Multi-Modality Imaging of Atheromatous Plaques in Peripheral Arterial Disease: Integrating Molecular and Imaging Markers

Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of the limb arteries, primarily due to atherosclerosis. Non-invasive multi-modality imaging approaches using computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging have emerged as valuable tools for assessing PAD atheromatous plaques and vessel walls. This review provides an overview of these different imaging techniques, their advantages, limitations, and recent advancements. In addition, this review highlights the importance of molecular markers, including those related to inflammation, endothelial dysfunction, and oxidative stress, in PAD pathophysiology. The potential of integrating molecular and imaging markers for an improved understanding of PAD is also discussed. Despite the promise of this integrative approach, there remain several challenges, including technical limitations in imaging modalities and the need for novel molecular marker discovery and validation. Addressing these challenges and embracing future directions in the field will be essential for maximizing the potential of molecular and imaging markers for improving PAD patient outcomes

CT imaging features of carotid artery plaque vulnerability

Despite steady advances in medical care, cardiovascular disease remains one of the main causes of death and long-term morbidity worldwide. Up to 30% of strokes are associated with the presence of carotid atherosclerotic plaques. While the degree of stenosis has long been recognized as the main guiding factor in risk stratification and therapeutical decisions, recent evidence suggests that features of unstable, or 'vulnerable', plaques offer better prognostication capabilities. This paradigmatic shift has motivated researchers to explore the potentialities of non-invasive diagnostic tools to image not only the lumen, but also the vascular wall and the structural characteristics of the plaque. The present review will offer a panoramic on the imaging modalities currently available to characterize carotid atherosclerotic plaques and, in particular, it will focus on the increasingly important role covered by multidetector computed tomographic angiography

Unstable carotid artery plaque: new insights and controversies in diagnostics and treatment

Cardiovascular disease is estimated to be the leading cause of death, globally causing 14 million deaths each year. Stroke remains a massive public health problem and there is an increasing need for better strategies for the prevention and treatment of this disease. At least 20% of ischemic strokes are thromboembolic in nature, caused by a thromboembolism from an atherosclerotic plaque at the carotid bifurcation or the internal carotid artery. Current clinical guidelines for both primary and secondary prevention of stroke in patients with carotid stenosis caused by atherosclerotic plaques remain reliant on general patient characteristics (traditional risk factors for stroke) and static measures of the degree of artery stenosis. Patients with similar traditional risk factors, however, have been found to have different risk of stroke, and it has in recent years become increasingly clear that the degree of artery stenosis alone is not the best estimation of stroke risk. There is a need for new methods for the assessment of stroke risk to improve risk prediction for the individual patient. This review aims to give an overview of new methods available for the identification of carotid plaque instability and the assessment of stroke risk

Plaque imaging volume analysis: technique and application

The prevention and management of atherosclerosis poses a tough challenge to public health organizations worldwide. Together with myocardial infarction, stroke represents its main manifestation, with up to 25% of all ischemic strokes being caused by thromboembolism arising from the carotid arteries. Therefore, a vast number of publications have focused on the characterization of the culprit lesion, the atherosclerotic plaque. A paradigm shift appears to be taking place at the current state of research, as the attention is gradually moving from the classically defined degree of stenosis to the identification of features of plaque vulnerability, which appear to be more reliable predictors of recurrent cerebrovascular events. The present review will offer a perspective on the present state of research in the field of carotid atherosclerotic disease, focusing on the imaging modalities currently used in the study of the carotid plaque and the impact that such diagnostic means are having in the clinical setting

Blood Flow Regulates Atherosclerosis Progression and Regression

Atherosclerosis is the most prevalent pathology of cardiovascular disease with no known cure. Despite the many systemic risk factors for atherosclerosis, plaques do not form randomly in the vasculature. Instead, they form around bifurcations and the inner curvature of highly curving arterial segments that contain so-called disturbed blood flow that is low in magnitude and multidirectional over the cardiac cycle. Conversely, straight, non-bifurcated arterial segments that contain moderate-to-high and unidirectional (i.e., normal) blood flow are protected from plaque development. Thus, blood flow is a key regulator of atherosclerosis that may be able to be leveraged to develop new therapeutics. Towards this end, we performed two studies using a mouse model of atherosclerosis where a blood flow-modifying cuff was placed around the left carotid artery to induce disturbed blood flow and, in turn, plaque development. In the first study, we evaluated the hypothesis that injected nanoparticles had different accumulation kinetics in different types of disturbed flow (low versus multidirectional). We found that the blood flow profile did not affect accumulation, but the resultant plaque phenotype did. This suggests that nanoparticles could be used to target certain plaque types. In the second study, we evaluated the hypothesis that restored normal blood flow in atherosclerotic arteries promotes plaque stabilization. Our findings supported this hypothesis and also showed that the combination of normal blood flow and atorvastatin produced additive beneficial effects that led to plaque regression. This result suggests that mechanical stimuli can be therapeutic. Since the endothelium directly senses blood flow and plays a key role in atherosclerosis development, we finally characterized how different flow profiles affect atheroprotective versus atherogenic endothelial signaling molecules. Ultimately, this work provides a foundation for the development of a new therapeutic for atherosclerosis based on the beneficial effects of normal blood flow. Advisor: Ryan M. Pedrig