Stroke and heart attack are major killers, not only in the Western world but, increasingly, throughout the developing industrial nations. The cost of these diseases is counted not only in lives lost, but in the health care costs incurred by those patients suffering the chronic manifestations of stroke and cardiac failure. While the acute and more chronic aspects of these diseases appear quite disconnected (for example, brain disease versus heart disease), and we are used to thinking of these conditions in terms of these end-organ manifestations, they do, in fact, share a common causality: vascular disease within the blood vessel supplying the end-organ tissue.
In the case of stroke, this is in the carotid artery, and for heart attack, the coronary artery, so coronary thrombosis is synonymous with heart attack. While much medical attention has been focused on the acute diagnosis and treatment of both of these conditions to avoid or restrict end-organ damage, knowing that the acute disease is preceded by a protracted period of developing vascular disease provides the opportunity to detect and treat the vascular disease before it has the opportunity to cause downstream end-organ disease. The diagnostic challenge is, therefore, to identify biomarkers that discriminate between those people with and without high-risk vascular disease.
Until recently, the most common and reliably used measure of vascular disease has been the degree of narrowing of the blood-vessel lumen (stenosis). It is known that as vascular disease progresses, the degree of stenosis will also increase. This has been readily measurable using techniques such as conventional angiography, ultrasound, and (more recently) CT and MR angiography. The diagnostic usefulness of stenosis, however, only becomes manifest once the disease is severe. Regrettably, symptom-provoking vascular disease is not confined to this advanced-disease group and often occurs in patients with lesser degrees of stenosis. In recent years, we have gained a better understanding of the biology of vascular disease, which accounts for this disconnection between stenosis and symptoms, but also gives us clues about newer markers of vulnerability.
It is now clear that much of the early phase of vessel-wall disease, which causes wall thickening, results in an outward expansion with no significant luminal encroachment (positive remodeling); hence the hidden advance of significant and potentially dangerous disease. The pathobiology of vessel-wall disease has also been better defined. It is now apparent that atherosclerotic disease is fundamentally an inflammatory disease that drives a number of discrete processes that result in progression and destabilization of the atherosclerotic plaque, with eventual complication and rupture.
One major manifestation of this chronic inflammatory process is neoangiogenic intraplaque hemorrhage (IPH). The plaque itself causes the growth of disorganized and fragile neovessels, much as a malignant tumor would, in order to sustain its increase in size. These vessels, however, are leaky and prone to rupture, thus allowing the egress of red blood cells into the substance of the vessel wall itself. This introduces two important elements directly into the vessel wall. First, as the red blood cells break down, their surface membranes are deposited deep within the plaque. These membranes are rich in cholesterol—higher in it than any other cell membrane in the body—and the add to the fatty lipid core at the heart of the atherosclerotic plaque, fueling the inflammatory process.
Second, the hemoglobin within the red cell is released from its protecting membrane. Extracellular hemoglobin is highly inflammatory, and in the intraplaque environment, it is relatively hidden from the normally protective mechanisms present within the circulation. Intraplaque hemorrhage therefore provides two separate but additive elements that have the ability to drive, and even accelerate the atherosclerotic process. Within the plaque’s inflammatory milieu, therefore, there exist a number of potential biomarkers that signal increased risk. One of these is the presence of hemoglobin.
MRI has the ability to differentiate between tissues based on their molecular environment and their influence on local protons. High signal intensity on T1-weighted image acquisitions occurs when there is shortening of proton relaxation within the static field. This is most commonly brought about by the