Andreas Wahle

Effect of Endothelial Shear Stress on the Progression of Coronary Artery Disease, Vascular Remodeling, and In-Stent Restenosis in Humans In Vivo 6-Month Follow-Up Study

Background—Native atherosclerosis and in-stent restenosis are focal and evolve independently. The endothelium controls local arterial responses by transduction of shear stress. Characterization of endothelial shear stress (ESS) may allow for prediction of progression of atherosclerosis and in-stent restenosis. Methods and Results—By using intracoronary ultrasound, biplane coronary angiography, and measurement of coronary blood flow, we represented the artery in accurate 3D space and determined detailed characteristics of ESS and arterial wall/plaque morphology. Patients who underwent stent implantation and who had another artery with luminal obstruction <50% underwent intravascular profiling initially and after 6-month follow-up. Twelve arteries in 8 patients were studied: 6 native and 6 stented arteries. In native arteries, regions of abnormally low baseline ESS exhibited a significant increase in plaque thickness and enlargement of the outer vessel wall, such that lumen radius remained unchanged (outward remodeling). Regions of physiological ESS showed little change. Regions with increased ESS exhibited outward remodeling with normalization of ESS. In stented arteries, there was an increase in intima-medial thickness, a decrease in lumen radius, and an increase in ESS at all levels of baseline ESS. Conclusions—The present study represents the first experience in humans relating ESS to subsequent outcomes in native and stented arteries. Regions of low ESS develop progressive atherosclerosis and outward remodeling, areas of physiological ESS remain quiescent, and areas of increased ESS exhibit outward remodeling. ESS may have a limited role in in-stent restenosis. This technology can predict areas of minor plaque likely to exhibit progression of atherosclerosis.

Assessment of diffuse coronary artery disease by quantitative analysis of coronary morphology based upon 3-D reconstruction from biplane angiograms

Quantitative evaluations on coronary vessel systems are of increasing importance in cardiovascular diagnosis, therapy planning, and surgical verification. Whereas local evaluations, such as stenosis analysis, are already available with sufficient accuracy, global evaluations of vessel segments or vessel subsystems are not yet common. Especially for the diagnosis of diffuse coronary artery diseases, the authors combined a 3D reconstruction system operating on biplane angiograms with a length/volume calculation. The 3D reconstruction results in a 3D model of the coronary vessel system, consisting of the vessel skeleton and a discrete number of contours. To obtain an utmost accurate model, the authors focussed on exact geometry determination. Several algorithms for calculating missing geometric parameters and correcting remaining geometry errors were implemented and verified. The length/volume evaluation can be performed either on single vessel segments, on a set of segments, or on subtrees. A volume model based on generalized elliptical conic sections is created for the selected segments. Volumes and lengths (measured along the vessel course) of those elements are summed up. In this way, the morphological parameters of a vessel subsystem can be set in relation to the parameters of the proximal segment supplying it. These relations allow objective assessments of diffuse coronary artery diseases.

4-D Cardiac MR Image Analysis: Left and Right Ventricular Morphology and Function

In this study, a combination of active shape model (ASM) and active appearance model (AAM) was used to segment the left and right ventricles of normal and Tetralogy of Fallot (TOF) hearts on 4-D (3-D+time) MR images. For each ventricle, a 4-D model was first used to achieve robust preliminary segmentation on all cardiac phases simultaneously and a 3-D model was then applied to each phase to improve local accuracy while maintaining the overall robustness of the 4-D segmentation. On 25 normal and 25 TOF hearts, in comparison to the expert traced independent standard, our comprehensive performance assessment showed subvoxel segmentation accuracy, high overlap ratios, good ventricular volume correlations, and small percent volume differences. Following 4-D segmentation, novel quantitative shape and motion features were extracted using shape information, volume-time and dV/dt curves, analyzed and used for disease status classification. Automated discrimination between normal/TOF subjects achieved 90%-100% sensitivity and specificity. The features obtained from TOF hearts show higher variability compared to normal subjects, suggesting their potential use as disease progression indicators. The abnormal shape and motion variations of the TOF hearts were accurately captured by both the segmentation and feature characterization.

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. Catheter Cardiovasc Interv 2003;60:67–78.

Plaque development, vessel curvature, and wall shear stress in coronary arteries assessed by X-ray angiography and intravascular ultrasound

The relationships among vascular geometry, hemodynamics, and plaque development in the coronary arteries are complex and not yet well understood. This paper reports a methodology for the quantitative analysis of in vivo coronary morphology and hemodynamics, with particular emphasis placed on the critical issues of image segmentation and the automated classification of disease severity. We were motivated by the observation that plaque more often developed at the inner curvature of a vessel, presumably due to the relatively lower wall shear stress at these locations. The presented studies are based on our validated methodology for the three-dimensional fusion of intravascular ultrasound (IVUS) and X-ray angiography, introducing a novel approach for IVUS segmentation that incorporates a robust, knowledge-based cost function and a fully optimal, three-dimensional segmentation algorithm. Our first study shows that circumferential plaque distribution depends on local vessel curvature in the majority of vessels. The second study analyzes the correlation between plaque distribution and wall shear stress in a set of 48 in vivo vessel segments. The results were conclusive for both studies, with a stronger correlation of circumferential plaque thickness with local curvature than with wall shear stress. The inverse relationship between local wall shear stress and plaque thickness was significantly more pronounced (p<0.025) in vessel cross sections exhibiting compensatory enlargement (positive remodeling) without luminal narrowing than when the full spectrum of disease severity was considered. The inverse relationship was no longer observed in vessels where less than 35% of vessel cross sections remained without luminal narrowing. The findings of this study confirm, in vivo, the hypothesis that relatively lower wall shear stress is associated with early plaque development.

Fluid dynamic analysis in a human left anterior descending coronary artery with arterial motion.

A computational fluid dynamic (CFD) analysis is presented to describe local flow dynamics in both 3-D spatial and 4-D spatial and temporal domains from reconstructions of intravascular ultrasound (IVUS) and bi-plane angiographic fusion images. A left anterior descending (LAD) coronary artery segment geometry was accurately reconstructed and subsequently its motion was incorporated into the CFD model. The results indicate that the incorporation of motion had appreciable effects on blood flow patterns. The velocity profiles in the region of a stenosis and the circumferential distribution of the axial wall shear stress (WSS) patterns in the vessel are altered with the wall motion introduced in the simulation. The time-averaged axial WSS between simulations of steady flow and unsteady flow without arterial motion were comparable (−0.3 to 13.7 Pa in unsteady flow versus −0.2 to 10.1 Pa in steady flow) while the magnitudes decreased when motion was introduced (0.3–4.5 Pa). The arterial wall motion affects the time-mean WSS and the oscillatory shear index in the coronary vessel fluid dynamics and may provide more realistic predictions on the progression of atherosclerotic disease.

Validation of an accurate method for three-dimensional reconstruction and quantitative assessment of volumes, lengths and diameters of coronary vascular branches and segments from biplane angiographic projections.

The goal of the study was the validation of an accurate method for three-dimensional reconstruction and quantitative assessment of volumes, lengths and diameters of coronary vascular branches and segments from biplane angiographic projections. Methods: The accuracy was tested in a complex phantom. In vivo, inter- and intraobserver agreement were assessed by analysis of routine angiograms. The sensitivity was evaluated using angiograms of patients having diagnostic vasoactive pharmacological intervention. Two-dimensional quantitative coronary angiography (2-D QCA) and 3-D QCA were compared concerning the accuracy of diameter evaluation. Results: 3-D QCA yields accurate results ( <3% error) even based on nonorthogonal views, provided that projections parallel to the object are avoided. The inter- and intraobserver variability is ≤ 5%. Significant (p < 0.01) changes of the volume (36–39%) and the diameter (19–21%) are detected following pharmacological intervention. 2-D QCA and 3-D QCA agree in short matched segments without foreshortening. 2-D QCA is rather sensitive to foreshortening and not suitable for evaluation of diameters of longer branches or total coronaries. Conclusion: 3-D QCA permits an accurate, reproducible and sensitive comprehensive three-dimensional geometric analysis of the coronaries and is superior to 2-D QCA with respect to extended diameter evaluation.

Congenital aortic disease: 4D magnetic resonance segmentation and quantitative analysis

Automated and accurate segmentation of the aorta in 4D (3D+time) cardiovascular magnetic resonance (MR) image data is important for early detection of congenital aortic disease leading to aortic aneurysms and dissections. A computer-aided diagnosis (CAD) method is reported that allows one to objectively identify subjects with connective tissue disorders from 16-phase 4D aortic MR images. Starting with a step of multi-view image registration, our automated segmentation method combines level-set and optimal surface segmentation algorithms in a single optimization process so that the final aortic surfaces in all 16 cardiac phases are determined. The resulting aortic lumen surface is registered with an aortic model followed by calculation of modal indices of aortic shape and motion. The modal indices reflect the differences of any individual aortic shape and motion from an average aortic behavior. A Support Vector Machine (SVM) classifier is used for the discrimination between normal and connective tissue disorder subjects. 4D MR image data sets acquired from 104 normal volunteers and connective tissue disorder patients MR datasets were used for development and performance evaluation of our method. The automated 4D segmentation resulted in accurate aortic surfaces in all 16 cardiac phases, covering the aorta from the aortic annulus to the diaphragm, yielding subvoxel accuracy with signed surface positioning errors of -0.07+/-1.16 voxel (-0.10+/-2.05mm). The computer-aided diagnosis method distinguished between normal and connective tissue disorder subjects with a classification correctness of 90.4%.

3D heart-vessel reconstruction from biplane angiograms

Biplane angiography generates just two time equivalent X-ray images. These X-ray systems can be rotated independently from each other (restricted by possible collisions only). The article explains how highly accurate 3D models of vessel systems can be reconstructed, visualized, and quantitatively evaluated from these X-ray images.

Standardized evaluation methodology and reference database for evaluating IVUS image segmentation

This paper describes an evaluation framework that allows a standardized and quantitative comparison of IVUS lumen and media segmentation algorithms. This framework has been introduced at the MICCAI 2011 Computing and Visualization for (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams that participated. We describe the available data-base comprising of multi-center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the creation of the reference standard and the evaluation measures. The approaches address segmentation of the lumen, the media, or both borders; semi- or fully-automatic operation; and 2-D vs. 3-D methodology. Three performance measures for quantitative analysis have been proposed. The results of the evaluation indicate that segmentation of the vessel lumen and media is possible with an accuracy that is comparable to manual annotation when semi-automatic methods are used, as well as encouraging results can be obtained also in case of fully-automatic segmentation. The analysis performed in this paper also highlights the challenges in IVUS segmentation that remains to be solved.