肝细胞肝癌超声造影与微血管密度的相关性研究

目的 探讨肝细胞肝癌(HCC)的超声造影定量参数与其组织中微血管密度(MVD)的相关性,探讨超声造影无创评价HCC血管生成的价值.方法 应用Sequoia 512超声诊断仪及造影剂SonoVue对28个HCC病灶行超声造影检查,脱机应用新型超声造影定量分析软件(SW-UCS)获得肿瘤及同深度癌旁肝实质的感兴趣区的时间强度曲线(TIC)和灌注定量参数.术后病理切片行CD34免疫组织化学染色并测得MVD.分析比较超声造影定量参数与MVD的相关性.结果 HCC与肝实质TIC曲线可以直观反映HCC相对于肝实质"快进快出"的典型增强表现.两者曲线上升速率(a3)、达峰时间(TTP)、峰值强度(PI)、强度增量(ISI)、加速时间(AcT)差异有统计学意义(P＜0.05).HCC的MVD(49.36±12.57)明显高于癌旁肝实质(32.46±11.78).两者差异有统计学意义(P=0.000).HCC的PI、ISI、曲线下面积(AUC)与MVD呈正相关,峰值减半斜率(a2)与MVD呈负相关(P＜0.05).结论 HCC的超声造影定量参数与MVD有一定的相关性,能无创地评估活体内HCC的血管生成.     

超声造影定量分析技术评价肝癌肿瘤血管生成的临床研究

目的 探讨实时超声造影定量分析技术评估肝癌肿瘤血管生成的可行性.方法 对33例经手术病理证实的原发性肝癌于术前1周进行超声造影,造影时仪器预设置和造影剂用量保持一致,动态影像经专用软件脱机分析和数学模型拟合,获得基础强度、强度增量(ASI)、峰值减半斜率(a2),上升斜率(a3)、显影时间(AT)、达峰时间(TTP)、上升时间(ACT)、峰值强度(PI)和曲线下面积(AREA)等参数.肝癌手术标本进行CD34抗体染色,由计算机读片记录肿瘤微血管密度(MVD),统计其与各超声造影参数的相关性.结果 肝癌病灶区的ASI、a2、a3、AT、TTP、PI和ACT与肝实质相应参数比较,差异均有统计学意义(P＜0.01);肿瘤区参数a2与MVD均值有相关性,肿瘤区标化的ASI和AREA参数与MVD均值有相关性,均为P＜0.05.结论 超声造影定量分析能客观地显示肝癌微循环的血流灌注情况,从而无创评估肝癌的肿瘤血管生成情况.     

肝细胞癌的超声造影定量参数与肿瘤内新生动脉的相关性研究

目的 探讨肝细胞癌(hepatocellular carcinoma,HCC)的超声造影(contrast-ehhanced ultrasonography,CEUS)定量参数与HCC内新生动脉的关系.方法 对115例HCC的CEUS图像进行脱机分析和免疫组化染色,获得感兴趣区的灌注曲线及CEUS定量参数:峰值强度(maximum of intensity,IMAX)、上升时间(rise time,RT)、达峰时间(time to peak,TTP)、平均渡越时间(mean trasit time corresponding to the center of grayity,mTT)、上升斜率(rise slope,RS)和始消时间(washout time,WT).获得82例HCC内的非成对动脉数,将CEUS定量参数和非成对动脉数进行统计学分析.结果 HCC中非成对动脉数与RT、TTP、RS呈中度相关,r分别为-0.446,-0.432,0.431(P＜0.05),与IMAX和WT呈弱相关,r分别为0.303和0.285(P＜0.05).结论 HCC内的新生动脉是HCC动脉相增强的病理生理基础,CEUS定量参数反映了肿瘤灌注情况,与HCC中的非成对动脉数有关.

Abstract：

Objective To explore the relationships between the quantitative parameters for contrastenhanced ultrasonography(CEUS) in hepatocellular carcinoma (HCC) and arteries in neoangiogenesis.Methods One hundred and fifteen HCCs in CEUS were analyzed off-line with dynamic vascular curve of ImageArena and immunohistochemical stained in the tissue slices.Parameters including maximum of intensity(IMAX),rise time(RT),time to peak(TTP),mean trasit time corresponding to the center of gravity(mTT) ,rise slope(RS) and washout time(WT) were analyzed by statistics.Unpaired arteries(UAs)of 82 HCC cases were succesfully stained.Results The number of UAs had moderate correlation with RT (r = - 0.446),TTP (r = - 0.432) and RS (r = 0.431) (P ＜ 0.05),and it had mild correlation with IMAX (r = 0.303) ,WT (r = 0.285) (P ＜0.05).Conclusions Neoangiogenesis is a functional adaptation to altered vascular dynamics.Quantitative parameters of CEUS,reflecting hemodynamics of tumors,are correlated with UAs.     

肝细胞癌的超声造影定量参数与肿瘤内新生动脉的相关性研究

Objective To explore the relationships between the quantitative parameters for contrastenhanced ultrasonography(CEUS) in hepatocellular carcinoma (HCC) and arteries in neoangiogenesis.Methods One hundred and fifteen HCCs in CEUS were analyzed off-line with dynamic vascular curve of ImageArena and immunohistochemical stained in the tissue slices.Parameters including maximum of intensity(IMAX),rise time(RT),time to peak(TTP),mean trasit time corresponding to the center of gravity(mTT) ,rise slope(RS) and washout time(WT) were analyzed by statistics.Unpaired arteries(UAs)of 82 HCC cases were succesfully stained.Results The number of UAs had moderate correlation with RT (r = - 0.446),TTP (r = - 0.432) and RS (r = 0.431) (P ＜ 0.05),and it had mild correlation with IMAX (r = 0.303) ,WT (r = 0.285) (P ＜0.05).Conclusions Neoangiogenesis is a functional adaptation to altered vascular dynamics.Quantitative parameters of CEUS,reflecting hemodynamics of tumors,are correlated with UAs.     

肝细胞性肝癌超声造影分型与血管生成相关性研究

目的 探讨肝细胞性肝癌(HCC)超声造影(CEUS)灌注显像分型与血管生成之间的关系,探讨该分型的临床意义.方法 HCC患者89例113个病灶,选择反映大血管构筑形态的动脉相早期强化形式以及与微血管分布、部位及密度相关的增强后肿瘤大小变化及边界清晰与否等灌注参数进行观察分析.全部病例经病理证实,部分病例行免疫组化染色,测定微血管密度(microvessel density,MVD).结果 依CEUS改变将HCC灌注显像分为4型:树枝型、混合型、环绕型、网络型.树枝型异型性血管多,病理Ⅲ、Ⅳ级占79.1%,MVD高于其他各型.环绕型血管形态相对较规则,Ⅲ、Ⅳ级仅占12.5%,MVD低于其他类型.综合CEUS灌注特征并与病理分级、生长方式、MVD等对照,树枝型以浸润性生长为主,具有较强侵袭倾向.环绕型以膨胀性生长为主.其余两型介于二者之间为过渡型.结论 CEUS灌注显像分型能够反映肿瘤血管构型及微血管密度与部位,并与肿瘤病理分级、生长方式等具有相关性.     

靶向超声造影评价裸鼠肾癌新生血管的实验研究

目的 探讨以血管内皮生长因子受体2 (VEGFR2)为靶点的靶向超声造影评价裸鼠肾癌新生血管的应用价值.方法 建立人肾透明细胞癌皮下移植瘤裸鼠模型,制备携VEGFR2抗体的靶向造影剂(MBV),每只裸鼠分别随机注射普通造影剂(MBC)和MBV并行超声造影检查,比较两种造影剂的视频强度,并对肿瘤组织行VEGFR2免疫组化检测.结果 超声造影示MBV组视频强度(6.50±1.43)Db,MBC组视频强度(2.59±0.99)Db,两者差异有统计学意义(P<0.01),且MBV组持续强化时间较MBC组长,免疫组化结果证实肿瘤血管内皮VEGFR2高表达.结论 以VEGFR2为靶点的靶向造影剂可特异性增强肾癌显影,对评估肿瘤新生血管有重要价值.

Abstract：

Objective To investigate the value of contrast enhanced ultrasound(CEUS) with microbubbles targeted to vascular endothelial growth factor receptor type 2 (VEGFR2) for imaging tumor angiogenesis in murine tumor models.Methods Established human renal cell carcinomas(RCC) subcutaneous xenograft tumor model in nude mice,microbubbles targeted to VEGFR2(MBV) was prepared,control microbubbles(MBC) and MBV were injected respectively in each mouse,the intensity of each microbubble was compared,the expressions of VEGFR2 in tumors were tested by immunohistochemistry.Results CEUS imaging showed the intensity of MBV and MBC was (6.50±1.43)dB,(2.59±0.99)dB,respectively.There was significantly higher intensity when using MBV compared with MBC (P<0.01).The time to wash out was longer in MBV contrast group compared with MBC group.Immunohistochemistry showed VEGFR2 was highly expressed in novel vessel walls.Conclusions Contrast microbubbles targeted to VEGFR2 can specially enhance the images of RCC and has tremendous significance in the assessment of angiogenesis.     

超声造影时问强度量化分析与肝细胞肝癌VEGF表达及微血管密度间关系的初步研究

目的 探讨超声造影动态增强定量分析与肝细胞肝癌(HCC)VEGF表达及微血管密度(MVD)间的关系.方法 对73例HCC患者超声造影结果进行时间强度量化分析;通过免疫组织化学方法检测不同分化程度肝细胞癌VEGF的表达,同时CD34染色计数肿瘤MVD;分析超声造影时间强度量化分析和VEGF表达、MVD以及临床病理因素之间的关系.结果 HCC不同病理分化程度组间超声造影到达时间差异无统计学意义,增强时间、消退时间及曲线下面积各组间差异有统计学意义(P<0.05).37例(50.7%)HCC组织中VEGF呈阳性表达.VEGF表达阳性组MVD明显高于VEGF表达阴性组(P<0.01).VEGF阳性表达组中增强时间、消退时间及曲线下面积与阴性表达组间差异有统计学意义(P<0.05).增强时间与MVD呈显著负相关(r=-0.615),曲线下面积与MVD呈显著正相关(r=0.563).结论 通过超声造影时间强度曲线分析,可以初步评估肿瘤的分化程度,反映肿瘤内新生血管,为评估HCC的抗血管治疗提供了新的依据.

Abstract：

Objective To detect the correlations between vascular endothelial growth factor (VEGF) expression, microvessel density ( MVD) and time intensity parameters of contrast enhanced ultrasound in hepatocellular carcinoma (HCC). Methods Seventy-three patients of HCC were analyzed with time intensity curve of contrast enhanced ultrasound. VEGF and CD34 in different degree of differentiated HCC specimens were detected by immunohistochemistry. The correlations between VEGF, MVD and time intensity parameters were analyzed. Results Arrival time had no significant difference among different differentiated groups. However, the area under the curve, enhanced time and washout time had significant difference among different differentiated groups respectively ( P <0. 05). There was a positive correlation between VEGF expression and MVD in HCC. MVD was associated with enhanced time and the area under the curve ( r = - 0. 615,0. 563,respectively). The area under the curve,enhanced time and washout time of VEGF positive expression group had significant difference comparing to those of VEGF negative expression group ( P < 0. 05). Conclusions It was helpful to assess HCC differentiated degree with time intensity parameters of contrast enhanced ultrasound.     

复发性与初发性肝细胞肝癌实时超声造影比较研究

目的 比较复发性与初发性肝细胞肝癌实时超声造影时相特征.方法 对初发性肝细胞肝癌患者83例(93个肿瘤)和复发性肝细胞肝癌患者56例(70个肿瘤)进行实时灰阶谐波超声造影,比较初发性肿瘤与复发性肿瘤的造影增强时相变化.结果 从注射造影剂开始到肿块回声较肝实质低的时间,复发性与初发性肝细胞肝癌组分别为(104.0±51.8)s和(85.5±43.0)s,两组间差别有显著统计学意义(P=0.010).复发性和初发性肝癌在门脉期中表现为等回声的比例分别为34.3%(24/70),17.2%(16/93),前者明显高于后者(P=0.012).结论 复发性肝细胞肝癌与初发性肝细胞肝癌超声造影表现有一定差异,认识这一规律将有助于复发性肝细胞肝癌的早期诊断.     

肝细胞癌超声造影增强范围病理意义的探讨

目的 探讨肝细胞癌超声造影增强范围较常规超声测值增大的病理学意义.方法 35例肝细胞癌患者手术前进行常规超声和超声造影检查,比较常规超声、超声造影及手术后肿瘤大小,显微镜下观察肝细胞癌边缘癌细胞浸润深度,分析比较超声造影增强范围较常规超声测值增大的组织病理学特征.结果 35例肝细胞癌中14例(40%)超声造影增强范围较常规超声测值增大,9例肝细胞癌增大区域为癌细胞浸润,2例为瘤周脂肪变性伴炎细胞浸润,2例瘤周腺瘤样增生伴炎细胞,1例瘤周炎细胞伴肝内多发肝细胞癌.以超声造影增强 范围较常规超声测值增大作为肝细胞癌局部浸润的诊断标准,超声造影诊断肝细胞癌局部浸润的敏感性为90%,特异性为80%,准确性为82.9%,阳性预测值为64.3%,阴性预测值为95.2%.结论 与常规超声比较,超声造影判断肝细胞癌局部浸润范围更准确.     

实时灰阶超声造影评价肝癌动物模型抗血管生成治疗的研究

SI)、曲线下面积(AUC)和血流量系数(BF)明显低于对照组,另外峰值减半斜率(a2)和曲线上升斜率(a3)明显大于对照组(P<0.05).定量参数与肿瘤体积增长率正相关(P<0.05).a3和ISI与坏死指数负相关(r=-0.54,P=0.008;r=-0.46,P=0.027).结论 实时灰阶超声造影能反映肿瘤内血流灌注变化,有助于监测肿瘤抗血管生成治疗的血管反应.     

超声造影定量分析评价兔粥样斑块内新生血管与病理的对照研究

目的 比较超声造影定量计算动脉粥样硬化动物模型斑块的增强强度与免疫组化微血管染色的结果,评价超声造影定量分析斑块内血管新生的可靠性.方法 高脂喂养建立动脉粥样硬化模型成功的实验兔9只,实时谐波超声造影观察兔腹主动脉超声造影增强,随后用QLab定量分析软件分别计算动脉斑块内增强强度(EI)及斑块内增强强度与腹主动脉管腔内增强强度的比值(ratio).免疫组织化学方法显示斑块内血管内皮细胞中的第Ⅷ因子相关抗原F8染色斑块内的微血管,比较超声造影定量分析与免疫组化微血管染色结果的相关性.结果 9只兔超声造影定量分析EI及ratio值分别为(3.91±0.87)dB及0.30±0.06,免疫组化染色显示9只兔腹主动脉标本中F8染色阳性5例,阴性4例.超声造影定量分析EI与F8染色有相关性(r =0.779,P=0.013),ratio值与F8染色有相关性(r =0.693,P=0.019).结论 超声造影定量分析的强度参数EI及ratio能够在一定程度上反映斑块内新生血管增生的程度,有助于对斑块稳定性的评价.     

肝细胞癌超声造影增强达峰时间与微血管密度相关性研究

目的探讨超声动态增强达峰时间(Tmax)与肝细胞癌(HCC)血管生成变化的关系。方法对34例经手术或穿刺病理证实的HCC患者进行实时超声造影,通过绘制时间-强度曲线,记录Tmax;经HE染色进行肿瘤病理分级,应用CD34行免疫组化微血管密度(MVD)检测,分析Tmax与MVD的关系。结果34例HCC中高分化6例,中分化15例,低分化13例,高分化组、中分化组、低分化组MVD分别为43.5±12.9、67.2±13.3、82.1±17.8,不同分化程度HCC间MVD差异有统计学意义(F=13.46,P=0.001);Tmax分别为(33.0±5.1)s、(27.7±4.2)s、(22.7±3.3)s,不同分化程度HCC间Tmax差异有统计学意义(F=14.08,P<0.001);Tmax与MVD呈负相关(Y=-0.16X+37.9,r=-0.605,P<0.0001)。结论超声动态增强Tmax在一定程度上可以间接提示HCC的微血管密度,有助于判定HCC的分化程度。     

肾细胞癌的超声造影研究

目的 总结和探讨肾细胞癌的超声造影特征.方法 70例肾细胞癌共72个病灶接受了常规超声和超声造影检查,分析病灶的常规超声及超声造影表现特征.超声造影使用造影剂声诺维和对比脉冲序列成像技术.结果 常规超声显示低、等、高回声的病灶分别为44.4%(32/72)、25.0%(18/72)和30.6%(22/72).病灶彩色血流信号显示率为38.9%(28/72),动脉峰值流速(43.7±16.8)cm/s(24.8～95 cm/s),阻力指数0.63±0.11(0.53～0.80).超声造影显示皮质期63个(87.5%)病灶表现为等或高增强,9个(12.5%)为低增强.63个等或高增强病灶中48个(76.2%)实质期及晚期减退至低增强,15个(23.8%)仍保持等或高增强.9个皮质期表现为低增强病灶,晚期仍为低增强.75.0%(54/72)病灶不均匀增强,内可见无增强区,87.5%(63/72)的病灶可显示代表假包膜的高增强环.结论 超声造影病灶皮质期不均匀等或高增强,实质期或晚期呈低增强,以及假包膜增强是肾细胞癌的重要表现,能将有助于肾细胞癌的诊断及鉴别诊断.     

兔动脉粥样硬化斑块超声造影参数与微血管密度的相关性研究

目的 探讨兔动脉粥样硬化斑块超声造影参数与微血管密度(MVD)的相关性.方法 26只雄性新西兰大白兔经球囊扩张损伤腹主动脉并高脂喂养12周后,常规超声检测到32个斑块,测量斑块的大小、管腔面积狭窄率及斑块厚度,运用实时超声造影技术对32个斑块进行超声造影检查,采用ACQ分析软件脱机进行声学定量分析,获取斑块的始增时间(AT)、到达时间(TTP)、峰值强度(PI)和基础强度(BI),计算增强强度(EI,EI=PI- BI).行病理组织学检查及抗CD34免疫组化染色,计数微血管密度(MVD),分析其与造影参数的相关性,根据病理结果将斑块分为易损斑块和稳定型斑块.结果 易损斑块组(13个)的EI和MVD均高于稳定型斑块组(19个),差异均有统计学意义[EI:(26.36±1.44)dB对(23.90±2.92)dB,t=-3.243,P=0.001; MVD:(5.23±1.16)/mm2对(2.47±1.12)/mm2,Z=- 4.378,P＜0.001].两组间斑块大小、管腔面积狭窄率、斑块厚度及超声造影参数PI、AT、TTP差异均无统计学意义(P＞0.05);斑块的EI值与MVD呈显著正相关(r=0.676,P＜0.001).结论 超声造影参数EI值能较好地反映兔动脉斑块内的新生血管情况,有望作为临床评价斑块稳定性的的一项可靠指标.     

脑胶质瘤超声造影定量参数与微血管密度的相关研究

目的 探讨术中超声造影在评价不同病理级别脑胶质瘤血管生成变化中的应用价值.方法 对33例脑胶质瘤患者行超声造影检查,实时观察肿瘤血流灌注情况及增强特点,绘制时间-强度曲线获取定量指标.术后对切除的病灶行常规病理检查和免疫组织化学检测,记录肿瘤的微血管密度,定量分析不同级别脑胶质瘤血流灌注指标与术后病理微血管密度的相关性.结果 低级别和高级别脑胶质瘤的造影达峰时间和微血管密度值比较差异均有统计学意义(P=0.0001);不同分化程度的脑胶质瘤超声造影达峰时间与微血管密度之间呈负相关关系(r=-0.79,P=0.0001).结论 术中超声造影可以实时动态地观察微血管的灌注情况,超声造影可提示肿瘤内微血管密度,有助于术者准确判定脑胶质瘤病理分级,指导肿瘤的手术切除.

Abstract：

Objective To investigate the value of intraoperative contrast-enhanced ultrasound(CEUS) in evaluating pathological grades of cerebral gliomas. Methods Intraoperative CEUS was performed in 33 patients of cerebral gliomas of different pathological grades. Real-time blood perfusion and enhance characteristics of these tumors were observed,quantitative parameters from the automatically derived time-intensity curve (TIC) were obtained, and compared with the tumor microvessel density (MVD) by immunostaining with anti-CD34. Results The time to peak was significantly shorter and the MVD was significantly higher in the high grade cerebral gliomas compared with the low grade ones ( P <0. 05). The time to peak was negatively correlated with the MVD by immunostaining (r = -0.79, P < 0. 05). Conclusions Intraoperative CEUS could be used to observe microvascular perfusion in real-time, and could indirectly reflect the information of MVD in cerebral gliomas, which is of help to grade cerebral gliomas and guide surgical resections.