Intima-media thickness

Intima-media thickness (IMT), also called intimal medial thickness, is a measurement of the thickness of artery walls, usually by external ultrasound, occasionally by internal, invasive ultrasound catheters, see IVUS, to both detect the presence and to track the progression of atherosclerotic disease in humans.

IMT has increasingly been used in medical research since the mid 1990's to track changes in arterial walls and is occasionally used in clinical medicine by more progressive clinicians. Historically, since the 1950's, focus was initially placed on detection and progression of the atherosclerotic process by its late affects on the lumens of arterial blood vessels, either narrowing or enlargement. This led to the still widely held beliefs that if the lumen looked OK, then little to no atherosclerotic disease was presumed to be present.

However, the atherosclerosis process occurs within the walls of blood vessels, not the lumen. Starting primarily in the 1980s, especially with improvements in both CAT scanner, see EBT, and ultrasound technology, see IVUS, plus better understanding of the atherosclerotic process from both basic science and clinical research efforts, attention started slowly and increasingly shifting to detecting and tracking arterial disease at earlier stages, well before changes to the lumen of the artery either occur or become detectable by any technology.

IMT Measurements in the Carotid Artery

Since the 1990's, both small clinical and several larger scale pharmaceutical trials have used CIMT (carotid IMT) as a surrogate endpoint for evaluating the regression and/or progression of atherosclerotic cardiovascular disease. Many studies have documented the relation between the carotid intima-media thickness and the presence and severity of atherosclerosis. In 2003 the European Society of Hypertension-European Society of Cardiology recommended the use of IMT measurements in high-risk patients to help identify target organ damage not revealed by other exams such as the electrocardiogram.

Though it seems clear that carotid intima-media thickness is strongly associated with atherosclerosis, it is worth noting that not all the processes of thickening of the intima-media are due to atherosclerosis. Intimal thickening is in fact a complex process, depending on a variety of factors, not necessarily related to atherosclerosis. Local hemodynamics plays an important role, higher blood pressure and changes in shear stress being potential causes of intimal thickening. Changes in shear stress and blood pressure may cause a local delay in lumen transportation of potentially atherogenic particles, which favors the penetration of particles into the arterial wall and consequent plaque formation. However non-atherosclerotic reactions may also exist, as in intimal hyperplasia and intimal fibrocellular hypertrophy, two different compensatory reactions of the arterial wall to changes in shear stress, which also consist in thickening of the arterial wall. In some cases, more than one of these reactions may be present, and indeed as all of these are associated to particular flow conditions, they are often found in common areas, such as the inflow side of branches, the inner curvature at bends and opposite the flow divider at bifurcations. However, changes in the IMT above thresholds of around 900 μm almost certainly are indicative of an atherosclerotic pathology.

Mechanisms such as these may perhaps at least in part explain why the carotid artery seems to be a preferential site for analyzing the relation between wall thickness and atherosclerosis. In general, wall thickening may be in the intimal layer or in the muscular, medial, layer. As the carotid artery is an elastic artery, the muscular media is relatively small. Hence, thickening of the carotid arterial wall is due essentially to intimal thickening. In muscular arteries wall thickening may imply instead (or also) a thickening of the medial wall. Whether or not wall thickening in the carotid artery and the femoral artery (or other muscular arteries) have the same meaning is as yet uncertain. Several studies seem to suggest that the mechanisms underlying their evolution may at least in part differ, with consequently possibly different clinical implications.

Another issue to consider, once the choice to examine the carotid artery has been defined, is on which segment of the carotid artery to perform the measurement. Often, the measurement of the IMT is measured in three tracts: in the common carotid, at one or two cms from the flow divider, at the bifurcation and in the internal carotid artery.

From an academic standpoint, the region to select for IMT measurement is still an object of study. IMT measurements of the deep wall, by ultrasound, are generally more reliable than measurements performed on the outer wall. This difference in the accuracy of near and far wall measurements may be a problem, as some studies have used both measurements to quantify the IMT.

A practical approach to tracking disease presence and progression on any given individual is to select and track those regions with the greatest thickness, i.e. greatest disease burden, as opposed to arbitrarily selecting a particular segment in which the individual may not have much pathology.

Ultrasound Methods

By ultrasound, IMT can be measured from either outside the body, in larger arteries which are relatively close to the skin (e.g. carotids, brachial, radial and/or femoral arteries), and/or internally by IVUS using special catheters which use ultrasound to look at blood vessels from inside out.

Key advantages of external ultrasound methods are:a. lower cost compared with most other methodsb. relative comfort and convenience for the patient being examinedc. lack of need for any IV’s of other body invasive methods (uaually) andd. lack of any X-Ray radiation;Ultrasound can be used repeatedly, over years, without compromising the patient's short or long term health status.

One 20 year [http://www.nhlbi.nih.gov National Intitutes of Health] ongoing study, called [http://www.nhlbi.nih.gov/funding/inits/archive/hc0404/sow.pdf CARDIA] , which began recruitment in 1985, is focusing on the efficacy of CIMT to identify subclinical cardiovascular disease at earlier, younger stages in over 5000 individuals.

Both the [http://www.aha.org American Heart Association] [ [http://circ.ahajournals.org/cgi/reprint/101/1/e16 Prevention Conference V : Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III - Greenland et al. 101 (1): e16 - Circulation ] ] and the [http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm National Cholesterol Education Program, Third Adult Treatment Panel report, i.e. ATP III] have encouraged the clinical use of CIMT, but caution that the procedure be done with attention to accuracy and reliability.

As of 2007, while IMT has increasingly become easier to measure using higher grade equipment and careful attention to image quality, most clinical carotid ultrasound software in widespread use in the United States is not designed to easily facilitate measurement of IMT and most clinical untrasound technicians remain unfamiliar with either performing or the importance of IMT measurements. Instead, most carotid ultrasound examinations remain focused on the older concept of measuring blood velocities within the lumen as an indication of the anatomic changes which occur after disease has progressed to advanced stages of severity.

Radiographic Methods

By radiographic, i.e. X-Ray, methods, after arteries have developed advanced calcified atherosclerotic plaque, IMT can also be semi-estimated by the distance between the outer edges of calcification (actually this leaves out most of the media) and the outer edges of an angiographic dye column within the artery lumen. This is a far more complex technique; it is invasive to the body due to the use of X-Ray radiation, catheters and angiographic contrast agents.

The radiographic approach can sometimes be done during angiography, however usually only when an artery segment happens to be visualized on end so that the calcification within the outer edges of plaques can be sufficiently seen.

Radiographic IMT is more often approximated using advanced CAT scanners due to the ability to use software to more slowly and carefully process the images (after the patient's scan has been completed) and then examine artery segments from whatever angle appears most appropriate.

However, one of the concerns with all CAT scanners, both EBT and perhaps more so with the spiral scanners (which are more commonly used because they are less expensive to purchase), is the dose of X-Ray delivered to the patient’s body and concerns about the safety of repeated doses of X-Ray to track disease status over time.

References

* Bortel L: "What does intima–media thickness tell us?", Journal of Hypertension, 23:37–39, 2005.
* Wong M, Edelstein J, Wollman J, Bond MG: "Ultrasonic-pathological comparison of the human arterial wall: verification of intima-media thickness", Arteriocl. Thromb., 1:482-486, 1993.