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不同功能磁共振成像技术在乳腺癌中的应用进展
冯雯 刘欣然 卢星如 雷军强

Cite this article as: FENG W, LIU X R, LU X R, et al. Progress in the application of different functional magnetic resonance imaging techniques in breast cancer[J]. Chin J Magn Reson Imaging, 2024, 15(1): 217-223.本文引用格式:冯雯, 刘欣然, 卢星如, 等. 不同功能磁共振成像技术在乳腺癌中的应用进展[J]. 磁共振成像, 2024, 15(1): 217-223. DOI:10.12015/issn.1674-8034.2024.01.037.


[摘要] 乳腺癌成为全球第一大癌症,充分了解不同功能MRI技术在乳腺癌中的应用有利于推进乳腺癌诊疗的发展。本文通过介绍不同功能MRI技术在乳腺癌早期诊断和晚期预后评估中展现出的临床科研价值,说明基于灌注、代谢、扩散、合成相关MRI,使肿瘤组织微血管渗透、分布、血流动力学状态,肿瘤代谢物含量、间质成分变化及组织固有属性等特征可视化,旨在总结各成像序列在乳腺癌应用中的优势和前景,以期为后续乳腺癌影像科学研究提供新方向,从而帮助影像医师更加全面地了解乳腺癌相关MRI技术手段。
[Abstract] Breast cancer is the number one cancer in the world. Fully understanding the application of different functional magnetic resonance imaging techniques in breast cancer is conducive to promoting the development of breast cancer diagnosis and treatment. This paper introduced the excellent clinical and scientific value of different functional magnetic resonance imaging techniques in early diagnosis and late prognosis of breast cancer, with making use of perfusion, metabolism, diffusion and synthetic magnetic resonance imaging, so that the characteristics of the permeability, distribution and hemodynamic state of the microvascular of tumor tissue, the content of metabolites, the change of tumor stroma and the inherent attribute can be visualized. This paper aimed at summarizing the advantages and prospects of various MRI imaging sequences of breast cancer, in order to provide a new direction for the future research, so as to help radiologists more comprehensively understand the MRI techniques of breast cancer.
[关键词] 乳腺癌;多模态;磁共振成像;功能磁共振成像;合成磁共振成像;影像学技术
[Keywords] breast cancer;multimodality;magnetic resonance imaging;functional magnetic resonance imaging;synthetic magnetic resonance imaging;radiological technology

冯雯 1, 2, 3, 4   刘欣然 1, 2, 3, 4   卢星如 2, 3, 4   雷军强 2, 3, 4*  

1 兰州大学第一临床医学院,兰州 730000

2 兰州大学第一医院放射科,兰州 730000

3 甘肃省智能影像医学工程研究中心,兰州 730000

4 甘肃省放射影像医学临床医学研究中心,兰州 730000

通信作者:雷军强,E-mail:leijq2011@126.com

作者贡献声明::雷军强设计本研究的方案,对稿件重要内容进行了修改;冯雯起草和撰写稿件,获取、分析和解释本研究的文献;刘欣然、卢星如获取、分析本研究的文献,对稿件重要内容进行了修改;冯雯、卢星如分别获得了甘肃省教育科技创新项目、甘肃省自然科学基金项目资助。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: 甘肃省教育科技创新项目 2022B-025 甘肃省自然科学基金项目 21JR1RA079
收稿日期:2022-09-09
接受日期:2024-01-04
中图分类号:R445.2  R737.9 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2024.01.037
本文引用格式:冯雯, 刘欣然, 卢星如, 等. 不同功能磁共振成像技术在乳腺癌中的应用进展[J]. 磁共振成像, 2024, 15(1): 217-223. DOI:10.12015/issn.1674-8034.2024.01.037.

0 引言

       近年来MRI在乳腺癌(breast cancer, BC)疾病管理过程中发展迅速,尤其在初诊分期、治疗决策及预后评价等方面承载重要价值,并根据不同模型权衡利弊,明确风险分层[1]。根据GLOBOCAN2020最新数据,BC超过肺癌位居全球癌症发病率首位,新发病例约230万[2],提升BC早诊早治技术迫在眉睫。BC进展机制包含肿瘤氧合水平、代谢物含量、间质成分及血流渗透变化,更深层面包括细胞凋亡逃避、细胞无限分裂、血管生成、抵抗抗生长信号及诱导自身生长信号等能力。临床中根据不同分子预后标志物表达及不同时序治疗方式的组合对BC开展诊治工作[3]。不同功能MRI功能序列不断推陈出新,新兴序列相互验证,技术设施日益完善,为BC诊治提供多角度影像学信息。近年来大部分研究均会从乳腺良恶性病变的鉴别[4]、BC新辅助治疗疗效的状态[5, 6]、BC人工智能的初探[7, 8]等方面进行阐述,目前鲜有文章通过总结BC灌注、代谢、扩散、合成相关技术应用的最新优势、最突出的局限性以及有待研究的具体技术方向而说明BC组织的不同属性特点,本文旨在介绍不同功能MRI技术在BC中的应用进展,以期为后续BC个性化诊疗提供新的技术手段和科研基础。

1 乳腺癌灌注、代谢及扩散相关技术应用

1.1 乳腺癌灌注相关MRI(组织微血管渗透、分布、动力学改变)

1.1.1 无对比剂灌注成像

       正常乳腺组织由胸廓内动脉、肋间动脉和胸外侧动脉供血,通常灌注较低,高灌注BC显影明确。动脉自旋标记(arterial spin labeling, ASL)在无对比剂时通过纵向磁化标记感兴趣组织的供应血管实现灌注量化,并识别不同BC亚型的血管分布。速度选择性ASL(velocity selective arterial spin labeling, VS-ASL)则是利用高于某截止速度的流速标记血液,若截止速度足够低,可基本消除传输延迟,VS-ASL将可能成为动态对比增强MRI(dynamic contrast-enhanced MRI, DCE-MRI)的非对比增强替代方案[9, 10]。BUCHBENDER等[9]研究评估非增强ASL技术用于量化BC灌注的可行性,ASL作为一种非增强成像技术,通过改变纵向磁化来标记供应组织的动脉血液,由于ASL信号变化与血流成正比,因此可以很容易地对组织灌注进行MRI量化,结果表明浸润性导管癌(invasive ductal carcinoma, IDC)的平均ASL灌注高于正常乳腺实质及浸润性小叶癌(P<0.05)。FRANKLIN等[10]研究利用李克特三点量表证实了VS-ASL测量BC灌注和血管分布的可行性,结果表明肿块病变的可见性平均得分为1.27,伪影得分为1.53。非肿块性病变的平均可见性评分为2.11,伪影评分为2.11。其中病变可见性评分越高,病变与周围组织区分度越差;伪影评分越高,伪影与血液信号强度相似度越高。未来ASL技术应着眼于优化脂肪和腺体组织的抑制技术、解决乳腺高脂肪含量引起的B1+和B0场不均匀、区分动静脉信号、解释病灶附近病理血管床所致的灌注节段性增加、探索最佳截止流速、减少致密型乳房图像中脂肪和腺体之间的高对比度造成的减影伪影、解决因内乳动脉流速较低及传输延迟导致的ASL信号丢失、提供早期灌注及血管壁通透性信息等问题。

1.1.2 对比剂灌注成像

       近年来DCE的科研方向不仅着眼于原发病灶的分期分型,而且重视瘤周组织及腋窝淋巴结(axillary lymph node, ALN)的量化特征,MENG等[11]研究利用Kaiser评分对243名女性的268个BI-RADS 4病灶分析,Kaiser score的总体诊断性能(AUC=0.902)显著高于表观扩散系数(apparent diffusion coefficient, ADC)(AUC=0.81;P=0.004);无论乳腺背景实质强化如何,Kaiser score+(ADC与Kaiser score相结合的指标)和Kaiser score均具有良好的诊断性能。XU等[12]将294名患者DCE动脉早期第一个增强后图像分割,使用AK软件将原始ROI等距三维扩张4 mm获取瘤周ROI,共提取208个瘤内及瘤周放射组学特征。结果显示结合瘤内和瘤周的放射组学特征是术前预测浸润性乳腺癌(invasive breast cancer, IBC)导管内成分的最佳模型。GAN等[13]研究基于深度学习(deep learning, DL)技术提取腋窝区、可见ALN及BC原发灶的影像组学特征,提示联合放射组学特征和临床因素的临床放射组学模型可提高对腋窝病理完全缓解的预测能力。但ALN影像和病理结果之间的对应关系仍是ALN的研究难点,部分患者行乳腺MRI扫描时无法覆盖全部腋窝区域,未来是否能通过改变检查体位、使用特殊腋窝线圈或在ALN中放置标记夹等方式提高转移性ALN的检出有待研究。

       DCE高空间分辨率可描绘肿瘤精细结构和形态,但描述对比剂的摄取需要高时间分辨率。传统DCE-MRI往往在时间分辨率和空间分辨率间难以取舍,MORRISON等[14]研究显示与目前临床标准治疗(clinical standard-of-care, SOC)-MRI扫描相比,基于笛卡尔采集的K空间共享三维容积快速动态成像(differential subsampling with cartesian ordering, DISCO)具有相同的高空间分辨率,其有效时间分辨率是SOC-MRI的6倍,并提供17个额外的时间帧,脂肪抑制也得到改善,显示更高的峰值增强,并且DISCO能在动态对比流入阶段的高时间/中等空间分辨率模式与延迟阶段在高空间/低时间分辨率模式之间无缝切换,比传统低空间分辨率动态图像更清晰[15]。KIM等[16]研究显示超快DCE-MRI的最大斜率(OR=0.982,P=0.040)与病理完全缓解(pathological complete response, pCR)相关;在病变开始增强和增强后二者时间点获得的肿瘤体积比与三阴性乳腺癌(triple-negative breast cancer, TNBC)的pCR独立相关(OR=14.811,P=0.005)。常规DCE扫描时间为pre63.7 s+5期318.5 s=382.2 s,而超快DCE为pre6.5 s+9期58.5 s=65.0 s,且乳腺超快DCE-MRI时间分辨率超高,约4⁓7 s。研究表明超快DCE-MRI的流入斜率是BC患者pCR的独立预测因素,且流入斜率值可识别具有不同pCR率人表皮生长因子受体2(human epidermal growth factor receptor 2, HER-2)阳性癌症的两个亚群[17]。动态磁敏感增强(dynamic susceptibility contrast, DSC)序列因信噪比(signal-to-noise ratio, SNR)较低很少集成在乳腺DCE-MRI协议中。STADLBAUER等[18]研究仅注射一剂对比剂获得了三种灌注MRI数据(梯度回波DSC、自旋回波DSC和DCE灌注),其中DSC包含60次动态测量,分析定量血氧水平依赖(quantitative blood oxygenation level-dependent, qBOLD)中氧代谢和血管结构图无创评估乳腺肿瘤缺氧和新生血管形成。总之,ASL技术可能成为增强序列的替代方案,为BC的鉴别诊断、灌注和血管分布信息提供支持;DCE序列可为NAC后pCR提供独立预测因子,其组学研究可全体积挖掘BC肿瘤异质性;DISCO序列能够又快又准实现早期诊断BC;DSC有望无创评估BC的缺氧和血管形成状态。

1.2 乳腺癌代谢相关MRI(肿瘤代谢物含量变化)

1.2.1 酰胺质子转移加权成像

       化学交换饱和转移(chemical exchange saturation transfer, CEST)成像是基于磁化传递及化学交换理论的新技术,酰胺质子转移加权成像(amide proton transfer-weighted imaging, APTWI)是CEST成像的一种。APTWI利用酰胺质子与自由水质子化学交换,将酰胺质子浓度变化转变为自由水信号变化,无创监测肿瘤细胞的代谢及病理生理转归,将MRI技术扩展到蛋白质层面[19, 20]。LIU等[21]研究显示APTWI具有鉴别乳腺良恶性病变的潜力,并与BC的肿瘤分级、T分期和增殖活性相关,其中APTWI信号与Ki-67指数(r=0.364)显著相关。ZHANG等[22]通过非对称磁化转移率(MTRasym -3.5 ppm)和3.5 ppm处洛伦兹线形拟合(Lor3.5)两种方法比较APTWI信号,结果得出与pCR患者的基线组相比,第二周期(two cycles, C2)组平均Lor3.5在0.9 µT时显著降低(P=0.03),基线-C2的APTWI信号变化是有效的早期反应标志物。ZHANG等[23]研究表明APTWI与DCE-MRI术前区分良恶性病变均优于扩散加权成像(diffusion weighted imaging, DWI),并兼具肿瘤细胞活性的补充信息。而研究[24, 25]表明体素内不相干运动(intravoxel incoherent motion, IVIM)、扩散峰度成像(diffusion kurtosis imaging, DKI)和APTWI均可用于乳腺良恶性病变的鉴别诊断,其中DKI较APTWI更具优势,可能是由于水分子扩散的差异比蛋白质及多肽含量的差异更为显著,且微环境中影响蛋白质和多肽含量的因素仍不明确。而周仕豪等[26]研究显示APTWI和DKI技术在鉴别乳腺良恶性病变时均表现出较高的诊断效能,且多参数联合应用的诊断效能显著提高,其中DKI参数可提示不同病理因素的BC对瘤周区域的影响。文洁等[27]证实了乳腺良恶性病变较正常组织有更高的APTWI效应,其效应可反映BC的浸润程度和细胞增殖指数,提示APTWI能够用于预测BC的预后。总之,APTWI作为无创宏观MRI技术,来获取微观分子层面物质变化,无论是在BC鉴别诊断方面,还是pCR状态判定及预测预后方面均具有一定的价值和潜力,但蛋白质分子相较于水分子,影响其变化的因素较多,且APTWI在BC中的应用技术尚不成熟,扫描时间亟待缩短,需要大规模的实验来进一步验证明确的诊断效能。

1.2.2 氧代谢成像

       缺氧(低氧合状态)被认为是肿瘤本身的一种微环境特征,乏氧性肿瘤可能会对放、化疗抵抗[28, 29]。根据氧合血红蛋白(反磁性)和脱氧血红蛋白(顺磁性)之间的磁化率差异,基于有效横向弛豫时间T2*与组织氧合之间的间接关系建立函数来描述血氧水平依赖(blood oxygenation level dependent, BOLD)效应。STADLBAUER等[18]计算qBOLD中的氧提取分数、氧代谢率(metabolic rate of oxygen, MRO2)、线粒体氧张力(mitochondrial oxygen tension, mitoPO2)值,结果显示与良性乳腺肿瘤相比,IDC的MRO2更高(P=0.007),mitoPO2更低(P=0.021),反映IDC会消耗更多氧气。FUSCO等[30]研究表明BOLD-MRI衍生参数不能区分乳腺良恶性病变,而且与单独使用DCE-MRI相比,DCE-MRI、DWI-MRI和/或BOLD-MRI的联合使用在乳腺病变分类中并没有显著改善。但值得注意的是R2*和组织扩散系数(tissue diffusivity, Dt)之间呈负相关。WANG等[29]发现BOLD-MRI的R2*值与缺氧标志物碳酸酐酶Ⅸ正相关(r=0.616,P<0.001),但与血管内皮生长因子不相关(r=0.110,P=0.281),说明BOLD-MRI可评价IDC慢性缺氧,但不能评价血管生成;而且ALN转移阳性的R2*值高于无ALN转移的R2*值(t=2.882,P=0.005),目前R2*与其他类型BC、氧分压(oxygen pressure, PO2)的关系,乳腺BOLD-MRI与缺氧类型的关系,供血不足或低PO2是否影响乳腺脂肪信号等问题尚不明确,未来可开发缺氧相关成像标志物并指导缺氧激活的靶向治疗。

1.2.3 钠离子代谢成像

       钠离子(Na+)在细胞代谢中起重要作用,与正常腺体或脂肪组织相比,BC内部的钠钾泵电化学梯度变化使组织钠浓度(tissue sodium concentrations, TSC)显著增加。ZARIC等[31]证实7.0 T Na+磁共振成像(sodium magnetic resonance imaging, Na-MRI)中定量TSC可预测BC新辅助化疗(neoadjuvant chemotherapy, NAC)的早期治疗结果,肿瘤体积缩小及TSC降低表明癌症对NAC有反应。结果显示在第一个和第二个化疗周期后肿瘤体积缩小预测NAC反应的AUC为0.73 [95% 置信区间(confidence interval, CI):0.09,0.50;P=0.12]和0.93(95% CI:0.04,0.60;P<0.001),而TSC降低的AUC分别为0.96(95% CI:0.86,1.00;P<0.001)和1.000(95% CI:1.00,P<0.001),TSC有望成为识别BC预后不良和晚期进展的MRI标志物。王卓等[32]研究纳入88例乳腺IDC患者,结果显示mDixon-Quant衍生的、脂肪分数值和T2*值是乳腺IDC组织学分级的独立预测因素,两参数值联合有助于提高诊断的特异度,且与预后病理特征具有一定的相关性。目前,Na+浓度的潜在变化、最佳加权因子的确定、信噪比及空间分辨率的提高以及如何校正相控阵线圈的接收曲线均是Na-MRI需攻克的技术难点。

1.2.4 脂质代谢成像

       由于BC的进展与脂质成分改变有关,磁共振波谱(magnetic resonance spectroscopy, MRS)可监测乳腺组织中的脂质代谢物。BITENCOURT等[33]研究证明与正常纤维腺体组织相比,IBC中所有脂质代谢物的平均浓度均降低,表现为2.1+2.3 ppm脂肪峰降低;5.2+5.3 ppm脂肪峰在雌激素受体(estrogen receptor, ER)和孕激素受体(progesterone receptor, PR)不同状态的BC之间差异有统计学意义。CHEUNG等[34]采用术后离体BC行MRS扫描,得出淋巴血管浸润(lymphovascular invasion, LVI)阳性IBC的单不饱和脂肪酸(monounsaturated fatty acids, MUFA)、甘油三酯浓度显著低于LVI阴性IBC,LVI阴性BC中MUFA的增加表明过量饱和脂肪酸(saturated fatty acids, SFA)加速转化为膜磷脂合成和表皮生长因子信号传导,而LVI阳性BC中MUFA减少是由于SFA通过侵入淋巴管系统的肿瘤细胞对外输出。目前,MRS体素大小的设置、单体素或多体素的选择以及特殊类型BC产生的假阳性和假阴性结果等问题有待探索。总之,APTWI、BOLD-MRI、Na-MRI、MRS、mDixon-Quant能够分别对应BC的酰胺质子代谢状态、缺氧状态、钠浓度变化、脂质代谢及脂肪分数变化等。

1.3 乳腺癌扩散相关MRI(肿瘤间质成分变化)

1.3.1 常规DWI及其衍生扩散成像

       DWI通过ADC量化组织中水分子的扩散运动情况。LEE等[35]基于术前乳腺DWI-MRI模型预测经活检证实为乳腺原位导管癌患者分期的升级。目前人工智能席卷放射学诸多领域,在扫描技术方面,基于DL重建的DWI是一种新兴技术,能够使采集时间显著缩短,同时保持整体图像质量,并提高空间分辨率[36]。在诊断应用方面,ZHU等[37]利用3 303名女性患者的3 607个BC病灶,结果得出与单输入DWI或DCE模型相比,多输入DCE和DWI模型的敏感度、特异性和准确度显著提高,DL计算机辅助诊断模型有望提供BC初步诊断信息。DALMIS等[38]将人工智能乳腺分类系统应用于包含超快DCE、T2以及DWI的多参数MRI检查,区分乳腺良恶性病变最高AUC达到0.852,并且提高了诊断特异度。还有研究[39]利用多参数MRI的DL模型预测TNBC新辅助全身治疗的病理完全反应。在开发阶段,DL模型在训练集和验证集的AUC分别为0.97和0.82;在独立试验组中,AUC为0.86;在前瞻性盲法试验组中,该模型AUC为0.83,这些结果均表明,基于多参数MRI的DL模型可以潜在区分BC早期pCR或非pCR患者。IVIM使用多b值和双指数模型测量扩散参数,Dt和灌注参数包括伪扩散系数(pseudo-diffusion coefficient, Dp)、灌注分数(perfusion fraction, f)以及f和Dp的乘积(反映微血管血流)。拉伸指数模型(stretched-exponential, SEM)通过测量分布扩散系数和扩散异质性指数来评估体素内水分子扩散的异质性。DKI通过水的非高斯扩散运动反映组织异质性以及水分子与相邻组织间的相互作用[40, 41, 42, 43, 44]。HONDA等[45]前瞻性评估101名IBC患者的IVIM及非高斯扩散图像,结果得出峰度参数可能帮助识别远处转移风险升高的患者,并且与非高斯扩散参数相比,IVIM参数在预测BC远处转移方面略差。但是IVIM和非高斯扩散均可预测BC的ALN转移,其中D为最佳参数[46]。ALMUTLAQ等[40]研究评估DWI、SEM和IVIM对BC的NAC结果的预测能力,结果显示非单指数模型比单指数模型能更好地预测NAC反应。WANG等[41]研究表明D、D*、f和平均扩散峰度(mean kurtosis, MK)值是Ki-67表达的独立预测因子;其中D*与MK相结合评估BC诺丁汉预后指数更有价值;在分子分型方面,D、D*、平均扩散率(mean diffusion rate, MD)和MK组合,MK和f组合分别可提高Luminal型BC以及TNBC的诊断效能[33]。HER-2型BC的f和D*值较高,说明此型BC有更多的血管生成;TNBC的f和D*值较低,可能与坏死导致的肿瘤中心灌注减少有关[42]。ZHAO等[43]研究发现ALN转移阳性BC的D*和f更高,表明肿瘤增殖伴随着更多的血管生成。吴祺等[47]研究显示IVIM联合DCE-MRI有助于提高MRI对于非肿块强化(non-mass enhancement, NME)腺病和BC的鉴别诊断效能,且时间-信号强度曲线(time-signal intensity curve, TIC)类型和D*值是预测NME-BC的独立风险因素。王洪杰等[48]探究联合应用DWI、IVIM-DWI及DKI所获各参数对乳腺DCE-TIC-平台型良、恶性病变的鉴别诊断价值。多因素logistic回归分析得出D值及MK值为两组鉴别诊断的独立影响因素,其中MK值优势比最大,对应AUC为0.871,特异度为88.0%,敏感度为80.8%,准确度为78.6%。张锲等[49]研究对于乳腺良恶性病变的诊断,IVIM及DKI参数中的MK值具有较大的AUC,D值具有较高的敏感度和特异度,联合诊断中的D+MK值的AUC及敏感度最大。在扩散序列研究中,b值的选择是关键点也是争议点,DOUDOU等[44]认为IVIM的b值并不是越多越好,如何利用最少的b值得出最佳结果有待研究。目前所有IVIM研究共同的限制是模型高噪声敏感性,且回波时间可能会影像IVIM参数评估。与回波时间校正模型相比,标准IVIM模型高估了D*值5%~46%[50]。图像失真和低空间分辨率限制了常规DWI,而复合灵敏度编码(multiplexed sensitivity-encoding, MUSE)是一种多镜头分段EPI技术,通过交错轨迹的K空间来扩展灵敏度,改进矩阵反演条件,获得更高空间分辨率及SNR,基于MUSE的高分辨率扩散成像无需导航回波,扫描时间明显缩短。MUSE在病变诊断性能优于单次回波平面成像,且MUSE和局部低秩约束图像相对于单次激发DWI具有更优的分辨率(P<0.001)、更高的SNR(P<0.005)和更低的失真(P<0.05)[51, 52]。MUSE-DWI属于高空间分辨率技术,MUSE-DWI的ADC值在乳腺恶良性病变之间存在显著差异(P<0.001)[53]。目前MUSE受限于接收线圈的设计和组件数量,且无法与更大矩阵匹配。总之,常规DWI及其衍生扩散成像在BC研究的各个方面均有涉及,不仅成像速度快,而且空间分辨率较优,但是IVIM中的D值、DKI中的MK值今后能否替代传统DWI中的ADC值,IVIM或DKI序列能否叠加使用MUSE成为MUSE-IVIM或MUSE-DKI序列,他们在BC中的诊断效能能否进一步提升,以及基于除外DWI序列的其他扩散成像关于人工智能方面的应用均需要更多的研究进行验证说明。

1.3.2 扩散张量及扩散频谱成像

       扩散张量成像(diffusion tensor imaging, DTI)中的MD反映类似于水质子各向同性无限制的平均扩散水平,与扩散方向无关;各向异性分数(fractional anisotropy, FA)反映水分子各向异性成分占整个扩散张量的比例及三个正交方向上水的扩散作用。TSOUGOS等[54]研究显示BC的MD值和特征值(λ1、λ2、λ3)显著低于良性病变(P<0.000 1),而BC的FA值(0.20±0.07)显著高于良性病变(0.15±0.05)(P=0.000 3),其中MD和λ1是区分乳腺良恶性病变的最佳参数。LUO等[55]还发现乳腺肿块性病变较非肿块样病变FA值高。ABDEL等[56]研究得出复发性乳腺癌的FA值(P=0.003,0.02)显著高于保乳术后的FA值;而MD值(P=0.001,0.001)显著低于术后变化。NISSAN等[57]研究显示相对于正常哺乳期实质,妊娠相关乳腺癌的MD和λ1、λ2、λ3参数值降低,FA值增加。乳腺DTI目前存在磁敏感及运动伪影、脂肪抑制不佳、SNR及空间分辨率较低等技术限制。扩散频谱成像(diffusion spectrum imaging, DSI)是利用整个q空间中的多个b值和梯度方向自由重构模型,对水分子的扩散信号采样,通过概率密度函数定量估计。MAO等[58]研究显示DSI定量参数在预测HER-2表达优于ADC值。HER-2阳性BC组神经突定向分散和密度成像的细胞内体积分数(intracellular volume fraction of neurite orientation dispersion and density imaging, NODDI_ICVF)比阴性组低,可能与HER-2阳性BC的细胞密集性有关,且仅有NODDI_ICVF是HER-2状态的独立预测因子(P=0.001)。NODDI是一个基于细胞间隔和神经处理方向由DSI中推导出来的低复杂性生物物理模型。NODDI_ICVF表示水分子在中枢神经系统轴突和细胞中的扩散。NODDI_ICVF降低可能与HER-2阳性乳腺癌的高细胞性有关。综上,DWI、IVIM、SEM、DKI、MUSE、DTI、DSI等扩散相关MRI均对BC的早期诊断及预后评价有一定价值,尤其DWI对应的ADC值、IVIM对应的D值、DKI对应的MK值对于BC鉴别诊断、预测BC分型以及ALN状态判定有较大意义。

2 合成MRI序列在乳腺癌中的应用(组织固有属性)

       新定量MRI技术—合成磁共振成像(synthetic magnetic resonance imaging, SyMRI)是基于涡轮自旋回波读数方法进行饱和恢复的多回波采集并量化弛豫时间和质子密度,有多延迟多回波(multi delay multi echo,MDME)、一站式弛豫定量(magnetic resonance image complication, MAGiC)等技术,10 min内通过单次扫描获取多对比度加权图像,其中包括T1、T2(T1和T2时间均是组织固有属性,分别反映纵向磁化矢量恢复和横向磁化矢量衰减情况)及质子密度加权成像(proton density weighted imaging, PDWI)等,并计算注射对比剂之前参数值(pre-参数值)、之后的参数值(参数值-Gd)以及参数值前后变化率(Δ参数值%)。MATSUDA等[59]研究表明pre-T1是唯一独立区分良恶性乳腺肿块的定量值。GAO等[60]研究显示BC的pre-T2、pre-PD、ADC值均显著低于良性病灶(P均<0.05)。LI等[61]研究说明SyMRI直方图参数中pre-T2平均值区分BC亚型的能力较为突出;组织病理学级别较高的BC具有较高的pre-PD值和pre-T1值。此外,HER-2阳性肿瘤细胞密度和血管生成的增加也可能导致pre-PD值增加。MATSUDA等[62]研究显示pre-T2(P=0.037)是TNBC独立预测因子。MATSUDA等[63]研究显示增殖核抗原Ki-67高增殖组T1-Gd(P<0.001)和T2-Gd(P=0.042)的标准差高于低增殖组;T1-Gd标准差是Ki-67表达水平的独立预测因子。SUN等[64]研究显示BC的ΔT1%高于良性病变组(77.18% vs. 74.20%,P<0.001)。ΔT1%每增加一个单位,病变为BC的几率增加1.95倍(OR=1.947;95% CI:1.233~3.073;P=0.004)。常规SyMRI的缺点是扫描时间长,患者耐受性降低,平衡扫描时间和图像质量以及诊断准确性具有很大的挑战,LI等[65]利用DL算法与生成对抗网络模型,通过端到端训练生成高质量的快速SyMRI图像,仅用标准SyMRI一半的扫描时间输出相同甚至更高质量的MRI图像,有利于SyMRI在BC诊断中的临床应用。扫描顺序、扫描参数(回波时间、重复时间、脂肪抑制技术、磁场强度)的差异均会影响SyMRI参数,对于非肿块样强化、小病灶、BI-RADS中假阳性病变的区分也是SyMRI研究的难点,可通过多中心、多病种、全体积以及纹理分析探索BC异质性。所以,SyMRI序列在BC鉴别诊断、预测分子预后因素中有潜在价值,且对比剂前后的变化值发挥巨大作用,有待进一步深度挖掘。

3 总结

       总之,BC的不同功能MRI技术从灌注、肿瘤代谢、间质成分变化、组织固有属性等方面来阐释病变的解剖信息、发病机制、病理生理功能转换,并对BC早诊早治、风险判别及预后评价等提供全面的影像学信息,从而更深层面地了解BC的发生发展,为精准医疗奠定科学基础。当然,未来应深度挖掘更多MRI技术在BC中的应用细节,将临床诊疗需求作为出发点,全方位将BC不同功能MRI的科研价值发挥更大的作用。

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