DCE-MRI、IVIM-DWI評價(jià)大鼠C6膠質(zhì)瘤乏氧狀態(tài)
發(fā)布時(shí)間:2018-04-14 21:05
本文選題:動態(tài)增強(qiáng)磁共振 + 體素不相干運(yùn)動; 參考:《安徽醫(yī)科大學(xué)》2017年碩士論文
【摘要】:研究背景及目的膠質(zhì)瘤乏氧性會增加腫瘤惡性進(jìn)展和復(fù)發(fā)的機(jī)率,以及對放化療的抵抗,因此評估腫瘤的乏氧狀態(tài)可以判斷腫瘤的分化程度及病人的預(yù)后。以往乏氧的檢測方法為有創(chuàng)性、輻射性,不能動態(tài)檢測腫瘤內(nèi)的乏氧狀態(tài),所以迫切需要一種可以動態(tài)、可重復(fù)、無創(chuàng)的方法去檢測瘤內(nèi)部乏氧狀態(tài)。動態(tài)對比增強(qiáng)MRI(dynamic contrast-enhanced,DCE-MRI)定量掃描作為非侵襲方法可以獲取腫瘤的血流量、及血管的滲透性等參數(shù),用于評估瘤內(nèi)微環(huán)境;IVIM-DWI可以在體評估水分子的擴(kuò)散及血流灌注,且無需使用對比劑,可以在分子水平評估檢測腫瘤微環(huán)境。而乏氧標(biāo)記分子主要有缺氧誘導(dǎo)因子(hypoxia-inducible factor-1α,HIF-1α)、血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)等。本文采用實(shí)驗(yàn)大鼠腦膠質(zhì)瘤模型,將HIF-1α表達(dá)與DCE-MRI、IVIM-DWI定量參數(shù)對比研究,探索DCE-MRI聯(lián)合IVIM-DWI對腫瘤內(nèi)的乏氧狀態(tài)評估的可行性。材料和方法SD大鼠52只,雄性,清潔級,250-300 g;采集對數(shù)生長期的C6膠質(zhì)瘤細(xì)胞,建立SD大鼠C6腦膠質(zhì)瘤模型,于造模后第2W、3W、4W后行IVIM-DWI和經(jīng)股靜脈團(tuán)注順磁性釓類對比劑(釓噴酸葡胺(Gd-DTPA)DCE-MRI掃描,后處理軟件處理獲取偽彩圖和定量參數(shù)。每次掃描后處死14只SD大鼠行HE染色和HIF-1α免疫組化染色。對IVIM-DWI和DCE-MRI定量參數(shù)與HIF-1α表達(dá)的相關(guān)性行統(tǒng)計(jì)學(xué)分析。結(jié)果模型2W、3W、4W Ktrans值分別為0.097±0.065、0.194±0.094、0.134±0.069;Ve值分別為1.041±0.434、0.759±0.337、0.385±0.245;ADCstandard值分別為4.138±0.291、3.075±0.363、2.296±0.366;D值分別為5.156±0.457、4.545±0.402、2.620±0.454;D*值分比為10.014±0.613、6.708±0.596、4.025±0.504;f值分別為9.194±0.441、7.770±0.487、6.389±0.524;HIF-1α評分分別為2.0±0.961、6.5±3.653、4.071±2.129;3W、4W膠質(zhì)瘤模型DCE-MRI定量參數(shù)Ktrans、Ve及IVIM-DWI各定量參數(shù)與HIF-1α表達(dá)呈負(fù)相關(guān)關(guān)系(3W的相關(guān)系數(shù)分別為Ktrans:γ=-0.825;Ve:γ=-0.818;ADCstandardγ=-0.954;Dγ=-0.965;D*γ=-0.979;fγ=-0.987;4W的相關(guān)系數(shù)分別為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膠質(zhì)瘤模型定量參數(shù)Ktrans、Ve及IVIM各定量參數(shù)與HIF-1α表達(dá)無相關(guān)性(P0.05);Kep與HIF-1α表達(dá)各時(shí)間點(diǎn)均無相關(guān)性(P0.05)。結(jié)論DCE-MRI、IVIM-DWI技術(shù)能夠評價(jià)大鼠C6膠質(zhì)瘤模型的乏氧狀態(tài),腫瘤不同生長時(shí)期DCE-MRI、IVIM-DWI定量參數(shù)與腫瘤乏氧狀態(tài)的相關(guān)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 偽 HIF-1 偽, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor (VEGF).In this paper, the expression of HIF-1 偽 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 偽 immunohistochemical staining.The correlation between the quantitative parameters of IVIM-DWI and DCE-MRI and the expression of HIF-1 偽 was analyzed statistically.緇撴灉妯″瀷2W,3W,4W Ktrans鍊煎垎鍒負(fù)0.097鹵0.065,0.194鹵0.094,0.134鹵0.069;Ve鍊煎垎鍒負(fù)1.041鹵0.434,0.759鹵0.337,0.385鹵0.245;ADCstandard鍊煎垎鍒負(fù)4.138鹵0.291,3.075鹵0.363,2.296鹵0.366;D鍊煎垎鍒負(fù)5.156鹵0.457,4.545鹵0.402,2.620鹵0.454;D*鍊煎垎姣斾負(fù)10.014鹵0.613,6.708鹵0.596,4.025鹵0.504;f鍊煎垎鍒負(fù)9.194鹵0.441,7.770鹵0.487,6.389鹵0.524;HIF-1偽璇勫垎鍒嗗埆涓,
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