【作者】 廖锦堂；

【导师】 田勇泉；

【作者基本信息】 中南大学 ， 影像医学与核医学， 2008， 博士

【摘要】 目的(1)探讨不同分化程度肝细胞癌(hepatocellular carcinoma,HCC)超声造影定量参数的差异;(2)探讨超声造影定量参数与肿瘤微血管密度(micro-vessel density,MVD)的相关性。资料与方法44例肝细胞肝癌(HCC)的44个肿瘤被纳入本研究计划,包括高分化癌18例,中分化癌15例,低分化癌11例,所有病例手术前1周内行彩色多普勒超声检查,并应用低机械指数反向脉冲谐波显像(PIHI)技术对肝脏肿瘤进行实时超声造影,造影剂使用由意大利博来科公司生产的SonoVue(声诺维),首先观察肝脏及肝内肿瘤的二维声像,彩色多普勒观察肿瘤内血流分布,并给予分级,然后进行超声造影,记录造影全过程,约5分钟时间,然后在定量分析软件上仔细观察肿瘤在动脉期、门脉期、延迟期的造影增强表现,并在肿瘤内部和同一深度肝实质内分别选取感兴趣区域(避开坏死区及粗大血管),作出时间一强度曲线。在时间一强度曲线上读出肿瘤内部造影剂始增时间、达峰时间、峰值强度、同一时刻周围肝实质的强度,计算峰值加速时间(peak accelerating time,PAT)、增强斜率(enhancing sloperate,ESR)、相对峰值强度(relative peak intensity,RPI)、峰值强度增加率(peakintensity increasing rate,PIIR)。术后标本HE染色,由2名不知道造影结果的有丰富临床经验的病理学专家单独阅片做出分化程度分级的诊断,应用CD34单克隆抗体行免疫组化微血管密度检测。比较不同分化程度HCC组间肿瘤最大径、彩色血流分级、始增时间、达峰时间、峰值加速时间、峰值强度、增强斜率、峰值强度增加率的差别,分析达峰时间、峰值加速时间、增强斜率、峰值强度增加率与微血管密度的相关性。结果(1)高、中、低分化HCC组肿瘤最大径(分别为6.5±3.4cm、8.6±3.2cm、9.1±3.3cm)差异无显著性(P＞0.05);(2)彩色多普勒血流分级中,低分化组与高分化组间差异有显著性,其余各组间差异无显著性;(3)高、中、低分化组HCC始增时间(分别为14.7±3.4S、15.9±4.1S、14.5±2.8S)、峰值强度(分别为186.4±46.4dB、180.5±35.4dB、174.7±36.6 dB)差异无显著性(P＞0.05);高与中分化组间达峰时间差异无显著性(P＞0.05),余两组间差异有显著性(P＜0.05);不同分化程度HCC间峰值加速时间(分别为16.4±4.1S、12.3±5.6S、7.1±1.6S)、增强斜率(分别为12.0±2.9、17.8±5.6、25.7±7.5)差异有显著性(P＜0.001,P＜0.05);低分化组峰值强度增加率高于高分化组(P＜0.05),高分化组与中分化组、中分化组与低分化组比较差异无显著性(P＞0.05)。(4)高、中、低分化HCC组肿瘤微血管密度差异有显著性(P＜0.001);(5)达峰时间和峰值加速时间与肿瘤微血管密度呈显著负相关(P＜0.001和P＜0.001),增强斜率和峰值强度增加率与肿瘤微血管密度呈显著正相关(P＜0.001和P＜0.01)。结论(1)不同分化程度HCC超声造影达峰时间、峰值加速时间、增强斜率存在差异,低分化HCC达峰时间、峰值加速时间较短,增强斜率较大;高分化HCC达峰时间、峰值加速时间较长,增强斜率较小,提示达峰时间、峰值加速时间、增强斜率可能反映HCC的分化程度。(2)超声造影达峰时间和峰值加速时间与肝细胞癌MVD测值呈负相关,增强斜率、峰值强度增加率与MVD测值呈正相关,提示这些指标在一定程度上可以间接反映肝细胞癌的微血管密度,超声造影可能在术前活体上动态评估肿瘤的微血管生成情况,为制定手术方案、预测预后、评价抗血管生成药物的疗效提供影像学依据。更多还原

【Abstract】 Objective: 1. to compare the difference of quantitative parameters of contrast-enhanced ultrasound (CEUS) time-intensity curve in hepatocellular carcinomas (HCCs) with different histopathologic grading. 2. to investigate the relationship of these parameters and micro-vessel density (MVD) in HCCs.Methods: Forty-four patients with forty-four lesions confirmed as HCC pathologically by surgery were studied, including 18 well-differentiated nodules, 15 moderately differentiated nodules and 11 poor differentiated nodules. Each patient was examined by CEUS using pulse inversion harmonic imaging (PIHI) with low mechanical index and second generation micro-bubble contrast medium (SonoVue, Bracco, Milan, Italy) as echo-enhancing agent within a week before surgery. First the liver was scanned with a conventional sonogram and the Color Doppler flow signals of the lesions were scored. Then CEUS images were observed continually on real time and the entire scanning process was recorded for 5 minutes. Enhancement patterns of each lesion were analyzed during the whole vascular phase, consisting of arterial phase, portal venous phase and parenchymal phase. The regions of interests(ROI) was in the lesions and the paraneoplastic liver parenchyma approximately the same depth, avoiding necrosis and large vessels, and the time-intensity curve was made by QLAB or TIC software. The parameters (enhancement beginning time, peak intensity time, peak intensity of lesion and intensity of the same depth paraneoplastic liver parenchyma) were analyzed, and then these parameters were calculated: peak accelerating time(PAT), enhancing slope rate(ESR), relative peak intensity(RPI) ,peak intensity increasing rate(PIIR). The tumor specimens were stained with hematoxylin eosin (HE) and two professional pathologists, who were blinded to the results from CEUS, evaluated histopathologic grading alone. MVD in nodules were detected by staining immunohistochemically with anti-CD34 antibody.The difference of parameters in HCCs with different histopathologic grading were compared, such as largest average diameters, blood flow grade, enhancement beginning time, peak intensity time, peak accelerating time (PAT) , peak intensity of lesion, ESR,PIIR, and the relationship was analyzed between peak intensity time, peak accelerating time (PAT) , ESR, PIIR and MVD in HCCs.Results : (1)A11 tumors were classified into three groups, well-differentiated HCCs group (n=18) (largest average diameters, 6.5±3.4 cm), moderately differentiated HCCs group (n=15) (largest average diameters, 8.6±3.2 cm), and poorly differentiated HCCs group (n = 11) (largest average diameters, 9.1±3.3cm). There was no statistical significance in the largest average diameters of nodule with different histopathologic grading. (2)There was statistical significance in blood flow grade by Color Doppler sonography between well-differentiated HCC group and poorly differentiated HCC group , but no significant difference in well-differentiated and moderately differentiated HCC group, either in moderately and poorly differentiated HCC groups. (3)Enhancement beginning time and peak intensity of well, moderately, poorly differentiated HCCs group were (14.7±3.4S,15.9±4.1S,14.5±2.8S), (186.4±46.4dB,180.5±35.4 dB,174.7±36.6 dB) , respectively, either with no statistical significance(P >0.05).There was no statistical significance in peak intensity time between well-differentiated HCC group and moderately differentiated HCC group(P > 0.05), but significant difference in well-differentiated HCC group and poorly differentiated HCC group(P< 0.05), and in moderately differentiated HCCs group and poorly differentiated HCC group(P< 0.05). Enhancement time and ESR of well, moderately, poorly differentiated HCCs groups were (16.4±4.1S, 12.3±5.6S, 7.1±1.6S), (12.0±2.9, 17.8±5.6, 25.7±7.5), respectively, both with statistical significance(P <0.05). PIIR of poorly differentiated HCC group was higher than that of well differentiated HCC group(P< 0.05), but there was no significant difference between well-differentiated HCC group and moderately differentiated HCC group(P >0.05), neither between moderately differentiated HCC group and poorly differentiated HCC group(P >0.05).(4)Statistical significance was observed in MVD in well, moderately, poorly differentiated HCC group (P <0.001); (5)Peak intensity time and enhancement time were negatively correlated with MVD(P<0.001 and P<0.001), while ESR and PIIR were positively correlated with MVD (P <0.001 and P<0.01).Conclusion:1. The peak intensity time, peak accelerating time and ESR of different differentiation HCC is different. The peak intensity time and the peak accelerating time in poorly differentiated HCCs was shorter, and ESR was bigger, while they were longer or smaller in well-differentiated HCCs. These parameters reflect indirectly histological differentiation.2. Peak intensity time and peak accelerating time were negative correlated with MVD, and ESR and PIIR were positive correlated with MVD . These parameters of contrast-enhanced time-intensity curve may reflect indirectly micro-vessel density in HCC lesion. CEUS before operation can evaluate the generation of angiogenesis, and has a potential role in choosing treatment, evaluating prognosis, and evaluating effect of anti-angiogenesis drugs.更多还原