Current Drug Targets - Cardiovascular & Hematological Disorders - Volume 4, Issue 2, 2004

The reasons to measure atherosclerosis include 1) risk stratification and prediction; 2) evaluation of patient response to interventions; and 3) identification of novel genetic, cellular and molecular determinants of risk. Atherosclerosis can be quantified non-invasively using the increasingly reliable and precise modalities described in this issue, which include ultrasound and magnetic resonance imaging. While each modality assesses “atherosclerosis”, the particular morphological entities captured may reflect different aspects of atherogenesis with different biological determinants. For instance, among carotid ultrasound determinations, intima-media thickness (IMT) may reflect medial hypertrophy from hypertension, while plaque volume and stenosis and calcium deposition may additionally reflect foam cell proliferation, scarring and / or thrombosis. Clarifying the biological and clinical correlates of images may guide the choice of modality for specific applications. In addition, these tools are presently used to assess structures at a single time point. However, using them to follow temporal changes may further enhance their value. In this regard, certain modalities, such as ultrasound assessment of carotid plaque area or volume, may be more sensitive than others, such as assessment of IMT, for detecting temporal changes in atherosclerosis. Combining modalities - and adding new biomarkers of disease - may be necessary to grasp the full complex vascular phenotypic picture - “phenomics” - of both individual subjects and groups of patients. In evaluating new determinants and novel therapies, it will be important to consider the biology and clinical correlates of a specific measured atherosclerosis phenotype in order to select the most appropriate modality.

Atherosclerosis evolves from the vascular wall. The initial build-up starts at the inner layers of the intima media complex of the artery. To track these phases of the beginning of disease requires a technique that can reliably detect and follow the extent and severity non-invasively over time. The artery that is accessible and indicative for the process of atherosclerosis is the carotid artery. The Quantitative assessment of the Intima Media Thickness (IMT) using ultrasound is safe, validated and portable, is inexpensive, and can be used in multicenter studies. IMT coupled with an interactive large multi-ethnic may provide a reliable tool to predict the likelihood of cardiovascular complications like myocardial infarction or stroke. QIMT combines the quantitative analyses and assessment of the far wall of the common carotid artery in a specific area, proximal to the bulb, that includes a fully automatic algorithm interacting with an ethnically diverse database. Many new and exciting applications where the underlying disease has an impact on cardiovascular disease have been added to its cardiovascular current use. The standardization of the whole procedure from image acquisition, transport of images, computerized assessment of images and interactive assessment for a specific individual is critical in its new and expanded role. Unfortunately the vast majority of the current systems do not adhere to these requirements, leading to a false sense of security when a value is provided. Given the lack of standardization in most IMT programs, a new valid standard is urgently needed, with the dissemination of these new concepts of application happens. The QIMT method of assessment of the far wall of the common carotid artery is validated, reproducible and the preferred method proposed for standardization. Different specialties should be approached and contribute in the expansion of its use, as opposed to the current trend to limit QIMT to specific healthcare areas.

The MR imaging of carotid artery and aortic plaque has undergone significant improvement in the last decade. Early studies utilizing ex vivo specimens and spin echo or fast spin echo imaging, led to the conclusion that T2-weighting was the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2w signal intensities among the various plaque components, which can be partially offset by the use of qualitative or multi-spectral analysis of multiple contrast images. With improvements in coil design, sequence design, main field and gradient capabilities, accurate in vivo differentiation and measurement of these various plaque components should be possible in a few years. Carotid and aortic plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MR imaging of the diseased carotid artery and aortic wall may prove to be even more important than MR angiography or other current clinical tests.

Although ultrasonography is an important cost-effective imaging modality, technical improvements are needed before its full potential is realized for accurate and reproducible monitoring of carotid disease and plaque burden. 2D viewing of 3D anatomy, using conventional ultrasonography limits our ability to quantify and visualize carotid disease and is partly responsible for the reported variability in diagnosis and monitoring of disease progression. Efforts of investigators have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that are capable of acquiring B-mode, color Doppler and power Doppler images of the carotid arteries using existing conventional ultrasound systems, reconstructing the information into 3D images, and then allowing interactive viewing of the 3D images on inexpensive desktop computers. In addition, the availability of 3D ultrasound images of the carotid arteries has allowed the development of techniques to quantify plaque volume and surface morphology as well as allowing registration with other 3D imaging modalities. This paper describes 3D ultrasound imaging techniques used to image the carotid arteries and summarizes some of the developments aimed at quantifying plaque volume and morphology.

Coronary artery calcification has long been known to be associated with atherosclerosis and is intimately associated with atherosclerotic plaque development. Similarly, aortic valve degeneration and calcification appears to follow a pathophysiologic process very similar to atherosclerosis. Newer noninvasive technologies such as Electron Beam Tomography (EBT) allow the practicing physician to accurately detect and quantify cardiovascular calcification. It has recently become apparent that coronary calcium is an excellent marker of risk for myocardial infarction and sudden death in an individual patient and that aortic valve sclerosis is associated with high risk of coronary events. Besides identification and quantification of cardiovascular calcification, the EBT technology has also been employed to accurately measure the rate of progression of coronary calcification and it could become a very helpful tool to gauge effectiveness of therapy instituted to halt the progression of atherosclerosis. In this article we present a review of the studies published to date on the use of EBT imaging to gauge the effects of medical therapy on coronary and valvular calcification.

Complex blood flow dynamics are thought to play a key role in the development and treatment of atherosclerosis; however, the exact nature of this role is incompletely understood owing to the practical difficulties associated with measuring important local hemodynamic factors, notably wall shear stresses, in vivo. Only recently has it become possible to consider mapping these hemodynamic factors in a prospective, patient-specific manner via the coupling of in vivo medical imaging and computational fluid dynamics (CFD) modelling. CFD models derived from intravascular ultrasound have already been used to elucidate the role that hemodynamic forces play in mechanical and pharmacological interventions for coronary atherosclerosis. CFD models derived from magnetic resonance imaging and three-dimensional ultrasound provide a less invasive window into more superficial vessels such as the carotid bifurcation, and thus are promising tools for clarifying the role of, and eventually exploiting, purported local geometric and hemodynamic risk factors for atherosclerosis and its response to therapeutic options. Efforts to improve the ease and robustness with which these models are constructed have led to concomitant improvements in accuracy and precision, data for which are presented to facilitate estimation of sample sizes for future studies. Current limitations and anticipated future directions for these powerful new tools are discussed.