MRI测量氧摄取分数（OEF）确定脑缺血半暗带的实验研究

It is well known that the mismatch model between PWI and DWI cannot indicate cerebral ischemic penumbra(IP) accurately. PET is a more accuate imaging modality to detect IP, which has decreased cerebral blood flow(CBF) but elevated oxygen extraction fraction(OEF). However PET is not suitable for routine imaging study. Blood oxygen level dependent(BOLD) is the fundation of MRI measurement of OEF. Our previous study has demonstrated increased reversible transverse relaxation rate R2' in IP compared with that in infarction. R2' is a very important parameter for MRI measurement of OEF.But all the exsiting MRI sequences that were used for measurment of OEF have pitfalls.For example, we have already established a gradient-echo sampling of spin-echo (GESSE)sequence to provide MRI measurent of OEF in normal subjucts. But this method suffered from several major limitations, including lengthy scanning time, inability to cover large region of interst and sensitivity to motion artifact, making it difficult for rutine clinical application.The newly developed asymmetric spin echo EPI(ASE EPI) is the most promising technic for clincal application because of its shorter scanning time and larger coverage of ROI. So the purposes of this program are to establish an optimized ASE-EPI sequence for MRI measurement of OEF, to confirm its accuracy in normal monkey brain by comparing with OEF values measured by PET and blood gas analyses, to validate its value in detecting IP in monkey model of middle cerebral artery occlusion. The success of this program can bring a brand new technical tool for MRI measurement of OEF, which will be a surrogate of PET study and can be used as a routine clincal imaging modality. This method can be easily combined with the exsiting artery spin label technic of cerebral blood flow measurement(ASL-CBF) to afford an one-stop MRI evaluation of CBF and cerebral oxygen metabolism.

目前认为PWI和DWI不匹配模型不能准确显示脑缺血半暗带（IP）。PET氧摄取分数（OEF）升高的区域可更好显示IP，但不适于作为常规。血氧水平依赖效应（BOLD）为MRI测量OEF的基础。我们先前的研究证实IP组织的可逆性横向驰豫率R2'明显高于梗死脑组织，而R2'是计算OEF的重要参数。目前MRI测量OEF所使用的序列均存在不同缺陷，不适于临床。其中非对称自旋回波EPI（ASE EPI）序列以扫描时间短、覆盖范围广等优点最有希望用于临床。为此，本研究在对AS EEPI序列进行优化和优选数学模型的基础上，用其测量正常猴脑OEF值，通过与PET和血气测量结果比较，验证该方法的精确性；将该方法用于猴大脑中动脉闭塞（MCAO）模型，确定其对显示IP的价值。该方法有望取代PET，成为OEF的常规影像检查，和现有的MRI测量CBF（ASL-CBF）技术相结合，完成对脑血供和氧代谢一站式MRI评估。

研究表明目前广泛使用的PWI-DWI不匹配的方法不能准确显示脑缺血半暗带，结合脑血流和脑氧摄取分数（OEF）的方法可更准确显示脑缺血半暗带，PET是目前测量OEF的金标准，但并不普及。脱氧血红蛋白的BOLD效应使得MRI测量OEF成为可能，但需要解决扫描序列和数学模型的问题。主要研究内容包括：①MRI确定猴可复性大脑中动脉闭塞模型脑缺血半暗带的实验研究；② 脑梗死患者脑结构及功能可塑性fMRI研究；③正常人及急性期脑梗塞患者脑氧摄取分数及脑血流量的MRI研究。本研究在在优化ASE序列的基础上，实现了基于MRI的脑氧摄取分数测量，将其用于脑梗塞动物模型和脑梗塞患者。研究发现：①利用1H MRS可无创性测量脑温，梗死核心与IP的脑温演变规律不同，据此有助于评判缺血脑组织是否恢复。②ASE序列可用于测量OEF，并且显示脑缺血半暗带OEF升高的现象，有助于区分梗死核心和脑缺血半暗带。③脑梗死患者患侧初级运动皮层（M1区）存在结构损伤和功能重组，但两者并不重叠，即便在结构损伤的M1区也出现了广泛的功能重组，可能为患者运动功能恢复良好的内在神经机制；不同部位脑梗死所致脑结构改变不同；患侧锥体束的顺行和逆行性脱髓鞘改变是远隔病灶部位M1区出现结构损伤的主要因素；脑梗死后脑默认网络（DMN）损害先于认知功能障碍出现，可能是引起认知功能损害的始动因素。④正常人局部脑组织CBF及OEF均随年龄发生变化，但脑区不同；在不同发病时间的急性脑梗塞患者梗塞中心区周围可以发现OEF显著上升的区域，提示可能有缺血半暗带存在。本研究实现了基于MRI的脑OEF测量，对急性期脑梗塞患者，可用于显示脑缺血半暗带，指导溶栓治疗。对慢性期脑梗塞患者的fMRI研究显示了脑梗死后脑结构和功能的代偿机制，有助于指导康复治疗，改善患者预后。