| Background: Imaging examination is important in the diagnosis of breast solid tumor and differential diagnosis of malignant and benign tumor. In recent years, With the development of science and technology, the development of digital and network information technology promotes the great changes in imaging technology and its diagnosis. A large number of data show that the X-ray and ultrasound is the preferred screening for breast cancer. Ultrasonography of breast is convenient, fast, affordable, good image quality, and can obtain the information of real-time dynamic of lesions, the diagnostic value of which in breast tumors is getting more and more clinical recognition and popularity in China, especially for the dense mammary gland and earlier age of onset of breast cancer in China, the sensitivity of ultrasound diagnosis is superior to that X-ray mammography. At present, the conventional high frequency ultrasound and Doppler ultrasound has been used as a routine clinical examination of breast tumor. But some of the benign and malignant breast have overlapping features in the conventional two-dimensional ultrasonograph. Color Doppler ultrasound is difficult to show the microvessel with low velocity and flow in solid tumor of the breast, so the differential diagnosis ability of the conventional ultrasound of benign and malignant tumor is difficult to have a big breakthrough.Contrast enhanced ultrasound(CEUS) is a leap in the diagnosis of technology following a diagnosis of conventional ultrasound, its advantage as a blood pool imaging technology can display the real time dynamic microcirculation in organ or tumor, to identify benign and malignant according to the difference of time sequence of microvascular blood flow or the spatial distribution of microvessel within the tumor. Research shows that, tumor neovascularization is essential for tumor growth and metastasis, CEUS shows obvious advantages in displaying tumor neovascularization, to make up for the lack of color Doppler ultrasound which is difficult to display the tiny blood vessels and low blood flow. This technology has been relatively used in the diagnosis and differential diagnosis of liver tumor, its diagnosis value in clinical practices can be comparable with diagnosis value of CT and MRI. But so far the contrast image analysis method of breast tumor has not reached a unified, more research is the contrast enhancement patterns and time-intensity curve(TIC), the parameter of contrast enhancement patterns is observed by visual inspection of doctor, including the degree of enhancement, the direction of enhancement, enhanced homogeneity of lesion areas(whether or not there was a enhanced defect), enhanced type of lesion edge(whether or not there was a radiation enhancement), whether or not the lesion diameter expanded when the contrast agent reached the peak, et al. But according to the contrast enhancement pattern to analyze the image has subjective dependence on operator; TIC analysis is the determination of the signal intensity changes of contrast induced by the special analyzing software, with strength for the longitudinal coordinates, the time as the abscissa, to trace TIC curves in a certain period of time, then get the fitting TIC curve by fitting formula, and extract the parameters from the TIC, in order to achieve the quantitative analysis. but because of the difference between the different analysis software, the difference choice of operation method and the different systemic circulation in different patients, the reproducibility and objective of TIC curves and parameters is affected. So the current diagnostic criteria for CEUS of breast is not uniform, This study therefore was set, to contrast enhancement patterns and TIC analysis, combined with clinical, to select analysis method of the appropriate contrast image, which is more conducive to the identification of benign and malignant tumors in daily work.In 2014, America Radiological Society revised and published the fifth version of Breast Imaging Reporting and data system(BI-RADS), in which the ultrasonic terms of breast lesions has been standardized, for example: the description of mass shape, edge, calcification, aspect ratio, structure distortion and concomitant features, and the system formulated the classification standard(0 ~6) of benign and malignant breast lesions, to content the convenience communication between ultrasonic doctors and other image professional doctors and clinicians, and to help to record the census results and follow-up monitoring. However, because of some benign and malignant lesions are similar in two dimensional ultrasonography, especially BIRADS-US 3 and 4, There is some overlap characteristics of benign and malignant lesions, resulting in difficult classification. CEUS has advantages of displaying the tumor micro vessel shape and distribution. On the basis of conventional ultrasound imaging model, to compare the features of the contrast enhancement patterns of breast lesions, help to improve the accuracy of ultrasonic BI-RADS classification assessment of breast tumor malignant risk stratification.The development of breast cancer is controled and influenced by many kinds of cancer genes. Study on the expression of genes in breast cancer is helpful for judgment of prognosis of breast cancer patients after the operation. The C-erb B-2 gene is also called Nell or HER-2(Human epidermal growth factor receptor-2, HER-2) is considered to be closely related to the occurrence and development of breast cancer, Nm23 gene(Nm23 gene Nm23) originate from a special area of cancer gene of the p53 tumor suppressor, nm23 gene expression in breast cancer negatively correlated with metastasis the lymph node node. Contrast enhanced ultrasound can show microvascular changes in the lesion of the breast tumors. To study on the correlation between the expression of breast cancer gene and contrast enhancement characteristics of breast tumor, can help to improve the understanding of the image of contrast-enhanced ultrasound of breast cancer, and is expected to provide imaging basis for assessment of prognosis of breast cancer.The status of axillary lymph node is the most important factor in judging the prognosis of patients with breast cancer and in determining their adjuvant therapy. The traditional way is to use the axillary lymph node dissection(ALND) to evaluate the status of axillary lymph node metastasis. With the popularization of breast screening imaging and the development of imaging techniques, more early breast cancer(stage T0~T2N0M0) were detected. It has been reported that only about 30% to 40% early breast cancer patients have the ipsilateral axillary lymph node metastasis, which suggest that more than 60% early breast cancer patients who have not the axillary lymph node metastasis were treated with ALND. Sentinel lymph node(SLN) is the first station of tumor lymphatic drainage. Application of sentinel lymph node biopsy(SLNB) to determine whether or not there is axillary lymph node metastasis, has been adopted widely as a less invasive way. SLN positioning Before the biopsy is very important, so the development of highly sensitive, specific, economical and practical SLNB tracer is a hotspot of research. At present, Clinical routine tracer for SLN is radionuclide and tracer dye, or a combination of both, and the fluorescent dye, the positioning method is more accurate, but there are shortcomings.Objective:1. To compare the contrast predictive power of benign and malignant breast tumor of enhanced pattern with that of the quantitative Parameter of TIC curve, and to To investigate applicable evaluation method of contrast enhanced ultrasound image in clinical work, which is helpful to promote the clinical application of breast ultrasound, and provide more diagnostic information for improving the diagnosis and differential diagnosis of benign and malignant breast tumors.2. To retrospectively analyse and compare the diagnostic value of standard classification of conventional ultrasound BI-RADS with that of BI-RADS combined with contrast enhanced ultrasound image features. By increasing contrast enhanced ultrasound index, wheather or not, it is more useful to improve the classification accuracy of BI-RADS ultrasound to assess breast tumor malignant risk stratification.3. To explore the relationship between the parameters of contrast-enhanced ultrasound image and the molecular biology markers(C-erb B-2 and nm23) in breast cancer, in order to provide more imaging basis for clinical treatment and prognosis assessment.4. through the application of subcutaneous injection of ultrasound contrast agent to locate the sentinel lymph node in early breast cancer and determine the benign or malignant of the sentinel lymph node, and to sum up the characteristics of enhancement of the sentinel lymph node, to discuss the feasibility of percutaneous contrast-enhanced ultrasonography in detection of sentinel lymph node, and provide the basis for clinical therapy.Research methods:1. Clinical data: From 2011 September to 2014 May, 151 female patients with breast tumor lumps who were treated in Xingqiao Hospital and Affiliated Hospital of Chuanbei Medical College, were selected, all the patients were female, aged 19 to 68 years old, with the mean age as 44.7±8.2 years old. All patients were treated by the surgery or underwent ultrasound guided percutaneous biopsy to obtain the pathological results, and before the operation, all the patients underwent conventional ultrasound and contrast-enhanced ultrasound after signed informed consent obtain. Among the 151 cases, 142 cases were treated by operation, postoperative pathological results showed 103 malignant lesions(83 of invasive ductal carcinoma, 2 invasive lobular carcinoma, 3 mixed type carcinoma, 11 ductal carcinoma in situ, 1 tubular carcinoma, 2 mucous carcinoma, 1 cribriform carcinoma), these lesions are solitary; 39 cases were confirmed as benign lesions after operation, 9 patients for benign lesions confirmed with biopsy, which did not accept operation treatment, so a total of 48 cases were benign lesions(14 fibroadenoma, 16 adenosis, 8 adenosis tumor, 4 inflammatory lesions, 1 benign phyllodes tumor, 3 intraductal papilloma 1 plasma cell mastitis), in which there were 16 cases with two or more lesions or multiple bilateral lesions, select the largest one as the research object, so there were a total of 151 lesions.2. Instruments and contrast agent: The ultrasonic instrument were i U22 ultrasonic diagnostic apparatus(Philips) and Twice ultrasonic diagnostic apparatus(Mylab). The ultrasound contrast agent was Sonovue(Bracco Milan, Italy).3. Methods: Selected cases were examined by high frequency ultrasound, then the conventional ultrasonic characteristics were analysed and the image were classified according to BI-RADS; Selected cases were accepted CEUS examination through elbow vein injection of Sono Vue. The ipsilateral axillary lymph nodes of the breast cancer lesion which were confirmed by puncture biopsy, treated by percutaneous lymph node CEUS, and imaging process were recorded. The enhancement patterns of contrasting lesion are were analyzed and recorded, including the degree of enhancement, the direction of enhancement, enhanced homogeneity of lesion areas, whether or not the lesion diameter expanded when the contrast agent reached the peak, whether or not there was a enhanced defect and the enhanced type of lesion edge(whether or not there was a radiation enhancement), and then by combined with the characteristics of the lesion enhancement pattern, the breast tumors were BI-RADS classified and recorded. The time-intensity curve(TIC) towards the interested region of 122 lesions were obtained after contrast enhanced ultrasound, and the perfusion parameters towards different regions could also be obtained through the curve, including the peak intensity, area under the curve, peak time, increasing slope, decreasing slope, increasing-start time, relative peak intensity, relative area under the curve, relative peak time, relative increasing slope, relative decreasing slope and relative increasing-start time, these total 12 indicators were used as the quantitative diagnosis basis of lesions.By comparing the enhancement pattern indexes and TIC curve parameters between malignant of benign breast lesions and that of malignant lesions, to extract parameters which had significant difference between the benign and malignant lesions, with pathological results as the gold standard, to perform the Logic analysis of the multi factor.With pathological results as the gold standard, the BI-RADS classification of conventional ultrasound were compared which that of BI-RADS classification combined with contrast enhanced ultrasound.The total of 69 breast cancer lesions were collected, their postoperative pathological section were collected and immunohistochemical staining was performed, and the expression of nm23 and C-erb B-2 were observed and recorded, to make statistical analysis between the CEUS enhanced pattern indexes and TIC curve parameters and C-erb B-2 and Nm23.In 41 lesions, which were postoperative staging of early breast cancer, the sentinel lymph node showed by percutaneous CEUS was recorded, and compared with the results of Pathology. To analysize the accuracy of percutaneous CEUS localization of sentinel lymph node and enhancement features of sentinel lymph node.Research Results:1. the enhancement pattern of the malignant nodules showed high enhancement(92.1%, 70/76), inhomogeneous enhancement with filling defect of contrast agent(59.2%, 45/76), expanded diameters(72.4%, 55/76)and the edges exhibiting the feature of radial enhancemen(65.8%, 50/76), which were compared with benign nodules, the difference was statistically significant(P<0.05). Logistic regression analysis showed diagnostic significance of the degree of enhancement, enhanced homogeneity of lesion areas, whether or not the lesion diameter expanded when the contrast agent reached the peak, their prediction accuracy of benign and malignant tumors was 90.9%. In the quantitative parameters of TIC, the malignant nodules showed high peak intensity, relatively early start time, relatively high peak intensity and relatively large area under the curve which were compared with benign nodules, the difference was statistically significant(P<0.05). Logistic regression analysis showed that only the relative peak intensity has significant meaning in the diagnosis of benign and malignant tumors, but the prediction accuracy was only 62.6%. The ROC generated by contrast enhancement pattern analysis and TIC analysis were 0.909 and 0.749 Respectively, the difference was statistically significant(P<0.05).2. After combined with contrast enhanced ultrasound characteristics, the changes of BI-RADS classification mainly occurred in the class 3 and class 4. Conventional ultrasound BI-RADS and BI-RADS classification combined with CEUS in judgment of malignant and benign breast lesions are not consistent, Kappa=0.679, p=0.069>0.05. With pathological results as the gold standard, by combined with contrast enhanced ultrasound the BI-RADS’s diagnostic specificity(70.8%), accuracy(86.1%), positive predictive values(87.3),and negative predictive value(82.9%) were significantly improved, while specificity, accuracy, positive predictive value and negative predictive value of conventional BI-RADS classification diagnostic were 52.1%, 72.8%, 80.5%, 75.7%, but the sensitivity did not change significantly.3. ①The positive expression rate of C-erb B-2 and nm23 in breast cancer were 66.7%(46/69) and 27.5%(19/69), respectively.The positive expression of nm23 in the group with C-erb B-2 positive expression was 13%, which was higher than that in he group with C-erb B-2 negative expression. ②In the group with C-erb B-2 positive expression, lesions showed high enhancement, heterogeneous enhancement or lesions with the perfusion defect area, peripheral radial enhancment, relative rise slope and relative peak intensity in the time intensity curves, compared with the group with C-erb B-2 negative expression, the difference was statistically significant(P<0.05). ③In nm23 negative group, the lesion showed high enhancement, peripheral radial enhancment, and the time intensity curve showing the relative rising high slope, compared with the nm23 positive group, the difference was statistically significant(P<0.05).4. The accuracy of the percutaneous CEUS to show SLN was 78.6%(44/56), sentinel lymph node metastasis was showed inhomogeneous enhancement, peripheral enhancement, enhanced defect. The accuracy of percutaneous CEUS judging whether or not there were SLN metastasis was 84.1%, sensitivity 78.9%, specificity 88%, positive predictive value was 83.3%, negative predictive value was 84.6%.Conclusion: 1. In enhancement pattern of contrast enhanced ultrasound: high enhancement, inhomogeneous enhancement with filling defect of contrast agent, expanded diameters and the edges exhibiting the feature of radial enhancemen is helpful for diagnosis of breast malignant lesions, among which inhomogeneous enhancement with filling defect of contrast agent, expanded diameters shows greater diagnostic value. In the parameters of TIC curve, high peak intensity, relatively early start time, relatively high peak intensity and relatively large area under the curve can help in diagnosis of breast malignant lesions, among which the relative high peak intensity show the diagnostic value of the maximum.2. In contrast enhanced ultrasound of breast tumor diagnosis, enhancement pattern is more intuitive, more accessible, more conducive to the diagnosis of benign and malignant breast lesions than that of TIC curve analysis, as well as the application of clinical.3. On the basis of conventional ultrasound BI-RADS classification, combined with contrast enhanced ultrasound image features can improve the accuracy of ultrasonic BI-RADS classification assessment of breast tumor malignant risk stratification.4. Contrast-enhanced ultrasound perfusion pattern as well as the expression of certain parameters are closely linked with the expression of C-erb B-2 and nm23, there are certain clinical effect for the features of contrast-enhanced ultrasound in predicting breast cancer prognosis and outcome.5. The detection of percutaneous CEUS testing sentinel lymph node in early breast cancer has a certain clinical value, the metastatic lymph nodes showed inhomogeneous enhancement, or ring enhancement with central enhancement defect. |
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