首页
Ultrasound Multimodality Examination Improves the Diagnostic Efficiency of Non-Mass-Like Breast Lesions
-
摘要:目的
本研究的超声多模态检查是指高频超声（ultrasound, US）、声辐射力脉冲成像（acoustic radiation force impulse, ARFI）、超声造影（contrast-enhanced ultrasound, CEUS）这三种超声检查方式联合使用。本研究拟分析超声多模态检查对乳腺非肿块型病变（non-mass-like lesions, NMLs）良恶性的鉴别诊断价值。
方法回顾性分析乳腺非肿块型的病例，病灶性质均经病理检查证实。依据灰阶超声图像特征，将病例分为Ⅰ～Ⅴ类型，并根据是否伴有钙化，将其中Ⅰ型及Ⅱ型又分为Ⅰa型、Ⅰb型和Ⅱa型、Ⅱb型，统计分析各分型恶性比例。建立US、US+ARFI、US+CEUS、US+ARFI+CEUS的logistic诊断恶性病例的回归模型，绘制受试者工作特征（ROC）曲线，计算曲线下面积（area under the curve, AUC），并进行比较。分析US、ARFI与CEUS串联实验对不伴钙化的恶性NMLs（不典型恶性NMLs）的检出率。
结果最终纳入研究病例407例，均为女性，年龄22～81岁，平均年龄（47.0±11.0）岁。其中良性病例220例，恶性病例187例。恶性占比从高到低分别为Ⅰb型>Ⅱb型>Ⅲ型>Ⅴ型>Ⅰa型>Ⅱa型>Ⅳ型，伴有钙化的低回声区恶性比例明显高于不伴钙化的病灶。US、US+ARFI、US+CEUS、US+ARFI+CEUS的logistic回归模型诊断恶性病例的AUC及95%置信区间（CI）分别为0.895（0.862～0.927）、0.908（0.878～0.937）、0.921（0.893～0.948）、0.927（0.902～0.952）。4个回归模型的AUC相比，差异有统计学意义（P<0.001）。US对不伴钙化的NMLs的检出率为80.7%，若US与CEUS、ARFI联合，当病灶CEUS评分为4分或5分或ARFI中的剪切波速度（shear-wave velocity, SWV）≥4.28 m/s时判断为恶性，此时可以检出86.4%的不伴钙化的恶性NMLs病灶。
结论伴有钙化的乳腺NMLs恶性风险高，均建议行病理学检查明确诊断；不伴钙化的乳腺NMLs可以联合多模态超声检查，有助于提高诊断效能。
Abstract:ObjectiveThis study is focused on ultrasound multimodality examination, which refers to the combined use of three ultrasound examination modalities, ultrasound (US), acoustic radiation force impulse (ARFI) imaging, and contrast-enhanced ultrasound (CEUS). The purpose of this study is to analyze the value of applying ultrasound multimodality examination in the differential diagnosis of benign and malignant breast non-mass-like lesions (NMLs).
MethodsCases of breast NMLs were analyzed retrospectively, and the nature of all the lesions was verified by pathological examination. Based on the gray-scale ultrasound image characteristics, the cases were classified into types Ⅰ to Ⅴ, and type Ⅰ and type Ⅱ were further classified into 4 subtypes, Ⅰa, Ⅰb, Ⅱa, and Ⅱb, according to whether there was also calcification, and the proportion of malignant cases in each subtype was statistically analyzed. Logistic regression models of US, US+ARFI, US+CEUS, and US+ARFI+CEUS for the diagnosis of malignant cases were established, ROC curves were drawn, the area under the curve (AUC) was calculated, and comparisons were made accordingly. The detection rate of malignant NMLs without calcification (atypical malignant NMLs) by the combination examination of US, ARFI, and CEUS was analyzed.
ResultsA total of 407 cases were included in the study. All subjects were female, aged 22 to 81 years, with the average age being (47.0±11.0) years. There were 220 benign cases and 187 malignant cases. Ranked from the highest to the lowest, the malignancy proportion of the different types was Ⅰb>Ⅱb>Ⅲ>Ⅴ>Ⅰa>Ⅱa>Ⅳ. The malignant proportion of the low echo area with calcification was significantly higher than that of the lesions without calcification. The AUC (95% confidence interval [CI]) for diagnosing malignant cases with the logistic regression models of US, US+ARFI, US+CEUS, and US+ARFI+CEUS were 0.895 (0.862-0.927), 0.908 (0.878-0.937), 0.921 (0.893-0.948), and 0.927 (0.902-0.952), respectively. Comparison of the AUC of the 4 regression models showed significant differences (P<0.001). The detection rate of US for NMLs without calcification was 80.7%. When US was used in combination with ARFI and CEUS, 86.4% of the malignant NMLs lesions without calcification could be detected if the lesion CEUS score was 4 or 5 points or if shear-wave velocity (SWV)≥4.28 m/s.
ConclusionBreast NMLs with calcification show high risks of malignancy, and a pathological examination is always recommended for a conclusive diagnosis. Ultrasound multimodality examination can improve the diagnostic accuracy of breast NML without calcification.
-
抑郁症是常见的精神疾病，以情绪低落、快感缺失、长期失眠及认知障碍为主要临床表现，重度抑郁症患者往往具有自杀倾向[1]。随着都市生活节奏的加快，人们承受的压力日益增大，抑郁症发病率逐年增高。全球目前约有3.5亿人受到抑郁症的困扰，探索抑郁症的治疗方法成为医学界研究热点[2]。奥氮平(OAL)是一种作用于多巴胺和5-羟色胺受体的非典型抗精神病药，可通过拮抗多巴胺受体减少精神病患者的阳性症状，如幻觉、妄想、言语、思维及行为紊乱，通过拮抗5-羟色胺受体减少精神病患者的阴性症状，如情绪低落、冷漠、快感缺失及注意力不足[3]。同时，OAL也是治疗双相抑郁症的主要药物之一[4]，其与氟西汀联合使用可显著地缓解双相抑郁症状[5]。目前，OAL在国内临床应用时间并不长，其对患者海马神经元产生的影响还有待深入研究。因此，本实验通过建立大鼠慢性不可预见性应激(CUS)模型，对OAL在海马神经元中的影响及作用机制进行深入探究。
1. 材料与方法
1.1 实验动物和试剂
42只3周龄SPF级SD大鼠购自河南远大生物制药有限公司，许可证号：SYXK(豫)2017-0014；OAL购自美国Eli Lilly; Tunnel试剂盒及BCA试剂盒购自上海碧云天；白介素(IL)-1β及IL-18 ELISA试剂盒购自美国Invirtrogen；实验所用蛋白抗体均购自美国Cell Signaling Technology；二抗均购自北京中杉金桥；si-Atg5购自上海生工生物。
1.2 大鼠分组及处理
将42只SD大鼠分为对照，CUS、OAL (0.5、1、2 mg/kg)、si-Atg5及OAL (2 mg/kg)+si-Atg5组，每组6只。除对照组以外，其余各组均建立大鼠CUS抑郁症模型，OAL用药浓度[6]及大鼠CUS抑郁症模型建立方法[7]参考既往文献。通过旷场实验、糖水偏好实验检测造模情况。造模成功后，OAL(0.5、1、2 mg/kg)组分别灌胃给予0.5、1、2 mg/kg OAL，si-Atg5组用si-Atg5腺病毒转染大鼠，OAL (2 mg/kg)+si-Atg5组用si-Atg5腺病毒转染大鼠并灌胃给予2 mg/kg OAL，CUS组则给予等量生理盐水，每日1次，持续给予3周后，收集大鼠外周血，处死大鼠后剥离大脑海马CA3区组织，石蜡包埋脑组织，用于后期检测。
1.3 旷场实验
造模前后将各组大鼠单独置于透明观察室，适应10 min后，记录其5 min内自发活动路程。观察后，每只大鼠用清洁剂清洗并干燥。
1.4 糖水偏好实验
将各组大鼠单独置于饲养笼中，进行预实验，第一日，笼中放置2瓶1%蔗糖溶液，第二日用自来水取代其中1瓶蔗糖溶液。适应后，断粮水供应24 h，于上午9点进行正式实验。笼中分别放置100 mL自来水及蔗糖溶液各1瓶，1 h后，记录蔗糖溶液及自来水消耗体积，糖水偏好率=糖水消耗量/(水消耗量+糖水消耗量)×100%。
1.5 HE染色
将脑海马区组织石蜡包埋切片，然后将切片脱蜡、水洗、苏木精液染色、水洗；再用1%盐酸酒精分化，水洗；0.6%氨水返蓝，水洗；0.5%伊红液染色，水洗；接着脱水，二甲苯透明；最后中性树胶封片，每组取6张切片，在400倍显微镜观察海马区组织损伤情况。
1.6 Tunnel检测
将大鼠大脑海马组织石蜡切片脱蜡修复，内源性过氧化物酶作用5 min后，PBS洗涤。滴加Tunnel检测液37 ℃避光孵育1 h后，PBS洗涤。利用DAB显色液避光显色，苏木精复染。暗室内观察切片，显微镜视野下，棕色为凋亡细胞，蓝色为正常细胞。每组取6张切片于400倍镜下观察。凋亡率(%)=凋亡细胞数/细胞总数×100%。
1.7 ELISA检测大鼠血清IL-1β和IL-18质量浓度
利用ELISA试剂盒测定IL-1β、IL-18血清质量浓度，步骤参考试剂盒说明书。避光显色，利用酶标仪读取吸光度(A)值，根据标准样品曲线公式计算各样品A值对应的蛋白质量浓度。
1.8 Western blot检测海马CA3区脑组织蛋白水平
RIPA裂解海马CA3区脑组织，提取总蛋白。BCA试剂盒将蛋白定量并调平。取蛋白30 g，10% SDS-PAGE将蛋白分离，湿转法将蛋白转移至PVDF膜，脱脂奶粉室温封闭2 h，各蛋白对应一抗4 ℃孵育过夜，二抗37 ℃ 1 h，最后曝光显色，以GAPDH为内参，薄膜由Bio-rad凝胶DocEZ成像仪拍摄，利用Image J软件分析检测Capase-3、-9、NLRP3、LC3、Beclin1和P62蛋白条带的灰度值与内参蛋白带的灰度值比值。
1.9 统计学方法
所有数据先进行正态分布和方差齐性分析，符合条件的选用单因素方差分析或t检验，不符合条件的选用秩和检验。P < 0.05为差异有统计学意义。
2. 结果
2.1 旷场实验及糖水偏好实验结果
造模前各组大鼠自发活动总路程长度差异无统计学意义。造模后，与对照组比较，CUS组、si-Atg5组和DAL+si-Atg5组大鼠自发活动总路程长度、糖水消耗量及偏好率降低(P < 0.01)，说明造模成功。干预3周后，与CUS组比较，OAL (0.5 mg/kg)、(1 mg/kg)及(2 mg/kg)组中大鼠自发活动总路程长度、糖水消耗量及偏好率升高(P < 0.05)；si-Atg5组大鼠自发活动总路程长度、糖水消耗量及偏好率降低(P < 0.05)。与OAL (2 mg/kg)组比较，OAL (2 mg/kg)+si-Atg5组大鼠自发活动总路程长度、糖水消耗量及偏好率降低(P < 0.05)。见表 1。
表 1 造模前后各组大鼠旷场实验和糖水偏好实验结果(n=6)Table 1. Open field tests and post-intervention sucrose preference tests on rats (n=6)Group The total moving distance/cm Sucrose preference rate/% Before model After model Before model After model After drug Control 336.4±45.6 489.7±78.2 74.9±2.3 75.0±4.3 75.2±6.9 CUS 328.6±58.3 125.3±54.4** 74.8±3.2 45.7±6.5** 45.8±9.6** OAL (0.5 mg/kg) 331.3±47.6 378.3±96.5# 75.1±2.2 45.8±5.3** 55.2±9.6*，# OAL (1 mg/kg) 352.2±68.2 421.6±87.3# 74.9±2.4 45.6±6.8** 64.3±10.6# OAL (2 mg/kg) 345.7±52.1 463.2±89.7## 75.2±2.7 45.9±5.9** 74.9±9.6## si-Atg5 324.1±66.5 88.6±18.9**，# 74.8±3.4 45.8±4.9** 27.3±5.2**，# OAL+si-Atg5 336.3±72.3 217.6±36.5**，&& 75.0±4.5 45.7±5.2** 55.8±6.9*，& P < 0.05, ** P < 0.01, vs. control group; # P < 0.05, ## P < 0.01, vs. CUS group; & P < 0.05, && P < 0.01, vs. OAL (2 mg/kg) group 2.2 OLA对CUS大鼠海马神经细胞病理的影响
见图 1。与对照组比较，CUS组大鼠海马CA3区发生明显的病理损伤，细胞核浓缩，细胞质减少，细胞核染色加深；与CUS组比较，大鼠经过不同质量浓度的OAL治疗后，细胞核逐渐舒展，细胞形态恢复正常，神经突出逐渐长出；并且随着药物剂量的增加，组织细胞形态越接近对照组；si-Atg5组大鼠海马CA3区病理损伤加重，细胞核浓缩程度、细胞质减少程度、细胞核染色均加重；与OAL (2 mg/kg)组比较，OAL (2 mg/kg)+si-Atg5组大鼠海马区细胞核浓缩程度、细胞质减少程度、细胞核染色均加重。
![]()
图 1 各组大鼠海马CA3区细胞损伤。HE ×400Figure 1. The injury of tissue cells in the CA3 region of hippocampus by group. HE ×400A: Control group; B: CUS group; C: OAL (0.5 mg/kg) group; D: OAL (1.0 mg/kg) group; E: OAL (2.0 mg/kg) group; F: si-Atg5 group; G: OAL (2 mg/kg)+si-Atg5 group2.3 OLA对CUS大鼠海马神经细胞凋亡的影响
见图 2~图 4。与对照组比较，CUS组、OAL(0.5、1 mg/kg)组、si-Atg5组及OAL (2 mg/kg)+si-Atg5组大鼠海马CA3区凋亡细胞百分比(P < 0.01)、cleaved Caspase-3及cleaved Caspase-9表达(P < 0.01)升高。与CUS组比较，OAL (0.5 mg/kg)、(1 mg/kg)及(2 mg/kg)组中凋亡细胞百分比降低(P < 0.01)；OAL (0.5 mg/kg)组cleaved Caspase-3表达无明显变化，cleaved Caspase-9表达降低(P < 0.05)；OAL (1 mg/kg)及(2 mg/kg)组中cleaved Caspase-3、cleaved Caspase-9表达均降低(P < 0.05，P < 0.01)；si-Atg5组凋亡细胞百分比升高(P < 0.01)，cleaved Caspase-3、cleaved Caspase-9表达均升高(P < 0.01)。与OAL (2 mg/kg)组比较，OAL (2 mg/kg)+si-Atg5组凋亡细胞百分比升高(P < 0.01)，cleaved Caspase-3、cleaved Caspase-9表达均升高(P < 0.01)。
![]()
图 2 各组大鼠海马CA3区凋亡细胞。Tunnel染色 ×400Figure 2. Cell apoptosis in the CA3 region of hippocampus by group. Tunnel staining ×400A-G denote the same as fig1![]()
图 3 各组大鼠海马CA3区凋亡细胞百分比Figure 3. The apoptosis rate of cells in the CA3 region of hippocampus by groupA-G denote the same as fig 1.**P < 0.01, vs. control group; #P < 0.05, ##P < 0.01, vs. CUS group; &&P < 0.01, vs. OAL (2 mg/kg) group![]()
图 4 各组中cleaved Caspase-3、cleaved Caspase-9的表达Figure 4. The expressions of cleaved Caspase-3 and cleaved Caspase-9 in the CA3 region of hippocampus by groupA-G denote the same as fig 1.*P < 0.05,**P < 0.01,vs. control group; #P < 0.05, ##P < 0.01 ,vs. CUS group; &P < 0.05, &&P < 0.01,vs. OAL (2 mg/kg) group2.4 OLA对CUS大鼠神经细胞炎症反应的影响
见图 5、图 6。与对照组比较，CUS组、OAL(0.5、1 mg/kg)组、si-Atg5组及OAL (2 mg/kg)+si-Atg5组大鼠IL-1β、IL-18血清质量浓度、海马CA3区cleaved Caspase-1、NLRP3表达升高(P < 0.01)。与CUS组比较，OAL (0.5 mg/kg)组IL-1β质量浓度差异无统计学意义，OAL (1 mg/kg)及OAL(2 mg/kg)组中IL-1β质量浓度降低(P < 0.01)；同时，OAL (0.5 mg/kg)、(1 mg/kg)及(2 mg/kg)组中IL-18质量浓度(P < 0.05，P < 0.01)、cleaved Caspase-1、NLRP3表达(P < 0.05，P < 0.01)均降低；si-Atg5组大鼠IL-1β、IL-18血清质量浓度(P < 0.01)、海马CA3区cleaved Caspase-1、NLRP3表达(P < 0.01)升高。与OAL (2 mg/kg)组比较，OAL (2 mg/kg)+si-Atg5组大鼠IL-1β、IL-18血清质量浓度(P < 0.01)、海马CA3区cleaved Caspase-1、NLRP3表达(P < 0.01)升高。
![]()
图 5 各组大鼠血清IL-1β、IL-18质量浓度Figure 5. Serum concentrations of IL-1β and IL-18 by groupA-G denote the same as fig 1.**P < 0.01, vs. control group; #P < 0.05, ##P < 0.01, vs. CUS group; &&P < 0.01, vs. OAL (2 mg/kg) group![]()
图 6 各组大鼠海马CA3区组织cleaved Caspase-1、NLRP3的表达Figure 6. The expressions of cleaved Caspase-1 and NLRP3 in the CA3 region of hippocampus by groupA-G denote the same as fig 1.**P < 0.01, vs. control group; #P < 0.05, ##P < 0.01, vs. CUS group; &&P < 0.01, vs. OAL (2 mg/kg) group2.5 OLA对CUS大鼠神经细胞自噬的影响
见图 7。与对照组比较，CUS组大鼠海马CA3区LC3Ⅱ/LC3Ⅰ比值、Beclin1表达降低，P62表达升高(P < 0.01)。与CUS组比较，OAL (0.5 mg/kg)、(1 mg/kg)及(2 mg/kg)组中LC3Ⅱ/LC3Ⅰ比值、Beclin1表达升高(P < 0.01)；OAL (0.5 mg/kg)组P62表达差异无统计学意义，(1 mg/kg)及(2 mg/kg)组中P62表达均降低(P < 0.01)；si-Atg5组LC3Ⅱ/LC3Ⅰ比值、Beclin1表达降低(P < 0.05，P < 0.01)，P62表达升高(P < 0.01)。与OAL (2 mg/kg)组比较，OAL (2 mg/kg)+si-Atg5组LC3Ⅱ/LC3Ⅰ比值、Beclin1表达降低(P < 0.01)，P62表达升高(P < 0.01)。
![]()
图 7 各组中LC3、Beclin1、P62的表达Figure 7. The expressions of LC3, Beclin1 and P62 in the CA3 region of hippocampus by groupA-G denote the same as fig1. *P < 0.01, vs. control group; ##P < 0.01, vs. CUS group; &P < 0.01, vs. OAL (2 mg/kg) group3. 讨论
抑郁症可引起患者精神沉郁、快感缺失，改善患者精神状态是抑郁症治疗药物的首要目的[8]。研究发现，脑组织中5-羟色胺水平降低是引起抑郁症发生的重要原因[9]，抗抑郁药OAL是多巴胺/5-羟色胺受体双摄取抑制剂，主要用于治疗双相抑郁症。有报道表明，OAL联合5-羟色胺再摄取抑制剂可显著提高神经元细胞培养上清中5-羟色胺的浓度[10]。本研究发现，0.5、1、2 mg/kg OAL均可显著提高CUS大鼠自发活动总路程、糖水消耗量及偏好率，且随OAL浓度的增加，其对CUS大鼠的作用愈明显。通过对大鼠行为学表现评估表明，OAL可显著改善CUS大鼠的精神状态。
有研究发现，在抑郁症患者脑组织中，海马区神经元细胞发生过度凋亡[11]。海马CA3区是介导应激反应的主要脑区，也是调控人类情绪、记忆及内分泌的重要部位，抑制海马神经元细胞凋亡已成为有效治疗抑郁症的目标[12]。研究表明，OAL对神经元细胞具有显著保护作用，可显著减弱血清戒断诱导的神经元细胞凋亡[13]，降低氧化应激条件下神经元细胞的凋亡水平[14]。在本研究中也发现1、2 mg/kg OAL均可显著降低大鼠海马CA3区凋亡细胞百分比，cleaved Caspase-3、cleaved Caspase-9及cleaved Caspase-1的表达。cleaved Caspase-3、cleaved Caspase-9及cleaved Caspase-1均属于Caspase蛋白水解酶家族，凋亡信号可通过触发Caspase级联反应完成细胞凋亡程序[15]。
炎症反应可显著诱导抑郁症的发生，同时，抑郁症可显著引起脑组织炎性浸润[16]。因此，抑制机体炎症反应是阻碍抑郁症发生发展的有效手段。研究发现，在神经退行性疾病多系统萎缩中，OAL可显著抑制模型小鼠中核因子-κB (NF-κB)的核易位，降低炎症因子IL-1β的表达水平[17]；在应激模型小鼠中，OAL可显著降低小鼠IL-1β和IL-6血清浓度[18]。在本研究中，1、2 mg/kg OAL可显著降低CUS大鼠IL-18及IL-1β血清浓度，同时，0.5、1、2 mg/kg OAL可显著抑制海马CA3区NLRP3炎症小体的表达。NLRP3炎症小体是炎症反应的关键核心，能招募并活化Caspase-1，促进炎症因子IL-1β和IL-18成熟，可作为各种炎症疾病的治疗靶点[19]。NLRP3炎症小体过度激活还可诱导神经元细胞凋亡的发生，抑制NLRP3炎症小体活化可显著减轻CUS模型小鼠抑郁样行为[20]。本实验结果提示，OAL可通过阻碍NLRP3炎症小体激活减轻CUS大鼠的炎症反应。
研究表明，自噬对抑郁症有正向调节作用，如抗抑郁药阿米替林及西酞普兰可提高神经元自噬水平，显著改善模型大鼠抑郁症状[21]；锂可通过诱导自噬显著减少病理朊蛋白的表达水平[22]。本研究中，0.5、1、2 mg/kg OAL均可提高大鼠海马CA3区LC3Ⅱ/LC3Ⅰ比值及Beclin1表达，1、2 mg/kg OAL可降低P62表达。Beclin1是促自噬蛋白，可诱导自噬相关蛋白定位于自噬体膜上，P62是自噬特异性底物，在自噬发生过程中被不断降解，LC3Ⅱ和LC3Ⅰ是LC3的不同表现形式，LC3Ⅰ转变成LC3Ⅱ标志着自噬的形成[23]。本实验结果表明，OAL可显著提高CUS大鼠海马CA3区神经元细胞自噬水平。
据报道，自噬与NLRP3炎症小体密切相关，自噬水平的升高可显著抑制NLRP3炎症小体的激活[24]，NLRP3炎症小体过度活化可引起自噬水平显著降低[25]。Atg5是重要的自噬相关介质，沉默Atg5可诱发NLRP3炎症小体过度活化[21]。本研究利用si-Atg5诱导NLRP3炎症小体过度激活发现，CUS大鼠海马CA3区LC3Ⅱ/LC3Ⅰ比值及Beclin1表达降低，cleaved Caspase-1、cleaved Caspase-3、cleaved Caspase-9表达升高，CUS大鼠自发活动总路程、糖水消耗量及偏好率显著减小。同时，2 mg/kg OAL对CUS大鼠产生的影响被si-Atg5显著减弱。实验结果表明，NLRP3炎症小体过度激活可显著降低CUS大鼠海马CA3区神经元自噬水平，提高炎症反应及细胞凋亡水平，加剧CUS大鼠抑郁症状，并减弱OAL产生的作用。虽然自噬与凋亡在代谢途径和形态学方面有着显著区别，但是他们发挥作用的信号通路却有着交互作用。此外也有研究报道，喜树碱可以通过促进NSCLC自噬而阻止细胞发生程序性死亡[26]。
综上所述，OAL可阻碍NLRP3炎症小体激活，显著减轻CUS大鼠炎症反应，抑制大鼠海马CA3区神经元细胞凋亡，提高神经元细胞自噬水平，改善大鼠的精神状态。同时，NLRP3炎症小体过度激活可显著降低CUS大鼠海马CA3区神经元自噬水平，提高炎症反应及细胞凋亡水平，加剧CUS大鼠抑郁症状，并减弱OAL产生的作用。提示OAL可通过抑制NLRP3炎症小体激活对抑郁症模型大鼠海马神经元产生保护作用，为OAL临床应用提供理论依据。
-
![]()
图 1 同一患者的恶性 NML在不同检查方法中的表现
Figure 1. Manifestations of malignant NML in the same patient by different examination methods
A, US image, type Ⅳ lesions of invasive breast cancer; B, ARFI image, SWV=3.08 m/s; C, CEUS image, with the CEUS score being 4 points; D, pathological image of HE staining (original magnification ×20).
![]()
图 2 US、US+ARFI、US+CEUS、US+ARFI+CEUS的logistic回归分析的ROC曲线
Figure 2. ROC curves of US, US+ARFI, US+CEUS, and US+ARFI+CEUS
Logistic regression analysis showed statistically significant differences in the AUC of each ROC curve (P<0.001), with US+ARFI+CEUS showing the best diagnostic effect.
表 1 NMLs 病例超声分型及恶性占比
Table 1 The ultrasonic classification and malignancy proportion of the NMLs cases
Type Total
(n=407)Malignance
(n=187)Benignity
(n=220)Malignancy
proportionⅠa 99 25 74 25.3% Ⅰb 96 79 17 82.3% Ⅱa 107 24 83 22.4% Ⅱb 54 42 12 77.8% Ⅲ 18 8 10 44.4% Ⅳ 17 2 15 11.8% Ⅴ 16 7 9 43.8% 
下载: 导出CSV
表 2 非肿块型病变超声征象
Table 2 Ultrasonic signs of non-mass-like lesions
Ultrasonic image feature n Malignancy Benignity Odds ratio P Average age/yr. 49.3 45.2 <0.001 Distorted structure/case <0.001 Yes 160 115 45 6.21 None 247 72 175 Posterior echo/case 0.128 Attenuation 184 114 70 3.35 No attenuation 223 73 150 CEUS/case <0.001 High enhancement 254 173 81 21.21 Other enhancement 153 14 139 Contrast score/case <0.001 5 points 88 71 (80.7%)* 17 4 points 97 76 (79.2%)* 21 3 points 69 26 (37.7%)* 43 2 points 136 13 (9.6%)* 123 1 poins 17 1 (5.9%)* 16 Axillary lymph nodes/case 6.22 0.021 Abnormal 114 87 27 Normal 293 100 193 Elastic score/case <0.001 ≥4.28 m/s 178 129 50 7.56 <4.28 m/s 229 58 170 Calcification/case <0.001 Micro-calcification 166 129 38 10.65 None 241 58 182 Peak systolic velocity/case 9.89 <0.001 ≥15.9 cm/s 75 64 11 <15.9 cm/s 332 123 209 * Malignancy proportion in brackets.
下载: 导出CSV
表 3 NMLs多模态超声logistic回归分析结果
Table 3 Results of the multimodal ultrasonic logistic regression analysis of NMLs
Variable β SE Wald df P OR 95% CI Distorted structure (X1) 0.684 0.350 3.818 1 0.051 1.982 0.998-3.935 Age (X2) 1.042 0.318 10.738 1 0.001 2.836 1.520-5.290 Classification (X3) 2.117 0.334 40.197 1 < 0.0001 8.309 4.318-15.989 Contrast score (X4) 1.905 0.348 30.040 1 < 0.0001 6.718 3.400-13.277 Attenuation (X5) 0.032 0.341 0.009 1 0.925 0.969 0.496-1.890 Axillary lymph nodes (X6) 0.633 0.371 2.907 1 0.088 1.884 0.910-3.900 Blood flow classification (X7) 0.607 0.448 1.833 1 0.176 1.884 0.762-4.420 Frequency spectrum (X8) 0.035 0.482 0.005 1 0.943 1.035 0.402-2.664 RI (X9) 1.095 0.455 5.781 1 0.016 2.989 1.224-7.299 AFRI imaging (X10) 0.866 0.345 6.315 1 0.012 2.378 1.210-4.672 Constant 3.482 0.369 88.796 1 < 0.0001 0.031 β: partial regression coefficient; SE: standard error; OR: odds ratio; CI: confidence interval.
下载: 导出CSV
表 4 超声多模态检查对不典型NMLs的诊断效能
Table 4 Diagnostic efficiency of ultrasonic multimodal examination of atypical NMLs
Type ARFI/CEUS* Pathological examination/case Sensitivity Specificity Accuracy rating Malignant Benign Ⅰa Malignant 20 25 80.0% 66.2% 69.7% Benign 5 49 Ⅱa Malignant 23 18 95.8% 75.0% 80.2% Benign 1 54 Ⅲ Malignant 7 5 87.5% 50.0% 66.7% Benign 1 5 Ⅳ Malignant 2 5 100% 66.7% 70.6% Benign 0 10 Ⅴ Malignant 5 4 71.4% 60.0% 64.7% Benign 2 6 Total Malignant 57 57 86.4% 68.5% 73.3% Benign 9 124 * When the lesion scored 4 or 5 in CEUS or SWV≥4.28 m/s in ARFI, it was considered malignant.
下载: 导出CSV
-
[1] 王知力, 唐杰, 李俊来, 等. 乳腺非肿块型病变的超声诊断. 中国医学影像学杂志, 2013, 21(1): 13–15. doi: 10.3969/j.issn.1005-5185.2013.01.004. WANG Z L, TANG J, LI J L, et al. Ultrasound diagnosis of non-mass-like breast lesions. Chin J Med Imaging, 2013, 21(1): 13–15. doi: 10.3969/j.issn.1005-5185.2013.01.004.
[2] CHA H, CHANG Y W, LEE E J, et al. Ultrasonographic features of pure ductal carcinoma in situ of the breast: correlations with pathologic features and biological markers. Ultrasonography, 2018, 37(4): 307. doi: 10.14366/usg.17039.
[3] ASSING M A, PATEL B K, KARAMSADKAR N, et al. A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer. Breast J, 2017, 23(6): 647–655. doi: 10.1111/tbj.12812.
[4] LIU X, WANG M H, WANG Q, et al. Diagnostic value of contrast-enhanced ultrasound for sentinel lymph node metastasis in breast cancer: an updated meta-analysis. Breast Cancer Res Treat, 2023, 202(2): 221–231. doi: 10.1007/s10549-023-07063-2.
[5] 肖晓云, 智慧, 杨海云, 等. 超声造影5分法诊断乳腺肿物的价值初探. 中华超声影像学杂志, 2012, 21(4): 328–331. doi: 10.3760/cma.j.issn.1004-4477.2012.04.018. XIAO X Y, ZHI H, YANG H Y, et al. Initial study of contrast-enhanced ultrasound 5-point scoring system in the diagnosis of breast tumor. Chin J Ultrasonogr, 2012, 21(4): 328–331. doi: 10.3760/cma.j.issn.1004-4477.2012.04.018.
[6] HSU H H, YU J C, LEE H S, et al. Complex cystic lesions of the breast on ultrasonography: feature analysis and BI-RADS assessment. Eur J Radiol, 2011, 79(1): 73–79. doi: 10.1016/j.ejrad.2009.12.037.
[7] 池月芮, 刘丽, 刘喜艳, 等. 常规超声分型和超声造影在乳腺非肿块型病变中的应用价值.肿瘤防治研究, 2022, 49(10): 1048-1053. doi: 10.3971/j.issn.1000-8578.2022.22.0128. CHI Y R, LlU L, LIU X Y, et al. Application value of conventional ultrasound classification and contrast-enhanced ultrasound in non-mass breast-like lesions. Cancer Res Prev Treat, 2022, 49(10): 1048–1053. doi: 10.3971/j.issn.1000-8578.2022.22.0128.
[8] PARK K W, PARK S, SHON I, et al. Non-mass lesions detected by breast US: stratification of cancer risk for clinical management. Eur Radiol, 2021, 31(3):1693-1706. doi: 10.1007/s00330-020-07168-y.
[9] UEMATSU T. Non-mass-like lesions on breast ultrasonography: a systematic review. Breast Cancer, 2012, 19(4): 295–301. doi: 10.1007/s12282-012-0364-z.
[10] 韩龄锋. 多模态超声联合评分法对乳腺非肿块型病变的诊断价值. 重庆: 西南医科大学, 2018. HAN L F. Diagnostic value of multimodal ultrasound and its combined scoring method for non-lump type lesions of the breast. Chongqing: Southwest Medical University, 2018.
[11] LI D D, XU H X, GUO L H, et al. Combination of two-dimensional shear wave elastography with ultrasound breast imaging reporting and data system in the diagnosis of breast lesions: a new method to increase the diagnostic performance. Eur Radiol, 2016, 26(9): 3290–300. doi: 10.1007/s00330-015-4163-8.
[12] 吴小茜, 江燕辉, 刘美伶, 等. 恶性乳腺非肿块型病变超声特征分析及列线图预测模型构建. 实用医学杂志, 2023, 39(1): 119–123. doi: 10.3969/j.issn.1006-5725.2023.01.021. WU X X, JIANG Y H, LIU M L, et al. Analysis of ultrasound characteristics of malignant breast non-mass-like lesins and development of a nomogram. J Pract Med, 2023, 39(1): 119–123. doi: 10.3969/j.issn.1006-5725.2023.01.021.
[13] LI M, LI Q, YIN Q, et al. Evaluation of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of breast cancer. Clin Transl Oncol, 2021, 23(4): 709–717. doi: 10.1007/s12094-020-02501-9.
[14] 周雅筠, 谢瑾, 张蓓, 等. 常规超声、超声造影、钼靶X线、磁共振成像及联合检测对早期乳腺癌患者的诊断价值. 贵州医科大学学报, 2023, 48(2): 172–176. doi: 10.19367/j.cnki.2096-8388.2023.02.008. ZHOU Y Y, XIE J, ZHANG B, et al. Diagnostic values of conventional ultrasound, contrast-enhanced ultrasound, mammography, magnetic resonance imaging and their combinations in diagnosing patients with early breast cancer. J Guizhou Med Univ, 2023, 48(2): 172–176. doi: 10.19367/j.cnki.2096-8388.2023.02.008.
[15] TOZAKI M, ISOBE S, YAMAGUCHI M, et al. Ultrasonographic elastography of the breast using acoustic radiation force impulse technology: preliminary study. Jpn J Radiol, 2011, 29(6): 452–456. doi: 10.1007/s11604-011-0561-2.
[16] 王洲, 刘芳欣, 殷延华, 等. 声触诊组织成像定量技术联合超声造影诊断乳腺原发性淋巴瘤1例. 中国医学影像技术, 2021, 37(1): 157. doi: 10.13929/j.issn.1003-3289.2021.01.040. WANG Z, LIU F X, YIN Y H, et al. Virtual touch tissue imaging quantification combined with contrast-enhanced ultrasound in diagnosis of breast primary lymphoma: case report. Chin J Med Imag Tech, 2021, 37(1): 157. doi: 10.13929/j.issn.1003-3289.2021.01.040.
[17] 马丹丹, 王涛, 刘国岩, 等. 乳腺造影评分法校正分类对乳腺肿块的鉴别价值. 长春中医药大学学报, 2023, 39(11): 1262–1265. doi: 10.13463/j.cnki.cczyy.2023.11.019. MA D D, WANG T, LIU G Y, et al. Value of correcting the classification of mammography scoring method in distinguishing benign and malignant breast masses. J Changchun Univ Tradit Chin Med, 2023, 39(11): 1262–1265. doi: 10.13463/j.cnki.cczyy.2023.11.019.
[18] 闫玉琪, 欧笛, 倪晨, 等. 超声造影及相关新技术在乳腺癌诊疗中的研究进展. 肿瘤影像学, 2023, 32 (6): 561−566. doi: 10.19732/j.cnki.2096-6210.2023.06.013. YAN Y Q, OU D, NI C, et al. Research progress of contrast-enhanced ultrasound and related new technologies in the diagnosis treatment of breast cancer. Oncoradiology, 2023, 32 (6): 561−566. doi: 10.19732/j.cnki.2096-6210.2023.06.013.
[19] 张庆坤, 冷晓玲, 张芬, 等. 超声造影对早发性乳腺癌的诊断价值. 中国超声医学杂志, 2015, 31(4): 305–307. ZHANG Q K, LENG X L, ZHANG F, et al. Diagnostic value of contrast-enhanced ultrasonography in early-onset breast cancer. Chin J Ultrasound Med, 2015, 31(4): 305–307.
[20] OLENA W, WEI Y. Imaging of breast cancers with predilection for nonmass pattern of growth: invasive lobular carcinoma and DCIS--does imaging capture it all? AJR, 2020, 215(6): 1504–1511. doi: 10.2214/AJR.19.22027.
开放获取 本文遵循知识共享署名—非商业性使用4.0国际许可协议（CC BY-NC 4.0），允许第三方对本刊发表的论文自由共享（即在任何媒介以任何形式复制、发行原文）、演绎（即修改、转换或以原文为基础进行创作），必须给出适当的署名，提供指向本文许可协议的链接，同时标明是否对原文作了修改；不得将本文用于商业目的。CC BY-NC 4.0许可协议详情请访问 https://creativecommons.org/licenses/by-nc/4.0
计量
- 文章访问数: 88
- HTML全文浏览量: 33
- PDF下载量: 8
