Numerical Modeling Of In Vivo Stress Of Human Blood Vessels And Its Applications

Cardiovascular disease is the leading cause of death in modern society.Mechanical stimuli play an important role in the remodeling and pathological changes of vascular tissues.In recent years,many scholars have been focusing on the pathological mechanism and health management of the cardiovascular system,and a lot of studies have been done in the fields of vascular mechanobiology and biomechanics.On one hand,current studies on cellular mechanotransduction have suggested that vascular cells exhibit distinct biological responses under different mechanical environments.However,the quantitative correlation in mechanical environment between the in vitro experiments and vascular physiological and pathological conditions in vivo is still ambiguous,and to what extent these obtained results can reveal the cardiovascular pathogenesis remains to be elucidate.On the other hand,the numerical methods based on nonlinear continuum mechanics have been widely adopted to investigate the in vivo mechanical stress of healthy and diseased vessels.However,at present there is still a lack of efficient and reliable approach to model the residual stress in blood vessels,therefore,the accuracy of the in vivo stress prediction is compromised.Regarding to the issues above,this study focused on the mechanical niches of vascular cells and the in vivo stress responses of pathological vascular tissues.This study quantitatively explored the effects of the physiological locations and aging on the mechanical environments around vascular cells by using semi-analytic method,and provided a spatial and temporal mechanical reference for vascular mechanobiological studies.This study proposed and validated a thermal expansion method to numerically rebuild the residual stress in blood vessels,and parametrically analyzed the in vivo stress of atherosclerotic plaques based on this numerical method,which helps to complement the clinical diagnosis and risk assessment for arterial stenosis.The main contents of this study are as follows:(1)Focusing on the characteristics of in vivo mechanical environments around the cells of vascular tissues,this study chose nine representative arteries of middle-aged humans,and analyzed their stress/strain and stiffness variations under different blood pressures based on nonlinear continuum mechanics.It is found that the in vivo mechanical environments of endothelial cells,vascular smooth muscle cells and fibroblasts in the vessel walls exhibit “site-specific” characteristics,and the stress/strain and wall stiffness experienced by vascular cells at different physiological locations are distinct.It is demonstrated that the intima is not always the region in which severe stretch presents under high blood pressures.High tension at the adventitia of the aortas supports the hypothesis of the outside-in inflammation dominated by aortic adventitial fibroblasts,and the negative strains and compression forces at the intima region of the ascending thoracic aorta offer an explanation for intimal buckling in aortic dissection.These results indicate that cellular studies at different mechanical niches should be “disease-specific” as well.Moreover,the results demonstrate considerable stress gradients across the wall thickness,which indicate micro-scale mechanical variations existing around the vascular cells,and imply that pathological changes are not static processes confined within isolated regions,but are coupled with dynamic cell behaviors such as migration.The results suggest that the mechanical stress/strain,stress gradient,and tissue stiffness are key factors constituting the mechanical niches,and the findings of in vivo negative strains and spatial gradients of mechanical environments may shed new light on “factor-specific” experiments of vascular cell mechanobiology.(2)Focusing on the variations of the in vivo mechanical environments around vascular cells during aging process,this study analyzed the mechanical stress/strain and wall stiffness of the human femoropopliteal arteries(FPAs)among different age groups.It is found that high stress region varies with age from the intima for young subjects to the adventitia for old subjects.The characteristics of the middle-aged FPA wall suggests that it is the most capable of resisting high blood pressures and maintaining a mechanical homeostasis during the entire life span.It is demonstrated that the variations of stress and strain rather than that of wall stiffness can be used as an indicator to illustrate the profile of FPA aging.Our results could serve as an age-specific mechanical reference for vascular mechanobiological studies,and allow further exploration of cellular dysfunctions in vessel walls during aging process.(3)Based on the thermal-structural coupled finite element method,this study proposed a thermal expansion method to estimate the in vivo stress of blood vessels under healthy and pathological conditions.This method provides a relatively simple and convenient means to accurately model the residual stress in blood vessels.The method is first verified with the opening-up process and the pressure-radius responses for single and multi-layer vessel models.It is then applied to study the stress variation under hypertension and vascular stenosis conditions.Our results show that specific or optimal residual stresses exist for different blood pressures which could help to form a homogeneous stress distribution across vessel walls.High elastic shear stress is identified on the shoulder of the plaque,which could contribute to the tearing effect in plaque rupture.The present study confirms that the proposed numerical method is capable for an efficient in vivo stress evaluation of patient-specific blood vessels for clinical purposes.(4)Focusing on the health management of patients with arterial stenosis in daily activities,this study built an in vivo stress model of human carotid bifurcation with atherosclerotic plaque,and analyzed the effects of blood pressure,flow rate,plaque stiffness,and stenosis on the elastic stress and fluid viscous stress around the plaque.According to the maximum values of the mechanical stress,this study defined the risk index to predict the risk level of plaque rupture under different exercise intensities.For carotid bifurcation where blood flow distributes,our results suggest that the stenosis ratio determines the contribution ratio of elastic shear stress and viscous shear stress in plaque rupture.The increase of plaque stiffness enhances the maximum elastic shear stress in plaque,which indicates that high stiffness plaque is more prone to rupture under the same stenosis ratio.High stress co-localization at the shoulder of plaques agrees with the region of plaque injury in clinical observations.It is demonstrated that due to stress-shield effect,the rupture risk of high stiffness plaque tends to decrease under high stenosis condition,which suggests the existence of a specific stenosis corresponding to the maximum risk.This study provides a stenosis-mechanical property-specific reference for blood pressure control in cardiovascular health management.