联合应用QSM和STI定量监测多发性硬化脑白质病灶动态演变及其成像机制研究

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of the central nervous system in young and middle-aged with the high rate of disability. With the multiplicity and complexity, the pathologic changes in brain white matter lesion are different degree of inflammation and demyelination. Monitoring the dynamic process within white matter lesion in MS is very critical for optimizing the treatment strategy. However conventional MRI techniques are limited to reveal the changes at microscopic level. Histological studies show iron and myelin distribution within white matter lesion are closely associated with the pathology. Our previous studies have shown that quantitative susceptibility mapping (QSM) can reflect brain iron distribution and susceptibility tensor imaging (STI) can reveal demyelination disease. On the basis of the preliminary studies, we will monitor the dynamic process within brain white matter lesion in EAE mice and MS patients with the application of QSM and STI, and describe quantitatively iron distribution and demyelination within white matter lesion through magnetic susceptibility and magnetic susceptibility anisotropy, which may reflect the activity of inflammation and changes of myelin layer. We will also determine the imaging mechanism combined with the methods of immunohistochemistry and PCR in vitro. The current study may provide proof that magnetic susceptibility and magnetic susceptibility anisotropy can be used as the biomarkers for the quantitative evaluation of MS severity, and the combined application of QSM and STI is a useful tool to monitor the dynamic process within white matter lesion in MS.

多发性硬化是好发于中青年的中枢神经系统炎症脱髓鞘疾病，致残率高。脑白质病灶病理表现复杂多变，为不同程度的炎症反应及脱髓鞘。监测脑白质病灶动态演变对优化治疗策略具有重要意义。然而目前的MRI技术具有相当的局限性。组织学研究表明脑白质病灶内铁和髓鞘的分布与病灶的病理表现存在着密切关系。前期研究证明QSM可以定量反映脑内铁的分布；磁化率张量成像（STI）可以定量检测白质脱髓鞘程度。在此基础上，本项目以EAE小鼠和MS患者为研究对象，采用QSM和STI定量监测脑白质病灶的动态演变过程，通过磁化率及磁化率各向异性的变化定量描述病灶内铁分布和脱髓鞘的变化，从而反映病灶内炎症反应的活动性及髓鞘层的变化；并结合EAE小鼠脑片免疫组织化学及PCR等方法探讨成像机制。这项研究证明磁化率及磁化率各向异性能够作为定量评价多发性硬化病情变化的生物学指标，联合运用QSM和STI是定量监测脑白质病灶动态演变的有效工具。

脑白质脱髓鞘病变致残率高。监测脑白质病灶动态演变对优化治疗策略具有重要意义。然而目前的MRI技术具有相当的局限性。前期研究证明QSM及磁化率张量成像（STI）可以定量检测白质脱髓鞘程度。在此基础上，本实验以Cuprizone介导的小鼠急性脱髓鞘为实验模型，采用QSM和STI定量监测脑白质病灶的动态演变过程。本实验采用0.2%Cuprizone饲料喂养小鼠6周，小鼠脑组织胼胝体MRI扫描，包括T1增强、T2增强，及QSM成像；小鼠脑片胼胝体染色，包括HE、LFB、、MBP；小鼠脑组织胼胝体MBP及PLP的mRNA表达水平检测。本实验中，Cuprizone介导的小鼠组织学染色表现出明显的脱髓鞘改变，MBP和PLP的mRNA表达明显降低。两组小鼠T1增强及T2增强MRI没有明显差异，实验组小鼠QSM值明显低于对照组，各向异性（MSA）明显低于对照组。在小鼠脱髓鞘病变中，QSM和STI的变化趋势和组织学结果一致，因此QSM和MSA可以作为监测脱髓鞘病变的生物学指标。联合运用QSM和STI是定量监测脑白质病灶动态演变的有效工具。