The handle http://hdl.handle.net/1887/66128 holds various files of this Leiden University dissertation.
Author: Li, Y.
Title: Fusion of X-ray angiography and optical coherence tomography for coronary flow simulation
Issue Date: 2018-10-09
Chapter 1
Introduction and Outline
1.1 Shear Stress
Shear stress (SS) is the tangential stress on the surface of the fluid border. Endothelial shear stress (ESS) represents the SS on the endothelial surface of the arterial wall, which is considered as the most important biomechanical marker in the natural history of coronary atherosclerosis and vascular remodeling (1). Figure 1-1 shows the formula to compute ESS. Early studies (2,3) implicated that the strength of ESS impacted the localization of atherosclerosis. Later, autopsy-based (4,5) and animal-based (6,7) studies were conducted to study the role of ESS in atheroma, intimal growth, inflammation, and thrombus development. With the development of coronary imaging techniques, in vivo studies (8-10) using computational fluid dynamics (CFD) explored the mechanical role of ESS in the initiation and development of atherosclerosis, plaque distribution and neointimal vascular response after coronary artery stenting. Most studies support the theory that low ESS plays a stimulating role in atherogenesis (11), neointimal hyperplasia (12), inflammation (13,14) and plaque thrombogenecity (11,15). Besides, oscillatory ESS was also identified as a stimulus factor for the development of atherosclerosis (16). The mechanism by which ESS modulates coronary atherosclerosis and vascular remodeling may be explained by the expression of atheroprotective and pro-atherogenic genes by endothelial cells (11,15). The local coronary region with low and oscillatory ESS may suppress the expression of the atheroprotective genes and promote the expression of the pro-atherogenic ones, leading to atherogenesis (15).
In contrary, high ESS may be atheroprotective. Figure 1-2 shows the mechanotransduction of ESS.
As ESS has a close relationship with vascular behavior at the molecular and cellular levels (11), the concept that in vivo assessment of local ESS could have clinical implication has been widely accepted. In vivo study of the local ESS might help to distinguish plaque that is prone to progress from early stage, to understand the natural history of high-risk plaques (15) and stent healing process after percutaneous coronary intervention (PCI), and even to optimize the treating strategies of PCI (8).
The techniques of CFD have been widely applied in the in vivo ESS studies (8,9). However, the role of ESS on the progression of
atherosclerosis has not been completely established. The prevailing low ESS theory has been recently questioned (17,18) and high ESS has also been proposed to be a key regulator of plaque rupture (19). Three- dimensional (3D) reconstruction techniques for coronary arteries are crucial in the CFD-based in vivo ESS investigations. With the development of coronary imaging techniques, improvement in 3D reconstruction of coronary artery model and standardization of SS analysis methods may help to resolve some inconsistent findings in previous studies (17).
Figure 1-1. Definition of endothelial shear stress (adapted from (15))
Figure 1-2. Endothelial mechanotransduction of endothelial shear stress (adapted from (11))
1.2 Three-Dimensional Coronary Artery Reconstruction
In vivo coronary reconstruction methods can be based on single imaging modalities (e.g., coronary computed tomography angiography (CTA) (20-22) or invasive X-ray coronary angiography (23)) as well as combined imaging modalities (e.g., X-ray coronary angiography fused with intravascular ultrasound (IVUS) (8) or optical coherence
tomography (OCT) (24)). For detailed assessment of ESS with CFD techniques, accurate 3D reconstruction of coronary arteries is crucial (25).
Coronary CTA can be used to create a 3D reconstruction of the entire coronary tree (26,27). However, due to its limited spatial resolution (0.35mm-0.625mm) and the presence of blooming artifacts by calcified plaques, it remains a suboptimal imaging modality for accurate ESS assessment (28). X-ray angiography is an invasive imaging modality, which has been considered as a standard tool for diagnosing coronary artery disease. With the developments in the past 20 years (29), the technique of 3D quantitative coronary angiography (QCA) has been greatly simplified (23), making it a feasible tool to reconstruct coronary artery from routinely acquired coronary angiographic images. Nevertheless, the assumption of elliptical cross- sectional shape in the 3D angiographic reconstruction cannot completely represent the luminal morphology of the diseased coronary artery. In addition, vessel overlap could deteriorate the quality of the angiographic reconstruction.
Compared with CTA and X-ray angiography, intracoronary imaging allows to assess vessel lumen, wall composition, and stent apposition and expansion with higher details. However, the curved nature of the vascular structure was not preserved during pullback of the imaging catheter. Therefore, the idea of combing accurate lumen information from intracoronary imaging and the 3D geometric roadmap from CTA or X-ray angiography was well received. Coronary reconstruction by fusion of IVUS and CTA is proved to be feasible for in vivo ESS analysis (28), but the reconstruction method by fusion of IVUS and biplane X-ray angiography was used more often due to the fact that IVUS imaging and X-ray coronary angiography can be performed at the same procedure (8,9). Compared with IVUS, OCT is a newer intravascular imaging modality with 10 fold increase in spatial resolution (10~15 μm versus 100~150 μm) (25). The micro-structure of coronary artery wall and the implanted stents can be accurately evaluated in OCT images (30). Figure 1-3 shows the comparison between IVUS and OCT imaging for coronary artery. Some studies have reported the feasibility of coronary artery reconstruction by fusion of OCT and X-ray angiography (31-33). However, the established 3D OCT reconstruction methods ignored the side branches if OCT was not performed in the side branches, which might lead to the overestimation of the flow and shear stress in the main vessels. The actual impact in typical clinical population was not understood. In addition, methodologies for in vivo reconstruction of coronary stents in the naturally bent shape were still lacking.
1.3 Motivation and Objectives
Ischemic heart disease is one of the leading causes of mortality in the world, especially in the developed countries (34). Understanding the physiological interactions among blood flow, vessel wall, or/and the implanted stent might help developing models to identify risk factors of rapid plaque progression from baseline physiological assessment, as well as changing treatment strategies. Intracoronary SS is generally believed to be a key physiological parameter that plays an important role in the atherosclerotic plaque formation and progression, and during the process of vascular healing after stent implantation. Nevertheless, methodologies for accurate assessment of SS in vivo are still lacking and standardization of the SS analysis is poor among different research groups. With the development of OCT imaging technique and increasing computational power, detailed analysis of SS by CFD becomes feasible.
As such, the objectives of this thesis are as follows,
1. To develop an approach to reconstruct coronary arteries including side branches in 3D by fusion of X-ray angiography and OCT, and to compute the local hemodynamics including SS and fractional flow reserve (FFR) based on the reconstructed geometry.
2. To develop an approach for accurate reconstruction of bioresorbable scaffolds (BRS) after implantation and to assess the local hemodynamics in the stented segments.
3. To validate the feasibility of the proposed approach in analysis of the actual SS patterns after BRS implantation in coronary bifurcations.
4. To propose a standard operation procedure for analysis of intracoronary SS in vivo.
Figure 1-3. Intracoronary imaging of a normal coronary artery.
A: IVUS image; B: OCT image. The normal 3 layered appearance of the coronary artery (intima, media and adventitial) can be obviously observed in OCT image.
1.4 Thesis Outline
This thesis is organized as follow:
Chapter 1 presents a brief overview of the ESS research and the coronary artery reconstruction methods. The motivation and objectives of this thesis are also described.
Chapter 2 presents a new method for in vivo reconstruction of the coronary tree by fusion of 3D angiography and OCT. Side branches from 3D angiography were utilized for creating the 3D OCT tree model and for correcting the rotational and longitudinal mismatches during the OCT pullback. 22 patients who were enrolled in the DOCTOR (Does Optical Coherence Tomography Optimize Revascularization) fusion study were included. For each available patient, the conventional single-conduit model and OCT tree model were reconstructed and CFD analysis was subsequently performed. ESS and the distal coronary pressure to aortic pressure ratio were compared between the conventional model that ignored the side ranches reconstruction and the OCT tree model that included the angiographic side branches.
Chapter 3 presents a new method for in vivo reconstruction of implanted BRS stents by fusion of X-ray angiography and OCT. The main technical procedures, including lumen segmentation, fusion of OCT and X-ray angiography, reconstruction of coronary geometries from discrete 3D point sets and CFD analysis were described. The feasibility of the methodology was validated. Steady flow simulation was performed to compare the 3D angiography model and the 3D OCT model with the reconstructed BRS.
Chapter 4 assesses the local hemodynamics after implantation of BRS in coronary bifurcations. Ten patients enrolled in the BIFSORB (The Bioresorbable Implants for Scaffolding Obstructions in Randomized Bifurcations) pilot study were included for analysis. For each patient, a 3D OCT tree model (TM) and a hybrid model with BRS (TM-BRS) were reconstructed by fusion of X-ray angiography and OCT. The impact of ignoring BRS reconstruction on ESS and computational FFR was investigated by comparing CFD analysis between the TM model and the TM-BRS model. Transient blood flow was used in the CFD analysis, from which time-average ESS, time-average ESS gradient and oscillatory shear index were derived for quantitative comparison. A hybrid model with virtual BRS stent, which was created by shrinking the thickness of the reconstructed BRS mode, was also constructed to investigate the impact of strut thickness on the local hemodynamics.
Chapter 5 used CFD to study the hemodynamic impact of ‘neo- carina’ after implantation of BRS in the side branch ostium which protruded into the main vessel. Reconstruction of the coronary bifurcation and the ‘neo-carina’ was performed by fusion of X-ray angiography and OCT. The impact of bifurcation angle on the local
blood flow pattern after forming the ‘neo-carina’ was investigated.
Chapter 6 summarizes the main findings for each chapter.
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