New Diagnostic Tools to Identify Vulnerable Carotid Plaques
Ultrasonography Conventional ultrasonography Ultrasound diagnosis in carotid artery disease began investigationally during the 1960s. 17,18 Doppler techniques were non-invasive, and proved useful for atherosclerotic disease in arteries accessible to ultrasound, combining anatomic and flow information. B-mode vessel analysis was established in the 1970s, 19 and these real-time images were provided by duplex scanning of the carotid bifurcations, enhanced using single-gated pulsed Doppler flow velocity detection. 20 B-mode echo became less accurate than pulsed Doppler for non-invasive imaging of the extracranial carotid arteries. One investigation in 1980 reported that the greatest accuracy with pulsed Doppler was for confirmation of normal vasculature (73%) and for diagnosing occluded internal carotid arteries (96%) in a study of 265 patients. False-positive and -negative results for pulsed Doppler were 11% and 14%, respectively, compared with 11% and 59% by B-mode ultrasonography. Percentage stenosis estimation was more accurate with B-mode techniques at this early time. 21 Real-time B-mode ultrasonography thus could detect stenoses greater than 40% with 79% accuracy, 81% sensitivity, and 77% specificity among 517 carotid arteries. However, plaque characteristics and mild disease could not be detected in those times. 22
After Pignoli et al validated the concept of intima-media thickness (IMT), B-mode ultrasound became widely available as a tool for epidemiologic investigation. 23 B-mode ultrasound has excellent correlation with traditional cardiovascular risk factors. 24-29 The B-mode method also revealed a relationship between the degree of carotid IMT and clinical outcomes. 30,31 The carotid IMT found by B-mode ultrasound is correlated with both cerebrovascular and coronary artery disease. 32,33 Moreover, increased IMT of the extracranial carotid arteries is a known predictor of coronary events, stroke, and mortality. 34 The importance of B-mode ultrasound is now recognized, and it is often performed early in cardiovascular screening. 35
Color Doppler and contrast ultrasonography Direct scanning of the extracranial carotid arteries using color-coded Doppler imaging was developed in the early 1980s, 36 and was first developed using continuous wave Doppler. A prospective study of Doppler examined 216 patients for possible carotid insufficiency and compared results with oculoplethysmography/carotid phonoangiography and periorbital directional Doppler sonography. For stenoses 65% or greater by angiography, Doppler imaging was 94% accurate, oculoplethysmography/ carotid phonoangiography 84%, and periorbital directional Doppler sonography 80%. 36 Color Doppler imaging is used today to detect abnormal blood flow using pulse wave Doppler spectral analysis. This is a color display of reflected Doppler frequencies from red blood cells. Technical expertise is needed to avoid misdiagnosis, and it uses parameter manipulations of color velocity scales, sampling window settings, and color gain control. 37
Contrast agents are useful for lesions difficult to detect by common duplex ultrasound. One example is in differentiating total from near-total occlusion. Advanced duplex ultrasonography has diagnostic limitations and frequently requires confirmation with angiography, 38,39 especially in the setting of near-total occlusion of the internal carotid artery, which must be distinguished from total occlusion. 40
Three-dimensional ultrasonography Three-dimensional (3D) ultrasound imaging began in the early 1980s, and was soon applied to carotid artery disease. 41 A major limitation of 2D imaging was the necessity for mental reconstruction of three-dimensional plaque shapes, stenotic lumina, and enlarged/remodeled vessels. Several studies of 3D ultrasound in carotid artery disease revealed favorable results. 42,43 One investigation demonstrated that 14 patients with both carotid angiography and 3D ultrasound showed good correlation in quantitative analysis of carotid stenosis (SEE: the standard error of the estimate = 12.4%, r = 0.76, mean difference = 7.0 ± 12.3% with diameter method; SEE = 10.5%, r = 0.82, mean difference = 1.8 ± 10.5% with the area method by 3D ultrasound). The investigators concluded that 3D ultrasound could be used for both qualitative and quantitative analysis of carotid plaques and could
detect and quantify significant carotid stenosis. 44 Another study found a positive predictive value and sensitivity approaching 100% for 3D color-flow duplex sonography in patients with high-grade internal carotid artery stenosis compared to angiography. 45 This method has important clinical implications for studies such as therapeutic efficacy with serial follow-up for progression or regression of plaque burden.