DCE-MRI、IVIM-DWI评价大鼠C6胶质瘤乏氧状态
发布时间：2018-04-14 21:05
本文选题：动态增强磁共振 + 体素不相干运动 ； 参考：《安徽医科大学》2017年硕士论文
【摘要】：研究背景及目的胶质瘤乏氧性会增加肿瘤恶性进展和复发的机率,以及对放化疗的抵抗,因此评估肿瘤的乏氧状态可以判断肿瘤的分化程度及病人的预后。以往乏氧的检测方法为有创性、辐射性,不能动态检测肿瘤内的乏氧状态,所以迫切需要一种可以动态、可重复、无创的方法去检测瘤内部乏氧状态。动态对比增强MRI(dynamic contrast-enhanced,DCE-MRI)定量扫描作为非侵袭方法可以获取肿瘤的血流量、及血管的渗透性等参数,用于评估瘤内微环境;IVIM-DWI可以在体评估水分子的扩散及血流灌注,且无需使用对比剂,可以在分子水平评估检测肿瘤微环境。而乏氧标记分子主要有缺氧诱导因子(hypoxia-inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)等。本文采用实验大鼠脑胶质瘤模型,将HIF-1α表达与DCE-MRI、IVIM-DWI定量参数对比研究,探索DCE-MRI联合IVIM-DWI对肿瘤内的乏氧状态评估的可行性。材料和方法SD大鼠52只,雄性,清洁级,250-300 g;采集对数生长期的C6胶质瘤细胞,建立SD大鼠C6脑胶质瘤模型,于造模后第2W、3W、4W后行IVIM-DWI和经股静脉团注顺磁性钆类对比剂(钆喷酸葡胺(Gd-DTPA)DCE-MRI扫描,后处理软件处理获取伪彩图和定量参数。每次扫描后处死14只SD大鼠行HE染色和HIF-1α免疫组化染色。对IVIM-DWI和DCE-MRI定量参数与HIF-1α表达的相关性行统计学分析。结果模型2W、3W、4W Ktrans值分别为0.097±0.065、0.194±0.094、0.134±0.069;Ve值分别为1.041±0.434、0.759±0.337、0.385±0.245;ADCstandard值分别为4.138±0.291、3.075±0.363、2.296±0.366;D值分别为5.156±0.457、4.545±0.402、2.620±0.454;D*值分比为10.014±0.613、6.708±0.596、4.025±0.504;f值分别为9.194±0.441、7.770±0.487、6.389±0.524;HIF-1α评分分别为2.0±0.961、6.5±3.653、4.071±2.129;3W、4W胶质瘤模型DCE-MRI定量参数Ktrans、Ve及IVIM-DWI各定量参数与HIF-1α表达呈负相关关系(3W的相关系数分别为Ktrans:γ=-0.825;Ve:γ=-0.818;ADCstandardγ=-0.954;Dγ=-0.965;D*γ=-0.979;fγ=-0.987;4W的相关系数分别为Ktrans:γ=-0.725;Ve:γ=-0.607;ADCstandardγ=-0.783;Dγ=-0.764;D*γ=-0.716;fγ=-0.725;P值均0.05),2W胶质瘤模型定量参数Ktrans、Ve及IVIM各定量参数与HIF-1α表达无相关性(P0.05);Kep与HIF-1α表达各时间点均无相关性(P0.05)。结论DCE-MRI、IVIM-DWI技术能够评价大鼠C6胶质瘤模型的乏氧状态,肿瘤不同生长时期DCE-MRI、IVIM-DWI定量参数与肿瘤乏氧状态的相关程度不同。
[Abstract]:Background and objective hypoxia in glioma can increase the probability of malignant progression and recurrence and resistance to radiotherapy and chemotherapy. Therefore, the evaluation of hypoxic status of tumor can judge the degree of differentiation and prognosis of the tumor.In the past, hypoxic detection methods were invasive, radiative, and could not dynamically detect the hypoxic state in tumor. Therefore, a dynamic, repeatable and non-invasive method was urgently needed to detect the hypoxic state inside the tumor.Dynamic contrast enhanced MRI(dynamic contrast-enhanced DCE-MRI can be used as a non-invasive method to obtain tumor blood flow and blood vessel permeability, which can be used to evaluate the diffusion and perfusion of water molecules in vivo.The tumor microenvironment can be evaluated at the molecular level without the use of contrast agents.Hypoxia labeled molecules mainly include hypoxia-inducible factor-1 伪 HIF-1 伪, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor (VEGF).In this paper, the expression of HIF-1 伪 was compared with that of DCE-MRIMr IVIM-DWI in order to explore the feasibility of DCE-MRI combined with IVIM-DWI in the evaluation of hypoxic state in the tumor.Materials and methods 52 SD rats, male, clean grade 250-300 g, were collected from C6 glioma cells at logarithmic growth stage to establish C6 glioma model in SD rats.IVIM-DWI and paramagnetic gadolinium contrast agent (Gd-DTPA-Gd-DTPA-DCE-MRI) were performed at 2W ~ 3W ~ 4W after modeling. The pseudochromogram and quantitative parameters were obtained by post-processing software.After each scan, 14 SD rats were killed for HE staining and HIF-1 伪 immunohistochemical staining.The correlation between the quantitative parameters of IVIM-DWI and DCE-MRI and the expression of HIF-1 伪 was analyzed statistically.缁撴灉妯″瀷2W,3W,4W Ktrans鍊煎垎鍒负0.097卤0.065,0.194卤0.094,0.134卤0.069;Ve鍊煎垎鍒负1.041卤0.434,0.759卤0.337,0.385卤0.245;ADCstandard鍊煎垎鍒负4.138卤0.291,3.075卤0.363,2.296卤0.366;D鍊煎垎鍒负5.156卤0.457,4.545卤0.402,2.620卤0.454;D*鍊煎垎姣斾负10.014卤0.613,6.708卤0.596,4.025卤0.504;f鍊煎垎鍒负9.194卤0.441,7.770卤0.487,6.389卤0.524;HIF-1伪璇勫垎鍒嗗埆涓，
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