Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology

BACKGROUND: Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology. METHODS AND RESULTS: Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mum thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86). CONCLUSION: Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque.     

Calcified plaque cross-sectional area in human arteries: correlation between intravascular ultrasound and undecalcified histology

BACKGROUND: The purpose of this investigation was to quantify the amount of intralesional calcium detected by intravascular ultrasound (IVUS) compared with undecalcified histology in human arteries. This method preserves intralesional calcium and reduces sectioning artifacts, thereby providing an accurate measure of calcium plaque morphology. METHODS AND RESULTS: Ten arterial segments (5 coronary, 5 iliac) were obtained at autopsy. IVUS imaging was performed with a 4.9F catheter at an automated pullback rate of 1.0 mm/s. The undecalcified arteries were dehydrated in ascending alcohol and polymerized in glycol methylmethacrylate. The arteries were cut into 200-microm sections with an Isomet low-speed saw and stained with Goldner's trichrome. The lumen cross-sectional area, the calcium plaque cross-sectional area, the calcium plaque depth, length, and angle of arc of calcified plaque were measured from the IVUS images and histologic sections. In 24 selected cross sections, there were 38 separate calcium plaques. An independent observer correctly identified 34 of 38 calcified plaques for a sensitivity of 89% and specificity of 97%. The total mean calcified plaque cross-sectional area measured from histology was 4.6 +/- 4.1 mm2 compared with 2.8 +/- 2.3 mm2 by IVUS (P =.002). Plaque depth measured by histology was 1.2 +/- 0.4 mm versus 0.7 +/- 0.2 mm by IVUS (P =.001). The length of calcium plaques measured by histology was 3.6 +/- 1.78 mm versus 3.6 +/- 1.5 mm for IVUS (r = 0.79). CONCLUSIONS: IVUS accurately depicts circumferential calcified lesions with high sensitivity (89%) and specificity (97%). However, IVUS underestimates the total calcified plaque cross-sectional area by 39%. This is mainly because of the inability of the ultrasound to penetrate intralesional calcium, which leads to an underestimation of the depth of calcium by 45%.     

Plaque characterization of atherosclerotic coronary arteries by intravascular ultrasound

Intravascular ultrasound provides cross-sectional images of arteries and enables accurate delineation of lumen dimensions and wall structure. Moreover, ultrasound characterization of atherosclerotic plaque subtypes may have important implications in determining the natural history and the clinical outcome of patients with coronary artery disease. The reliability of intravascular ultrasound to differentiate plaque morphology subtypes was studied in 60 coronary segments excised from 33 coronary arteries obtained from 17 patients at necropsy. Ultrasound was performed with a 25-MHz transducer mounted on the distal end of a rigid probe that was rotated manually inside the lumen artery. Plane film radiography was also performed to establish the presence of calcific deposits. A total of 82 histologic transverse sections corresponding to 82 ultrasound imaging sites were studied from the 60 coronary segments. Of the first 54 images, 36 were fibrous plaques and yielded dense homogenous echo reflections, 6 had discrete areas of lipid that were less echogenic and 12 had calcific deposits that cast echo-free shadows beyond areas of intense echo reflections. The predictive accuracy of evaluating plaque composition in the remaining 28 ultrasound imaging sites was 96%. Thus, anatomical structure of coronary arteries and composition of atherosclerotic lesions can be assessed accurately with intravascular ultrasound and may have potential for better understanding of the atherosclerotic process and provide guidance to interventional procedures.     

Coronary artery imaging with intravascular high-frequency ultrasound

Safe and effective clinical application of new interventional therapies may require more precise imaging of atherosclerotic coronary arteries. To determine the reliability of catheter-based intravascular ultrasound as an imaging modality, a miniaturized prototype ultrasound system (1-mm transducer; center frequency, 25 MHz) was used to acquire two-dimensional, cross-sectional images in 21 human coronary arteries from 13 patients studied at necropsy who had moderate-to-severe atherosclerosis. Fifty-four atherosclerotic sites imagined by ultrasound were compared with formalin-fixed and fresh histological sections of the coronary arteries with a digital video planimetry system. Ultrasound and histological measurements correlated significantly (all p less than 0.0001) for coronary artery cross-sectional area (r = 0.94), residual lumen cross-sectional area (r = 0.85), percent cross-sectional area (r = 0.84), and linear wall thickness (plaque and media) measured at 0 degrees, 90 degrees, 180 degrees, and 270 degrees (r = 0.92). Moreover, ultrasound accurately predicted histological plaque composition in 96% of cases. Anatomic features of the coronary arteries that were easily discernible were the lumen-plaque and media-adventitia interfaces, very bright echoes casting acoustic shadows in calcified plaques, bright and homogeneous echoes in fibrous plaques, and relatively echo-lucent images in lipid-filled lesions. These data indicate that intravascular ultrasound provides accurate image characterization of the artery lumen and wall geometry as well as the presence, distribution, and histological type of atherosclerotic plaque. Thus, ultrasound imaging appears to have great potential application for enhanced diagnosis of coronary atherosclerosis and may serve to guide new catheter-based techniques in the treatment of coronary artery disease.     

Reproducibility of intravascular ultrasound virtual histology analysis

OBJECTIVE: Intravascular ultrasound with virtual histology analysis (IVUS-VH) is a novel technology which allows for the identification of discrete atherosclerotic plaque components using radiofrequency backscatter data. Whether the composition of these plaques can be monitored accurately in a longitudinal fashion remains unclear. We sought to evaluate the reproducibility of plaque composition measurements as determined by IVUS-VH in a clinical setting. METHODS: Sixteen consecutive patients who underwent percutaneous coronary intervention were included in this study. Prior to and then again following intervention, IVUS images with VH processing were obtained with motorized pullback. Up to 4 frames were selected for analysis for each patient, with a total of 24 IVUS frames used. An IVUS frame was chosen with visible angiographic and ultrasound landmarks. The matching frame on the second pullback was identified using these landmarks. For each frame, vessel and lumen area as well as plaque composition by VH were determined. RESULTS: There was a high level of agreement between the two pullback measurements for lumen area, vessel area, and plaque burden (the Spearman rank-order correlation coefficients were 0.96, 0.96, and 0.95, respectively). Similarly, for plaque components by VH, the coefficients ranged from .90 to .97 and 0.84 to 0.92 for segmental volumetric analysis. The Bland-Altman plots indicated proportional error for the differences of the four measurements between the two pullback trials and were associated with high coefficients of reproducibility. CONCLUSIONS: Discrete measurements of plaque compositional area and volume in the clinical setting appear to have reproducibility comparable to that of traditional IVUS measurements.     

Determinants of coronary artery compliance in subjects with and without angiographic coronary artery disease

OBJECTIVES: The goal of this study was to determine factors contributing to the biomechanical properties of coronary arteries in people with and without angiographic coronary artery disease (CAD). BACKGROUND: The stiffness of the aorta is known to increase with increasing age and in the presence of CAD. However, little is known about the mechanics of coronary arteries, which may have important clinical consequences. METHODS: Intravascular ultrasound was used to determine the mechanical properties of coronary arteries and plaque behavior in subjects with CAD (n = 38), those with chest pain but angiographically normal coronary arteries (N) (n = 9) and those early (<2 weeks) after cardiac transplant (T) (n = 14). RESULTS: Coronary arteries dilated during systole in all groups, but cross-sectional compliance and distensibility were lowest in the proximal left anterior descending artery (LAD) in the subjects with CAD compared with the N and T groups (compliance: 1.2 +/- 0.2 vs. 1.7 +/- 0.5 and 2.7 +/- 0.6 x 10(-2) mm(2) mm Hg(-1) [mean +/- SEM] respectively, p < 0.02 CAD vs. T; distensibility: 0.8 +/- 0.2 vs. 1.7 +/- 0.5 and 1.7 +/- 0.3 x 10(-3) mm Hg(-1), p < 0.05 CAD vs. T). There was extensive plaque in the CAD group, and plaque was also present in the N group, but minimal atheroma was present in the T group. Plaque cross-sectional area diminished significantly during systole in both the LAD and circumflex arteries. Absolute changes were: 0.50 +/- 0.30, 0.33 +/- 0.11 and 0.68 +/- 0.13 mm(2) in the proximal LAD, distal LAD and proximal circumflex arteries, respectively. In subjects with atheroma, there was a significant correlation between cross-sectional compliance and plaque compression at all sites, and plaque compression was a significant determinant of cross-sectional compliance at both proximal sites in multiple regression analyses with age, mean arterial pressure and extent of plaque as the other independent variables. CONCLUSIONS: A major determinant of the systolic increase in coronary luminal area in patients with atheroma is a reduction in plaque cross-sectional area during systole.     

Discrimination of early/intermediate and advanced/complicated coronary plaque types by radiofrequency intravascular ultrasound analysis

Radiofrequency intravascular ultrasound (IVUS-RF) analysis, as an extension of conventional IVUS imaging, may provide more accurate plaque discrimination. Thirty-two autopsy atherosclerotic coronary arteries were investigated. Corresponding sectors in different plaques were matched by histologic and RF analysis. Histologic analysis utilized the American Heart Association plaque classification. The backscattered ultrasound RF signal was analyzed by fast-Fourier transform, providing the underlying frequency components of its power spectrum. The normalized backscattered signal power (in decibels [dB]) for frequencies between 15.3 and 40.3 MHz was then measured for plaque discrimination. Advanced/complicated plaque types showed a higher signal power at all frequencies than early/intermediate lesion types (p <0.001 to p = 0.005). Discrimination of advanced/complicated lesion types was best at 15.3 MHz, with a cut-off point of 2.5 dB (sensitivity 93%, specificity 79%), and second best at 17.6 MHz (sensitivity 87%, specificity 71%, cut-off point 1.9 dB). With conventional IVUS, plaque discrimination was weaker; the best sensitivity for diagnosing early/intermediate lesion types was reached for “soft plaque” (sensitivity 63%, specificity 73%). Compared with conventional IVUS, IVUS-RF can discriminate between advanced/complicated and early/intermediate coronary atherosclerotic lesions with relatively high sensitivity and specificity in vitro.     

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)     

Virtual histology: a window to the heart of atherosclerosis

Intravascular ultrasound has done much to improve our understanding of atherosclerosis and the impact of percutaneous intervention on the coronary artery. However, subjectivity in interpreting the acoustic reflection of the ultrasound signal has spawned the development of other progressive technologies. Virtual histology intravascular ultrasound (VHIVUS) utilises the ultrasound backscatter signal in order to colour code plaque into four pre-specified subtypes based on their histological composition. We review the background behind traditional grey scale intravascular ultrasound (IVUS) and examine the current evidence for VHIVUS and its potential for use in clinical interventional practice.     

Usefulness of high-frequency vascular ultrasound imaging and serum inflammatory markers to predict plaque rupture in patients with stable and unstable angina pectoris

It remains unclear what kind of morphologic and biochemical features best predict plaque rupture in patients with angina pectoris (AP). This study aimed to investigate whether combined high-frequency vascular ultrasound imaging and measurements of serum inflammatory biomarkers can predict coronary plaque ruptures in patients with AP. The study population consisted of 20 patients with stable AP and 40 patients with unstable AP. High-frequency vascular ultrasound imaging was performed in the 2 groups to measure intima-media thickness, the plaque acoustic density of the common carotid arteries, and the flow-mediated dilation of the brachial arteries. Serum lipid profile and inflammatory biomarkers were measured in all patients. Using intravascular ultrasound, a list of coronary imaging parameters was obtained. A multivariate logistic regression model was applied to calculate the odds ratio of each parameter to predict coronary plaque ruptures detected by intravascular ultrasound. Of 139 coronary artery plaques identified by intravascular ultrasound, 48 plaques (9 in stable AP and 39 in unstable AP) developed ruptures. Among measured parameters, the values of carotid intima-media thickness, coronary external elastic membrane area, plaque area, plaque burden, plaque eccentric index and remodeling index, serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were significantly higher in unstable AP than in stable AP (p <0.05 to 0.01). Of these parameters, carotid intima-media thickness, serum high-sensitivity C-reactive protein, and the coronary remodeling index were found to be significant predictors of coronary plaque rupture, with odds ratios of 9.51 (95% confidence interval 1.29 to 21.81), 3.02 (95% confidence interval 1.01 to 7.65), and 0.01 (95% confidence interval 0.00 to 0.34), respectively. In conclusion, combined high-frequency ultrasound imaging of coronary and carotid arteries and measurements of serum inflammatory markers are able to predict coronary plaque ruptures in patients with AP.     

Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology.

OBJECTIVES: The goal of the present study was to compare the accuracy of in vivo tissue characterization obtained by intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, known as Virtual Histology (VH), to the in vitro histopathology of coronary atherosclerotic plaques obtained by directional coronary atherectomy. BACKGROUND: Vulnerable plaque leading to acute coronary syndrome (ACS) has been associated with specific plaque composition, and its characterization is an important clinical focus. METHODS: Virtual histology IVUS images were performed before and after a single debulking cut using directional coronary atherectomy. Debulking region of in vivo histology image was predicted by comparing pre- and post-debulking VH images. Analysis of VH images with the corresponding tissue cross section was performed. RESULTS: Fifteen stable angina pectoris (AP) and 15 ACS patients were enrolled. The results of IVUS RF data analysis correlated well with histopathologic examination (predictive accuracy from all patients data: 87.1% for fibrous, 87.1% for fibro-fatty, 88.3% for necrotic core, and 96.5% for dense calcium regions, respectively). In addition, the frequency of necrotic core was significantly higher in the ACS group than in the stable AP group (in vitro histopathology: 22.6% vs. 12.6%, p = 0.02; in vivo virtual histology: 24.5% vs. 10.4%, p = 0.002). CONCLUSIONS: Correlation of in vivo IVUS RF data analysis with histopathology shows a high accuracy. In vivo IVUS RF data analysis is a useful modality for the classification of different types of coronary components, and may play an important role in the detection of vulnerable plaque.     

Reproducibility of coronary lumen, plaque, and vessel wall reconstruction and of endothelial shear stress measurements in vivo in humans.

The purpose of this study was to assess the reproducibility of an in vivo methodology to reconstruct the lumen, plaque, and external elastic membrane (EEM) of coronary arteries and estimate endothelial shear stress (ESS). Ten coronary arteries without significant stenoses (five native and five stented arteries) were investigated. The 3D lumen and EEM boundaries of each coronary artery were determined by fusing end-diastolic intravascular ultrasound images with biplane coronary angiograms. Coronary flow was measured. Computational fluid dynamics was used to calculate local ESS. Complete data acquisition was then repeated. Analysis was performed on each data set in a blinded manner. The intertest correlation coefficients for all arteries for the two measurements of lumen radius, EEM radius, plaque thickness, and ESS were r = 0.96, 0.96, 0.94, 0.91, respectively (all P values < 0.0001). The 3D anatomy and ESS of human coronary arteries can be reproducibly estimated in vivo. This methodology provides a tool to examine the effect of ESS on atherogenesis, remodeling, and restenosis; the contribution of arterial remodeling and plaque growth to changes in the lumen; and the impact of new therapies.     

血管内影像技术的新进展

近年来血管内影像技术,特别是血管内超声领域的研究进展,主要包括:(1)对易损斑块认识的不断深入和检测率的逐步提高;(2)更有效地指导冠状动脉介入治疗,特别是指导药物洗脱支架的置入和随访。多种新型血管内影像技术日趋成熟,包括虚拟组织学血管内超声、整合背向散射血管内超声、光学相干断层成像术、近红外光谱仪、血管镜及血管内磁共振与传统的灰阶血管内超声一起,推动着血管内影像技术进入崭新的阶段。     

Noninvasive tissue characterization of coronary arterial plaque by 16-slice computed tomography in acute coronary syndrome

Noninvasive characterization of coronary plaques is challenging for cardiologists. The authors' goal was to explore the clinical feasibility of newly developed 16-slice computed tomography (CT) in tissue characterization of coronary arterial plaques in patients with acute coronary syndrome. Sixteen patients with acute coronary syndrome underwent 16-slice CT (Aquillion, Toshiba) and coronary arteriography with intravascular ultrasound (IVUS) within 7 days. Twenty-three plaques were classified by IVUS according to plaque echogenicity: 6 soft plaques, 11 intermediate plaques, and 6 calcified plaques. Mean (+/- SD) CT numbers (Hounsfield units [HU]) of these 3 types of plaques were 50.6 +/-14.8 HU, 131 +/-21.0 HU, and 721 +/-231 HU, respectively. Sixteen-slice CT facilitates noninvasive tissue characterization of coronary arterial plaques.     

Comparison of measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multidetector computed tomography versus intravascular ultrasound

In 26 patients, 16-slice multidetector computed tomography (MDCT) with 0.75-mm collimation and intravascular ultrasound (IVUS) of 1 coronary artery were performed. At 100 sites within the coronary arteries, the measurement of cross-sectional luminal area and, if detectable, the cross-sectional area of atherosclerotic plaque was performed independently with IVUS and MDCT. The mean luminal area (r = 0.92), measured at 100 sites, and plaque area (r = 0.55), measured at 65 sites, were significantly correlated (p <0.001) between MDCT and IVUS. The mean luminal area and mean plaque area were slightly but significantly overestimated with MDCT. MDCT permits the noninvasive measurement of coronary cross-sectional luminal and plaque areas with moderate accuracy.     

虚拟组织学血管内超声的研究现状和展望

冠状动脉斑块的形态和组成反映了动脉粥样硬化的发展进程。病理研究将斑块分为稳定性斑块和不稳定性斑块,后者以大的脂质核心覆盖薄纤维帽为特征,是斑块破裂继发血栓形成导致急性冠状动脉综合征,或内膜增生致介入术后再狭窄的重要原因之一。虚拟组织学血管内超声能够有效地在体评价斑块的组成和性质。本综述主要介绍虚拟组织学血管内超声在心血管疾病尤其是介入心脏病学领域的研究进展。     

Intravascular ultrasonic evidence by constant cross-sectional area of atherosclerotic plaques during coronary vasomotion in humans

AIMS: This study aims to visualize ultrasonically deformation of atheroscleroticplaques in human coronary arteries during vasoconstriction andvasodilatation. METHODS AND RESULTS: Intravascular ultrasound detected occult atherosclerosis inangiographically normal coronary arteries of eight patientswith chest pain at rest. During the acetylcholine provocativetest, intravascular ultrasound monitored deformation of theatherosclerotic plaques. At the last step of the test, intracoronaryinjection of isosorbide dinitrate caused vasodilation. Undercontrol, acetylcholine-treated, and isosorbide dinitrate-treatedconditions, cross-sectional areas of sonolucent circle and vessellumen were measured. Subtraction of the latter from the formergave the area of atherosclerotic plaque. In the process of vasoconstrictionand vasodilation, the plaque area did not change significantly. CONCLUSION: The cross-sectional area of the atherosclerotic plaque appearedto be constant during vasomotion of human coronary arteries.     

Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study

Objectives. The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease.Background. Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance.Methods. Twenty-seven patients (mean age [±SD] 57 ± 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 dilferent coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (ΔA) and pressure (ΔP) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [ΔA/AJ/ΔP [mm Hg⁻¹×x 10³]).Results. Lumen area and plaque area were 12.6 ± 5.7 and 3 ± 3 mm², respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = −0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 ± 2.1 vs. 1.8 ± 1.2 mm Hg⁻¹, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 ± 1.9 vs. 1.6 ± 1.1 mm Hg⁻¹, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 ± 9.7 vs. 2.3 ± 1.6 mm Hg⁻¹, p < 0.01) but was similar in concentric and eccentric plaques (1.6 ± 1.5 vs. 1.6 ± 0.9 mm Hg⁻¹). Plaque area (r = − 0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance.Conclusions. Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.     

Pathologic validation of a new method to quantify coronary calcific deposits in vivo using intravascular ultrasound

Current methods of calcium quantification by intravascular ultrasound (IVUS) measure the arc of calcium using the cross-sectional image at the lesion and at the reference site while neglecting calcium elsewhere. Calcium at these sites may not adequately represent the extent of total epicardial coronary calcium. We devised a new method to quantify calcium as a percentage of the coronary luminal surface. This study examines whether this new method accurately reflects coronary calcium determined by histology. Seventeen postmortem coronary arteries were pressure-fixed and imaged by IVUS using a motorized pullback device. Total plaque-luminal circumferential length and calcified plaque-luminal circumferential length were measured from serial cross-sectional IVUS images every 1 mm. With use of Simpson's method, the total plaque and calcified plaque surface area was then calculated. Histologic sections were stained with hematoxylin-eosin and Movat pentachrome at 3-mm intervals. Calcium was independently quantified by planimetry under light microscopy. Histologic analysis (n = 253 sections) revealed a wide range of calcium (0 to 47 mm2; mean 12 +/- 16 mm3). The IVUS-derived calcified plaque surface area was 17 +/- 23 mm2), which represented 3.1 +/- 4.1% (range 0% to 13.9%) of the total plaque surface area. The histologic and IVUS quantification of calcium by this method was strongly related (r = 0.84, p <0.0001), which was an improvement over current 2-dimensional measures of calcium arc (r = 0.41, p = 0.18). Calculation of calcified plaque surface area from sequential IVUS images appears to accurately reflect the degree of total coronary calcification.     

Noninvasive detection of subclinical coronary atherosclerosis coupled with assessment of changes in plaque characteristics using novel invasive imaging modalities: the Integrated Biomarker and Imaging Study (IBIS).

OBJECTIVES: Our purpose was to assess noninvasive imaging in detection of subclinical atherosclerosis and to examine novel invasive modalities to describe prevalence and temporal changes in putative characteristics of "high-risk" plaques. BACKGROUND: Conventional coronary imaging cannot identify "high-risk" lesions. METHODS: Conventional (quantitative angiography and intravascular ultrasound [IVUS]) and novel imaging (IVUS-based palpography and gray scale echogenicity) were performed at baseline and 6 months later in 67 patients with diverse clinical presentations. Different imaging techniques were compared within a common segment defined by multislice computed tomography (MSCT). RESULTS: Compared with IVUS, the sensitivity, specificity, and positive and negative predictive value of MSCT for detecting significant plaque was 86%, 69%, 90%, and 61%, respectively. In coronary arteries with <50% stenosis, there were no temporal changes in luminal and plaque dimensions measured by quantitative coronary angiography or IVUS; however, a significant reduction in abnormal strain pattern was detected on palpography (density high strain spots/cm: 1.6 +/- 1.5 vs. 1.2 +/- 1.4, p = 0.0123. These changes were mainly related to significant changes in patients who presented with ST-segment elevation myocardial infarction. The assessment of plaque echogenicity showed no temporal changes. There were no correlations between circulating biomarkers and quantifiable imaging parameters. CONCLUSIONS: Mild angiographic disease is associated with large atherosclerotic plaques on MSCT. Conventional invasive coronary imaging reveals static luminal and plaque dimensions on standard medical therapy with plaque hypoechogenicity remaining unchanged over the 6-month period. By contrast, palpography measurements of strain correlate with clinical presentation and significantly decrease on standard medical therapy. Novel imaging modalities, such as palpography, might provide insights into plaque biology and might eventually serve as intermediate end points in interventional trials.