Exploring the natural history of atherosclerosis with intravascular ultrasound

Intravascular ultrasound has emerged as the preferred imaging modality for the characterization of atherosclerotic plaque within the coronary arteries. Ultrasonic imaging reveals the presence of more extensive atheroma than suggested by conventional angiography in patients with coronary artery disease. The ability to precisely quantify atheroma volume in an arterial segment at different time points provides the unique opportunity to investigate the factors that influence the natural history of atheroma progression. Accordingly, serial intravascular ultrasound has been incorporated into a number of clinical trials that have evaluated the impact of medical therapies that modify established risk factors and novel pathological targets. This article will review the increasing role of imaging modalities in the assessment of atherosclerosis and factors that influence its natural history.     

Assessment of coronary compensatory enlargement by three-dimensional intravascular ultrasound

Several techniques have been used to demonstrate that human arteries respond to atherosclerosis by increasing their total arterial area to prevent a decrease in blood flow. Three-dimensional reconstructions of coronary arteries can document this compensatory response accurately and specifically. Seven human coronary arteries were reconstructed using intravascular ultrasound and biplane angiography, and vessel geometries were quantified. In all seven vessels, as plaque area increased, overall vessel area increased (R = 0.986, 0.933, 0.984, 0.678, 0.763, 0.963, and 0.830), but luminal cross-sectional area did not significantly decrease. Focal compensatory enlargement was identified in each vessel, and in some cases this response appeared to occur until the vessel was 65% occluded. Luminal enlargement near the proximal ends was attributed to the natural taper of the vessel. The semi-automated, three-dimensional segmentation technique used in this study allows reproducible quantification, as there is no subjective manual tracing involved. Following the intravascular ultrasound transducer in time and space with biplane angiography allows for accurate reconstruction with or without automated pullback devices. Information on the rate of change of vessel measurements is also presented, which, when combined with visualization of accurate 3D geometry, provides a unique assessment of coronary compensatory enlargement. This reconstruction technique can be applied in a clinical environment with no major modification.     

血管腔内超声显像三维重建的实验研究

血管腔内超声显像三维重建术能够直观地显示血管和动脉粥样硬化斑块的空间结构，提供二维图像所不能得到的信息。本文用表面提取法成功地对７根正常根人离体血管标本进行腔内超声显像和三维重建。     

A randomized trial of transcutaneous extraction atherectomy in femoral arteries: Intravascular ultrasound observations

Objectives. The purpose of this study was to test the hypothesis that in occlusions of the superficial femoral artery, removal of atherosclerotic plaque would result in a higher long-term patency rate compared to balloon dilatation alone. A secondary hypothesis was that long term patency would be proportional to the amount of plaque removed. Methods. A randomized controlled study of patients with occluded superficial femoral arteries was performed comparing balloon dilatation alone versus a 2.7 mm or a larger (4.0 mm or 4.7 mm) transcutaneous extraction catheter (TEC) atherectomy device followed by balloon dilatation. The effect of these devices on plaque area was assessed directly by intravascular ultrasound imaging. Results. The mean occlusion length was 19.4 cm ± 11.7 cm. The mean lumen area increased from 4.7 mm² to 15.1 mm², primarily due to balloon dilatation, but the mean atheroma area of 19.8 mm² did not change with either size of TEC device. Although the initial procedure success rate was high (79%), the 6 month patency was only 45%. There was no difference in 6 month patency between the 3 groups. Conclusions. The data indicate that the TEC atherectomy devices do not remove a significant amount of atherosclerotic plaque in occluded superficial femoral arteries. The 6 month patency is no different with these atherectomy devices than with balloon dilatation alone. The larger (4.0 mm or 4.7 mm) TEC device does not remove any more tissue than the smaller (2.7 mm) device. The use of intravascular ultrasound to quantitate the effects of this atherectomy device provides important insights into the mechanism of action and lack of efficacy of the TEC atherectomy catheter. © 1995 John Wiley & Sons, Inc.     

Intravascular MRI

In patients with vascular disease, acute coronary syndromes and ischemic strokes develop suddenly and often unpredictably. In most patients, these clinical scenarios result from arterial thrombosis from one of three mechanisms: plaque rupture, plaque erosion, or calcified nodule. A number of diagnostic modalities have been used in the evaluation of these unstable, high-risk lesions that predispose to arterial thrombosis. Noninvasive MRI allows three-dimensional imaging with evaluation of vascular structures and depiction of components of atherosclerotic plaque. However, noninvasive MRI is limited in the evaluation of arteries of smaller caliber and deeper location, such as coronary, iliac, and renal arteries. To overcome these inherent limitations of noninvasive MRI, invasive approaches have been developed that include intravascular coils for lesion assessment and characterization, and a novel intravascular MRI catheter within which the magnets, radiofrequency transmitters, and receivers are miniaturized. This self-contained MRI catheter holds promise in the in vivo assessment of lipid-rich, potentially vulnerable plaques.     

Detection and characterization of vascular lesions by intravascular ultrasound: an in vitro study correlated with histology.

High-frequency intravascular ultrasound (30 and 40 MHz) was applied to study 112 human vascular specimens. The ultrasound images were compared with histologic cross-sections. In 44 out of 58 of the histologically classified muscular arteries, a hypoechoic middle layer was seen in the vessel wall, giving it a three-layered appearance. In 10 arteries, fibrous degeneration of the muscular media resulted in a homogeneous appearance of the vessel walls, whereas atherosclerotic plaque precluded the visualization of the arterial media in four of the arteries. A three-layered appearance was seen in seven of nine histologically classified transitional arteries, and a homogeneous arterial wall was seen in two of the nine. None of the 33 elastic arteries, veins, venous bypass, and Goretex conduits showed a hypoechoic medial layer. Histologically proved fibrous intimal thickening was echographically detected in 32 of 48 specimens (67%). It was noted that these intimal lesions were easier to detect with 40 MHz than with 30 MHz transducers. Hypoechoic areas of lipid deposition were detected in 32 of 36 specimens (89%) and could be distinguished from fibrous plaques. Histologically evident calcium deposits were detected with intravascular ultrasound in 35 of 36 specimens (97%). Measurement of plaque area was only possible in cross sections with a three-layered appearance. Quantitative analysis showed a significantly larger lumen area measured from ultrasonic images (26.3 +/- 21.3 mm2) than from histologic cross-sections (21.8 +/- 16.6 mm2, p less than 0.001), probably because of tissue shrinkage during processing for histology. A significant correlation (r = 0.96, p less than 0.001) between ultrasonic and histologic measurements of lumen areas was observed, with and a negligible interobserver and intraobserver variability. Plaque area and medial thickness correlated well with histology (r = 0.87, p less than 0.001 and r = 0.93, p less than 0.001, respectively). It appears from this in vitro study that intravascular ultrasound is an accurate technique for detection and characterization of atherosclerotic lesions. Vessel lumen area can be measured in most instances, whereas plaque area and medial thickness can only be reliably assessed in muscular arteries in which the hypoechoic media serves as a reference, and shadowing by calcium or attenuation by fibrous plaque components is absent.     

Variability of area measurements obtained with different intravascular ultrasound catheter systems: Impact on clinical trials and a method for accurate calibration.

BACKGROUND: Atherosclerotic plaque burden is the major end point in ongoing progression trials. Intravascular ultrasound allows precise measurements of coronary artery dimensions. However, the variability of measurements among different catheter systems is incompletely characterized. METHODS: Intravascular ultrasound imaging was performed in a cylindric phantom with 5 sections of different, known, cross-sectional area ranging from 3.24 to 27.99 mm(2). A total of 3637 measurements with different catheter systems (Atlantis SR and Ultracross, Scimed/Boston Scientific; and Invision and Avanar, Jomed) were performed. Measurements were divided into model building and validation datasets. For each catheter, calibration models were developed. RESULTS: Overestimation and underestimation of the true cross-sectional area of up to 18% was observed with different catheter systems. Calibration equations for the different systems could be developed that predicted the true diameter and area with high statistical precision (adjusted R(2) > 0.99). CONCLUSIONS: Area measurements vary among different intravascular ultrasound catheter systems. Calibration equations can correct for these differences and allow the comparison of measurements among catheters.     

Intracoronary IVUS for Evaluation of Atherosclerosis Progression

Serial imaging of the coronary arteries with intravascular ultrasound (IVUS) enables monitoring progression of atherosclerotic plaque and characterization of the clinical and pharmacological factors that influence it. These studies have demonstrated the importance of targeting the major cardiovascular risk factors, with evidence of slowing progression and in some cases promoting disease regression. In addition, technological advances in intravascular imaging also permit characterization of individual plaque components, enabling more comprehensive evaluation of anti-atherosclerotic therapies.     

血管内超声对粥样硬化冠状动脉成像的研究

研究目的在于评价血管内超声（ＩＶＵＳ）观察粥样硬化冠状动脉（ＣＡ）的安全性和可行性。利用３．５Ｆ，３０ＭＨｚ超声导管对１１例冠心病患者的２０支冠状动脉节段进行了检查，所有病人均顺利接ＩＶＵＳ检查，５例血管造影提示冠脉左主干正常的血管段，ＩＶＵＳ显示有内膜轻度增厚或局灶性斑块，１５支血管造影提示ＣＡ管腔狭窄的血管段，ＩＶＵＳ发现有中至重度的内膜增厚，操作中未发现严重并发症。结论：血管内超声检查是安全可行的，它可提供异常ＣＡ管壁形态学的详细信息。     

Currently available methodologies for the processing of intravascular ultrasound and optical coherence tomography images

Optical coherence tomography and intravascular ultrasound are the most widely used methodologies in clinical practice as they provide high resolution cross-sectional images that allow comprehensive visualization of the lumen and plaque morphology. Several methods have been developed in recent years to process the output of these imaging modalities, which allow fast, reliable and reproducible detection of the luminal borders and characterization of plaque composition. These methods have proven useful in the study of the atherosclerotic process as they have facilitated analysis of a vast amount of data. This review presents currently available intravascular ultrasound and optical coherence tomography processing methodologies for segmenting and characterizing the plaque area, highlighting their advantages and disadvantages, and discusses the future trends in intravascular imaging.     

Development of a 3 French Dual-Frequency Intravascular Ultrasound Catheter

Coronary plaque morphology, including plaque size and fibrous cap thickness, is thought to contribute to the risk of plaque rupture and future cardiac events. Dual-frequency intravascular ultrasound has been proposed as a possible technique to visualize both large-scale features and superficial detail of coronary plaque; however, it has not been found to be feasible within the constraints of a clinically functional intravascular ultrasound catheter. In this study, we describe the design and fabrication of a dual-frequency catheter using a bidirectional transducer stack with center frequencies of approximately 30 and 80?MHz. We describe how the high-frequency transducer achieves significantly improved axial and lateral resolution (16 and 120?µm, respectively, vs. 50 and 220?µm) at the expense of penetration depth. Finally, imaging of ex vivo human coronary artery segments reveals that the catheter can provide complementary images of the deeper arterial wall and superficial plaque features.     

Non-invasive measurement of coronary plaque from coronary CT angiography and its clinical implications

Coronary CT angiography (CTA) is increasingly used worldwide for direct, non-invasive evaluation of the coronary arteries. Advances in computed tomography (CT) technology over the last decade have enabled such reliable imaging of the coronary arteries. Beyond arterial stenosis, coronary CTA also permits assessment of atherosclerotic plaque (including plaque burden) and coronary artery remodeling, previously only achievable through invasive means. It has been shown that coronary plaque volumes for non-calcified and mixed plaques and the arterial remodeling index, correlate closely with invasive intravascular ultrasound. Several studies have also shown a strong relationship of adverse plaque features imaged by coronary CTA with acute coronary syndrome, all-cause death, major adverse cardiovascular events and myocardial ischemia. The aim of this review is to summarize current methods for quantitative measurement of atherosclerotic plaque features from coronary CTA and to discuss their clinical implications.     

Feasibility of three-dimensional intravascular ultrasonography: preliminary clinical studies.

The aim of this study was to demonstrate the clinical utility of reconstructed three-dimensional intravascular ultrasonography using a voxel-based volume rendering technique. Three-dimensional reconstruction of intravascular ultrasonographic data was performed in 12 patients with various vascular abnormalities during interventional radiology procedures. A stepping motor device was used to pull either a 12.5 or a 20 MHz catheter-based transducer through the lumen of a variety of vessels at a rate of 1.5 mm/s. Images were downloaded to a Life Imaging System for three-dimensional reconstruction. The value of three-dimensional ultrasonographic imaging was evaluated in comparison to conventional intravascular ultrasonography. A variety of abnormalities were demonstrated in reconstructed three-dimensional ultrasound imaging, including arterial atheroma and plaque, aneurysm and pseudoaneurysm, aortic dissection and stenosis (May-Thurner syndrome). The vascular branches and accessory vessels, as well as their relationships to each other, were easily demonstrated on three-dimensional imaging by selecting an appropriate angle, plane, and section of the image. The dimensions and shapes of the vascular lumen were determined in the longitudinal view. Three-dimensional information proved useful for determining the distribution and type of plaque in vessels. Reconstructed three-dimensional imaging allows for global evaluation of the dissection entry site, extent of the flap, and the false lumen of a pseudoaneurysm. Intravascular three-dimensional ultrasonography provides information complementary to that obtained with two-dimensional imaging. It supplies information about spatial relationships of anatomic structures that cannot be evaluated using conventional imaging methods.     

血管内超声溶栓治疗动脉硬化闭塞症的初步研究

目的 探讨经皮血管内超声溶栓再通动脉硬化闭塞症闭塞动脉的可行性。方法 14例有严重下肢缺血症状的动脉硬化闭塞症患者，用血管内超声溶栓仪进行了溶栓治疗。结果 超声溶栓探头在闭塞段血管内重建了通道，所有患者均实现了闭塞血管再通，6例仍有血管狭窄的患者行球囊扩张术。结论 血管内超声溶栓术可以用于再通闭塞的周围动脉，尤其是闭塞范围较长，药物溶栓治疗无效和患者禁忌药物溶栓治疗时，血管内超声溶栓是一种新的可靠的治疗手段。     

Imaging of the vulnerable plaque: new modalities

Atherosclerosis is currently considered to be an inflammatory and thus a systemic disease affecting multiple arterial beds. Recent advances in intravascular imaging have shown multiple sites of atherosclerotic changes in coronary arterial wall. Traditionally, angiography has been used to detect and characterize atherosclerotic plaque in coronary arteries, but recently it has been found that plaques that are not significantly stenotic on angiography cause acute myocardial infarction. As a result, newer imaging and diagnostic modalities are required to predict which of the atherosclerotic plaque are prone to rupture and hence distinguish "stable" and "vulnerable" plaques. Intravascular ultrasound can identify multiple plaques that are not seen on coronary angiography. Thermography has shown much promise and is based on the concept that the inflammatory plaques are associated with increased temperature and can also identify "vulnerable patients." Of all these newer modalities, magnetic resonance imaging has shown the most promise in identification and characterization of vulnerable plaques. In this article, we review the newer coronary artery imaging modalities and discuss the limitations of traditional coronary angiography.     

Peripheral vascular cutdown.

Critically ill patients who are not candidates for percutaneously placed arterial and venous lines require surgical cutdown. Although significant complications may arise from inadvertent injury to the vessel or associated structures during arterial and venous cutdown, these complications can be minimized by meticulous technique. With attention to site selection and catheter care, the useful life of these complex catheters approaches that of percutaneously placed devices. Finally, although the sequelae of placement by these techniques--including wound and catheter infection, distal ischemia, and vessel ligation--are increased, the need for appropriate intravascular access in these patients far outweighs the potential risks.     

Intravascular probe for detection of vulnerable plaque.

PURPOSE: Coronary angiography defines geometry of lumen of artery. However, perhaps 70% of heart attacks occur when minimally obstructive thin capped fibroatheroma rupture, causing thrombus and arterial occlusion. We have developed an intravascular imaging detector to identify vulnerable coronary artery plaque. PROCEDURE: Detector measures beta or conversion electron emissions from plaque-binding radiotracers. Detector assembly fits into a 2-mm diameter catheter and overcomes technical constraints of size, sensitivity, and conformance to intravascular environment. RESULTS: Device was tested by stepping test point sources past detector to verify function. System resolution is 6.7 mm and sensitivity is 400 cps/microCi one mm from detector. CONCLUSION: This prototype is a first step in imaging of labeled vulnerable plaque in coronary arteries. This type of system may assist in development of targeted and cost effective therapies to lower incidence of acute coronary artery diseases (CAD) such as unstable angina, acute myocardial infarction, and sudden cardiac death.     

Mechanisms and outcomes of angioplasty and atherectomy assessed by intravascular ultrasound imaging

Catheter-based intravascular ultrasound is a relatively new imaging tool to examine endovascular structure. One major goal for the development of intravascular ultrasound imaging has been to help clarify the mechanism of interventional therapies such as balloon angioplasty and directional atherectomy. Pathologic studies have suggested that plaque distribution and composition are key features that relate to initial and long-term success of coronary interventions. However, relatively little is known by angiography about the nature of plaque in the clinical setting. Intravascular ultrasound imaging provides a high resolution, “on-line” method of tracking the effects of catheter interventions such as balloon angioplasty and atherectomy. Because of its ability to visualize tissue beneath the luminal surface, ultrasound is generating new insights into the effect of plaque composition and distribution on the response to catheter therapies. With pre-procedure ultrasound imaging, it is increasingly possible to predict the result of a particular intervention, offering the potential for developing strategies of lesion-targeted therapy based on certain plaque characteristics. This article presents the early results of the GUIDE trial as a “works in progress” view of the role of intravascular ultrasound in helping interventionalists to understand—and to optimize—angioplasty and atherectomy. © 1993 John Wiley & Sons, Inc.     

Intravascular ultrasound estimation of arterial stenosis

The evaluation of the degree of reduction in the cross-sectional area of an artery has important pathophysiologic and therapeutic implications. Currently, no technique can easily provide this information. In this in vitro study we evaluated the potential of a new imaging technique, intravascular high frequency ultrasound angioscopy, in the estimation of percentage of cross-sectional area stenosis of an artery. To do this, we compared intravascular high frequency ultrasound to previously-validated external high frequency ultrasound and to anatomic estimation of arterial stenosis. Using a prototype intraluminal imaging catheter with a 20 MHz ultrasound transducer at its tip, we imaged 20 arterial segments of various size (15 to 90 mm2 lumen area by anatomy) in the control state and after experimental stenosis. These arterial segments were also imaged by external high frequency ultrasound. Lumen areas were measured from calibrated ultrasound images in the control state and after stenosis, and percentage of cross-sectional area stenosis was calculated. These data were compared to the percentage of area stenosis derived from calibrated anatomic photographs of the arteries taken in the control state and after stenosis. Both intravascular ultrasound angioscopy and external high frequency ultrasound yielded high-resolution, two-dimensional, circumferential images of the arteries. Alterations in vessel area and shape were apparent after creation of stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noncalcified Plaque in Cardiac CT: Quantification and Clinical Implications

Coronary computed tomography angiography (CTA) is being increasingly used for direct, noninvasive evaluation of the coronary arteries. Beyond stenosis, coronary CTA also permits assessment of atherosclerotic plaque (including total and noncalcified plaque burden) and coronary artery remodeling, previously only measurable through invasive techniques. It has been shown that coronary plaque volume for noncalcified and mixed plaques and the arterial remodeling index correlate closely with corresponding measures from invasive intravascular ultrasound. Several studies have also shown a strong relationship between adverse plaque features imaged by coronary CTA and acute coronary syndrome, major adverse cardiovascular events, and ischemia. The aim of this review is to summarize current methods for quantitative measurement of atherosclerotic plaque features from coronary CTA and to discuss the clinical implications of noncalcified plaque as detected by CTA and reported in the current literature.