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• 临床研究 •
表观扩散系数术前区分Luminal型与非Luminal型乳腺癌及其与Ki-67增殖指数的相关性研究
刘宏 刘显旺 刘光耀 周洁 周俊林

Cite this article as: LIU H, LIU X W, LIU G Y, et al. The value of apparent diffusion coefficient value in differentiating the Luminal-type and non-Luminal-type breast cancer and evaluating tumor cell proliferation activity[J]. Chin J Magn Reson Imaging, 2023, 14(4): 51-56.本文引用格式：刘宏, 刘显旺, 刘光耀, 等. 表观扩散系数术前区分Luminal型与非Luminal型乳腺癌及其与Ki-67增殖指数的相关性研究[J]. 磁共振成像, 2023, 14(4): 51-56. DOI:10.12015/issn.1674-8034.2023.04.010.


[摘要] 目的 探讨表观扩散系数（apparent diffusion coefficient, ADC）术前区分Luminal型与非Luminal型乳腺癌的效能及其与Ki-67增殖指数之间的相关性。材料与方法 回顾性分析经病理证实为Luminal型乳腺癌88例和非Luminal型乳腺癌30例，并检测其Ki-67增殖指数。在ADC图上测量病灶实质的最小ADC值（the minimum ADC, ADCmin）、平均ADC值（the mean ADC, ADCmean）和相应对侧正常乳腺腺体组织的ADC值，计算相对ADCmin（relative ADCmin, rADCmin）和相对ADCmean（relative ADCmean, rADCmean）。比较Luminal型与非Luminal型乳腺癌组间ADC值差异，绘制受试者工作特征（receiver operating characteristic, ROC）曲线，分析ADC值对Luminal型与非Luminal型乳腺癌的鉴别效能及其与Ki-67增殖指数间的相关性。结果 Luminal型乳腺癌组的ADCmin、ADCmean、rADCmin和rADCmean值均低于非Luminal型乳腺癌组，组间差异具有统计学意义（P均＜0.05）。ROC结果显示各ADC值均能对Luminal型与非Luminal型乳腺癌进行有效区分，其中，rADCmin鉴别效能最佳，最佳截止值为0.599，相应的曲线下面积（area under the curve, AUC）、敏感度、特异度分别为0.796 [95%（confidence interval, CI）：0.712～0.864]、90.91%（95% CI：82.90%～96.00%）和63.33%（95% CI：43.90%～80.10%）。乳腺癌ADCmin、ADCmean、rADCmin和rADCmean与Ki-67增殖指数间均呈不同程度的负相关关系[r=-0.343（95% CI：-0.493～-0.173）、r=-0.474（95% CI：-0.603～-0.321）、r=-0.325（95% CI：-0.478～-0.154）、r=-0.322（95% CI：-0.475～-0.150），P均＜0.05]。结论 ADC值可用于鉴别Luminal型与非Luminal型乳腺癌，可以在一定程度上评估肿瘤细胞增殖活性。
[Abstract] Objective To explore the efficacy of apparent diffusion coefficient (ADC) in distinguishing between Luminal and non-Luminal breast cancer and its correlation with Ki-67 proliferation index.Materials and Methods Eighty-eight cases of Luminal breast cancers and 30 cases of non-Luminal breast cancers were confirmed pathologically, and their Ki-67 proliferation index was assessed through immunohistochemistry. The minimum ADC value (ADCmin), the mean ADC value (ADCmean), and the ADC value of the corresponding contralateral normal breast gland tissue were measured on the ADC map. Additionally, the relative minimum ADC value (rADCmin) and the relative mean ADC value (rADCmean) were calculated. The differences in ADC values between the luminal and non-luminal breast cancer groups were compared, and the receiver operating characteristic (ROC) curves were drawn. Then, the differential efficacy of ADC values on luminal and non-luminal breast cancer and the correlation between ADC values and Ki-67 proliferation index were analyzed.Results The ADCmin, ADCmean, rADCmin, and rADCmean values of the Luminal breast cancer group were lower than those in the non-Luminal breast cancer group, and the differences were statistically significant (P＜0.05). The ROC results showed that each ADC value could effectively distinguish between Luminal type and non-Luminal type of breast cancer. Among them, rADCmin had the best discriminatory efficiency. The optimal cut-off value was 0.599, and the corresponding area under the curve (AUC), sensitivity, and specificity were 0.796 [95% (confidence interval, CI): 0.712-0.864], 90.91% (95% CI: 82.90%-96.00%), and 63.33% (95% CI: 43.90%-80.10%), respectively. There were different degrees of negative correlation between ADCmin, ADCmean, rADCmin, and rADCmean, and Ki-67 proliferation index [r=-0.343 (95% CI: -0.493--0.173), r=-0.474 (95% CI: -0.603--0.321), r=-0.325 (95% CI: -0.478--0.154), r=-0.322 (95% CI: -0.475--0.150), all with P＜0.05].Conclusions The ADC values can be used to distinguish between Luminal type and non-Luminal type breast cancer, and they can also have some value for assessing the proliferative activity of tumor cells.
[关键词] 乳腺癌；Luminal型；磁共振成像；表观扩散系数；Ki-67增殖指数；鉴别
[Keywords] breast cancer；Luminal；magnetic resonance imaging；apparent diffusion coefficient；Ki-67 proliferation index；differentiate

刘宏    刘显旺    刘光耀    周洁    周俊林 *  

兰州大学第二医院放射科，兰州大学第二临床医学院，甘肃省医学影像重点实验室，医学影像人工智能甘肃省国际科技合作基地，兰州　730030

通信作者：周俊林，E-mail：ery_zhoujl@lzu.edu.cn

作者贡献声明：周俊林设计本研究的方案，对稿件重要内容进行了修改；刘宏起草和撰写稿件，获取、分析或解释本研究的数据，获得国家自然科学基金项目资助；刘显旺、刘光耀、周洁获取、分析或解释本研究的数据，对稿件重要内容进行了修改；全体作者都同意发表最后的修改稿，同意对本研究的所有方面负责，确保本研究的准确性和诚信。


基金项目： 国家自然科学基金项目 82260361
收稿日期：2022-10-26
接受日期：2023-04-07
中图分类号：R445.2  R737.9 
文献标识码：A
DOI: 10.12015/issn.1674-8034.2023.04.010
本文引用格式：刘宏, 刘显旺, 刘光耀, 等. 表观扩散系数术前区分Luminal型与非Luminal型乳腺癌及其与Ki-67增殖指数的相关性研究[J]. 磁共振成像, 2023, 14(4): 51-56. DOI:10.12015/issn.1674-8034.2023.04.010.

0 前言

       乳腺癌是我国女性发病率最高的恶性肿瘤，其死亡率位居我国女性恶性肿瘤第四位[1]。乳腺癌属于激素依赖性肿瘤，其风险的增加与激素失衡密切相关，特别是雌激素[2, 3, 4]。雌激素由雌激素受体（estrogen receptor, ER）、孕激素受体（progesterone receptor, PR）介导参与细胞增殖，在不同乳腺癌患者中的表达具有差异，临床治疗方案及预后亦有不同[5, 6]。根据ER、PR表达状态将乳腺癌分为Luminal型（PR和ER任意一项阳性）和非Luminal型（PR和ER均为阴性），其中Luminal型最常见，约占乳腺癌的70%[7]。Ki-67增殖指数被认为代表肿瘤增殖状态，较高的Ki-67增殖指数与预后不良相关[8, 9, 10]。术前影像学标志物可以帮助评估乳腺癌分型及整个肿瘤的细胞增殖情况，扩散加权成像（diffusion weighted imaging, DWI）和表观扩散系数（apparent diffusion coefficient, ADC）值通常与肿瘤细胞密度或较少的细胞外空间相关。有研究已经证明了DWI及ADC值可以有效地区分乳腺良恶性肿瘤和乳腺癌的分级及分子亚型[11, 12, 13, 14, 15]，但DWI和ADC值对于乳腺癌分子亚型的鉴别价值因不同研究而异[14, 15, 16, 17]。另有研究发现可通过DWI定量参数评估乳腺癌的分子亚型与Ki-67增殖指数的相关性[17, 18]。本研究将探讨术前最小ADC值（the minimum ADC, ADCmin）和平均ADC值（the mean ADC, ADCmean）对Luminal型和非Luminal型乳腺癌的鉴别价值，并评估其与Ki-67增殖指数间的关系。

1 材料与方法

1.1 一般资料

       回顾性分析2021年12月至2022年7月兰州大学第二医院经病理证实的乳腺癌患者的临床及影像学资料。纳入标准：（1）经手术病理证实为乳腺癌，经免疫组化检测ER、PR和Ki-67增殖指数表达状态；（2）术前一周内行乳腺MRI检查，包括T1WI、T2WI、动态增强扫描和DWI序列。排除标准：（1）乳腺MRI检查前接受过放疗、化疗、手术等干预措施；（2）MRI图像质量差，不能满足ADC值测量需要。最终共纳入118例女性乳腺癌患者病例，均为单侧单发病灶。其中Luminal型乳腺癌88例，年龄（55±10）岁；非Luminal型乳腺癌30例，年龄（52±10）岁。本研究经兰州大学第二医院伦理委员会批准，免除受试者知情同意，完全遵守《赫尔辛基宣言》，伦理批准文号：2022A-490。

1.2 扫描仪器与参数

       采用Philips Ingenia 3.0 T 超导MRI扫描仪（飞利浦，荷兰），原机自带的乳腺专用8通道相控阵线圈行乳腺扫描，患者取俯卧位，双乳自然悬垂于专用线圈内。快速自旋回波（turbo spin echo, TSE）-T1WI序列扫描参数：TR 659 ms，TE 8 ms，FOV 530 mm×339 mm，矩阵256×256，层厚3 mm，层间距1 mm；TSE-T2WI序列扫描参数：TR 3931 ms，TE 60 ms，FOV 530 mm×339 mm，矩阵256×256，层厚3 mm，层间距1 mm；平面回波成像（echo planar imaging, EPI）-DWI序列扫描参数：TR 12500 ms，TE 66 ms，层厚3 mm，层间隔1 mm，矩阵256×256，b值取0、800 s/mm2；动态对比增强扫描参数：TR 4.5 ms，TE 2.3 ms，FOV 530 mm×339 mm，矩阵256×256，层厚2 mm，层间距0 mm，在横轴位上进行，第一个动态为蒙片，然后使用高压注射器经肘静脉注入对比剂钆喷酸葡胺（GD-DTPA），剂量0.1 mmol/kg，速率2.0 mL/s，15 mL生理盐水冲管，打药后继续扫描，连续采集7个时相。

1.3 图像分析和ADC值测量

       DWI原始图像传入工作站后自动生成ADC图像，由2名具有5年以上工作经验的乳腺影像诊断医师，对所有图像采用双盲法进行阅片。选择肿瘤径向最大的3个层面，每个层面避开坏死、囊变、出血区，在ADC图上选择肿瘤轮廓内视觉上ADC灰度下降最多的位置放置3个大小为40～50 mm2的感兴趣区（region of interest, ROI），所有ROI中最低的ADC值即为ADCmin值；ADC图上选择最大的肿瘤横截面，将最大的椭圆形或圆形ROI放置在肿瘤内，平均值即为ADCmean值；在对侧乳腺放置同样大小的ROI测量正常乳腺组织的ADC值，计算相对ADCmin（relative ADCmin, rADCmin；rADCmin=ADCmin/正常乳腺ADC）和相对ADCmean（relative ADCmean, rADCmean；rADCmean=rADCmean/正常乳腺ADC）。将两名医师测量的ADC值取均值后作为最终结果。

1.4 病理学评估

       病理学评估由1名具有10年工作经验的病理科医生完成。ER、PR评判标准[19]：ER和PR的阳性肿瘤细胞核≥1%为阳性，＜1%为阴性。HER-2评判标准[19, 20]：阴性和1+为HER-2阴性，3+为HER-2阳性；2+者需行荧光原位杂交法检测，其中基因扩增者为HER-2阳性，无扩增为HER-2阴性。Ki-67增殖指数[19]：选择瘤细胞染色密度最高的区域，对1000个细胞的染色情况进行计数，阳性细胞数/总细胞计数即为Ki-67增殖指数。

1.5 统计学方法

       采用MedCalc软件（Version 19.1, Mariakerke, Belgium）和SPSS软件（Version 25.0, Chicago, Illinois）进行统计分析，P＜0.05认为差异有统计学意义。组内相关系数（intra-class correlation coefficient, ICC）用于评估2名医师对ADC参数测量的一致性。使用Shapiro-Wilk检验分析各参数是否符合正态分布，符合正态分布的参数用（x¯±s）表示，并使用独立样本t检验进行组间差异比较；非正态分布的参数用M（Q1, Q3）表示，并使用Mann-Whitney U检验进行组间差异比较。计数资料采用卡方检验或者Fisher确切概率法。绘制ROC曲线评估各ADC值对Luminal型和非Luminal型乳腺癌的鉴别效能。采用Pearson相关系数分析乳腺癌ADCmin、ADCmean和rADCmin、rADCmean与Ki-67增殖指数间的相关性。

2 结果

2.1 Luminal型和非Luminal型乳腺癌组间各参数比较及各ADC值ROC曲线分析

       临床分期在Luminal型和非Luminal型乳腺癌组间差异具有统计学意义（P＜0.05），而直径和临床分级在两组间差异不具有统计学意义（P均＞0.05）。对2名医师所测量的ADCmin、ADCmean及对侧ADCmean进行一致性检验发现一致性较好（ICC均＞0.9，P＜0.05）。Luminal型乳腺癌组的ADCmin、ADCmean、rADCmin和rADCmean值均低于非Luminal型组，组间差异具有统计学意义（P均＜0.05）。详见表1、图1。

       ROC曲线结果显示各ADC值均能对Luminal型和非Luminal型乳腺癌进行有效区分。其中，rADCmin鉴别效能最佳，最佳截止值为0.599，相应的曲线下面积（area under the curve, AUC）、敏感度、特异度分别为0.796（95% CI：0.712～0.864）、90.91%（95% CI：82.90%～96.00%）和63.33%（95% CI：43.90%～80.10%），详见表2。对不同参数的ROC曲线进行了DeLong检验，发现rADCmean与rADCmin的AUC值差异具有统计学意义（P＜0.05）。Luminal型和非Luminal型乳腺癌典型病例分别见图2和图3。

图1  两组间各ADC参数比较柱状图。Luminal型乳腺癌组的ADCmin、ADCmean、rADCmin和rADCmean值均低于非Luminal型组。圆圈代表在均数1.5～3倍范围的极值，星号代表3倍均数以上的极值。ADCmin：最小ADC值；ADCmean：平均ADC值；rADCmin：相对最小ADC值；rADCmean：相对平均ADC值；ADC：表观扩散系数。
Fig. 1  Comparison histogram of ADC parameters between two groups. Histograms showing that ADCmin, ADCmean, rADCmin, and rADCmean in the Luminal-type group are lower than the non-Luminal-type group, respectively. Circles outliers between 1.5 times and 3 times the mean difference, star outliers that exceed the mean range by 3 times the distance. ADCmin: the minimum ADC value; ADCmean: the mean ADC value; rADCmin: the relative minimum ADC value; rADCmean: the relative mean ADC value; ADC: apparent diffusion coefficient.
图2  女，55岁，右侧乳腺浸润性导管癌Ⅱ级，ER（90%+）、PR（60%+）提示为Luminal型，Ki-67增殖指数约30%。2A：T1WI图像，病灶呈稍低信号，形态不规则，与周围组织分界欠清；2B：T2WI脂肪抑制图像，病灶以高信号为主，信号不均匀；2C～2D：分别为DWI序列与对应的ADC图，病灶扩散受限呈高信号，ADCmin=0.773×10-3 mm2/s，ADCmean=0.809×10-3 mm2/s，rADCmin=0.415，rADCmean=0.434；2E：动态对比增强图，病灶明显强化，强化均匀；2F：病理图（HE ×200）示瘤细胞（黑箭）呈条索状、实团状、不典型腺样结构，胞质红染，胞界不清，胞核增大并可见异型核细胞及核分裂象。
图3  女，42岁，右侧乳腺浸润性导管癌Ⅲ级，ER（-）、PR（-）提示为非Luminal型，Ki-67增殖指数约90%。3A：T1WI图像，右乳实性肿块，呈等或稍高信号，边界不清；3B：T2WI脂肪抑制图像，病灶呈稍高信号，信号欠均匀，表现为类圆形肿块，周围水肿明显；3C～3D：分别为DWI序列与对应的ADC图，病灶扩散受限呈高信号，ADCmin=0.571×10-3 mm2/s，ADCmean=0.685×10-3 mm2/s，rADCmin=0.837，rADCmean=1.004；3E：动态对比增强图，病灶明显强化，强化均匀；3F：病理图（HE ×200）示瘤细胞（黑箭）排列呈条索状、不典型腺样结构，浸润性生长，胞质红染，胞界不清，核深染，异型性明显，核分裂象多见。ER：雌激素受体；PR：孕激素受体；DWI：扩散加权成像；ADC：表观扩散系数；ADCmin：最小ADC值；ADCmean：平均ADC值；rADCmin：相对最小ADC值；rADCmean：相对平均ADC值。
Fig. 2  Female, 55 years old, the right breast invasive ductal carcinoma, WHO class Ⅱ, Luminal type, Ki-67 proliferation index 30%. 2A: The lesion shows a slightly low signal on T1WI, irregular shape, and poorly demarcated from the surrounding tissue; 2B: The lesion is characterized by high signal and uneven signal on T2WI; 2C-2D: The lesion shows high signal on DWI and low signal on ADC, ADCmin=0.773×10-3 mm2/s, ADCmean=0.809×10-3 mm2/s, rADCmin=0.415, rADCmean=0.434; 2E: The lesion shows significantly enhanced on the dynamic contrast enhancement image; 2F: Pathological image (HE ×200), the tumor cells (black arrow) appear as strands, solid masses, and atypical glandular structures, the cytoplasm stains red, and the cell boundaries are unclear, the nuclei are enlarged, and there are visible heteronuclear cells and nuclear division.
Fig. 3  Female, 42 years old, the right breast invasive ductal carcinoma, WHO class Ⅲ, non-Luminal type, Ki-67 proliferation index 90%. 3A: A solid mass in the right breast with equal or slightly elevated signal and indistinct boundary on T1WI; 3B: T2WI shows the lesion with a slightly high signal, the signal is not uniform, appeared as a circular mass, with peripheral edema; 3C-3D: The solid component shows high signal on DWI and low signal on ADC, ADCmin=0.571×10-3 mm2/s, ADCmean=0.685×10-3 mm2/s, rADCmin=0.837, rADCmean=1.004; 3E: The lesion shows significantly enhanced and uniform on the dynamic contrast enhancement image; 3F: Pathological image (HE ×200), the tumor cells (black arrow) exhibit a stromal appearance with atypical adenoid structures and infiltrative growth, the cytoplasm is red in color, and the cell boundaries are unclear, there is evidence of hyperchromatosis, atypia, and nuclear division. ER: estrogen receptor; PR: progesterone receptor; DWI: diffusion weighted imaging; ADC: apparent diffusion coefficient; ADCmin: the minimum ADC; ADCmean: the meam ADC; rADCmin: relative ADCmin; rADCmean: relative ADCmean.
表1  Luminal型和非Luminal型乳腺癌组间各参数比较
Tab. 1  Comparison of parameters between Luminal-type and non-Luminal-type breast cancer groups
表2  ADC值鉴别Luminal型和非Luminal型乳腺癌的ROC曲线分析
Tab. 2  ROC curve analysis of ADC values in differentiating Luminal-type and non-Luminal-type breast cancer

2.2 ADC值与Ki-67增殖指数的相关性分析

       Ki-67增殖指数[30（95% CI：20～50）]与乳腺癌ADCmin、ADCmean、rADCmin和rADCmean间均呈不同程度的负相关关系（r=-0.343、r=-0.474、r=-0.325、r=-0.322，P均＜0.05），即随着Ki-67增殖指数的增加，各ADC值均呈逐渐减低的趋势（图4）。

图4  乳腺癌各ADC值与Ki-67相关性热图。ADCmin、ADCmean、rADCmin和rADCmean与Ki-67增殖指数间均呈不同程度的负相关关系。ADCmin：最小ADC值；ADCmean：平均ADC值；rADCmin：相对最小ADC值；rADCmean：相对平均ADC值；ADC：表观扩散系数。
Fig. 4  Correlation heat map between ADC values and Ki-67 in breast cancer. The heat maps showing the correlation between ADC values (ADCmin, ADCmean, rADCmin, rADCmean) and the Ki-67 proliferation index in breast cancer revealed varying degrees of negative correlation. ADCmin: the minimum ADC; ADCmean: the meam ADC; rADCmin: relative ADCmin; rADCmean: relative ADCmean; ADC: apparent diffusion coefficient.

3 讨论

       本研究对比分析了Luminal型和非Luminal型乳腺癌间的ADC值差异，并进一步探讨了乳腺癌ADC值与Ki-67增殖指数间的关系，发现ADC值可用于术前鉴别Luminal型和非Luminal型乳腺癌，且发现乳腺癌ADC值与Ki-67增殖指数间呈负相关关系，说明ADC值在乳腺癌术前评估中具有一定的价值。

3.1 Luminal型和非Luminal型乳腺癌组间ADC值的对比分析

       本研究纳入的乳腺癌患者中，Luminal型发病率较高，占比74.58%，非Luminal型占比25.42%，与文献[7]报道类似。Luminal型和非Luminal型乳腺癌治疗方案不同，Luminal型乳腺癌为内分泌治疗敏感的肿瘤亚型，而非Luminal型乳腺癌患者内分泌治疗无明显反应[21]。因此，术前鉴别两者对临床制订合理的治疗方案具有重要意义。

       DWI是一种无创性的功能MRI，可以在术前反映肿瘤内部的病理生理状态，并可通过ADC值量化肿瘤细胞及细胞外空间的水分子运动和微循环灌注情况[22, 23, 24]。ADC值不仅取决于细胞外水分子的数量，还取决于间质流体压力（interstitial fluidpressure, IFP），肿瘤的IFP越高，水分子的运动速度越快。肿瘤的IFP主要由微血管系统决定，微血管分布情况与肿瘤的分子亚型及预后情况相关[25, 26]，而乳腺肿瘤存在广泛的微血管分布[27, 28]。从DWI中获得的定量ADC已被越来越多地用于提高对比增强MRI对乳腺癌[29, 30, 31, 32]的诊断准确性。本研究结果发现Luminal型乳腺癌组的ADCmin、ADCmean值均低于非Luminal型组，并且组间差异具有统计学意义（P均＜0.05），与既往研究结果一致[16,33]。ZHAI等研究[33]发现乳腺癌ADC值的变化与肿瘤增殖和ER β阳性细胞密度显著相关，并发现ER阳性乳腺癌（属Luminal型）的癌细胞密度较高、核浆比例大，水分子扩散受限程度更明显。本研究ROC分析结果发现，ADCmin鉴别Luminal型和非Luminal型乳腺癌的效能优于ADCmean，可能是因为ADCmin值测量范围较ADCmean小，且为肿瘤细胞最密集的区域，是最能代表肿瘤生物学行为的区域，避免了肿瘤异质性带来的干扰。此外，为排除个体差异对ADC值测量的影响，本研究采用rADC值（病变区域的ADC值和对侧相应正常乳腺组织的ADC值的比值）即对所测量ADC值进行了标准化处理，结果显示rADCmin和rADCmean鉴别Luminal型和非Luminal型乳腺癌的效能分别优于ADCmin和ADCmean，且经DeLong检验发现，rADCmean与rADCmin的AUC值差异具有统计学意义。在所有ADC值中，rADCmin具有最佳的评估效能，其鉴别Luminal型和非Luminal型乳腺癌的截止值是0.599，AUC、敏感度、特异度分别为0.796、90.91%和63.33%。既往虽然未见使用rADCmin进行乳腺癌的研究，但类似方法已经用于评估脑胶质瘤IDH-1突变状态[34]，并发现其具有很好的评估效能，说明rADCmin在反映肿瘤病理生理学特点方面具有一定的价值，或更有利于乳腺癌的综合性评估。

3.2 乳腺癌ADC值与Ki-67增殖指数的相关性分析

       Ki-67是核糖体合成的关键因素，其表达通常在G1晚期检测到，在S和G2阶段逐渐增加，在M期达到峰值后迅速降解[35]，对细胞增殖至关重要，与细胞合成代谢密切相关[36]，因此可以反映肿瘤增殖速度，目前主要用于鉴别肿瘤的良恶性、评估恶性肿瘤预后生存情况[37, 38]。本研究结果显示乳腺癌的ADCmin、ADCmean、rADCmin、rADCmean和Ki-67增殖指数均呈不同程度的负相关关系，即肿瘤的Ki-67增殖指数越高其ADC值越低，与既往研究结果一致[17,39]。ADC值可以量化反映肿瘤细胞内外水分子扩散情况，而Ki-67增殖指数较高时，肿瘤细胞增殖活性强、速度快，使肿瘤细胞体积增大、排列密集，减少了细胞内外水分子的活动空间，最终引起肿瘤细胞水分子扩散受限[31, 35]。因此，本研究结果显示的乳腺癌ADC值与Ki-67增殖指数呈负相关符合肿瘤细胞增殖状态，可以用于术前无创性评估乳腺癌的恶性程度。

3.3 本研究的局限性

       本研究具有以下几点局限性：第一，本研究为单中心回顾性研究，研究样本量相对较小；第二，在ADC值测量时，ROI应同时包括浸润性和导管内成分，但目前MRI很难对其进行鉴别，而本研究结果发现ADC值和Ki-67增殖指数之间显著相关，仍需大样本研究进一步验证。

4 结论

       综上，本研究结果表明ADC值可用于术前鉴别Luminal型和非Luminal型乳腺癌，其中rADCmin效能最佳；乳腺癌ADC值和瘤细胞增殖活性呈负相关，可为临床在术前制订合理的治疗方案提供参考。

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