基于磁共振-磁粒子成像-光学多模态影像监测干细胞治疗蒽环类药物心肌毒性的定量评估研究

Tumor chemotherapy drugs dose-dependent cardiotoxicity partly limit their widespread use, and complications such as heart failure can lead to patients’ death. Although clinical symptomatic treatment has achieved some certain effect, but myocardium damage still not reversible. Cell therapy has provided new idea of the cardiotoxicity treatment. Our previous studies found that stem cells can repair infarcted myocardium and improve cardiac function. In this study, our aim is to construct a chronic cardiotoxicity mouse model of doxorubicin and treat them by using bone marrow mesenchymal stem cells (BMSCs) and based on our previous studies of the multimodal imaging, we will introduce some new techniques, such as quantitative sequence of MRI and Magnetic Particle Imaging (MPI). Using T1 mapping, Dark blood, CINE and other organizational characteristics and functional sequences of MRI to qualitatively and quantitatively assess the changes of structure of myocardium and cardiac function. Using MPI and optical imaging to monitor the transplanted stem cells in vivo. Using pathologic and immune-histochemical and electron microscope as golden standard reference, to study changes of heart function after stem cell therapy, and to realize the early diagnosis of doxorubicin cardiotoxicity and evaluate the therapeutic effect of stem cell transplantation, which will lay the foundation for the future clinical application transformation.

肿瘤化疗药物剂量依赖的心脏毒性限制其广泛应用，心力衰竭等严重并发症可导致患者死亡。尽管临床对症的治疗方法取得了一定效果，但心肌一旦坏死就难以再生。细胞治疗技术为心脏毒性的治疗提供了新的思路。团队前期的研究发现干细胞能修复梗死心肌，并改善心功能。本研究拟构建慢性阿霉素心脏毒性小鼠模型，采用骨髓间充质干细胞（BMSCs）对阿霉素引起的心肌损伤进行治疗，在课题组前期多模态成像研究的基础上，引入磁共振的定量序列、磁粒子成像等新型成像手段。采用磁共振T1mapping、黑血（Dark blood）、CINE等多种组织特征和功能成像技术，对心肌结构和心脏功能改变进行定性以及定量评估，以磁粒子成像和光学成像对标记移植干细胞进行在体监测，以病理、免疫组化及电镜结果作为金标准对照，研究干细胞治疗后心脏功能的改变，实现对阿霉素心脏毒性早期诊断及干细胞移植的疗效监测，为将来的临床应用转化打下基础。

肿瘤化疗药物剂量依赖的心脏毒性限制其广泛应用，心力衰竭等严重并发症可导致患者死亡。尽管临床对症的治疗方法取得了一定效果，但心肌一旦坏死就难以再生。细胞治疗技术为心脏毒性的治疗提供了新的思路。团队前期的研究发现干细胞能修复梗死心肌，并改善心功能。本研究拟构建慢性阿霉素心脏毒性小鼠模型，采用骨髓间充质干细胞（BMSCs）对阿霉素引起的心肌损伤进行治疗，在课题组前期多模态成像研究的基础上，引入磁共振的定量序列、磁粒子成像等新型成像手段。采用磁共振T1mapping、黑血（Dark blood）、CINE等多种组织特征和功能成像技术，对心肌结构和心脏功能改变进行定性以及定量评估，以磁粒子成像和光学成像对标记移植干细胞进行在体监测，以病理、免疫组化及电镜结果作为金标准对照，研究干细胞治疗后心脏功能的改变，实现对阿霉素心脏毒性早期诊断及干细胞移植的疗效监测，为将来的临床应用转化打下基础。