心肌纤维化与肥厚型心肌病（HCM）患者的恶性心律失常、心衰、猝死等密切相关，因此实现心肌纤维化的早期诊断对预防HCM患者的恶性事件至关重要。但目前临床常规影像学技术难以实现早期预警。多模态分子成像能够联合多种影像技术的优势，在体、无创监测细胞和分子水平的异常，有望实现HCM心肌纤维化真正意义上的早期诊断。文献和前期研究发现HCM纤维化心肌中的骨桥蛋白（OPN）高表达。基于以上研究，本项目拟利用已掌握的包裹全氟戊烷（PFP）的相变型纳米粒为载体，吲哚菁绿（ICG）为荧光染料，构建一种OPN靶向的超声（US）/近红外荧光成像（NIR）多模态分子探针。在此基础上，利用已构建cTnTR92Q转基因HCM模型小鼠，验证探针实现心肌纤维化US/NIR成像的可行性和优越性，课题旨在建立以心肌纤维化直接指标为靶点的多模态影像诊断技术，以期为HCM患者的危险分层、预后评估及药物靶点的筛选提供临床依据。

Myocardial fibrosis is closely related to malignant arrhythmias, heart failure, and sudden death in patients with hypertrophic cardiomyopathy (HCM).Therefore, early diagnosis of myocardial fibrosis is essential to prevent malignant events in HCM patients, but it is difficult to achieve early warning with current clinical imaging technologies. Multimodal molecular imaging can combine the advantages of multiple imaging technologies to monitor abnormalities at the cellular and molecular levels in vivo and noninvasively, and is expected to realize the early diagnosis of HCM myocardial fibrosis in the true sense. The literature and our previous studies have found that osteopontin (OPN) is highly expressed in fibrotic myocardium of HCM. Basd on the above research, this project aims to use a skilled phase change nanoparticles encapsulating perfluoropentane (PFP) as a carrier and indocyanine green (ICG) as a fluorescent dye to construct an OPN-targeted ultrasound(US)/near infrared fluorescence imaging(NIR) multimodal molecular probes. Based on this, using the constructed cTnTR92Q transgenic HCM model mouse to verify the feasibility and superiority of the probe to achieve US/NIR imagingof myocardial fibrosis, the subject aims to establish a multimodal imaging diagnosis methods with direct indicators of myocardial fibrosis as the target, so as to provide clinical basis for risk stratification, prognosis evaluation and drug target selection for HCM patients.