pH值MR分子成像超早期评价新生鼠缺血缺氧心肌损伤

It is very important to reduce neonatal mortality and improve clinical outcome that positive prevention, early diagnosis and prompt treatment measures are taken for the hypoxic-ischemic (HI) multiorgan injury in newborns. Clinically, cardiac damage is the most prominent organ injury in addition to brain injury. After asphyxia, hypoxemia leads to intracellular lactic acid accumulation, pH decrease and tissue acidosis subsequent to anaerobic glycolysis. During acute hypoxic-ischemia, pH decreases are earlier than the cell necrosis. Therefore, the extent and degree of hyperacute myocardial injury will be able to determine if the pH can be detected noninvasively in vivo with sensitive imaging modalities. Since tissue pH decreases in response to abnormal glucose/oxygen metabolism during acute ischemia, we hypothesize that pH-sensitive amide proton transfer (APT) MR molecualr imaging may serve as a new surrogate metabolic imaging marker for hyperacute hypoxic-ischemic myocardial injury. In this proposal, we intend to explore the optimal pH-weighted APT imging sequence and confirm the feasibility, sensitivity and accuracy of assessment the hyperacute myocardial injury in HI newborns with this new method. With the pH-sensitive APT imaging, the hyperacute hypoxic-ischemic myocarial injury could be monitored dynamically. We are hopeful that this project would lead to provide scientific evidences for making prompt therapeutic decisions for hyperacute hypoxic-ischemic myocardial injury. Furthermore, the study program may be potential to establish a new methodological strategy to promptly diagnosis and treat the neonatal hypoxic-ischemic multiorgan injury.

新生儿窒息导致缺血缺氧多器官损伤的早期诊断和综合防治对降低新生儿死亡率和改善临床预后意义重大。其中心肌损伤发生率高，仅次于大脑，值得高度重视。窒息后低氧血症使葡萄糖无氧酵解导致细胞内乳酸堆积，pH值下降，细胞酸中毒。缺血缺氧时组织内pH值降低明显早于细胞坏死，如能对活体内pH变化进行无创影像监测，将可超早期判断心肌损伤的程度和范围。因此，本研究拟采用基于pH 值加权成像的氨基质子转移（APT）磁共振分子成像新技术检测缺血缺氧心肌损伤区域的pH值改变，证实该技术对新生鼠缺血缺氧心肌损伤进行超早期诊断的可行性、敏感性和准确性；通过APT成像动态监测pH 值变化，获得反映缺血缺氧心肌细胞代谢情况的pH 值时空分布图，从而为临床治疗时机的选择提供科学依据；并为新生儿窒息导致缺血缺氧多器官损伤的早期临床诊治提供新方法和新思路。

心脑组织缺血缺氧后使葡萄糖无氧酵解导致细胞内乳酸堆积，pH值下降，细胞酸中毒；缺血缺氧时组织内pH值降低明显早于细胞坏死，如能对活体内pH变化进行无创影像监测，将可超早期判断心脑组织损伤的程度和范围。因此，本研究采用基于pH 值加权成像的氨基质子转移(APT)磁共振分子成像新技术检测缺血缺氧心肌损伤区域的pH值改变，证实该技术对缺血缺氧心肌损伤进行超早期诊断的可行性、敏感性和准确性;通过APT成像动态监测pH 值变化，从而为临床治疗时机的选择提供科学依据;并为缺血缺氧多器官损伤的早期临床诊治提供新方法和新思路。相关研究在国际重要学术刊物neuroimage（IF：5.78）、J Cardiovasc Magn Reson（IF：5.75）等发表SCI论文12篇，MEDLINE收录的中文核心期刊文章1篇；在国际学术大会做学术报告和成果展出5次，相关文章正在准备投稿并申请专利。申请者带领团队获荣获四川省青年科技创新研究团队；项目培养硕士生2名，博士生3名，博士后出站1名；申请人入选“国家创新人才推进计划中青年科技创新领军人才”。