基于IVIM-DWI的成人肾脏肿瘤影像生物学标记及其病理学基础研究

Based on our previous study-investigation of renal cell carcinom diffusion features using diffusion-weighted imaging and apparent diffusion coefficient (ADC) values, this project will enroll patients with renal tumors in light of the given criteria and all subjects will underwent intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) scans.In this study, firstly the reproducibility and repeatability of IVIM-DWI technique in renal tumors were evaluated, whichi is pivotal for IVIM-DWI application in kidney, even in abdomen; then the optimization of b values were perfomred regarding to the selection and distributioni of b values, considering both clinical and scientific requirements and patients' tolerability. Moreover the IVIM-DWI parameters-pure diffusion (D), pseudodiffusion (D*) and perfusion fraction (f) were calculated based on biexponential model, and the efficacy of distinguishing renal tumors including renal cell clear cell carcinoma, papillary renal cell carcinoma, chromophobic renal cell carcinoma , renal pelvic cancer, angiomyolipoma and oncocytoma using these parameters was evaluated. Then the diagnostic efficacy of D,D* and f in characterizing renal tumor was individually analyzed and compared between them. At last, through pathologic analysis, the pathologic types of renal tumors were determined according to the 2004 WHO classification of genitourinary tumors, then the tumor microvessel density and tumor cellularity were inspected.All these efforts can not only provide the reasonable explanation for IVIM-DWI parameters related to both diffusion and perfusion from pathologic perspective, but also determine whether or which parameters can become the imaging biomarkers of renal tumors with different entity, which eventually will provide quantitative and objective evidence for quanlitative diagnosis of renal tumors in adults.

本课题将在前期工作-利用磁共振弥散加权成像进行肾细胞癌弥散特性研究的基础上通过纳入肾脏肿瘤的成人患者进行体素内不相干运动模型-磁共振弥散加权成像（IVIM-DWI），探索IVIM-DWI技术在肾脏肿瘤的可重复性，优化IVIM-DWI扫描时多个扩散敏感因子（b值）的数量和分布，在此基础上探索常见肾脏肿瘤-肾透明细胞癌、乳头状肾细胞癌、嫌色细胞癌、肾盂癌、血管平滑肌脂肪瘤、嗜酸细胞腺瘤的IVIM-DWI弥散及灌注参数-真正弥散系数（D），假性弥散（D*）及灌注分数（f），同时分析各参数区别肾脏肿瘤的不同病理类型的效能，然后通过病理学研究分析肾脏肿瘤细胞密度及微血管密度，从病理学角度阐释IVIM-DWI肾脏肿瘤弥散及灌注特性的生物学基础，不仅为IVIM-DWI参数的合理阐释提供病理依据，并可判断各参数是否真正能作为肾脏肿瘤的影像生物标记，从而为成人肾脏肿瘤的定性诊断提供客观、准确的依据。

本课题在前期工作的基础上，通过纳入正常成年人及肾脏肿瘤的患者进行体素内不相干运动模型-磁共振弥散加权成像（intravoxel incoherent motion diffusion-weighted imaging, IVIM-DWI），评价肾脏肿瘤、正常肾皮质和髓质IVIM-DWI参数测量和短期内重复扫描参数的可重复性以及b值对各参数及其鉴别肾脏良恶性病变效能的影响，探讨各参数诊断肾脏肿瘤的价值以及对肾透明细胞癌分化程度和血管生成的评价价值。.主要研究结果包括：1.肾脏肿瘤、正常肾皮质和肾髓质的ADC和D值有着极好的可重复性，f次之，D*最差；短期内两次扫描参数的可重复性差；灌注相关参数D*及重复扫描的可重复性有待提高。2. b值的设置对肾脏病变的ADC和D值以及肾皮质的ADC、D和f有影响，对D*的影响较小，对ADC和D值鉴别肾脏良恶性病变的诊断效能没有影响。ADC和D值能够鉴别肾脏良恶性病变，D的诊断效能高于ADC。3. IVIM-DWI参数在鉴别ccRCC、non-ccRCC以及良性肿瘤中具有一定的价值，可以为鉴别诊断提供更多的诊断信息：ADC值在鉴别ccRCC与non-ccRCC的诊断效能最大（AUC：0.762，YI：0.535）；D鉴别ccRCC与良性肿瘤的诊断效能高于ADC，当D＞1.05×10-3 mm2/s时，诊断为ccRCC的敏感度为83.5%，特异度为94.4%；D和D*有助于鉴别良性肿瘤与non-ccRCC，D≤1.05×10-3 mm2/s及D*＞36.2×10-3 mm2/s时，诊断为良性肿瘤的敏感度分别为94.4%和83.3%，特异度分别为60.0%和65.0%。4. IVIM-DWI诸参数尚不能评价肾透明细胞癌的血管生成，但参数D能够定量评价肿瘤的分化程度并且诊断效能高于ADC值：在评价肿瘤分化程度时，D值的诊断效能高于ADC值，当D＞1.23×10-3 mm2/s时，其诊断为LG-ccRCC的敏感度为73.0%，特异度为76.0%。.本课题组的主要结果表明IVIM-DWI技术应用于成人肾脏肿瘤患者具有较好的可重复性，优化了b值的数量和分布，并在此基础上探索了常见肾脏良、恶性肿瘤的IVIM-DWI各参数及其区别不同病理类型肾脏肿瘤的效能以及与肿瘤分化程度和血管生成的关系，从而为成人肾脏肿瘤的定性、定量诊断提供了更多的依据。