多模态MRI对重型地中海贫血造血干细胞移植术前危险分级及术后疗效评估的研究

MRI has special advantages in monitoring bone marrow fat changed and quantitative tissue iron deposited. It’s an effective and noninvasive method for evaluating the treatment of bone marrow transplantation and diagnosis of iron overloaded in major thalassemia. At present, the evaluation the function of bone marrow transplant is mainly by MRS, and most is evaluation patients with blood diseases of none iron overloaded. So can we use all kinds methods of MRI to evaluate the risk factors and effective of treatment of major thalassemia with hematopoietic stem cell transplantation? Because the degree of disease of patient was closely related with the effective of transplantation. The aims of this study are to prove the MRI functional imagings (MRS, DWI and IDEAL-IQ) can evaluate accurately the changes of fat in bone marrow, then find the optimal method by iron overload and marrow fat rabbit model. Furthermore, according to the results of the animal study and comparatively analysis the datas obtained by multimodal MRI with the Pesaro score standard, then applying MRI method to assess the function of marrow and the degree of iron-overloaded in cardiac and hepatic of major thalassemia patients with hematopoietic stem cell transplantation. Finally developing a reliable and noninvasive techniques to evaluate marrow transplantation and lay the foundation for clinician to early diagnosis and treatment and help to reduce mortality.

MRI在监测骨髓脂肪变化、定量脏器铁沉积等方面具有独特优势，是对骨髓移植术前危险分层及术后评价、诊断铁过载的有效、无创的方法。目前利用其评价移植患者的骨髓功能主要是通过MRS的方法，且大多数是评价无骨髓铁沉积的血液病患者。那么是否可以联合利用其多种优势对铁过载的重型地中海贫血患者造血干细胞移植术前后危险因素和疗效做出评估？因为患者病情程度与移植前预处理方案及移植后效果密切相关。本研究旨在通过建立铁过载并骨髓脂肪化的动物模型，证明MRI功能成像（MRS、DWI和IDEAL-IQ）可以准确评价铁过载状态下骨髓脂肪含量变化，并寻找最优的检查方法。进而以动物研究结论为基础，通过多模态MRI检查获得的患者数据与临床Pesaro评分标准比对分析，评估临床重型地中海贫血患者造血干细胞移植术前及术后骨髓功能及心、肝脏铁负荷水平变化，为临床移植前危险分层及术后疗效的评价提供一种无创、准确且方便的检查方法。

MRI在监测骨髓脂肪变化、定量脏器铁沉积等方面具有独特优势，是对骨髓移植术前.危险分层及术后评价、诊断铁过载的有效、无创的方法。本研究通过建立铁过载并骨髓脂肪化的家兔模型，得到经原子分光光度仪测量骨髓脂肪含量与Qdixon、Histo测定的脂肪分数无线性相关（r=0.369，p=0.176、r=0.029，p=0.918），骨髓脂肪百分比与Qdixon测定的腰椎脂肪分数无线性相关（r=0.103，p=0.726、r=0.067，p=0.813），骨髓脂肪百分比与Histo测定的腰椎脂肪分数呈正相关（r=0.722，p=0.002、r=0.601，p=0.018）。证明MRI功能成像（Histo）可以准确评价铁过载状态下骨髓脂肪含量变化。进而以动物研究结论为基础，通过多模态MRI检查获得的患者数据与临床Pesaro评分标准比对分析，评估临床重型地中海贫血患者造血干细胞移植术前及术后骨髓功能及心、肝脏铁负荷水平变化，为临床移植前危险分层及术后疗效的评价提供一种无创、准确且方便的检查方法。地中海贫血患者大部分都有脏器铁负荷情况，移植后心、肝铁过载水平短时间内没有一定的变化规律，长时间监测提示肝脏、心脏铁过载随时间延长逐渐好转，R2*值逐渐降低，以肝脏变化显著，心脏变化浮动不大。不管移植前后，肝脏R2*值与SF均有正的相关性，心脏R2*值与SF没有很好的相关性。移植前不同铁蛋白组的肝脏R2*值差异有统计学意义，低铁蛋白组的肝脏R2*值小于高铁蛋白组。移植后不同铁蛋白组移植后肝脏R2*值差异有统计学意义，低铁蛋白组的肝脏R2*值小于高铁蛋白组。肝脏、心脏移植术后是否祛铁治疗R2*值间的差异无统计学意义。移植前和移植后各因素分组肝脏T2*值差异无统计学意义；移植前心脏T2*值在不同地贫类型、严重程度组间差异有统计学意义。干细胞移植后心脏T2*与移植年龄和年龄呈弱负相关（r=-0.274、-0.267，P=0.039，0.041）。地中海贫血患者大部分都有脏器铁负荷情况，移植后短时间内仍存在铁过载，需按时监测随访。肝脏和心脏T2 *成像是评估肝脏和心脏铁超负荷的一种简单、可行且无创的方法，可为地中海贫血患者造血干细胞移植后监测脏器铁过载情况。