急性排斥反应(AR)是心脏移植术后最常见的并发症和致死原因，目前临床AR缺乏高分辨与敏感的早期无创检测手段。针对AR早期大量CD3+T淋巴细胞浸润的特征，本项目创新性提出基于高分辨率超声成像的AR精准诊疗一体化方法，利用高频超声实现对靶向粘附载药纳米气泡（NB）声探针的敏锐成像，构建小鼠AR模型和开展大样本实验，评估靶向给药的疗效。具体包括：①建立NB非线性声学散射的数学模型，实现对组织/管脉结构中NB的敏锐声成像；②制备靶向NB声探针（CD3-NB），并构建多功能靶向载药NB（CD3-NB-FK506）用于定点给药；③建立小鼠AR模型，利用高分辨超声联合CD3-NB声探针成像评估AR，对比病理金标准，优化高分辨成像诊断AR最佳策略；④超声辐照靶向粘附载药NB探针释放FK506达到对AR靶向治疗，开展病理对照组比对实验。本项目的成功实施将为AR的早期精准诊疗一体化提供新的思路和方法。

Acute rejection (AR) after heart transplantation is the most common complication and the leading cause of death. Currently the early diagnosis is unavailable due to lack of noninvasive monitor methods with high specificity and sensitivity. According to the fact that CD3+ T Cell invasion is the major pathological process in the early stage of AR, an early integration method to detect and treat AR precisely is proposed based on the development of high-resolution ultrasound imaging and targeted nanometer-microbubble (NB). This project includes the combination of high-resolution ultrasound and targeted drug-loaded NB to establish the sensitive imaging, construction of AR model in mouse using large samples, and effect evaluation of the targeted drug delivery. To be specific, objectives include: (1) establishment of the nonlinear mathematical model of acoustic scattering for NB to achieve NB’s sensitive imaging in tissue or vascular structure;(2) to produce targeted NB probe carrying CD3 (CD3-NB) and multi-function drug-loaded NB carrying both CD3 and FK506 (CD3-NB-FK506); (3) to establish AR model in mouse to implement early diagnosis through high resolution ultrasound combined with CD3-NB, which could be compared with pathological result to optimize the diagnostic strategy;(4) to deliver FK506 into targeted pathological tissue simultaneously through ultrasound exposure to treat AR by the comparison with pathological result. Eventually an integration method to diagnose early and treat precisely for patents with AR would be achieved.