Intravascular ultrasound imaging of the coronary arteries: an in vitro evaluation of measurement of area of the lumen and atheroma characterisation

Objective—To assess the accuracy of measurement of area of the lumen, and sensitivity, and specificity of detection of atheroma in coronary arteries in vitro with a commercially available 20 MHz intravascular ultrasound system.

Setting—A teaching hospital department of cardiology with the support of the department of cardiovascular pathology.

Procedure—10 segments of coronary artery were removed from cadaver hearts. Intravascular ultrasound imaging was performed at fixed levels and the vessels were then sectioned and photographed before histological preparation. An independent blinded observer measured luminal area and assessed the presence of atheroma on the intravascular ultrasound images of 76 vessel sections (304 quadrants). The sensitivity and specificity of detection of atheroma was assessed in comparison with the histologically prepared sections. Luminal areas from intravascular ultrasound, photographs of cross sections of the vessels and histological sections were compared with the technique of limits of agreement.

Results—Overall 36% of the 304 quadrants studied histologically had identifiable atheroma. Intravascular ultrasound sensitivity for atheroma was 0·593 and the specificity was 0·839. The positive predictive value was 0·674, and the relative risk 3·139. Values for area of the vessel lumen were on average 9·4 mm² (confidence interval (CI) 8·6–10·2 mm²) larger than those measured from photographs and 10·7 (CI 9·8–11·6 mm²) larger than those measured from the histological sections.

Conclusions—The intravascular ultrasound system assessed in this study significantly overestimated coronary vessel luminal area and had low sensitivity and specificity for detection of atheroma. Improvements in image resolution are required before this system can provide useful information on coronary artery size and morphology.

     

Intravascular ultrasound imaging in human peripheral and coronary arteries in vivo.

To determine the feasibility of intravascular ultrasound imaging in vivo, a miniaturized high frequency transducer catheter was introduced into human peripheral (n = 10) and coronary (n = 4) arteries. Cross-sectional ultrasound images were obtained from iliofemoral arteries in 10 patients using a 20 MHz transducer catheter (1.2 mm in diameter) and from coronary arteries in 4 patients using a 30 MHz transducer catheter 5 French size (Fr) following successful coronary angioplasty. Ultrasound images obtained from peripheral arteries showed a three-layered appearance (echo-reflective intima, echo-lucent media and echo-reflective adventitia) in the normal arteries. In diseased arteries, the location, amount and extent of atheromatous plaque were clearly documented. The arterial diameters measured by ultrasound closely correlated with the measurements by angiography (r = 0.91) in the peripheral arteries. Coronary angiograms obtained following balloon angioplasty revealed smooth edges at the dilatation sites without significant narrowing in all patients. However, a significant amount of residual atheromatous plaque was clearly observed on the ultrasound images at the previously dilated sites. Coronary dissection, which was identified as an echo-lucent area behind the plaque, was noted in 2 patients. Ultrasound images also revealed the presence of calcium in the plaque which was unrecognized on the angiograms in 3 patients. In addition, direct measurement of the lumen cross-sectional area was possible on the ultrasound images.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary arteries

Intravascular ultrasound demonstrated plaque ruptures that occurred in regions involved with large complicated atherosclerotic plaques in the coronary artery. Because intravascular ultrasound evaluates both plaque and luminal dimensions, it contributes to our understanding of the pathophysiology of coronary artery disease.     

Intravascular ultrasound imaging of coronary arteries. Is three layers the norm?

BACKGROUND. The purpose of this study was to evaluate the significance of the three-layered appearance of coronary arteries in adolescence and adults from intravascular ultrasound scans and to correlate these observations with histopathology. METHODS AND RESULTS. Sixteen intact hearts were excised at autopsy from patients with no clinical history of coronary artery disease. The patients' ages ranged from 13 to 55 years. A 30-MHz ultrasound imaging catheter was used to obtain images throughout the epicardial coronary vasculature. A total of 72 image cross sections was marked by epivascular sutures, and the corresponding histological sections were examined. Ultrasound images were classified into two groups: images exhibiting three-layered appearance and images without distinct layering. Histological analysis revealed a significantly greater degree of intimal thickening in segments with three layers (243 +/- 105 microns) than in nonlayered segments (112 +/- 55 microns). Discriminant analysis of these data predicted the threshold between the two groups to be 178 microns. Measurements of medial thickness were not different between these two groups (235 +/- 61 versus 210 +/- 76 microns). In the nonlayered group, the average patient age was 27.1 +/- 8.5 years, whereas in the three-layered groups, the average age was 42.8 +/- 9.8 years. CONCLUSIONS. The intracoronary ultrasound image appearance of young, morphologically normal coronary artery walls is homogeneous without layering. A three-layered appearance suggests the presence of at least 178 microns of intimal thickening and is seen more frequently with advancing age.     

Intravascular ultrasound molecular imaging of atheroma components in vivo

OBJECTIVES: Our purpose was to quantitate and confirm specific echogenic immunoliposome (ELIP) atheroma component enhancement in vivo. BACKGROUND: Targeted ELIPs for ultrasonic detection and staging of active molecular components of endothelium and atheroma have been developed. METHODS: In Yucatan miniswine, the endothelium was injured from one femoral and one carotid artery, and animals were fed a high-cholesterol diet for two months to create various stages of atheroma. Arteries were imaged with intravascular ultrasound (IVUS) 5 and 10 min after ELIP injection (5-mg dose). Anti-intercellular adhesion molecule-1 (ICAM-1), anti-vascular cell adhesion molecule-1 (VCAM-1), anti-fibrin, anti-fibrinogen, and anti-tissue factor (TF) conjugated ELIPs were used, and immunohistochemistry (IHC) confirmed the presence or absence of molecular expression. Two blinded observers determined if each segment was enhanced by ELIP. Three-dimensional image reconstruction and videodensitometric analysis determined the mean gray-scale (MGS) change of the luminal border. RESULTS: To determine endothelial injury component enhancement, anti-fibrinogen ELIP enhanced exposed fibrin in all arteries (MGS increased 22 +/- 5%; 6 arteries; 2 animals). To determine enhancement of molecular components in atherosclerotic arteries, observers detected enhancement 5 min after anti-VCAM, anti-ICAM, anti-TF, anti-fibrin, and anti-fibrinogen conjugated ELIPs. Furthermore, ELIP enhanced atheroma MGS by 39 +/- 18% (n = 8). The IHC staining confirmed the expression of respective molecular targets in all enhanced segments. CONCLUSIONS: It was shown that ELIPs specifically enhance endothelial injury/atheroma components. This allows better characterization of the type and extent of active atheroma components and may allow more directed therapy.     

Intravascular ultrasound imaging of angiographically normal coronary arteries: a prospective study in vivo.

Intravascular ultrasound imaging (IVUS) was performed to elucidate the discrepancy between clinical history and angiographic findings and to measure the diameter and area of the lumen of the normal left coronary artery in 55 patients who presented with chest pain but had normal coronary angiograms. The left coronary artery (LCA) was scanned with a 4.8F, 20 MHz mechanically rotated ultrasound catheter at 413 sites. Atherosclerotic lesions were identified at 72 (17%) sites in 25 patients. The mean (SD) (range) plaque area was 5.55 (3.56) mm2 (2-26 mm2) and it occupied 28.8 (9.6)% (13-70%) of the coronary cross sectional area. Calcification was detected at 24 (33%) atherosclerotic sites in nine patients. The correlation coefficients for the lumen dimensions measured at normal sites by IVUS and by angiography were r = 0.93 (SEE = 0.43) mm for lumen diameter and r = 0.89 (SEE = 4.27) mm2 for lumen area (both p < 0.001). 16 of the 30 patients in whom no atherosclerotic plaques were detected in the LCA lumen by IVUS had no risk factors of coronary artery disease. The cross sectional area of 90 consecutive images of left main coronary artery (LMCA), proximal left anterior descending coronary artery (proximal LAD), and mid LAD was measured in these 16 subjects. The mean (SEM) areas at end diastole were LMCA 17.33 (7.98) mm2; proximal LAD 13.56 (5.85) mm2; mid LAD 9.75 (4.67) mm2. During the cardiac cycle the cross sectional area changed by 10.2 (4.0)% in the LMCA, by 8.3 (4.7)% in the proximal LAD, and by 9.8 (4.0)% in the mid LAD. In 11 patients with plagues the change in cross sectional area in plague segments (5.8(3.1)%) was significantly lower than in the segments from patients without plagues (p < 0.001). Lumen area reached a maximum in early diastole rather than in late diastole. IVUS can imagine atherosclerotic lesions that are angiographically silent; it also provides detailed information about plague characteristics. The variation in coronary cross sectional area during the cardiac cycle should not be ignored during quantitative analysis. Maximum dimensions in normal segments are reached in early diastole. Further studies are needed to clarify the clinical significance of atherosclerosis detected by IVUS in patients presenting with chest pain but normal coronary angiography.     

Intravascular ultrasound imaging of angiographically normal coronary arteries: an in vivo comparison with quantitative angiography

Intravascular ultrasound, a new technique for real-time two-dimensional visualization of arteries and veins, delineates vessel wall morphology and measures luminal dimensions. This imaging method has been validated with in vitro systems and in peripheral vessels, but there are few in vivo coronary artery studies. Twenty cardiac transplant recipients with no angiographic coronary artery disease were scanned with a 30-MHz intravascular ultrasound catheter from the left main coronary ostium to the mid-left anterior descending coronary artery. Simultaneous angiographic measurements were performed at 76 sites. Ultrasound end-diastolic diameters in two perpendicular axes were 3.8 +/- 0.9 and 3.9 +/- 0.6 mm, respectively, and mean diameter derived from an area determined by planimetry was 3.9 +/- 0.9 mm. Angiographic coronary artery diameters measured with a computer-assisted edge detection system perpendicular to the long axis of the vessel and to the long axis of the catheter were 3.4 +/- 0.8 and 3.6 +/- 0.8 mm, respectively. Luminal diameters measured with the two imaging systems correlated closely, with an r value of 0.86 when ultrasound was compared with the angiographic diameter measured perpendicular to the vessel and 0.88 when compared with the angiographic diameter measured perpendicular to the imaging catheter. Eighty-three percent of the ultrasound-measured diameters were above the line of identity when compared with the simultaneous angiographic measurement. The more the imaging catheter deviated from the long axis of the vessel, the greater was the discrepancy between the ultrasound and angiographic measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravascular ultrasound imaging and three-dimensional modeling of arteries

In this article, we describe the reconstruction of arterial structures using solid modeling. The alternative approaches to three-dimensional modeling are discussed and the voxel space system we use for intra-arterial imaging, based on ultrasonic data, is described. The complete three-dimensional ultrasonic imaging system comprising a purpose-built, catheter-mounted ultrasound probe, ultrasonic transceiver, and computer system is presented. This system has been used to recreate three-dimensional computer models of arterial sections in vitro and in vivo. Examples to illustrate the power and flexibility of voxel space modeling in terms of postprocessing and software manipulation are given. Preliminary work on tissue differentiation, using arterial models and color coding of the image, and three-dimensional presentation of flow data is included.     

Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens

BACKGROUND. Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. METHODS AND RESULTS. A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media. CONCLUSIONS. Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.     

Intravascular ultrasound of the coronary arteries: Current applications and future directions

Although angiography is widely applied in the diagnosis of the coronary artery disease (CAD), studies have questioned the accuracy of radiographic methods. Miniaturized intravascular ultrasound devices offer several potential advantages, including a tomographic orientation and the ability to characterize atherosclerotic plaques. Two dissimilar technical approaches to transducer design have emerged: mechanically rotated devices and multi-element arrays, each yielding small coronary catheters (1.1–1.8 mm in diameter). Initial studies of coronary ultrasound have demonstrated few serious untoward effects. In most normal subjects, the vessel wall is laminar in appearance with an intimal leading edge and subintimal sonolucent layer averaging ≤0.20 mm in thickness. In most CAD patients, the thickness of the leading-edge or sonolucent zone is abnormally increased. Atherosclerotic abnormalities are frequently evident in segments with no angiographic lesion. At sites with a circular lumen shape, minimum diameter by ultrasound and angiography correlate closely, R = 0.93. At sites with an eccentric lumen, significant disagreement between angiography and ultrasound diameter is evident, R = 0.78. Correlation between angiography and ultrasound from percent stenosis is moderate, R = 0.63. Following balloon angioplasty percutaneous transluminal coronary angioplasty (PICA), morphologic findings include complex cracks, splits, and dissections, and minimum lumen diameter by angiography and intravascular ultrasound correlate poorly. Recent advances have improved the utility of coronary ultrasound, including smaller catheters and a device combining a miniature imaging transducer (1.16 mm) with a low profile balloon (0.028–0.033 inch). Important current limitations include inability to visualize the smallest coronaries and tight stensoses. The future of coronary ultrasound is promising, propelled by the unique capability of this modality to image atherosclerotic plaques directly.     

Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension

OBJECTIVE: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). METHODOLOGY: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. RESULTS: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 +/- 27.0 vs 132.5 +/- 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 +/- 23.4 vs 85.0 +/- 14.3 counts, P < 0.01). CONCLUSIONS: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity.     

Intravascular ultrasound imaging: in vitro validation and pathologic correlation

Intravascular ultrasound imaging is a new method in which high resolution images of the arterial wall are obtained with use of a catheter placed within an artery. An in vitro Plexiglas well model was used to validate measurements of the luminal area, and an excellent correlation was obtained. One hundred thirty segments of fresh peripheral arteries underwent ultrasound imaging and the findings were compared with the corresponding histopathologic sections. Luminal areas determined with ultrasound imaging correlated well with those calculated from microscopic slides (r = 0.98). Three patterns were identified on the ultrasound images: 1) distinct interface between media and adventitia, 2) indistinct interface between media and adventitia but different echo density layers, and 3) diffuse homogeneous appearance. The types of patterns depended on the relative composition of the media and adventitia. Calcification of intimal plaque obscured underlying structures. Atherosclerotic plaque was readily visualized but could not always be differentiated from the underlying media.     

Intravascular ultrasound imaging: in vivo peripheral and coronary artery studies

Recent in vitro studies have demonstrated that intravascular ultrasound can obtain high-resolution cross-sectional images of arterial vessels. To further expand the use of this technique for in vivo visualization of peripheral and coronary vessels, we imaged 24 femoral and 13 carotid arteries from 19 sheep. Using a manual rotation technique, high-resolution images were obtained in 95% of the vessel sites with a rigid probe and in 82% of the vessel sites with a flexible catheter. In 14 of these arteries, good correlation was found between the lumen diameter measured by ultrasound and by angiography (P less than .001, r = .91). In addition, 6 left circumflex coronary arteries were imaged from 6 additional sheep by motor-driven rotation of the ultrasound probe at 1,800 rotations per minute, obtaining clear delineation of coronary lumen morphology and lumen-intima interface. Strong correlation was found also between intravascular ultrasound and cineangiography for coronary artery diameter measurement (P less than .001, r = .96). These studies demonstrate that this technique can provide high-resolution images of arterial vessels in vivo and may have unique advantages in diagnosis of atherosclerotic vascular disease and in the guidance of new catheter-based therapeutic modalities.     

Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis.

Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis.     

冠状动脉轻中度病变血管内超声显像与冠状动脉造影对比分析

目的 :经血管内超声 (IVUS)进一步评价冠状动脉 (冠脉 )造影 (CAG)对轻中度冠脉病变诊断的准确性。方法 :对 10 4例临床诊断为冠心病 (CHD)或可疑CHD的患者 ,均详细询问病史 ,行心电图、超声心动图、CAG及IVUS检查。数据经t检验 ,χ2 检验及相关性检验。结果 :①临床症状及心电图改变 :典型心绞痛 5 7例 ,不典型心绞痛 4 7例。心电图呈缺血性ST T改变 6 2例 ,心房颤动 8例 ,右束支传导阻滞 4例 ,室性心律失常 10例 ,正常心电图 2 0例。②IVUS及CAG结果比较 :10 4例共 113处血管病变 ,CAG示面积狭窄为 0～ 85 .12 (5 8.0 7±17.4 2 ) % ,IVUS示面积狭窄为 0～ 92 .34(74 .0 0± 14 .91) % (P <0 .0 5 )。病变长度CAG为 6～ 4 0 (14 .12±10 .0 8)mm ,IVUS为 4～ 5 5 (2 1.16± 2 5 .17)mm ,(P <0 .0 5 )。CAG示 8例钙化性斑化 ,IVUS示 4 7处钙性斑块(P <0 .0 1)。CAG示偏心性斑块 13处 ,IVUS示偏心性斑块 73处 (P <0 .0 1)。③IVUS与CAG面积狭窄程度呈正相关 (r =0 .5 2 ,P <0 .0 1)。结论 :CAG显示的血管病变程度明显轻于IVUS ,漏诊率为 8%。CAG对钙化性病变检出率亦明显低于IVUS ,低估病变的程度 ,而IVUS可弥补这一不足。但CAG仍是检测CHD较普遍的方法 ,对心绞痛和心电图有缺血性ST T改变而CAG正常者 ,     

Intravascular ultrasound lumen area parameters for assessment of physiological ischemia by fractional flow reserve in intermediate coronary artery stenosis

BackgroundA fractional flow reserve (FFR) of <0.8 is currently used to guide revascularization in lesions with intermediate coronary stenosis. Whether there is an intravascular ultrasound (IVUS) measurement or a cutoff value that can reliably determine which of these intermediate lesions requires intervention is unclear.AimsWe assessed IVUS measurement accuracy in defining functional ischemia by FFR.MethodsThe analysis included 205 intermediate lesions (185 patients) located in vessel diameters >2.5 mm. Positive FFR was considered present at <0.8. IVUS measurements were correlated to the FFR findings in intermediate lesions with 40%–70% stenosis. Fifty-four (26.3%) lesions had FFR<0.8.ResultsThere was moderate correlation between FFR and IVUS measurements, including minimum lumen area (MLA) (r=0.36, P<.001), minimum lumen diameter (MLD) (r=0.25, P=<.001), lesion length (r=?0.43, P<.001), and area stenosis (r=?0.33, P=.01). A receiver operating characteristic curve (ROC) identified MLA<3.09 mm² (sensitivity 69.2%, specificity 79.5%) as the best threshold value for FFR<0.8. The correlation between FFR and IVUS was better for large vessels compared to small vessels. ROC analysis identified the best threshold value for FFR<0.8 of MLA<2.4 mm² [area under curve (AUC)=0.74] in lesions with reference vessel diameters of 2.5–3 mm, MLA<2.7 mm² (AUC=0.77) in lesions with reference vessel diameters of 3–3.5 mm, and MLA<3.6 mm² (AUC=0.70) in lesions with reference vessel diameters >3.5 mm.ConclusionAnatomic measurements of intermediate coronary lesions obtained by IVUS show a moderate correlation to FFR values. The correlation was better for larger-diameter vessels. Vessel size should always be taken into account when determining the MLA associated with functional ischemia.     

Intravascular ultrasound for the evaluation of therapies targeting coronary atherosclerosis

Many cardiovascular events are clinical manifestations of underlying atherosclerotic disease. The progression of atherosclerosis, traditionally measured by angiography, is predictive of future clinical events and is a valid surrogate marker of cardiovascular (CV) disease. There is growing interest in using novel surrogate end points in clinical trials to expedite the development of new CV therapies. Innovative imaging technologies, such as intravascular ultrasound (IVUS), may carry advantages for the evaluation of coronary atherosclerotic burden and disease progression. Unlike angiography, which displays only the opacified luminal "silhouette," IVUS provides transmural imaging of the entire arterial wall and permits both detection of early-stage atherosclerosis and accurate cross-sectional and even 3-dimensional quantification of plaques. Intravascular ultrasound is now used to guide therapeutic interventions and for diagnostic purposes, primarily for the evaluation of ambiguous lesions and left main coronary artery disease. In addition, clinical studies are using IVUS serially to measure plaque progression, which appears to be related to future CV events. Although the probative force of clinical end point studies still is stronger, IVUS is catching up. Currently, several trials of CV therapies use IVUS-determined plaque progression as the end point. The rationale for using IVUS-based surrogate end points in clinical trials is discussed in the present review. Key advantages of using IVUS-based surrogate end points versus clinical outcome include smaller patient numbers and substantially shorter trial durations; this reduces costs and may expedite the development and testing of new drugs. We expect in the near future a further increase of the use of IVUS-based surrogate end points in trials that evaluate novel CV therapies targeting on coronary atherosclerosis.