Takehiro Nakahara

Coronary Artery Calcification: From Mechanism to Molecular Imaging

Vascular calcification is a hallmark of atherosclerosis. The location, density, and confluence of calcification may change portions of the arterial conduit to a noncompliant structure. Calcifications may also seed the cap of a thin cap fibroatheroma, altering tensile forces on the cap and rendering the lesion prone to rupture. Many local and systemic factors participate in this process, including hyperlipidemia, ongoing inflammation, large necrotic cores, and diabetes. Vascular cells can undergo chondrogenic or osteogenic differentiation, causing mineralization of membranous bone and formation of endochondral bone. Calcifying vascular cells are derived from local smooth muscle cells and circulating hematopoietic stem cells (especially in intimal calcification). Matrix vesicles in the extracellular space of the necrotic core serve as a nidus for calcification. Although coronary calcification is a marker of coronary atheroma, dense calcification (>400 HU) is usually associated with stable plaques. Conversely, microcalcification (often also referred to as spotty calcification) is more commonly an accompaniment of vulnerable plaques. Recent studies have suggested that microcalcification in the fibrous cap may increase local tissue stress (depending on the proximity of one microcalcific locus to another, and the orientation of the microcalcification in reference to blood flow), resulting in plaque instability. It has been proposed that positron emission tomography imaging with sodium fluoride may identify early calcific deposits and hence high-risk plaques.

From inflammation to calcification in atherosclerosis

Selecting appropriate therapy for a specific patient with cardiovascular disease requires markers of both disease severity and location to identify the risk of a clinical event. Classic markers, such as the Framingham Risk Score, identify a population at risk, but do not perform well for an individual patient. To get patient specific information at a reasonable cost will likely require a two-step process. Step one would identify the presence of disease with an inexpensive laboratory assay; step two would be a non-invasive imaging technique to localize atheroma at risk of forming an occlusive thrombus. At this time we do not have a sensitive and specific screening blood test. There are, however, multiple imaging techniques that may provide information on the geographic distribution of lesions at moderate or high risk of rupture. PET/CT imaging can identify three markers that may be helpful for the imaging evaluation:

Finding Calcium in Noncalcified Lesions: 18F-Fluoride Offers Insights into Atheroma Evolution

Intimal arterial calcification is “a pervasive and likely inevitable program that is intimately entwined with aging, atherosclerosis, and cardiovascular disease” (1). Since 1990, vascular calcification has been quantitated (2) and correlated with the likelihood of cardiovascular events (3). The clinical significance of intimal arterial calcification, however, remains controversial. Shaw et al. (4) reviewed the issues in a recent editorial entitled, “The Never-Ending Story on Coronary Calcium: Is It Predictive, Punitive, or Protective?” To understand why this controversy exists, it may be helpful to evaluate the pathophysiology of atheroma. Calcification of atheroma occurs in inflamed lesions. Lesions are inflamed because low-density lipoprotein (LDL) cholesterol is trapped in the subintimal space, irritating the overlying endothelium and leading to the production of chemotactic factors. The

Molecular Imaging of Apoptosis in Cancer Therapy-Related Cardiac Dysfunction Before LVEF Reduction

Detecting chemotherapy-related cardiac dysfunction (CRCD) before a decrease in left ventricular ejection fraction (LVEF) or an enzyme leak may help employ strategies to preserve ventricular function. Although the mechanisms of CRCD are not fully elucidated, myocyte apoptosis has been proposed to

99MTC-DURAMYCIN IMAGING DETECTS DOXORUBICIN CARDIAC INJURY BEFORE ONSET OF VENTRICULAR DYSFUNCTION

Background: Although the remission rate of cancer has increased, early and late cardiotoxicity due to chemotherapy remains a problem. Early detection of cardiotoxicity should allow preservation of normal ventricular function. The novel strategies of early detection have included genotypic (miRNA