二叶式主动脉瓣（BAV）是最常见的先天性心血管畸形，继发二叶式主动脉病（BA）可造成严重并发症。目前缺乏对该病变升主动脉进行预后评估的理想方法。前期工作中，我们搭建了多模态多光子成像平台，整合受激拉曼、二次谐波和双光子荧光对BA进行病理检测，利用光学层析成功显示血管平滑肌、胶原纤维和弹性纤维，并初步揭示壁面切应力（WSS）导致细胞外基质中胶原纤维数量和排列异常的特征性改变。我们提出假说，WSS可独立于遗传因素，促进主动脉壁基质重构和扩张。本项目首先利用该成像技术检测人体BA和对照主动脉组织，与传统病理检查对比，定量分析以评价其检测有效性，并确立WSS造成主动脉壁基质重构的特征性改变。其次通过手术缝合相邻瓣叶构建无遗传因素参与的BAV大动物模型，验证多模态多光子光学层析实现对主动脉壁在体病理检测的有效性，并结合4D Flow MRI和分子生物学技术研究WSS促进主动脉管壁重构的机制。

Bicuspid aortic valve (BAV) is the most common congenital cardiovascular malformation, secondary bicuspid aortopathy (BA) can result severe complications. Currently, there is no ideal method for prognosis and evaluation for the diseased ascending aorta. In preliminary work, we established multi-mode, multi-photon imaging platform, which intergrated stimulated raman scattering, second harmonic generation and two-photon fluorescence imaging techniques. With this new technology we performed pathology analysis for bicuspid aortopathy and successfully illustrated the imaging of vascular smooth muscle cells, collagen fibers and elastin fibers. And the characteristic pathological changes of abnormal amount and arrangement of collagen fibers in BA extracellular matrix were preliminarily revealed. We hypothesized that, WSS could promote matrix remodeling and dilation of the aortic wall independent of genetic factors. In this project, firstly, we will use the imaging technology to detect the aorta tissue of BA patients and controls. Comparing with traditional pathology method, we will quantitatively evaluate the effectiveness of the new imaging technology, and establish the characteristic changes in aortic wall matrix remodeling caused by WSS. Secondly, we will establish BAV large animal model without genetic factors by surgically cusp fusion, test the effectiveness of in vivo pathology analysis for aortic wall by multi-mode multi-photon optical tomography, and integrate 4D Flow MRI and molecular biology techniques to study the mechanism of WSS promoted aortic wall remodeling.