基于多模态MRI技术的糖尿病中枢神经系统早期微血管病变预警体系的建立

Diabetes ( mainly type II diabetes ) lead to the central nervous system (CNS) function impairment, especially the mild cognitive impairment (MCI) that increased the risk of progression to dementia. It was regarded that neurodegeneration contributes to the diabetic MCI, however, recent research suggested that CNS microvascular alterations are the mechanism for early diabetic MCI. But there still lacks an early warning system for the CNS micro-vascular alterations during early diabetes. Latest neuroimaging techniques enable the measurement of brain blood flow, blood-brain barrier (BBB) and the nuclei deposition of iron to reflect CNS microvascular alterations. But these techniques are complicated and can not fully reflect the microangiopathy with one single technique. We previous observed that 44.4% of diabetic patients demonstrate MCI and established the coprehenive protocols of measuring brain blood flow, BBB and the nuclei deposition of iron simultanosly based on the multimodal MRI technique so as to relect the microvascular alterations reliablly and validibly. Therefore, we intend to integrate psychological mesurement and clinical biochemical examination, and to establish the early warning system for the central nervous system micro-vascular alterations during early diabetes based on the multi-modal MRI technique. The reliability and validity of this sysem will be testd in the diabetic rat model. The early warning system will likely assist in screening patients with diabetic microvascular alterations, to perform early intervention so as to prevent or delay the progression from diabetic MCI to dementia.

糖尿病（主要是II型糖尿病）损害中枢神经系统（CNS）功能，尤其是导致轻度认知损害（MCI），增加进展为痴呆的风险。以往认为神经变性导致糖尿病MCI，近年发现微血管病变可能是其早期机制，但目前尚缺乏糖尿病患者早期微血管病变的预警体系。最新神经影像学技术可以测量大脑微血流、血脑屏障（BBB）和核团铁沉积，反映CNS的微血管病变，但操作复杂，不能全面反映微血管病变。本课题组前期观察到44.4%的糖尿病患者出现MCI，采用多模态MRI技术可以同时测量大脑微血流、BBB和核团铁沉积，提高了监测微血管病变的信度和效度。因此，我们拟综合心理行为学和临床生化等指标,利用多模态MRI技术建立糖尿病早期微血管病变的预警体系。并在糖尿病大鼠模型上通过干预血糖水平，测试该预警体系的灵敏度和特异度。该预警体系将有可能协助筛选糖尿病微血管病变患者，进行早期干预，对预防和延缓其向痴呆发展具有重要的理论和临床实践意义。

目的.T2DM影响中枢神经系统（Central nervous system, CNS），损害患者的认知功能，很大一部分患者最终进展为痴呆。因此，早期揭示T2DM患者CNS改变的神经影像学特征，对于早期干预、延缓或预防认知功能障碍具有重要意义。.方法.本研究纳入50名T2DM患者和50名年龄、性别和教育程度匹配的健康对照。采用3.0T磁共振扫描仪采集大脑ASL、BOLD、3D-T1WI结构像、DTI等数据，比较两组受试的大脑体积，脑血流量（arterial spin labeling, ASL）、脑功能连接（functional connectivity，FC）脑白质各向异性分数（Fractional anisotropy, FA）和平均扩散系数（Mean diffusivity, MD）值的差异，以及神经血管偶联情况。.结果.与健康对照相比， T2DM患者大脑体积未见显著减少（P > 0.05）；2 型糖尿病患者左侧颞上回、右侧内侧和旁扣带回、右侧后扣带回、左侧距状裂周围皮层和左侧中央前回等脑区的脑血流量显著减少；双侧大脑半球白质完整性广泛受损，除胼胝体膝部和体部，与健康对照相比，在T2DM患者左侧大脑半球的内囊前肢、前上部辐射冠、扣带束及上额枕束完整性受损最为显著，FA值和MD值存在显著差异（P < 0.05）；而右侧大脑半球上辐射冠、后辐射冠、扣带束及上纵束完整性受损最为显著，存在显著差异（P < 0.05）；双侧大脑半球上辐射冠MD值均升高，以左侧升高更为显著（P < 0.05）。在脑区水平，12 个脑区发现神经血管偶联指标显著差异。.结论.2型糖尿病患者未发现显著的全脑灰质总体积改变，但存在显著的脑区血流量降低，T2DM患者双侧大脑半球广泛白质区域完整性降低，以左侧为著；而神经血管失偶联影像学指标改变与大脑功能指标之间存在显著的相关关系。有助于诊断糖尿病引起的认知功能障碍，以及监测疗效。