Shear-stress and wall-stress regulation of vascular remodeling after balloon angioplasty: effect of matrix metalloproteinase inhibition.

BACKGROUND: Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown. METHODS AND RESULTS: PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and -49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up. CONCLUSIONS: Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.

Relationship between neointimal thickness and shear stress after Wallstent implantation in human coronary arteries.

BACKGROUND: In-stent restenosis by excessive intimal hyperplasia reduces the long-term clinical efficacy of coronary stents. Because shear stress (SS) is related to plaque growth in atherosclerosis, we investigated whether variations in SS distribution are related to variations in neointima formation. METHODS AND RESULTS: In 14 patients, at 6-month follow-up after coronary Wallstent implantation, 3D stent and vessel reconstruction was performed with a combined angiographic and intravascular ultrasound technique (ANGUS). The bare stent reconstruction was used to calculate in-stent SS at implantation, applying computational fluid dynamics. The flow was selected to deliver an average SS of 1.5 N/m(2). SS and neointimal thickness (Th) values were obtained with a resolution of 90 degrees in the circumferential and 2.5 mm in the longitudinal direction. For each vessel, the relationship between Th and SS was obtained by linear regression analysis. Averaging the individual slopes and intercepts of the regression lines summarized the overall relationship. Average Th was 0.44+/-0.20 mm. Th was inversely related to SS: Th=(0.59+/-0.24)-(0.08+/-0.10)xSS (mm) (P<0.05). CONCLUSIONS: These data show for the first time in vivo that the Th variations in Wallstents at 6-month follow-up are inversely related to the relative SS distribution. These findings support a hemodynamic mechanism underlying in-stent neointimal hyperplasia formation.

True 3-dimensional reconstruction of coronary arteries in patients by fusion of angiography and IVUS (ANGUS) and its quantitative validation.

BACKGROUND: True 3D reconstruction of coronary arteries in patients based on intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS information (ANGUS). The clinical applicability of ANGUS was tested, and its accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who were investigated 6 months after stent implantation, a sheath-based catheter was used to acquire IVUS images during an R-wave-triggered, motorized stepped pullback. First, a single set of end-diastolic biplane angiographic images documented the 3D location of the catheter at the beginning of pullback. From this set, the 3D pullback trajectory was predicted. Second, contours of the lumen or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular rotation of the reconstruction was optimized by quantitative matching of the silhouettes of the 3D reconstruction with the actual biplane images. Reconstructions were obtained in 12 patients. The number of pullback steps, which determines the pullback length, closely agreed with the reconstructed path length (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions showed high correlation (0.84 to 0.97) with corresponding measurements in the actual biplane angiographic images. CONCLUSIONS: With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.

Chromatic distortion during angioscopy: assessment and correction by quantitative colorimetric angioscopic analysis.

Angioscopy represents a diagnostic tool with the unique ability of assessing the true color of intravascular structures. Current angioscopic interpretation is entirely subjective, however, and the visual interpretation of color has been shown to be marginal at best. The quantitative colorimetric angioscopic analysis system permits the full characterization of angioscopic color using two parameters (C1 and C2), derived from a custom color coordinate system, that are independent of illuminating light intensity. Measurement variability was found to be low (coefficient of variation = 0.06-0.64%), and relatively stable colorimetric values were obtained even at the extremes of illumination power. Variability between different angioscopic catheters was good (maximum difference for C1, 0.022; for C2, 0.015). Catheter flexion did not significantly distort color transmission. Although the fiber optic illumination bundle was found to impart a slight yellow tint to objects in view (deltaC1 = 0.020, deltaC2 = 0.024, P < 0.0001) and the imaging bundle in isolation imparted a slight red tint (deltaC1 = 0.043, deltaC2 = -0.027, P < 0.0001), both of these artifacts could be corrected by proper white balancing. Finally, evaluation of regional chromatic characteristics revealed a radially symmetric and progressive blue shift in measured color when moving from the periphery to the center of an angioscopic image. An algorithm was developed that could automatically correct 93.0-94.3% of this error and provide accurate colorimetric measurements independent of spatial location within the angioscopic field. In summary, quantitative colorimetric angioscopic analysis provides objective and highly reproducible measurements of angioscopic color. This technique can correct for important chromatic distortions present in modern angioscopic systems. It can also help overcome current limitations in angioscopy research and clinical use imposed by the reliance on visual perception of color.

Shear stress in atherosclerosis, and vascular remodelling.

Shear stress plays a role in lipid accumulation in primary atherosclerosis and vascular remodelling. We will present applications of a new technique, which enables to quantify shear stress in 3D vessel reconstructions. The method is based on 3D IVUS reconstructions of blood vessels either obtained by IVUS pull back (external iliac artery) or by a combination of angiography and IVUS (curved coronary artery). Distribution of wall thickness of a curved human right coronary artery was such that low wall thickness occurred where shear stress was high, and wall thickness was high where shear stress was low. Consequently, an inverse relationship between shear stress and wall thickness was detected. Although vascular remodelling after PTA in external iliac arteries of atherosclerotic Yucatan pigs was predicted both by acute gain and decrements in shear stress, the decrement in shear stress appeared a better predictor. In conclusion, shear stress appears to play a role in primary atherosclerosis and vascular remodelling after PTA.

Composition of human thrombus assessed by quantitative colorimetric angioscopic analysis.

BACKGROUND: Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception substantially limit the theoretic potential of angioscopic color. We used a novel application of tristimulus colorimetry to quantify thrombus color to both aid in its detection and assess its composition. METHODS AND RESULTS: A series of human thrombus models were constructed in vitro. Spatial homogeneity was ensured by light and electron microscopy. Quantitative colorimetric angioscopic analysis demonstrated excellent measurement reproducibility (mean difference, 0.07% to 0.17%), unaffected by illuminating light intensity (coefficient of variation, 0.21% to 3.67%). Colorimetric parameters C1 and C2 were strongly correlated (r=.99, P<.0001) with thrombus erythrocyte concentration. Principal components analysis transformed these parameters into a single value, the thrombus erythrocyte index, with little (0.06%) loss of content. Measured and predicted concentrations were similar (mean difference, 0.16 erythrocytes per 1 ng). Randomly ordered images were also subjected to visual analysis by three experienced angioscopists, with suboptimal levels of both intraobserver (mean kappa=0.63) and interobserver (mean kappa=0.48) agreement. In addition, visual ranking resulted in a Kendall rank coefficient of 0.72 to 0.76 versus a perfect 1.00 from quantitative measurement. CONCLUSIONS: Quantitative colorimetric angioscopic analysis provides a new, objective, and reproducible analytic tool for assessing angioscopic images of human thrombus. Even under ideal circumstances, experienced angioscopists do a poor job of assessing color (and therefore composition) of human thrombi. This technique can, for the first time, provide quantitative information of thrombus composition during routine diagnostic imaging.

Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics.

The predilection sites of atherosclerotic plaques implicate rheologic factors like shear stress underlying the genesis of atherosclerosis. Presently no technique is available that enables one to provide 3D shear stress data in human coronary arteries in vivo. In this study, we describe a novel technique that uses a recently developed 3D reconstruction technique to calculate shear stress on the endothelium with computational fluid dynamics. In addition, we calculated local wall thickness, the principal plane of curvature, and the location of plaque with reference to this plane, relating these results to shear stress in a human right coronary artery in vivo. Wall thickness and shear stress values for the entire vessel for three inflow-velocity values (10 cm/second, 20 cm/second, and 30 cm/second equivalents with the Reynolds numbers 114,229, and 457) were as follows: 0.65 +/- 0.37 mm (n = 1600) and 19.6 +/- 1.7 dyne/cm2; 46.1 +/- 8.1 dyne/cm2 and 80.1 +/- 16.8 dyne/cm2 (n = 1600). Curvature was 25 +/- 9 (m-1), resulting in Dean numbers 20 +/- 8; 46 +/- 16, and 93 +/- 33. Selection of data at the inner curvature of the right coronary artery provided wall thickness values of 0.90 +/- 0.41 mm (n = 100), and shear stress was 17 +/- 17, 38 +/- 44, and 77 +/- 54 dyne/cm2 (n = 100), whereas wall thickness values at the outer curve were 0.37 +/- 0.17 mm (n = 100) and shear stress values were 22 +/- 17, 60 +/- 44, and 107 +/- 79 dyne/cm2 (n = 100). These findings could be reconciled by an inverse relationship between wall thickness and shear stress for each velocity level under study. For the first time for human vessels in vivo, evidence is presented that low shear stress promotes atherosclerosis. As the method is nondestructive, it allows repeated measurements in the same patient and will provide new insights in the progress of atherosclerosis.

True reconstruction of vessel geometry from combined X-ray angiographic and intracoronary ultrasound data.

At present a rapidly expanding variety of methods appear to provide three-dimensional (3-D) reconstructions of blood vessels in a patient. Generally the results of such methods look very realistic. However, only a few produce a true 3-D reconstruction. We strongly suggest that for a true 3-D reconstruction of a blood vessel the following criteria should at least be fulfilled: (1) the arterial wall rather than the lumen must be reconstructed; (2) the spatially curved course of the vessel must be included; and (3) the orientation of local vessel wall characteristics, for example, plaque eccentricity, with respect to the luminal course must be correctly maintained. Currently, only methods combining biplane X-ray angiography and intravascular ultrasound imaging (IVUS) have succeeded in providing true 3-D reconstruction of a segment of a vessel. Accuracy of those reconstructions is derived from studies using phantoms having precisely known geometry. In patients, data on accuracy are more difficult to obtain. Nevertheless, a comparison can be made between the actual length of an IVUS pull-back trajectory and its reconstructed length showing relative differences of less than 3%. Further knowledge can be obtained by comparing simulated angiograms derived from the 3-D reconstruction with the real contrast angiograms. True 3-D reconstruction methods of the vessel wall and lumen, applicable in the individual patient, have become feasible and produce accurate results. Application of such a method will be helpful to understand immediate and long-term vessel remodelling induced by all types of catheter interventions and in the study of progression or regression of atherosclerotic wall disease.

Color quantification in angioscopic video images.

Colors in video representations of angioscopic images are up until now described by an human observer. Differences in settings of the monitor and the inherent poor ability of the human eye to classify colors objectively results in a very poor intraobserver as well as interobserver variability. A PC-based method is described to measure colors in a video image and to present the results in a novel C-diagram. Results with this method for standard calibrated colors are given. Possible sources of error are discussed and methods to minimize these errors are presented.

Comparison of models for quantitative left ventricular wall motion analysis from two-dimensional echocardiograms during acute myocardial infarction.

To develop quantitative analysis of regional left ventricular wall motion in the absence of a gold standard, an objective statistical measure to compare models of wall motion is described. This measure can be derived from wall motion analysis of subgroups of patients with different patterns of wall motion. A priori knowledge of the exact localization of wall motion abnormalities is not needed. Two-dimensional echocardiograms were analyzed from 79 patients with myocardial infarction. The following 4 models were compared: Model I was based on the descent of the base toward the stable apex during systole. Models II and III measured area reduction with fixed- and floating-reference systems, respectively. Model IV was the centerline model. Classification by the electrocardiogram of the myocardial infarction as anterior (n = 37), posterior (n = 17) and inferior (n = 25) provided the a priori probability for classification of myocardial infarction. The a posteriori probability for classification of myocardial infarction was derived from the detection of wall motion abnormalities by echocardiographic analysis. The mean difference between a posteriori and a priori probability is a measure for the diagnostic value of the model, and was measured for 200 regions/patient. Use of the described measure revealed model I to be the most informative model and model III the least informative. Thus, the described statistical measure contributes to the development of regional wall motion analysis.

Electrical nerve and muscle stimulation by radio frequency surgery: role of direct current loops around the active electrode.

Tissue cutting by electrosurgery is often accompanied with stimulation of nerves and muscles, despite the high frequency of the alternating current being applied. The main source of this stimulation is thought to be the generation of low frequency current by the nonlinear sparking process. However, measurement of this low-frequency current, in the generator electrode's circuit, showed relatively small values, barely sufficient to support this hypothesis. In this study more powerful low frequency current could be identified, indeed also originating from the nonlinear sparking process. Local direct and low frequency currents, at a level of tens of milliamperes, appeared to be generated between different sites of the active electrode-tissue interface. Probably these local currents have not been noticed before as they cannot be detected in the outer chain of generator, electrodes, and connecting wires. This finding may explain why most measures, intended to prevent stimulation by modifying this outer chain, had only limited success.

Two-dimensional echocardiographic analysis of the dynamic geometry of the left ventricle: the basis for an improved model of wall motion.

To establish an appropriate echocardiographic model for wall motion analysis we first determined the precise dynamic geometry of the left ventricle during systole, as visualized by two-dimensional echocardiography. With the epicardial apex and the aortic-ventricular and mitral-ventricular junctions as anatomic landmarks, we quantitatively analyzed apical long-axis views in 61 normal subjects, 41 patients with anterior myocardial infarction, and nine patients with posterior myocardial infarction. Thoracic impedance registration allowed exclusion of extracardiac motion from the measurements. In normal subjects the epicardial apex moved outwardly only 0.6 +/- 0.3 mm (mean +/- standard error). Examination of 15 hearts fixed in formalin revealed apical myocardial thickness of 1.5 +/- 0.2 mm. These data suggest that the observed inward motion of the endocardial apex (4.1 +/- 0.7 mm) resulted from obliteration of the apical cavity as a result of inward motion of the adjacent walls. Translation of the base was considerable in normal subjects (14.1 +/- 0.4 mm) and decreased in myocardial infarction (9.1 +/- 0.5 mm, p less than 0.0001). Unequal shortening of the adjacent walls in anterior and posterior myocardial infarction caused basal rotation in the opposite direction (-9.1 +/- 0.8 degrees and 9.7 +/- 1.4 degrees, respectively, p less than 0.0001 versus that of normal subjects, -3.4 +/- 0.7 degrees). Long-axis rotation was not clinically significant (less than 1 degree). We conclude that during ventricular contraction the apex serves as a stable point, whereas the base translates toward the apex because of shortening of the adjacent walls. We then propose a model for analyzing regional wall motion from two-dimensional echocardiograms on the basis of these observations.