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基于光学多模分子影像技术的抗肝肿瘤药物疗效评估
梁倩
Subtype硕士
Thesis Advisor杜洋
2019-05
Degree Grantor中国科学院大学
Place of Conferral中国科学院自动化研究所
Degree Name工程硕士
Degree Discipline计算机技术
Keyword光学多模分子影像,自发荧光断层重建,药效评估,阿帕替尼,索拉菲尼,肝癌
Abstract

在中国,肝癌是一种发病率高和死亡率高的癌症。靶向药物治疗是肝癌晚期患者的常见治疗方法。临床阶段采用的药效评估方法为计算机断层扫描成像(Computed Tomography, CT)和磁共振成像(Magnetic Resonance Imaging, MRI),依据肿瘤解剖结构层面的变化信息评估药物治疗效果,往往会使得患者错过最佳治疗期及错失最佳药物选择机会。因此,预临床与临床阶段均需要更灵敏、更有效的药效评估方法。分子影像技术能够在分子细胞水平上无创、动态地研究药物在生物体内的时空分布,揭示生物体的生物活动及药物的治疗响应,能够在早期阶段评估药物是否有效。光学多模分子影像技术充分发挥光学成像的高灵敏度和CT成像的高空间分辨率优势,克服单一模态成像的局限性。本文采用光学多模分子影像技术,主要通过自发荧光成像、自发荧光断层成像、激发荧光成像、计算机断层扫描血管造影成像技术,对肝肿瘤两种代表性靶向药物阿帕替尼和索拉菲尼进行全面系统的药物疗效评估,在分子细胞水平动态、非侵入地评估阿帕替尼和索拉菲尼药物的抗肝肿瘤及抗血管生成效果。同时,本文基于稀疏度自适应子空间追踪算法进行自发荧光断层重建,三维层面上评估阿帕替尼和索拉菲尼药物的抗肝肿瘤疗效,表明该方法具有一定的生物应用价值,阿帕替尼和索拉菲尼均能有效抑制肝肿瘤生长,为临床阶段药效评估提供新的思路及参考依据。

Other Abstract

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and is a leading cause of cancer-related deaths in China. And targeted drug therapy is a common treatment approach for advanced HCC patients. Imaging techniques as computed tomography (CT) and magnetic resonance imaging (MRI) are typically used in the anticancer drug efficacy evaluation in clinic. However, these techniques can only evaluate the therapeutic efficacy when the tumor shows anatomic changes, when patients miss the optimal treatment window and miss the opportunity of the best drug selection. Hence more sensitive and effective imaging methods for the early evaluation of drug efficacy are needed in both preclinical and clinical HCC studies. Molecular imaging allows non-invasive and dynamic investigation of temporal and spatial distribution of the drugs at the molecular and cellular levels in intact living subjects, which can reveal biological activity and drug responses, thereby allowing the assessment of drug efficacy at an early therapeutic stage. Optical multimodality molecular imaging technique takes full advantages of high sensitivity of optical imaging and high spatial resolution of CT, which overcomes the limitations of single imaging modality. In this study, we systemically investigated the anti-tumorigenic and anti-angiogenic efficacy of apatinib and sorafenib in HCC at the molecular and cellular levels using optical multimodality molecular imaging techniques, which include bioluminescence imaging (BLI), bioluminescence tomography (BLT), fluorescence molecular imaging (FMI), and computed tomography angiography (CTA). We carried out BLT based on the algorithm of sparsity adaptive subspace pursuit. And the result showed that we can asses the therapeutic efficacy of apatinib and sorafenib in HCC at the three-dimensional level, which confirmed that this method had potential prospects of biological applications. Apatinib and sorafenib can effectively inhibit HCC growth. These findings may provide preclinical evidence for further investigations on the clinical drug efficacy evaluation for HCC patients.

Pages84
Language中文
Document Type学位论文
Identifierhttp://ir.ia.ac.cn/handle/173211/23856
Collection中国科学院分子影像重点实验室
毕业生_硕士学位论文
Recommended Citation
GB/T 7714
梁倩. 基于光学多模分子影像技术的抗肝肿瘤药物疗效评估[D]. 中国科学院自动化研究所. 中国科学院大学,2019.
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