乳腺良恶性肿瘤微血管构筑的异质性及其血流动力学的功能变化

Heterogeneity of angioarchitecture and their hemodynamic changes in benign and malignant breast tumors

目的探讨乳腺良恶性肿瘤及其小同灌注区域在血管构筑、血流动力学功能、超微结构及其微血管分布方面的差异性。方法应用实时灰阶超声造影微血管成像（MVI）技术，榆测30例乳腺恶性肿瘤（33个病灶）和30例乳腺纤维腺瘤（34个病灶）的微血管造影特征。应用时间-强度曲线（TIC）定量分析技术，榆测瘤灶边缘及中心部Ⅸ域灌注参数及平均灌注参数峰值强度（PI）、曲线下面积（AUC）、达峰时间（TTP）和廓清时间（WOT）。府用透射电镜观察瘤内新生血管超微结构改变，应用免疫组化技术检测CD34的表达。结果乳腺良恶性肿瘤造影后，病灶呈不均匀增强、允盈缺损、紊乱的血管网、血管扩张、血管迂曲征象的差异有统计学意义（P〈0.05）。恶性组病灶中，TIC多数（29／33，87.9％）早速升缓降型；良性组病灶中，TIC多数（27／34，79.4％）呈缓升速降型。恶性组平均AUC和WOT大于良性组（P〈0.05）。两组平均PI和TTP比较，差异无统计学意义（P〉0.05）。恶性组病灶边缘各灌沣参数与中心区域相比，筹异有统计学意义（P〈0.05）；良性组病灶边缘各灌注参数与中心区域相比，差异无统计学意义（P〉0.05）。恶性组新生血管内皮细胞超微结构不同于正常血管内皮细胞，具有分裂旺盛的瘤性特征，癌灶边缘以扩张、迂曲的大m管为多，癌灶中心常见狭窄、闭塞的幼稚新生血管及固缩、变形的内皮细胞和周细胞。恶性组的微血管密度（34.84±8.34）显著高于良性组（18.65±4.69，P〈0.05），微血管丰富区位于癌巢边缘。结论实时趟声造影灌注模式、TIC形态、各平均灌注参数及区域灌注参数的差片，为乳腺良恶性肿瘤的鉴别诊断提供了重要依据。肿瘤间质中新生微血管密度、形态、分布、结构及功能的差异性，是影像学评价肿瘤血管生成的基础。

Objective To explore the differences between the angioarchitecture, hemodynamics, ultrastructure of neovasculr endothelial cells, and vascular distribution in different perfusion regions in benign and malignant breast tumors. Methods 30 cases of breast carcinoma （33 lesions） and 30 cases of breast fibroadenoma （34 lesions） were examined by contrast enhanced microvascular imaging （MVI）, and perfusion indexes were collected both inside and at the margin of each focus according to time-intensity quantitative analysis, including peak intensity （PI）, area under the curve （AUC）, time to peak （TTP） and wash-out time （WOT）. The ultrastructure of neovascular endothelial cells was examined by transmission electron microscopy. The expression of CD34, VEGF, Flk-1/KDR in both two groups were detected by immuhistoehemistry. Results Significant differences were found between the two groups characterized with filling defect, vascular distortion, dilatation and uneven enhancement. Most of the curves of malignant group （87.9%, 29/33 ） ascended rapidly and dropped slowly while those of the benign group （79.4% ,27/34） ascended slowly and dropped rapidly. The AUC and WOT of malignant tumor group were significantly higher than those of benign group, while the PI and TTP had statistically no significant difference. In the malignant tumor group, PI, AUC and WOT collected from the margin of loci were significantly different from those collected inside the loci, however, there was no significant difference in the benign group. The margin of loci was characterized with dilated and distorted vessels, and the center of the loci was occupied by narrow or occluded blood vessels, sometimes with contracted endothelial cells and pericytes. Abundant microvascular areas located at the margin of foci. The ultrastructure of endothelial cells in the newly formed blood vessels of malignant group showed strong ability to divide, which was different from normal endothelium cells. Conclusion The perfusion pattern, mode of time-intensity curve, mean perfusion parameter and variation of regional perfusion parameters provide a valuable diagnostic basis in distinguishing benign and malignant breast tumors. The density, morphology, distribution, structure and function of newly formed mierovessels in tumor foci are also crucial factors when tumors are assessed by imaging examination.