bioRxiv2020
Atherosclerotic plaque rupture is responsible for a majority of acute vascular syndromes and this study aims to develop a prediction tool for plaque progression and rupture. Based on the follow-up coronary intravascular ultrasound imaging data, we performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression. Four main pathophysiological processes, i.e., lipid deposition, inflammatory response, migration and proliferation of smooth muscle cells (SMCs), and neovascularization were coupled based on the interactions demonstrated by experimental and clinical observations. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. The heterogeneity of plaque microenvironment for each patient was demonstrated by the growth curves of the main microenvironmental factors. The possible plaque developments were predicted by incorporating the systematic index with microenvironmental indicators. Five microenvironmental factors (LDL, ox-LDL, MCP-1, SMC, and foam cell) showed significant differences between stable and unstable group (p < 0.01). The inflammatory microenvironments (monocyte and macrophage) had negative correlations with the necrotic core (NC) expansion in the stable group, while very strong positive correlations in unstable group. The inflammatory microenvironment is strongly correlated to the NC expansion in unstable plaques, suggesting that the inflammatory factors may play an important role in the formation of a vulnerable plaque. This prediction tool will improve our understanding of the mechanism of plaque progression and provide a new strategy for early detection and prediction of high-risk plaques. Author summaryBesides the traditional systematic factors, the influences of the local microenvironmental factors on atherosclerotic plaque progression have been demonstrated. Mathematical and computational modeling is an important tool to investigate the complex interplay between plaque progression and the microenvironment, and provides a potential way toward the prediction of plaque vulnerability according to the comprehensive evaluation of both morphological and/or biochemical factors in tissue level with microenvironmental factors in cellular level. We performed patient-specific multi-physical modeling study on four patients to obtain the evolutional processes of the microenvironment during plaque progression and predicted the possible plaque developments. A scoring table integrating the dynamic microenvironmental indicators with the classical risk index was proposed to differentiate their progression to stable and unstable plaques. Based on patient-specific imaging data, the mathematical model will provide a novel method to predict the changes of plaque microenvironment and improve ability to access the personal therapeutic strategy for atherosclerotic plaque.