【作者】 刘勇；

【导师】 汤光宇；

【作者基本信息】 同济大学 ， 影像医学与核医学， 2005， 硕士

【摘要】 第一部分乳腺癌诊断：结合乳腺影像报告数据系统和MR动态增强参数评价目的：结合美国放射学会的乳腺影像报告数据系统（breast imaging reporting and dada system，BI-RADS）和多种动态增强参数，评价动态增强MR对乳腺癌的诊断准确率，并分析乳腺良、恶性占位的特点。材料与方法：67例临床扪诊或钼靶检查有或疑似有乳腺肿块的乳腺疾病患者术前行动态增强MRI检查（dynamic contrast-enhanced MRI，DCE-MRI）。参照BI-RADS评分标准进行分析、评分，并根据时间—信号强度曲线（time-signal intensity curve，TIC）测量动态增强参数：最大增强线性斜率(steepest slope，S_max)、最大增强率(maximum enhancement，E_max)、增强峰值（peak height，PH）、峰值时间(time-to-peak，T_peak)、增强后第1、2、3、4、5、6分钟时增强率（E₁、E₂、E₃、E₄、E₅、E₆）等。所有病人在MRI检查后10天内手术。仅对手术证实乳腺有肿块的病例进行分析。比较良、恶性乳腺肿块的BI-RADS系统各评分指标和动态增强参数间的差异。结果：经手术病理证实，有肿块的乳腺癌34例和良性乳腺占位19例归入研究对象。良、恶性肿瘤的形状和边缘无明显统计学差异（P=0.0571，P=0.1322）。而良、恶性乳腺肿瘤间DCE—MRI的强化模式、强化曲线、早期强化率有明显统计学意义（x²=15.566，P=0.001；x²=26.198，P=0.001；x²=6.176，P=0.0456）。其中廓清型TIC、边缘环形强化及延迟期不均匀强化高度提示恶性。渐进型TIC和强化均匀提示良性。BI—RADS评分法示：34例乳腺癌分别为Ⅴ级21例，Ⅳ级10例，Ⅲ级3例。19例良性占位分别为Ⅰ级6例、Ⅱ级5例、Ⅲ级6例，Ⅴ级2例。但良、恶性乳腺肿块强化曲线均呈平台型的分别为31.6％和38.2％，无统计学差异，重叠明显。良、恶性乳腺肿块的动态增强参数S_max、E_max、E₁、E₂、T_peak有明显的统计学差异（P=0.0330，P=0.03731，P=0.04186，P=0.04916，P=0.04225）。结合BI—RADS评分标准和动态增强参数，DCE-MRI诊断乳腺癌的准确率明显提高，诊断敏感性和特异性分别为97.1％、89.4％。结论：1、建立在多因素分析系统上的BI—RADS评分法规范了乳腺癌的MR诊断，是一个合适而全面的动态评估标准，随着BI-RADS分级的增加，恶性的可能性亦增大。但良、恶性乳腺占位的形态学改变和TIC类型有重叠。2、良、恶性乳腺占位的DCE—MRI多项动态增强参数有差异，结合BI—RADS评分标准和动态增强参数，可明显提高乳腺癌诊断的敏感性及特异性。第二部分乳腺癌MRI动态增强参数与血管生成的相关性研究目的1、比较乳腺癌、乳腺纤维瘤、乳腺腺病及正常乳腺组织在微血管密度计数（microvessel density，MVD）和血管内皮生长因子（vascular endothelial growth factor，VEGF）表达中的差异，研究乳腺癌微血管分布特点。2、探讨乳腺癌MRI动态增强参数与肿瘤血管生成的关系。材料与方法29例乳腺癌患者行前瞻性DCE—MRI检查，计算动态增强参数：最大增强线性斜率(steepest slope，S_max)、最大增强率(maximum enhancement，E_max)、增强峰值（peak height，PH）、峰值时间(time-to-peak，T_peak)、增强后第1、2、3、4、5、6分钟的信号强度改变率（E₁、E₂、E₃、E₄、E₅、E₆），所有病例的手术病理标本行免疫组化染色，测定MVD计数和评估VEGF表达，分析各参数与乳腺癌的MVD和VEGF表达的相关性。并比较乳腺癌与12例乳腺纤维腺瘤、10例乳腺病、10例癌旁正常组织的MVD计数和VEGF表达情况。结果29例乳腺癌MVD均数为65.09±15.81条／200×，明显高于纤维腺瘤组、乳腺腺病组及正常组（P=0.0426，0.0177，0.0023），差异有显著意义。69％（20／29）乳腺癌VEGF表达阳性，也明显高于其余各组（P=0.0351，0.0071，0.0013）。肿瘤边缘区域的MVD高于中央区域（t=2.6347，P=0.0157）。腋窝淋巴结转移组的MVD高于无转移组（t=2.3029，P=0.0310）。DCE-MRI各参数S_max、E_max、PH、E₁、E₂、E₃、E₄、E₅、E₆与乳腺癌MVD呈正相关，其中以S_max（r=0.807，P＜0.001）和E₁（r=0.746，P＜0.01）与MVD相关性最强。T_peak与MVD呈负相关关系（r=-0.425，P＜0.05）。结论1、乳腺癌的MVD计数和VEGF表达明显高于乳腺良性病变及正常组织。乳腺癌血管生成是其DCE-MRI强化模式的的病理生理学基础。2、乳腺癌DCE-MRI的参数S_max、E₁、E_max、E₂等与肿瘤的MVD计数及VEGF表达相关。MR动态增强扫描作为一种无创性技术，可较好地反映肿瘤血管生成的程度，有助于评估乳腺癌的生物学行为及其预后。更多还原

【Abstract】 part IBreast cancer diagnosis: evaluation by combining breast imaging reporting and dada system and dynamic contrast enhanced MRI derived parameters ObjectiveTo evaluate diagnosis accuracy in dynamic contrast enhanced MRI （DCE-MRl）of the breast cancer by combined breast imaging reporting and dada system （BI-RADS ） of American College of Radiology and enhancement parameters. The MR characteristics of benign and malignant breast masses were discussed.MethodsSixty-seven patients with suspicious mammographic or palpable mass findings underwent preoperative DCE-MR imaging of the breast. Each lesion was prospectively analyzed by two independent radiologists for morphologic and dynamic enhancement characteristics in terms of BI-RADS. DCE-MRI parameters such as steepest slope （Smax）, peak height （PH）, time of peak signal change（Tmax）, maximum enhancement（Emax） and the change in signal intensity in percent at 1（E₁）,2（E₂）, 3（E₃）,4（E₄）,5（E₅）and 6（E₆） minutes were calculated based on time-signal intensity curves（TIC）. All patients were operated in 10 days after MR examination. Only those with breast mass identified in operation were included in the study. Both indexes from BI-RADS and parameters derived from DCE-MRI were compared between benign and malignant breast masses.ResultsThirty-four cases of breast cancer and nineteen cases of benign breast lesion with breast mass were included in the study. There was no statistical significant difference between malignancy and benign in the edge or shape of mass （P＝0.0571, P=0.1322）. The difference in the enhancement pattern, TIC and initial enhancement between the benign and the malignant group was statistically significant （x²=15.566, P=0.001; x²=26.198, P=0.001: x²=6.176, P=0.0456）. Of them, wash-out curve and peripheral enhancement and late inhomogeneous contrast enhancement were suggestive of malignant. Flow-in TIC and late homogeneous contrast enhancement were suggestive of benign. According to BI—RADS criteria, 34 cases of breast cancer were categorized as grade V（n=21）, gradeⅣ（n=10）,gradeⅢ（n=3） and 19 cases of benign breast lesion were categorized as gradeⅠ（n=6）, gradeⅡ（n=5）, gradeⅢ（n=6）, gradeⅣ（n=2）, respectively. Plateau type of TIC was gotten in 31.6%（6/19） benign and 38.2%（13/34） malignant breast masses, which showed no statistically significantly difference.The difference in the DCE-MRI parameters such as S_max、E_max、E₁、E₂、T_peak, between the benign and the malignant group was statistically significant（P＜0.05）, respectively. The DCE-MRI diagnostic accuracy was much improved by combined BI-RADS and dynamic parameters with a sensitivity of 97.1%（33/34） and a specificity of 89.4%（17/19）.Conclusion1、BI—RADS diagnostic criteria based on a multifactorial analysis is a suitable and comprehensive diagnostic method in the interpretation of DCE-MRI of breast cancer. The possibility of malignancy becomes more indicative with the grade increase derived from BI—RADS. However, there is an overlap to some extent in the morphology and TIC type between benign and malignancy.2、The difference in some enhancement parameters of DCE-MRI was statistically significant between benign and malignant breast mass. Combining BI-RADS of American College of Radiology and enhancement parameters derived from TIC is very helpful to improve the diagnostic accuracy of breast cancer.PartⅡCorrelative study of enhancement parameter of dynamic contrast-enhanced MR/and angiogenesis in breast cancerObjective1、To evaluate the tumor angiogenesis in breast cancer by comparing the difference of microvessel density （MVD） and vascular endothelial growth factor （VEGF） among the patients with breast cancer, with breast fibroadenomas, with breast mastopathy and the normal tissue beside the cancer.2、To explore the relationship between dynamic contrast-enhanced MRI （DCE-MRI）-derived parameters and tumor angiogenesis in breast cancer and the clinical value of DCE-MRI in monitoring the breast cancer’s angiogenesis.MethodsTwenty-nine patients with breast cancer underwent DCE-MRI using Philips Intera 1.5 T MR system and dedicated breast coil prospectively before operation. DCE-MRI derived parameters such as steepest slope (S_max), maximum enhancement (E_max), peak height（PH）, and the enhancement rates of signal intensity at first（E₁）, second （E₂）, third（E₃）, forth（E₄）, fifth（E₅）and sixth（E₆） minutes of time-signal intensity curve were calculated. MVD were counted and VEGF expression were assessed in these patients with immunohistochemical staining method. The parameters were correlated statistically with MVD counts and VEGF expression in breast cancer. The MVD counts and VEGF expression were also compared among the patients with breast cancer, with fibroadenoma, mastopathy and the normal tissue beside the cancer.Results The mean value of MVD（65.09±15.81/200×） in patients with breast cancer were significantly higher than those with fibroadenoma, mastopathy and the normal tissue beside the cancer （P=0.0426, 0.0177, 0.0023）.Twenty cases of breast cancer demonstrated positive VEGF expression, which were significantly more than the cases of fibroadenoma, mastopathy and the normal tissue besidethe cancer （P=0.0351, 0.0071, 0.0013） . Moreover, the MVD counts at cancer peripheral region were more than those at central region （t=2.6347, P=0.0157）. There was a significant difference between MVD counts of breast cancers with metastasis（73.23±23.02） to axillary lymph nodes and MVD counts of those without metastasis（59.34±18.03, t=2.3029, P=0.0310）.The enhancement parameters Smax、Emax、PH、E₁、E₂、E₃、E₄、E₅、E₆correlated positively with MVD respectively. Of them, the highest correlation was found between S_max and MVD （r= 0.807, P＜0. 001）. Tpeak correlated negatively with MVD counts（r=-0.425, P＜0.05）.Conclusion1. The MVD counts and VEGF expression in patients with breast cancer were significantly higher than those with benign breast lesions. Tumor angiogenesis in breast cancer reflects its pathophysiological basis of the enhancement patterns on dynamic contrast-enhanced MR imaging.2. The DCE-MRI derived parameters such as S_max、E_max、PH、E₁、E₂、E₃、E₄、E₅、E₆ correlated positively with MVD counts and VEGF expression in patients with breast cancer. DCE-MR imaging as a non-invasive method can accurately monitor tumor angiogenesis, which is helpful to evaluate the biological behavior and the prognosis of breast cancer.更多还原