自发性T2DM恒河猴心肌与骨骼肌微循环损伤的定量磁共振基础研究

Diabetes mellitus (DM) is one of the most prevalent metabolic diseases in the world, and its complications lead to significant morbidity and mortality. Sustained hyperglycemia is strongly associated with microvascular dysfunction that is one of major mechanisms of complications in myocardial and skeletal muscle in DM. Assessment of microvascular dysfunction is important for the prognosis and prediction of adverse events. However, there is no noninvasive and accurate approach to quantify microvascular dysfunction dynamically. In this study, we will use our innovative MR microcirculation imaging techniques (quantitative rest and stress MR perfusion and oxygenation imaging) in myocardial and skeletal muscle to quantify microvascular dysfunction in rhesus monkeys with spontaneous type 2 diabetes at 3.0 T clinical MR system. We will then investigate weather blood flow, blood volume, oxygen extraction fraction can be the imaging biomarkers for microvascular dysfunction in myocardial and skeletal muscle. The correlation and difference of these imaging biomarkers in microvascular dysfunction of myocardial and skeletal muscle will be explored. The findings from this study may potentially provide early warning for adverse outcomes of DM. In addition, the study may reveal the theoretic basis of type 2 DM as the main cause of complications with skeletal and myocardial muscle and provide related imaging biomarkers. This will allow non-invasive monitoring DM complications in patients dynamically. Therefore, the noninvasive microcirculation imaging approach may offer accurate and reliable information about the efficacy of medical interventions in DM.

2型糖尿病（T2DM）发病率高，主要危害在于其并发症；长期高血糖致血管损伤是T2DM导致心肌与骨骼肌并发症的主要发病机制。评估微循环血管损伤对并发症的预后判断及后期不良事件的发生具有重要意义。目前尚缺乏可精准、无创、动态、定量评价微循环损伤的方法。本项目以自发性T2DM恒河猴为动物模型，采用临床型3.0T MRI，利用本课题组心肌、骨骼肌的创新优势技术（静息态及负荷态定量灌注、定量血氧成像）获取T2DM心肌骨骼肌微循环损伤信息；探索MRI所获血流量、血容积、氧摄取分数是否能成为评估心肌骨骼肌微循环损伤的影像学定量标志物；阐述该标志物能否反映T2DM微循环损伤心肌骨骼肌之间的相关性及异质性，对糖尿病并发症的早期发生提供预警信息；揭示T2DM微循环损伤是心肌与骨骼肌并发症的理论基础；为临床无创动态监测T2DM糖尿病并发症的发生发展，为临床药物干预的转归提供较精准的信息反馈奠定基础。

2型糖尿病（T2DM）发病率高，主要危害在于其并发症；长期高血糖致血管损伤是T2DM导致心肌与骨骼肌并发症的主要发病机制。评估微循环血管损伤对并发症的预后判断及后期不良事件的发生具有重要意义。目前尚缺乏可精准、无创、动态、定量评价微循环损伤的方法。本项目以自发性T2DM恒河猴为动物模型，采用临床型3.0T MRI，利用本课题组心肌、骨骼肌的创新优势技术（静息态及负荷态定量灌注、定量血氧成像）获取T2DM心肌骨骼肌微循环损伤信息；探索MRI所获血流量、血容积、氧摄取分数是否能成为评估心肌骨骼肌微循环损伤的影像学定量标志物；阐述该标志物能否反映T2DM微循环损伤心肌骨骼肌之间的相关性及异质性，对糖尿病并发症的早期发生提供预警信息；揭示T2DM微循环损伤是心肌与骨骼肌并发症的理论基础；为临床无创动态监测T2DM糖尿病并发症的发生发展，为临床药物干预的转归提供较精准的信息反馈奠定基础。