications [1]. Despite these advances further evolution of non-invasive imaging for evaluation of atherosclerosis could promote the prevention or treatment of atherothrombotic disease. The ideal clinical imaging modality for atherosclerosis should be safe, accurate, inexpensive, non-invasive or minimally invasive, and reproducible, thus allowing longitudinal studies in the same patients. Imaging should possibly also assess the extent of atherosclerotic disease and reliably predict clinical events. Vascular imaging can potentially offer a comprehensive assessment of atherothrombosis in the following clinical and research areas: 1) detection of pre-clinical disease, thus improving primary prevention; 2) assessment of the burden, extent and progression/or regression of atherosclerosis; 3) definition of stable vs. unstable atherosclerotic plaque improving secondary prevention and treatment; 4) “in vivo” understanding of mechanisms of disease.
This review stems out of a European Society Working Group meeting on Peripheral Circulation hold in Zürich in 2010 where European and American experts discussed and summarized this important rapidly growing clinical and research field from different perspectives.
Section snippets
Imaging atherosclerosis: the cardio-pathologist's view
Atherosclerosis is a systemic, mainly lipid-driven inflammatory disease of the arterial wall leading to multifocal plaque development [2]. The disease begins early in life but it usually takes decades to develop symptomatic lesions, offering excellent opportunities for timely detection and treatment of subclinical atherosclerosis to prevent disease progression responsible for morbidity and mortality.
During a life-time, most atherosclerotic plaques remain asymptomatic, some may become
Ultrasound
Ultrasound (US) has been the first platform to visualize in vivo‖ the human vessel wall and atherosclerosis. The paradigm application of US is the Duplex-US of the carotid artery which allows measurement of carotid Intima Media thickening (c-IMT), a surrogate endpoint to assess the natural history of atherosclerosis and the effects of interventions potentially able to modify atherosclerosis progression [12], [13]. With well-trained operators, c-IMT has been shown to be accurate with excellent
Assessment of plaque burden
Intravascular imaging contributed to the understanding of atherosclerosis in humans and to the translation of novel therapies to the clinic. Grayscale intracoronary ultrasounds (ICUS), for example, can measure the longitudinal changes in plaque burden by summing cross-sectional plaque volume along coronary arteries. ICUS studies have evaluated the effect of various lipid lowering drugs on atherosclerotic burden. Whereas the efficacy of lowering LDL-C with inhibitors of hydroxymethylglutaryl
Molecular imaging of atherosclerosis (Fig. 6 and Table 2)
Most imaging modalities interrogate structure or anatomy rather than the biological characteristics of atherosclerotic plaques. Recent observations emphasize the importance of plaque characteristics, beyond mere size or degree of stenosis, as clinically relevant key features [5], [100], [101]. Molecular imaging aims to leverage recent advances in understanding the biology of plaques related to their thrombotic complications, as an avenue to adding a new dimension to atherosclerosis imaging [102]
Conclusions
While we know a great deal on molecular mechanisms of plaque evolution, investigated in atherosclerotic animals, the transition from plaque stability to instability has been hampered by a lack of experimental models, that reflect faithfully human disease. The abrupt clinical presentation of acute coronary events strongly indicates discontinuity in the natural history of atherothrombosis. The causes of such discontinuity are complex and probably multiple; in a subset of patients they are related
Acknowledgments
AG and RC are receiving grants by the Swiss Heart Foundation and Swiss National Research Foundation (research grant Number SNF-320000-109905). AG, JL, CV and FC on behalf of the ESC Working Group Peripheral Circulation.
References (114)
- et al.
Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: a pathologic study
J Am Coll Cardiol
(2007) - et al.
Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography carotid intima-media thickness Task Force. Endorsed by the Society for vascular Medicine
J Am Soc Echocardiogr
(2008) - et al.
Carotid intima-media thickness and the presence or absence of plaque improves prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study
J Am Coll Cardiol
(2010) - et al.
The ARBITER 6-HALTS trial (Arterial biology for the investigation of the treatment effects of reducing Cholesterol 6-HDL and LDL treatment Strategies in atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration
J Am Coll Cardiol
(2010 Jun 15) - et al.
Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10–year follow-up study (the CAFES-CAVE study(1)
Atherosclerosis
(2001) - et al.
Atheroma of the aortic arch: an important and poorly recognised factor in the aetiology of stroke
Lancet Neurol
(2004) - et al.
The BioImage study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease-study design and objectives
Am Heart J
(2010) - et al.
Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques
JACC Cardiovasc Imaging
(2010) - et al.
An echolucent carotid artery intimamedia complex is a new and independent predictor of mortality in an elderly male cohort
Atherosclerosis
(2009) - et al.
3rdEffect of simvastatin (80 mg) on coronary and abdominal aortic rterial calcium
Am J Cardiol
(2007)