实时超声造影检测乳腺癌前哨淋巴结的实验研究

目的探讨经皮下注射超声造影剂Sonazoid检测荷瘤兔乳腺癌前哨淋巴结的可行性。方法采用组织块悬液原位注射法制作兔VX2乳腺癌模型14只,经皮下注射Sonazoid对荷瘤兔模型肿块进行超声造影检查,定位同侧腋下前哨淋巴结,并分析造影增强声像图表现特征。然后采用99Tcm硫化物核素法及皮下注射美蓝的方法定位前哨淋巴结,三种方法对比并与手术及病理结果相对照。结果经手术和病理证实的25个前哨淋巴结中,超声造影检出20个,检出率为80.00%(20/25);99Tcm硫化物核素法检出率是76.00%(19/25),皮下注射美蓝检出率是80.00%(20/25),超声造影与另两者比较检出率相当(χ2=0.15,P>0.05)。超声造影对判定前哨淋巴结转移与否的灵敏度、特异度和正确率分别为94.11%、66.67%和90.00%。结论经皮下注射超声造影剂Sonazoid可较好地检测出前哨淋巴结,并能发现良恶性淋巴结的不同灌注特征,可为前哨淋巴结转移提供一种新的诊断依据。     

灰阶超声造影结合MRI:重新认识乳腺肿瘤生长方位

目的采用超声造影(CEUS)结合MRI观察乳腺肿瘤生长方位。方法收集103例接受检查和治疗的乳腺肿瘤患者,包括良性肿瘤35例(良性组)、恶性肿瘤68例(恶性组),常规超声(CUS)显示为非平行位生长,观察同切面CEUS显示的肿瘤生长方位;对其中20例行MR检查,观察肿瘤与邻近皮肤的关系,并与CEUS显示的肿瘤方位进行比较。结果CEUS后,良性组4例生长方位改变,31例无改变;恶性组59例生长方位改变,9例无改变(χ2=55.210,P<0.001)。以病理结果为金标准,根据CEUS生长方位改变诊断乳腺良恶性肿瘤的敏感度为93.65%(59/63),特异度77.50%(31/40),阳性预测值86.76%(59/68),阴性预测值88.57%(31/35)。MRI显示19例乳腺癌生长方位与CEUS一致(P=0.500)。CEUS判定肿瘤方位与MRI一致性良好(Kappa=0.828)。结论CUS显示非平行位生长乳腺良性肿瘤多与CEUS一致,而乳腺恶性肿瘤CEUS后多表现为平行位生长。CEUS与MRI显示肿瘤生长方位一致性良好。CEUS判定乳腺肿瘤生长方位较CUS更可靠。     

乳腺纤维瘤病的临床病理特征

  目的  探讨乳腺纤维瘤病的临床病理特征及鉴别诊断要点。  方法  回顾性分析5例乳腺纤维瘤病患者的临床资料并进行组织形态学、免疫组织化学研究, 对其临床表现、病理形态特点及鉴别诊断进行总结。  结果  5例均为女性, 发病年龄24~75岁, 平均年龄53岁。3例行乳腺病灶活检术, 2例行乳腺单纯切除术。乳腺纤维瘤病由梭形细胞(纤维母细胞/肌纤维母细胞)构成, 背景是丰富的胶原纤维, 有程度不等的玻璃样变性。细胞数量不等, 没有或仅有轻度的细胞不典型性和多形性, 核分裂象少见。免疫组织化学染色5例vimentin均阳性, SMA均部分阳性, 3例β-catenin阳性, 而cytokeratin、desmin、EMA、S-100和CD68均阴性。  结论  乳腺纤维瘤病是一种罕见乳腺肿瘤, 呈进行性、侵袭性生长。     

超声造影评估乳腺癌新辅助化疗疗效的价值

目的 探讨超声造影评估乳腺癌新辅助化疗疗效的价值。方法收集在我院行乳腺癌新辅助化疗并手术的患者51例,分别于化疗前及手术前行超声造影检查, 评估其化疗前后超声造影指标的变化。结果 超声造影可有效反应肿瘤的化疗效果。化疗前无效组中出现灌注缺损区和放射状血管的概率明显高于有效组(p<0.05)。同无效组相比,有效组多表现为峰值强度低,达峰时间长,区域血流量和血流速度较低(p<0.05)。结论 超声造影对乳腺癌新辅助化疗疗效的预测及评估有一定的临床价值。     

超声造影对乳腺导管内乳头状瘤的诊断价值简

目的探讨超声造：影对乳腺导管内乳头状瘤的诊断价值。方法回顾性分析2011年8月至2012年3月在北京协和医院进行乳腺手术的96例患者共96个病灶的超声造影,其中经病理证实为导管内乳头状瘤11例。超声造影增强形式分为无增强、周边增强、均匀增强、区域增强和不均匀增强,分析导管内乳头状瘤的造影特征,并与病理所见进行对照。结果11例导管内乳头状瘤经常规超声仅检出6例,病灶1．6～3．9cm;经超声造影发现另外4例,均为均匀增强,病灶0．5—1．2cm。11例导管内乳头状瘤中,均匀增强6例（54．5％）,区域增强4例（36．4％）,无增强1例（9．1％）。超声造影增强区组织病理学特点是扩张导管内乳头状突出物,以纤维血管为轴心,树枝样生长,提示导管内乳头状瘤;非增强区组织病理学特点主要是扩张导管和纤维组织。结论乳腺导管内乳头状瘤超声造影主要为均匀增强和区域增强,超声造影表现与组织病理学特征有关。超声造影有助于提高常规超声对导管内乳头状瘤的检出率。     

超声造影联合空心针活检在浸润性乳腺癌前哨淋巴结转移评估中的价值

目的 探讨超声造影联合空心针组织穿刺活检评估浸润性乳腺癌患者腋窝前哨淋巴结(sentinel lymph node,SLN)转移的价值.方法 120例浸润性乳腺癌患者行乳腺癌根治术前均行常规超声及超声造影检查,记录SLN数目及超声造影增强模式,对超声造影检出SLN者行超声引导下空心针组织穿刺活检;乳腺癌根治术中行SLN...     

超声造影联合声触诊组织成像定量技术诊断乳腺癌前哨淋巴结

目的 观察超声造影(CEUS)联合声触诊组织成像定量(VTIQ)技术诊断乳腺癌前哨淋巴结(SLN)的价值.方法 对37例经病理确诊乳腺癌患者行乳腺超声造影,追踪显像淋巴管,观察SLN增强模式,评价CEUS对SLN的检出率及定位及定性诊断准确率;采用VTIQ测量CEUS所见SLN的剪切波速度平均值(SWVmean).绘制...     

Correlation of real-time gray scale contrast-enhanced ultrasonography with microvessel density and vascular endothelial growth factor expression for assessment of angiogenesis in breast lesions.

OBJECTIVE: The purpose of this study was to determine the correlation of real-time gray scale contrast-enhanced ultrasonographic (CEUS) patterns and parameters with microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression for assessment of angiogenesis in breast lesions. METHODS: Real-time gray scale CEUS was performed in 53 women with breast lesions. Contrast-enhanced ultrasonographic patterns and quantitative parameters were analyzed. Mean MVD and VEGF expression in breast lesions were measured by immunohistochemical analysis. RESULTS: Surgical pathologic analysis showed 25 benign and 28 malignant lesions. Different CEUS patterns were observed in the high- and low-MVD and -VEGF groups. Microvessel density and VEGF expression were significantly associated with heterogeneous enhancement with or without perfusion defects and radial or penetrating vessels surrounding the lesions (P< .05). The enhancement order and degree were significantly related to MVD (P< .01) but not correlated with VEGF expression (P> .05). Malignant and benign lesions did not differ significantly in time-intensity parameters (P> .05). The peak intensity, rise in intensity, maximum rise slope of the curve, wash-out slope of the curve, and area under the time-intensity curve (area) were statistically correlated with MVD (P< .05). The highest correlation (r=0.56; P< .001), however, was between the area and MVD. No significant association was found between any CEUS parameters and VEGF expression (P> .05). CONCLUSIONS: Contrast-enhanced ultrasonographic patterns and parameters of breast lesions are more closely correlated with MVD than VEGF expression. Real-time gray scale CEUS has a potential role in evaluating angiogenesis in breast lesions, but CEUS parameters are not correlated with the malignancy or benignity of breast tumors.     

Breast tumor size assessment: comparison of conventional ultrasound and contrast-enhanced ultrasound

Accurate assessment of tumor size is necessary when selecting patients for breast-conserving surgery. In the study of breast contrast-enhanced ultrasound (CEUS), we found that tumor size discrepancy between CEUS and conventional ultrasound (US) existed in some breast lesions, for which the reasons are not clear. Breast CEUS examinations were performed in 104 patients with breast lesions. The measurement of the 104 breast tumors on conventional US was obtained and compared with the measurement on CEUS. A difference in measuring tumor size of >3 mm for tumors up to 1.7 cm and 4 mm for tumors ≥1.7 cm, was defined as a significant discrepancy between conventional US and CEUS. The histopathological examination of size discrepancy was performed and the margin characteristics of breast cancers with larger measurements were compared with those with unchanged measurements. Among the 104 lesions (43 malignant, 60 benign, 1 borderline), the size of 27 breast cancers and one granulomatous mastitis appeared larger at CEUS. Pathologic examinations of the region corresponding to the measurement discrepancy were mainly ductal carcinomas in situ (DCIS), invasive carcinoma with a DCIS component, adenosis with lobular hyperplasia in breast cancers and inflammatory cell infiltration in one granulomatous mastitis. Well-defined margin characteristics were significantly different between breast cancers with larger measurements at CEUS and those with unchanged measurements of size (p = 0.002), whereas no significant difference was found between the two groups in ill-defined, spiculated, hyperechoic halo, microlobulated and angulated margins (p = 0.463, 0.117, 0.194, 0.666 and 0.780, respectively). This initial study suggests that significant discrepancy of breast lesion measurement between conventional US and CEUS is more likely presented in breast cancer than benign lesions. The pathologic findings corresponding to the region of size increased at CEUS are malignant in most malignant lesions and benign in benign lesions. It is difficult to predict whether the size measurement of the breast cancer increases at CEUS based on the margin characteristics showed on conventional US. (E-mail: yuxinjiangxh@yahoo.com.cn)     

超声新技术提升乳腺影像报告和数据系统分类特异度应用进展

乳腺影像报告和数据系统（BI-RADS）建议对4a类及以上的肿物予病理学检查,但活检恶性率偏低,提升BI-RADS的特异度是亟待解决的问题。作为我国最常见的乳腺影像学检查方法之一,超声诊断结果对临床决策至关重要。本文对近年来超微血管成像、全自动乳腺容积扫描、弹性成像、超声造影和人工智能技术辅助超声BI-RADS精准分类的研究进展进行综述。     

Contrast‐Enhanced Breast Ultrasonography

Objective. The purpose of this study was to identify histopathologic correlates for the varied appearances of breast masses on contrast‐enhanced ultrasonography (CEUS). Methods. Contrast‐enhanced ultrasonography was performed in 104 patients (age range, 19–86 years) after administration of a sulfur hexafluoride microbubble contrast agent, and enhancement patterns were classified as no enhancement, peripheral enhancement, homogeneous enhancement, regional enhancement, and heterogeneous enhancement. All patients' histologic slides were reviewed and correlated with CEUS findings. Results. In malignant masses, heterogeneous enhancement corresponded to tumor cell cords or clusters in a variable amount of desmoplastic stroma. Homogeneous enhancement corresponded to hypercellularity in the whole mass, or ductal carcinoma in situ (DCIS) was predominant. Regional enhancement corresponded to a DCIS component. Peripheral enhancement corresponded to a DCIS component, hypercellularity or adenosis at the periphery, and low‐degree cellularity, degeneration, fibrosis, or necrosis in the center. No enhancement was present in 1 case of low‐grade DCIS. In benign masses, heterogeneous enhancement corresponded to loose cell proliferation in a more sclerotic stroma. Homogeneous enhancement corresponded to diffuse hypercellularity, an inflammatory cell infiltrate, or intraductal papilloma. Regional enhancement corresponded to focal hypercellularity or intraductal papilloma within a dilated duct. No enhancement corresponded to desmoplastic stroma. Peripheral enhancement was shown in 1 case of granulomatous mastitis with an inflammatory infiltrate at the periphery and necrosis in the center. Conclusions. Breast mass CEUS findings correlated with histologic features.     

CEUS的定性指标和定量参数在乳腺良恶性结节中的临床诊断价值

目的 探讨乳腺CEUS的定性指标和定量参数在鉴别乳腺良恶性结节中的诊断价值。方法 选取经超声引导下活检或术后病理证实的乳腺结节233例,其中恶性结节95例,良性结节138例。通过超声造影检查,观察乳腺病灶区的定性指标和定量参数,对其进行单因素分析,筛选出有统计学意义的定性指标和定量参数进行二元Logistic回归分析,得出ROC曲线评价其诊断恶性结节的效能。结果 单因素分析结果中显示CEUS的增强强度、增强速度、增强后形态、增强后范围、增强后边界、有无毛刺、有无灌注缺损和Peak%是诊断乳腺恶性结节的重要指标和参数（P<0.05）。Logistic回归分析结果得出,优化后的诊断指标和参数为增强后范围、有无灌注缺损、有无毛刺、增强后边界、增强后形态（P<0.05）。Logistic回归模型预测乳腺恶性结节的准确率为81.5%,ROC曲线下面积为0.894,敏感性和特异性分别为0.811、0.841。结论 乳腺CEUS的增强后范围、有无灌注缺损、有无毛刺、增强后边界、增强后形态建立的Logistic回归模型有助于诊断乳腺癌。     

超声弹性成像联合超声造影在早期乳腺癌诊断中的价值研究

目的探究超声弹性成像联合超声造影在早期乳腺癌中的诊断价值。方法对乳腺病灶切除术患者113例(140个乳腺肿块)分别进行超声弹性成像技术、超声造影、超声弹性成像联合超声造影检查,以病理结果为对照,比较诊断灵敏度、特异度、准确度。结果140个病灶中,恶性90例(病灶98个),良性23例(病灶42个)。超声弹性成像与超声造影诊断早期乳腺癌灵敏度、特异度、准确度分别为73.47%、80.95%、75.71%与77.55%、85.71%、80.00%,差异均无统计学意义(χ^2分别=0.44、0.34、0.74,P均>0.05);超声弹性成像联合超声造影诊断的灵敏度、特异度、准确度分别为91.84%、90.47%、91.43%,灵敏度和准确度均明显高于单纯采用超声弹性成像或超声造影,差异均有统计学意义(χ^2分别=7.71、11.52、7.46、12.59,P均<0.05)。结论超声弹性成像联合超声造影在早期乳腺癌中具有良好诊断效果与鉴别诊断价值。     

Detecting Metastasis of Lymph Nodes and Predicting Aggressiveness in Patients With Breast Carcinomas

Objective. The purpose of this study was to evaluate the contrast‐enhanced ultrasonographic (CEUS) characteristics of metastatic lymph nodes (LNs) and to determine the correlation of CEUS parameters with the tumor aggressiveness in patients with breast cancer. Methods. Real‐time gray scale CEUS of axillary LNs was preoperatively performed in 51 consecutive patients with breast carcinoma who were scheduled for axillary lymph node dissection. The CEUS characteristics assessed by a direct visualization method and quantification software were compared with pathologic findings. Expression of human epidermal growth factor receptor 2 (HER‐2/neu) in the primary tumor was detected by immunohistochemical analysis. Correlation analysis of CEUS parameters with HER‐2/neu expression and the LN stage was performed. Results. Of the LNs examined, 27 were metastatic, and 25 were diagnosed as reactive hyperplasia. Lymph nodes with metastasis were characterized by centripetal progress (66.7%) and a heterogeneous pattern (55.6%) or no or scarce perfusion (25.9%). However, LNs with nonmetastases were characterized by with centrifugal enhancement (56.0%) and a homogeneous pattern (80.0%). The difference between the hyperintense and hypointense regions was higher in metastatic LNs than nonmetastatic ones (P < .001). No significant differences were found in the arrival time, time to peak intensity, and peak intensity between the two groups. A histopathologic diagnosis could be predicted with sensitivity, specificity, and accuracy of 92.6%, 76.0%, and 84.6% respectively, by a standardized difference between maximum and minimum signal intensity (SI_max–SI_min) value of 28. Human epidermal growth factor receptor 2 expression and the LN histopathologic stage were significantly associated with the SI_max–SI_min. In metastatic LNs, the relationship between the diagnostic sensitivity of CEUS and the transverse diameter of LNs remained statistically significant (P < .05). Conclusions. Noninvasive CEUS can play a role in discriminating metastatic from nonmetastatic LNs and predicting the aggressiveness in patients with breast cancer.     

乳腺超声造影预测模型的建立及其对乳腺良恶性病变诊断效能的分析

目的分析乳腺超声造影（CEUS）的增强特征，构建乳腺病变CEUS预测模型，探讨该模型对乳腺良恶性病变的诊断价值。 方法选取2016年6月至2018年8月于丽水市人民医院及浙江大学医学院附属第二医院就诊的乳腺病变患者192例共195个病灶，所有病灶均为常规超声检查BI-RADS分类4类及以上，均经穿刺活检或手术取得病理结果。将病例分为CEUS组120例共123个病灶，均经CEUS检查；CEUS＋动态增强磁共振（DCE-MRI）组72例共72个病灶，均接受CEUS及DCE-MRI检查。对CEUS组120例患者的CEUS模式特征进行单因素及多因素Logistic回归分析，筛选预测乳腺恶性病变的CEUS危险因素，并建立预测模型，绘制ROC曲线。以CEUS＋DCE-MRI组72例患者的病理结果为"金标准"，分别计算CEUS预测模型与DCE-MRI对乳腺良恶性病变的诊断效能。 结果Logistic回归分析结果显示诊断乳腺恶性病灶的CEUS特征性表现为增强后病灶范围增大（OR=12.941，P=0.003），"蟹足"征或血管扭曲缠绕（OR=7.553，P=0.009），灌注缺损（OR=5.670，P=0.024）。建立的风险预测模型即Logistic回归方程为：Y=-4.108＋2.560X₆＋2.022X₇＋1.735X₈。该模型预测乳腺良恶性病灶的ROC曲线下面积为0.953。以穿刺或术后病理结果为"金标准"，CEUS风险预测模型诊断乳腺良恶性病变的敏感度、特异度、阳性预测值、阴性预测值以及准确性分别为93.0%、73.3%、93.0%、73.3%、88.9%；DCE-MRI诊断乳腺良恶性病变的敏感度、特异度、阳性预测值、阴性预测值以及准确性分别为94.7%、73.3%、93.1%、78.6%、90.3%。CEUS风险预测模型与DCE-MRI诊断乳腺良恶性病变的一致性较高（Kappa值=0.70）。 结论乳腺CEUS预测模型对鉴别良恶性病灶具有较高的诊断效能，且操作相对简单、检查时间短、可重复性好、价格相对低廉，不失为诊断乳腺良恶性病变的一种有效和可靠方法。     

乳腺病变超声造影微血管显像增强形式:与病理对照观察

目的 探讨乳腺病变超声造影微血管显像的病理组织学基础.方法 对104例患者行超声造影微血管显像,观察乳腺病变的微血管显像增强形式,并与病理结果 对照.结果 超声造影微血管显像增强区主要是原位癌、浸润癌生长旺盛区、导管内乳头状瘤、腺病的小叶增生明显区、纤维腺瘤的生长活跃区、富含血管的间质;未增强区或增强不明显区主要是纤维组织、黏液变、导管扩张.结论 乳腺超声造影微血管显像可以反映病变的病理组织学特征.     

常规超声与超声造影在乳腺病变诊断中的对比

目的 比较常规超声(US)、CEUS单独及联合应用诊断乳腺病变的价值。 方法 对79例单发乳腺病变患者分别进行US和CEUS检查,分析病灶的US及CEUS增强特征,并与病理结果对照。采用评分法绘制ROC曲线,通过计算曲线下面积比较两种方法单独及联合应用的诊断效能。 结果 US、CEUS单独及联合应用ROC曲线下面积分别为0.878、0.884、0.953,Z检验结果显示联合应用的诊断价值优于单独使用US和CEUS检查(P<0.05)。 结论 US和CEUS检查均为有效的诊断方法,两者联合应用可提高对乳腺病变的诊断效能。     

超声造影在常规超声BI-RADS 4类病变中的应用——与DCE-MRI的对比研究

目的探讨超声造影(CEUS)在常规超声BI-RADS 4类乳腺病变中的临床应用价值,并与动态增强磁共振(DCE-MRI)对比研究。方法选取86个常规超声发现的BI-RADS 4类乳腺病灶,均进行超声造影及磁共振增强检查,采用BI-RADS分类法进行重新分类,以病理结果为金标准,比较两种影像学检查方法的诊断效能。结果乳腺恶性病变65个,良性病变21个,CEUS和DCE-MRI两种诊断方法的敏感度、特异度、阳性预测值、阴性预测值分别为89.23%、80.95%、93.55%、70.83%;92.31%、85.71%、95.24%、78.26%,二者差异无统计学意义(P0.05)。常规超声BI-RADS 4类病变降至3类:CEUS 17个,DCE-MRI 18个;BI-RADS 4类升至5类病变:CEUS 11个,DCE-MRI 13个。结论在常规超声的基础上,超声造影对于常规超声BI-RADS 4类乳腺病变,能够进一步提供更多的诊断信息,与增强磁共振具有较好的一致性,具有较好的临床应用价值。     

Contrast-Enhanced Ultrasound-Guided Fine-Needle Aspiration for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer

The purpose of this study was to assess whether translymphatic contrast-enhanced ultrasound (CEUS) combined with fine-needle aspiration (FNA) can be used pre-operatively to assess the status of axillary lymph nodes in early-stage breast cancer patients. Furthermore, we wanted to determine whether this less invasive method could potentially be a pre-operative surgical strategy. One hundred sixty-four sentinel lymph nodes (SLNs) were detected by CEUS after intradermal injection of microbubbles in 126 cases. One hundred twenty of 126 cases (95.24%) were accurately diagnosed with the SLN-FNA method. All 6 false-negative cases were due to micrometastasis or macrometastasis. There were no false-positive results after CEUS-guided FNA biopsy based on post-operative histopathological results. In conclusion, translymphatic CEUS combined with SLN-FNA is a less traumatic approach that has high accuracy in the pre-operative evaluation of axillary lymph node status. It might have the potential to be as reliable an indicator for axillary lymph node dissection as SLN biopsy.     

Dynamic Visualization of Lymphatic Channels and Sentinel Lymph Nodes Using Intradermal Microbubbles and Contrast‐Enhanced Ultrasound in a Swine Model and Patients With Breast Cancer

Objective. Sentinel lymph node (SLN) identification using intradermal micro‐bubbles and contrast‐enhanced ultrasound (CEUS) has been recently reported in swine models and patients with breast cancer. The objective of this study was to investigate the dynamics of intradermally administered microbubbles as they travel to draining SLNs in pigs. We also performed a detailed study of the passage of microbubbles through breast lymphatic channels in a small group of patients with breast cancer. Methods. Nine anesthetized healthy pigs were used for the study, and 5 female patients with primary breast cancer were recruited. Pigs received intradermal injections of a microbubble contrast agent in several territories to access lymphatic drainage to regional lymph nodes. Patients had periareolar intradermal injection of the microbubble contrast agent. Ultrasound examination was performed in the real‐time contrast pulse sequencing mode with a commercial scanner. Results. Sentinel lymph nodes were identified rapidly (<1 minute) and consistently in pigs. Intradermal microbubble injection and CEUS were found to have perfect concordance with the Evans blue dye method in locating swine SLNs. In all 5 patients with breast cancer, the microbubble contrast agent entered breast lymphatic channels and traveled to draining ipsilateral axillary SLNs within 3 minutes. Conclusions. Intradermally injected microbubbles traverse readily though lymphatic channels in pigs and human breast tissue. The ability to rapidly identify SLNs in the diagnostic period would enable targeted biopsy and may facilitate preoperative axillary staging in patients with early breast cancer.