血友病性骨关节病早期磁共振功能影像异常机制的实验研究

Haemophilia is a group of blood disorders characterized by lack of coagulation. Haemophilic arthropathy (HA) is one of the most disabling consequences of haemophilia，and is primarily caused by recurrent episodes of hemorrhage into the joint in young children. The key point of preventing HA is the interventional therapy in early stage onset. The imaging changes in early or reversible stage for patients of HA had been ignored before and seldom investigated in the literatures. In this study New Zealand rabbit joint hemorrhagic models were generated to simulate the status of early stage joint hemorrhage in patients with haemophilia, and 3.0T MRI functional imaging were applied to reveal the relationship between joint hemorrhagic and imaging changes of cartilage injury. The rabbit models were divided to five subgroups according to the bleeding volume and bleeding frequency in the joints. Dynamic changes of articular cartilage damage evolution process and synovitis progress at different times could be monitored on the sequence of 3.0T MRI functional imaging, such as T2-mapping. By correlation analysis between the quantitative data in MRI, such as T2 value calculated at the ROI of abnormal articular cartilage with evaluation of water content and collagen content in immunohistochemistry, we can obtain the MRI features at early, even reversible stage before morphologic changes of synovium and joint cartilage damage. Furthermore, the relationship and pathogenesis between the bleeding volume and bleeding frequency of the joints with irreversible damage of joints could be recognized, and would offer theoretical evidence to the benefit of early prophylaxis, intervention and therapy for HA patients.

血友病是一组遗传性凝血功能障碍性疾病，血友病性骨关节病始发于儿童关节内出血，反复积血导致关节退变和毁损几乎是血友病患者的共同结局，早期干预治疗是有效预防血友病性骨关节病的关键所在。以往文献很少对血友病性骨关节病患者早期可逆阶段的影像变化进行研究。本课题应用新西兰大白兔关节内出血模型模拟血友病性骨关节病患者早期关节内出血的状态，采用3.0T MRI功能成像的方法揭示关节内出血与软骨损伤的关系。根据关节内出血的量及出血次数将模型分5个亚型，用3.0T磁共振T2-mapping等功能成像动态监测不同时间段软骨的变化，通过测量软骨T2值等指标的变化，并与软骨中胶原含量等的改变进行相关性分析，得到形态学异常前的早期阶段、甚至是关节软骨及滑膜损伤可逆阶段的MRI表现，由此进一步认识血友病性骨关节病关节内出血的量及出血次数与关节不可逆损害之间的关系和发病机理，为临床早期预防、干预和治疗提供理论上的依据。

本课题通过建立新西兰大白兔关节内出血模型，模拟血友病性骨关节病患者早期关节内出血的状态，采用3.0T MR功能成像的方法揭示关节内出血与软骨损伤的关系。主要内容：（1）通过注入自体静脉血的方法成功建立关节内出血的兔动物模型；兔子膝关节软骨体积小且薄，随月龄变化大，实验认为8月龄左右的雄兔子软骨显影最佳（股骨髁间窝处厚约1.3mm左右）；（2）探索出一套专用兔膝关节3.0T MR扫描参数设置，自制了能置于MR仪器内的固定兔双膝关节的装置；（3）研究认为，在软骨出现轻微病理学改变时滑膜增厚不明显；在软骨损伤的超早期、形态学没有明显变化时T2值会有轻微的升高，T2-mapping伪彩图亦会有与组织学相对应的轻微变化。为血友病患者早期干预治疗和有效预防血友病性关节病提供了影像学依据。有关高场9.4T MRI的相关研究正在进行中。