T1模糊聚类法定量动态增强磁共振成像与肾细胞癌肿瘤血管生成的相关性研究

Antiangiogenic therapy has become more common for the treatment of renal cell carcinoma(RCC). The significant advance in the treatment of patients with RCC has resulted in improved survival in selected patients. But till now, there is not an accurate means of diagnosing tumor angiogenesis and monitoring treatment response aside from physical changes in the size of the tumor, which lag behind the physiological changes, and there is not accepted antiangiogenic therapy evaluation method in clinical practice. In recent years, quantitative dynamic contrast-enhanced MRI (DCE-MRI) has been approved to be the most potential tool for evaluating tumor angiogenesis in vivo, which can repeat and sample the entire tumor noninvasively, and no radiation exposure. T1-FCM is a new quantitative DCE-MRI method which combines a fixed-T1, fuzzy c-means(FCM) technique with a reference region(RR) model to estimate pharmacokinetic parameters without measuring the arterial input function or baseline T1. Compared with other methods，it does not need a long imaging time and is relatively insensitive to the effects of noise. The aim of this study is to correlate the quantitative DCE-MRI parameters (Ktrans,Ve)by T1-FCM method with microvessel density (MVD), vascular endothelial growth factor(VEGF) and vascular endothelial growth factor receptor(VEGFR) in renal cell carcinoma，and demonstrate its feasibility and accuracy in assessing tumor angiogenesis. By observing the change in these parameters after antiangiogenic therapy, we will assess the value of this new method in evaluating antiangiogenic therapy response in renal cell carcinoma, and its feasibility in predicting clinical outcome. This study will prove a new technique for clinical practice in evaluating treatment response and prediction of prognosis.

近年开展的抗肿瘤血管生成靶向治疗使肾细胞癌患者生存期明显提高，但临床上一直缺乏合适的评价疗效和判断预后的方法。定量动态增强MRI（DCE-MRI）被认为是最具潜力的评估肿瘤血管生成的影像学方法，具有无创、可重复、反映肿瘤全貌及功能特征等优势。T1模糊聚类法是近年新提出的定量DCE-MRI后处理方法，其采集数据时间短，对时间分辨率的要求低，且测量精度受噪声影响小。本项目拟通过研究基于该方法测定的肾细胞癌DCE-MRI参数(Ktrans,Ve)与反映肿瘤血管生成的病理学金标准(MVD、VEGF、VEGFR)的相关性，了解该方法评价肾细胞癌肿瘤血管生成的可行性及准确性；并通过观察肾细胞癌患者抗肿瘤血管生成治疗前后定量DCE-MRI参数的变化，了解基于该方法的DCE-MRI在评价抗肿瘤血管生成治疗中的价值，以及治疗前基线参数估计患者预后的可行性。本研究将为临床提供新的评价疗效和判断预后的技术手段。

近年开展的抗肿瘤血管生成靶向治疗使肾细胞癌患者生存期明显提高，但临床上一直缺乏合适的评价疗效和判断预后的方法。定量动态增强MRI（DCE-MRI）被认为是最具有潜力的评估肿瘤血管生成的影像学方法，具有无创、可重复、反映肿瘤全貌及功能特征等优势。近年来，定量DCE-MRI的后处理方法，也在不断被开发和完善。本项目拟通过研究肾细胞癌的DCE-MRI参数与反映肿瘤血管生成的病理学金标准（MVD/VEGF/VEGFR）的相关性，了解其在评估肾细胞癌肿瘤血管生成的可行性及准确性，并通过观察肾细胞癌患者抗肿瘤血管生成治疗前后的定量DCE-MRI参数的变化，了解其在评价抗肿瘤血管生成治疗中的价值，以及治疗前基线参数估计患者预后的可行性。.本研究分两部分，定量DCE-MRI与病理学的对照研究及定量DCE-MRI在评估抗肿瘤血管生成治疗中的价值。.研究成果如下：.1..明确了肾脏肿瘤DCE-MRI的扫描方法及参数设置，为其成为临床常规检查提供了依据。.2..验证了“DCE-MRI参数与反映肿瘤血管生成的病理学金标准间存在相关性”的假说，明确了DCE-MRI无创性反映肿瘤血管生成信息的可行性。.3..揭示了肾脏透明细胞癌与非透明细胞癌的DCE-MRI参数存在差异，且提出诊断阈值。.4..提示DCE-MRI参数不能反映肾细胞癌的分化程度，不能进行肾脏肿瘤良恶性的鉴别。.5..DCE-MRI可以通过各参数的变化来反映抗肿瘤血管生成治疗的疗效.6..疗前基线DCE-MRI参数与近期疗效无相关性，与远期疗效的相关性有待进一步随访证实。.7..抗肿瘤血管生成治疗后病变形态学的变化与DCE-MRI反映的功能性变化之间，未发现明显的相关性。.