基于定量磁共振成像技术的膝关节软骨退变机制研究

There are 1.2 billion Osteoarthritis (OA) patients in China. OA induced disability ranks as the second cause in the world. Knee cartilage is mainly constituted with collagen fibers, water, and proteoglycan. Alternations of collagen fibers and proteoglycan are highly related to OA pathology. The quantification of cartilage composition is essential for early OA diagnosis and disease treatment evaluation. Although magnetic resonance imaging (MRI) is a non-invasive technique which has shown promise for imaging the cartilage matrix composition, it is still challenging for characterizing the collagen fibers within the cartilage. Our previous work has successfully demonstrated susceptibility tensor imaging (STI) could be a promising tool to quantify the susceptibility of collagen fibers and measure the collagen fiber orientations of the ex vivo cartilages. In this project, we aim to develop a new STI technique to broaden its application to in vivo characterize the collagen structure changes of cartilage damage induced by OA. Together with the quantification of proteoglycan using T1ρ imaging, we expect to monitor and quantify the cartilage degeneration and damage, which is potentially useful for early knee OA detection and the evaluation of disease progression.

我国骨关节炎患者约1.2亿，致残率居全球第二位。关节软骨基质中胶原纤维的损伤和蛋白多糖的流失是引发关节炎的核心病理改变。软骨成分的定量测量对疾病的早期诊断和疾病治疗评估具有重要意义。磁共振成像是目前评价关节软骨病变最有效的无创技术，但对软骨胶原纤维结构定量测量存在挑战。申请人前期首次突破性地应用磁化率张量成像技术（STI），成功获得了动物离体软骨胶原纤维的磁化率数值和空间结构。且STI测量离体软骨胶原纤维结构的准确性已经得到原子力学显微镜的证实。本项目将针对在体软骨MRI成像对比度低且不能准确定量的缺点，进一步开发STI成像技术，以磁化率为定量指标，定量测量在体膝关节软骨胶原纤维的结构。同时联合应用定量影像技术（T1ρ）评估蛋白多糖的含量，构建人类在体膝关节软骨成分退化模型，探索建立软骨退变的磁共振定量测量平台，并为骨关节炎疾病的早期诊断、早期干预与疾病监测提供无创影像学标记物。

在我国社会老龄化加速的当下，关节软骨退变是人类老化进程中不可忽视的重要健康问题，对家庭和社会造成严重的经济负担。由于缺乏有效评估关节软骨退变的手段，OA的发现往往处于中晚期，错过了早期诊疗的窗口期。因此，开发新的磁共振成像技术手段，在体定量关节软骨结构和分子成分的改变具有重要意义，并有望实现OA的早期识别与病程监测。针对现有技术的不足，本项目开发了新型定量磁化率(QSM)和磁化率张量(STI)成像算法，可以更加精准的评估软骨胶原纤维的磁化率各向异性，具有很高的精度。进一步，探究了QSM对于软骨老化和衰退定量的优势和准确性，证实了QSM和STI技术在监测人体在体软骨成分退化过程中的能力。进一步，联合T1p成像技术，构建了在体膝关节软骨的老化模型。本项目证实了QSM和STI技术为关节软骨的早期诊断提供了重要的技术手段。