多模态磁共振功能成像在骨髓瘤疗效监测应用价值的动物实验研究

Multiple myeloma is a kind of malignant hyperplasia disease in plasmacyte. Its morbidity is in the second place in hematological malignant tumors, and it is still increasing annually. The targeted inhibition of tumor angiogenesis and proteasome inhibitor are new means for myeloma treatment. Currently, the clinical approaches of therapeutic monitoring are serological examination and bone marrow aspiration. However, they cannot be employed in the early curative effect evaluation. Besides, the bone marrow aspiration is an invasive examination which cannot be conducted repeatedly. Therefore, more effective therapeutic monitoring method is urgently needed. Multi-modal MR functional imaging (including diffusion-weighted imaging (DWI) and dynamic enhanced imaging) is a potential way, for DWI can quantitatively reflect the tumor cell proliferation situation while dynamic enhanced imaging can observe the tumor micro-vascular conditions. There are researchers who have already applied it into the therapeutic monitoring of malignant tumors like breast cancer. This research plans to adopt the myeloma model of nude mouse and utilize the proteasome inhibitor (bortezomib) and the targeted inhibition of tumor angiogenesis (thalidomide) which are common in clinical application as the therapeutic drugs. During the treatment period, MRI and pathological examinations are carried out regularly so as to collect relevant imaging parameters and pathological information. It also explores the application value of multi-modal MR functional imaging in the therapeutic monitoring of myeloma. It is expected to establish an imaging method that can be applied in the therapeutic monitoring of myeloma.

多发性骨髓瘤是浆细胞恶性增殖性疾病，发病率位于血液系统恶性肿瘤第二位，发病率逐年增高。肿瘤血管生成靶向抑制和蛋白酶体抑制剂是骨髓瘤治疗的新途径。目前临床用于监测疗效的方法是血清学检查和骨髓穿刺，但不能早期评价疗效，且骨髓穿刺为有创检查，更不能反复多次进行，迫切需要更有效的疗效监测方法。多模态MR功能成像（包括弥散加权成像和动态增强成像）是一种有潜力的方法，弥散加权成像可以定量反映肿瘤细胞增殖情况，动态增强成像可以观察肿瘤微血管情况，有研究者已将其应用于乳腺癌等恶性肿瘤的疗效监测。本研究拟采用裸鼠骨髓瘤模型，使用临床常规应用的蛋白酶体抑制剂（硼替佐米）和肿瘤血管生成靶向抑制剂（沙利度胺）作为治疗药物，治疗同时定期进行磁共振功能成像和病理学检查，采集相关影像参数及病理信息。探讨多模态MR功能成像在骨髓瘤治疗监测中的应用价值，有望建立一种可用于骨髓瘤疗效监测的影像学方法。

多发性骨髓瘤是浆细胞恶性增殖性疾病，发病率位于血液系统恶性肿瘤第二位， 发病率逐年增高。肿瘤血管生成靶向抑制和蛋白酶体抑制剂是骨髓瘤治疗的新途径。目前临床用于监测疗效的方法是血清学检查和骨髓穿刺，但不能早期评价疗效，且骨髓穿刺为有创检查，更不能反复多次进行，迫切需要更有效的疗效监测方法。多模态 MR 功能成像（包括弥散加权成像和动态增强成像）是一种有潜力的方法，弥散加权成像可以定量反映肿瘤细胞增殖情况，动态增强成像可以观察肿瘤微血管情况。本研究采用裸鼠骨髓瘤模型，使用临床常规应用的蛋白酶体抑制剂（硼替佐米）和肿瘤血管生成靶向抑制剂（沙利度胺）作为治疗药物，治疗同时定期进行磁共振功能成像和病理学检查，采集相关影像参数及病理信息。探讨多模态 MR 功能成像在骨髓瘤治疗监测中的应用价值，建立一种可用于骨髓瘤疗效监测的影像学方法。.MRI作为无创的在体肿瘤结构及功能成像方式，具有较高的软组织分辨率等优点，但是通过MRI常规平扫序列有时难以进行脊柱肿瘤的有效鉴别，而DCE-MRI通过连续采集对比剂注入后的影像，并通过后处理综合分析药代动力学过程，可评价肿瘤的诊断以及治疗前后瘤内微血管结构和功能变化，本研究对脊柱肿瘤患者进行MRI动态增强扫描，通过药代动力学定量参数后处理分析，获得反映组织血流灌注状态的参数，评价肿瘤的血流动力学特点。对多种脊柱良恶性病变进行研究分析，分析MRI动态增强参数与肿瘤病理类型之间的相关性，确定了MRI动态增强参数对于病变之间鉴别诊断的价值。此项研究不仅为脊柱肿瘤病变的鉴别诊断和临床治疗提供了参考依据，也减少了患者做CT引导下穿刺活检等有创检查的痛苦以及其他检查的费用。