MRI Of Atherosclerosis Research Articles

Molecular MRI of Atherosclerosis with USPIO

Inflammation in atherosclerosis is a risk factor for plaque rupture and atherothrombosis. USPIO-enhanced MRI is capable of evaluating the inflammatory activity in vivo on a cellular as well as a sub-cellular level. This paper reviews the recent advances in USPIO-enhanced MRI of atherosclerotic plaque inflammation. Imaging strategies for evidentiating the presence of the USPIO label in plaques take advantage of the susceptibility effect induced by the nanoparticles in their surroundings to obtain a negative contrast (T2* weighted imaging) or a positive contrast (the White Maker and Susceptibility Gradient Mapping). Quantitative methods have more recently been adapted to in vivo imaging of USPIO in atherosclerotic plaques, and showed great promise in detecting treatment responses. When they are not taken up rapidly from blood by the reticulo-endothelial system (RES), USPIOs nanoparticles passively target inflammation in atherosclerosis by engulfment in intra-plaque phagocytic cells. This has been demonstrated in both animal models and human patients. However, by modifying the surface of coating materials, nanoparticles can actively target atherosclerosis molecular and cellular actors in animal models. The goal of molecular imaging of atherosclerotic plaques is to identify events in the early onset of the disease, as well as critical evolution to vulnerable plaques. USPIO agents are preferred as basis to develop targeted agents because of the ability to overcome the toxicity issue of long-term body residence of Gd-based agents, and their lower sensitivity based on their relaxivity properties. MRI agents capable of efficiently targeting oxidized LDL, cell adhesion molecules (VCAM-1, P-selectin, E-selection), apoptosis and activated platelets have been demonstrated in animal models. The use of these methodologies at the clinical level will depend on the availability and toxicity profiles of the agents, and will require standardized state of the art imaging techniques.

MRI of atherosclerosis: from mouse to man

Atherosclerosis and its thrombotic complications still remain the major cause of morbidity and mortality in western societies. Atherogenesis in humans generally occurs over decades, and lesion evolution and growth may vary according to heredity, gender, lifestyle and environmental conditions. However, the development of animal models of experimental atherosclerosis and the emergence of several imaging modalities have provided indispensable knowledge to our understanding of the fundamental mechanisms of disease progression and allowed the in vivo detection of atherosclerosis in animals and humans. MRI has evolved as one of the leading noninvasive imaging modalities to visualize the vessel wall with high spatial resolution and without ionizing radiation. This article summarizes the currently available animal models of experimentally induced atherosclerosis and the application of MRI in preclinical and clinical imaging studies.

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.

Novel Transgenic Rabbit Model Sheds Light on the Puzzling Role of Matrix Metalloproteinase-12 in Atherosclerosis

Matrix metalloproteinases (MMPs), also termed matrixins, are known to affect atherosclerosis in many diverse ways.1–3 Apart from a role in the progression of atherosclerotic lesions, MMPs have also been involved in plaque destabilization and rupture and in the development of aneurysms. Despite intense research efforts during the last decade, it has been challenging to formulate a unifying model on the specific role of MMPs in atherosclerosis. In fact, mouse genetic studies have yielded controversial insights, highly dependent on genetic background, dietary regimen, and arterial site of analysis, whereas human genetic association studies do not prove causality of MMPs in atherosclerosis. Moreover, the lack of specific inhibitors precluded pharmacological dissection of the role of MMPs in vivo. There is thus a need for alternative strategies to decipher the MMP puzzle in atherosclerosis. In this issue of Circulation , Liang et al4 used a novel approach: They generated transgenic rabbits to study the role of MMP-12, also known as macrophage elastase, in atherosclerosis. Their results indicate that MMP-12 causes media destruction and pseudoaneurysm formation and, more surprisingly, accelerates plaque growth in an animal model that more closely resembles atherosclerosis in humans. Article p 1993 MMPs belong to one of the most ancient families of enzymes that arose in evolution soon after the first signs of life to regulate, in general, interactions of cells with the extracellular matrix (ECM). To cope with this formidable challenge, more than 65 structurally related MMPs developed in bacteria, plants, nematodes, fruit flies, sea urchins, and vertebrates. One of their key activities is breaking down ECM substrates in the basement membrane and interstitial matrix.1,2 As such, MMPs facilitate migration of macrophages and smooth muscle cells (SMCs) in atherosclerotic plaques by degrading ECM barriers, exposing novel ECM adhesion sites, and relieving the binding between basement membrane …

New Investigator Awards

Beginning in 2005, three new investigators will be honored each year for their outstanding papers in Arteriosclerosis, Thrombosis, and Vascular Biology . The first authors of one original paper each year in each section of the journal (Vascular Biology, Atherosclerosis and Lipoproteins, and Thrombosis) will be honored. Goals of the awards are to recognize outstanding work …