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提升定量MRI在头颈部疾病诊疗中的价值
鲜军舫

Cite this article as: Xian JF. Improve the value of quantitative MRI in the diagnosis and treatment of head and neck diseases[J]. Chin J Magn Reson Imaging, 2022, 13(11): 1-5.本文引用格式:鲜军舫. 提升定量MRI在头颈部疾病诊疗中的价值[J]. 磁共振成像, 2022, 13(11): 1-5. DOI:10.12015/issn.1674-8034.2022.11.001.


[摘要] 虽然头颈部结构微细复杂,但高分辨率MRI显著提高了头颈部结构和病变的显示能力。本文论述了定量MRI在视神经炎、甲状腺相关性眼病、视网膜母细胞瘤侵犯筛板后视神经、鼻咽癌、口咽癌、喉癌、甲状腺癌、鼻腔鼻窦内翻性乳头状瘤、涎腺多形性腺瘤、淋巴瘤和炎性假瘤等头颈部疾病的显示与评估、鉴别诊断、分期与分级、疗效评估与预测、预后预测以及发生机制研究方面的作用,并阐明了存在的问题与未来解决思路。未来建议严格做好临床研究设计,确定纳入和排除标准,按照统一的诊断、评估和预测标准,以患者为中心、以临床问题为导向,开展全国多中心大样本量前瞻性研究,进一步提升定量MRI在头颈部疾病诊疗中的价值,并在临床推广应用,提高诊疗水平,保障人民健康。
[Abstract] The anatomic structures in head and neck are tiny and complex, but high resolution MRI significantly improve the diagnostic performance of MRI in the demonstration of anatomic structures and lesions in head and neck region. Quantitative MRI plays an important role in the identification, diagnosis, stage, grade, evaluation of treatment response, and prediction of prognosis as well as elucidation of the pathological mechanisms of head and neck diseases, such as optic neuritis, thyroid-associated ophthalmopathy, post-laminar optic nerve invasion from retinoblastoma, nasopharyngeal carcinoma, oropharyngeal carcinoma, laryngeal carcinoma, thyroid carcinoma, sinonasal inverted papilloma, pleomorphic salivary adenoma, lymphoma, inflammatory pseudotumor, etc. The problems and the problem-solving strategies are also described. In the future, the study design will be conducted strictly with inclusion and exclusion criteria defined. According to the same criteria of the diagnosis, evaluation, and prediction of the head and neck diseases, national large-sample multicenter prospective researches will be developed so as to establish patient-centered and problem-guided protocols of quantitative MRI of the head and neck diseases. These protocols will further improve the value of quantitative MRI in the diagnosis and treatment of head and neck diseases, which will be applied nationwide promoting diagnosis and treatment of head and neck diseases and protecting people's health.
[关键词] 视神经炎;甲状腺相关性眼病;视网膜母细胞瘤;鼻咽癌;口咽癌;喉癌;甲状腺癌;内翻性乳头状瘤;多形性腺瘤;淋巴瘤;炎性假瘤;青光眼;磁共振成像;动态对比增强;扩散加权成像;动脉自旋标记;诊断;疗效评价;发病机制;预后预测
[Keywords] optic neuritis;thyroid-associated ophthalmopathy;retinoblastoma;nasopharyngeal carcinoma;oropharyngeal carcinoma;laryngeal carcinoma;thyroid carcinoma;inverted papilloma;pleomorphic adenoma;lymphoma;inflammatory pseudotumor;glaucoma;magnetic resonance imaging;dynamic contrast enhancement;diffusion weighted imaging;arterial spin labeling;diagnosis;treatment response evaluation;pathological mechanism;prognosis prediction

鲜军舫 *  

首都医科大学附属北京同仁医院放射科,北京100730

鲜军舫,E-mail:cjr.xianjunfang@vip.163.com

作者利益冲突声明:全体作者均声明无利益冲突。


        
        鲜军舫,男,教授,一级主任医师,博士研究生导师,首都医科大学附属北京同仁医院医学影像中心主任、放射科主任。中华医学会放射学分会常务委员兼医学影像质量控制与管理规范工作组组长、中华医学会放射学分会第15届委员会头颈学组组长、中国医疗保健国际交流促进会影像医学分会主任委员、白求恩公益基金会影像诊断专业委员会副主任委员等。国务院政府特殊津贴专家、国家人力资源和社会保障部“有突出贡献的中青年专家”、国家卫生计生突出贡献中青年专家,入选国家百千万人才工程、北京市高层次创新创业人才支持计划领军人才和北京市医管中心“登峰”人才培养计划,北京市医管局“扬帆”计划眼耳鼻喉影像重点医学专业负责人。《磁共振成像》副主编、《Chinese Medical Journal》编委、《中华放射学杂志》编委和《中华解剖与临床杂志》副总编辑等。获国家科技进步二等奖2项、省部级科技成果一等奖2项和二等奖2项等奖项。

基金项目: 国家自然科学基金 81871340,82071906,82202100,81571649 北京市医院管理局临床医学发展专项 ZYLX201704 北京市医院管理中心“登峰”计划专项 DFL20190203
收稿日期:2022-11-11
接受日期:2022-11-13
中图分类号:R445.2  R76  R77 
文献标识码:A
DOI: 10.12015/issn.1674-8034.2022.11.001
本文引用格式:鲜军舫. 提升定量MRI在头颈部疾病诊疗中的价值[J]. 磁共振成像, 2022, 13(11): 1-5. DOI:10.12015/issn.1674-8034.2022.11.001

       虽然头颈部结构微细复杂,但高分辨率MRI设备和技术显著提高了头颈部结构和病变的显示能力,为病变的定位、累及范围及与周围重要结构关系的评估提供了更准确的信息[1, 2, 3, 4, 5, 6, 7]。除了提供形态学信息以外,头颈部定量MRI,包括源于动态对比增强MRI(dynamic contrast enhancement-magnetic resonance imaging, DCE-MRI)、扩散磁共振成像(diffusion magnetic resonance imaging, dMRI)、磁共振波谱成像(MR spectroscopy, MRS)和动脉自旋标记(arterial spin labeling, ASL)灌注成像以及基于MRI影像组学等获得的MRI定量参数,可反映病变的对比剂药物血流动力学特点、细胞密度和水分子运动的分子信息、组织成分、代谢和血流等,可用于头颈部疾病的早期诊断、鉴别诊断、分期与分级、活动性、疗效评估与预测及预后预测的定量分析,为诊断和治疗前后评估及预测提供重要的量化依据[6, 7, 8, 9, 10, 11, 12, 13, 14],为个性化精准诊疗提供客观依据。另一方面,MRI定量参数作为研究头颈部疾病发生机制的重要指标,为探索和揭示头颈部疾病的发生机制提供了新的方法和平台,为寻找新的诊治方案和开发新的药物提供了依据[3,6, 7,15, 16, 17, 18, 19]。本文论述了定量MRI在头颈部疾病显示与评估、鉴别诊断、分期与分级、活动性、疗效评估与预测、预后预测以及发生机制研究方面的作用,阐明存在的问题与未来发展思路,以期进一步提升定量MRI在头颈部疾病诊疗中的价值。

1 早期异常的显示、诊断和预测

       对于MRI形态学改变不明显的头颈部病变或病变累及结构的显示和评估,困扰着临床医师和影像医师,是临床诊断和分期的瓶颈[3,10,14,20, 21, 22],MRI定量参数可有助于早期显示和判断,已广泛用于头颈部各个部位,在腮腺、泪腺、视神经等早期异常、增大不明显的淋巴结转移以及恶性肿瘤侵犯视神经等影响分期的重要结构受累等方面应用更多[14, 21, 22],为临床诊断和疾病分期提供了重要的客观量化依据。例如,扩散加权成像(diffusion weighted imaging, DWI)、扩散张量成像(diffusion tensor imaging, DTI)、扩散峰度成像(diffusional kurtosis imaging, DKI)和扩散频谱成像(diffusion spectrum imaging, DSI)等获得的dMRI定量参数,将视神经炎及相关疾病累及视神经的显示和评估的准确率不断提升[10,23, 24],3D ASL结果显示非动脉炎性前部缺血性视神经病变的视神经头和视神经眶内段前部的血流速度显著降低[13],为诊断提供了重要的客观定量信息和依据。多回波Dixon序列和T2图(T2 mapping)序列能够定量评价原发性干燥综合征早期腮腺脂肪沉积和炎性反应的特点,T2值对早期腮腺损伤的评价具有较大潜能,与脂肪分数和表观扩散系数(apparent diffusion coefficient, ADC)值联合可进一步提高诊断效能[14]。视网膜母细胞瘤侵犯筛板后视神经是眼球摘除的指征及分期的重要依据,常规MRI征象显示的准确率较低[25],视神经的ADC值联合常规MRI征象可提高视神经形态学改变不明显的视神经侵犯的诊断效能[21]。基于视网膜母细胞瘤的影像组学可定量预测视网膜母细胞瘤侵犯筛板后视神经,显著提高了敏感度[26]。尽管定量MRI对这些疾病的显示和评估能力大幅度提高,但对较细小的颅神经或结构的早期异常改变的显示与判断仍是巨大挑战,而且头颈部结构复杂,MRI定量参数序列获得的图像存在一定的伪影或变形,导致的假象可能相对较多,未来发展趋势是提高空间分辨率和组织对比分辨率,既提高病变显示和诊断的敏感度和准确率,又具有较高的可靠性和重复性。

2 提高良恶性病变的鉴别诊断能力

       在常规MRI表现的基础上,源于DCE的半定量参数和曲线类型、源于DWI的ADC值以及联合对头颈部各部位良恶性病变鉴别、不同良性病变及不同恶性肿瘤鉴别提供了更多信息,鉴别诊断准确率明显提高,在头颈部MRI定量参数的应用和报道最多[2,6, 7,9]。尽管如此,仍不能满足临床需求,尤其是淋巴瘤与炎性病变、良性肿瘤与其恶变等的鉴别诊断准确率不高。为提升鉴别准确率,包括DCE-MRI、DWI-MRI和酰胺质子转移MRI测量获得的定量参数为鉴别诊断提供了更多信息和依据[11, 12,27, 28, 29]。与半定量参数相比,源于DCE的定量参数,包括转运常数(volume transfer constant, Ktrans)、血液回流常数(rate constant, Kep)、血管外细胞外间隙容积分数(extracellular space volume fraction, Ve)更客观地反映病变的血流动力学表现,进一步提高了头颈部良恶性病变的鉴别诊断能力[6, 7,27],而且与半定量参数联合,对鼻腔鼻窦内翻性乳头状瘤等良性肿瘤与恶变的鉴别优于源于DCE的半定量参数,多元回归分析结果显示Ve和Kep两个定量参数是鉴别鼻腔鼻窦内翻性乳头状瘤与恶变的独立影响因素,二者联合鉴别效能较高[11]。磁共振体素内不相干运动扩散加权成像(intravoxel incoherent motion-DWI, IVIM-DWI)获得的真扩散系数(D)或慢扩散系数(ADCslow)去除了灌注对扩散图像信号衰减的贡献[假扩散系数(D*)或快扩散系数(ADCfast)],反映组织内真实的扩散情况,提高了比较难鉴别的淋巴瘤与炎性病变的鉴别诊断效能[12]。基于头颈部MRI的影像组学广泛用于头颈部各部位良恶性病变的鉴别,并将影像组学MRI与临床资料、重要血清生物学指标等联合建立列线图,作为鉴别诊断的定量分析模型,提高了鉴别诊断能力[20]

3 定量评估或预测病变分期和分级

       不同分期或分级的病理特征及治疗方案截然不同,准确评估或预测头颈部疾病的分期或分级能为制订个体化的治疗方案提供重要客观依据[2,4,6, 7,9,21,25, 26,30],源于多参数MRI的定量参数单独和联合有助于提高评估或预测分期或分级的效能,并能为其提供定量评估标准。由于篇幅的限制,仅以评估甲状腺相关性眼病(thyroid-associated ophthalmopathy, TAO)的临床活动性分期及头颈部鳞状细胞癌分级和分期为例。源于T2图、DCE和DWI的定量或半定量参数均可定量分析和提高判断TAO的临床活动性分期的准确性;联合IVIM-DWI和T2图的眼外肌定量测量参数有助于判断TAO的诊断和活动性分期并提高准确性[31];联合泪腺磁化传递率(magnetization transfer ratio, MTR)和T2WI序列上泪腺与同侧颞肌信号强度比判断TAO的临床活动性分期的效能显著提高,而且能够提供量化的判断依据[32]。基于增强MRI的影像组学和临床指标列线图术前预测鼻腔鼻窦鳞状细胞癌组织学分级的效能较高[30]。基于多参数MRI影像组学及临床特征的可解释性机器学习预测模型NPC-Wise在预测鼻咽癌远处转移风险方面具有较高效能[33]。采用MRI定量参数准确进行分期或分级能够为个性化治疗提供有价值的客观决策依据。

4 疗效与预后的评估和预测

       目前头颈部实体肿瘤的放化疗和靶向药物治疗效果评估仍然是根据实体肿瘤标准RECIST 1.1(response evaluation criteria in solid tumors, RECIST 1.1)评估,但时间明显滞后,很多研究者采用DCE、DWI和ASL等序列的定量参数及影像组学模型评估放化疗和靶向药物治疗的早期疗效及预测近期疗效和预后,集中体现在头颈部鳞癌,尤其是在我国发病率较高的鼻咽癌,报道的评估或预测准确率都较高并优于RECIST 1.1[6, 7,20,34, 35, 36, 37]。源于DCE和DWI的定量参数评估和预测放化疗效果在以前述评或专家论坛中阐述较多了[6, 7,20],不再赘述。中晚期鼻咽癌化疗前的ASL灌注参数血流量与临床分期和病理类型联合构建的列线图预测放化疗是否有效的准确率较高,与临床实际观察结果具有较好的一致性[35]。多参数MRI影像组学特征构建的列线图可较好预测晚期鼻咽癌患者的无进展生存情况,优于临床指标构建的列线图,并可对患者的无进展生存率进行个体化预测[36]。MRI多序列模型融合影像组学模型能较好地预测局部晚期鼻咽癌患者同步放化疗疗效,明显优于临床模型或单一序列MRI模型[34]。基于多参数MRI的影像组学结合临床影像特征的列线图模型在放化疗前预测鼻咽癌患者Ki-67表达状态方面具有较高的效能,优于单一模型,有望作为一种无创的预测工具[37]

5 免疫治疗疗效评估带来的机遇与挑战

       虽然联合放化疗或靶向药物治疗方案明显改善了头颈部恶性肿瘤的预后,但仍有25%~40%的患者对一线治疗无应答或达到缓解后短期内复发,称为难治性头颈部恶性肿瘤[38]。近年来,免疫治疗成为实体性恶性肿瘤研究的最大进展[3942],为难治性头颈部恶性肿瘤带来了希望,初步研究报道采用PD-1/PD-L1(programed death-1,程序性死亡受体1;ligand 1,配体1)抑制剂治疗显著改善了难治性头颈部恶性肿瘤的预后[39]。PD-1抑制剂通过阻断PD-1/PD-L1信号通路,肿瘤免疫微环境(tumor immune microenvironment, TIME)中激活T细胞攻击肿瘤细胞,肿瘤PD-L1表达阳性,PD-1抑制剂才有作用的靶点,PD-L1表达水平已作为实体肿瘤PD-1抑制剂治疗公认的标志物[39,43],而且初步研究报道PD-L1阳性的晚期难治性头颈部恶性肿瘤患者对PD-1抑制剂的反应率明显高于PD-L1阴性患者[44],PD-L1表达水平有望成为头颈部恶性肿瘤PD-1抑制剂治疗的标志物,但其检测需要有创性的组织活检,多次实施患者不易接受,而且活检只能对肿瘤有限的区域取材,不能反映肿瘤的整体特点[39]。需要特别关注的是,PD-1抑制剂治疗有其特殊的治疗反应模式——假性进展:在治疗初期,TIME中细胞毒性T细胞浸润杀伤肿瘤细胞,T细胞激活、增殖、浸润,肿瘤内T细胞等增殖而肿瘤细胞还未减少,导致肿瘤体积暂时增大[40],而现在常用MRI包括DCE和DWI以及PET-CT常将其误判为肿瘤进展,导致治疗停止,患者错失治疗机会[39]。如何在治疗早期准确判断假性进展?在TIME中,由于浸润杀伤肿瘤细胞的T细胞的体积小于肿瘤细胞,因此肿瘤的细胞构成发生改变、平均细胞体积变小;T细胞杀伤肿瘤细胞后,肿瘤的细胞密度减低,虽然表现为假性进展的肿瘤在形态学上显示增大,但肿瘤的TIME改变特点与治疗有效者相似,表现为肿瘤的细胞构成发生改变、平均细胞体积变小以及细胞密度减低,对于这些改变特点的准确显示有助于准确判断是假性进展还是真性进展[39,45]。初步研究结果同时表明:反映肿瘤细胞构成和细胞外间隙变化等改变的T1图和T2图有助于鉴别炎性病变和恶性肿瘤并预测靶向治疗的疗效[41,46];最近开发的一种高级扩散序列——基于有限扩散时间谱的组织微结构参数成像(imaging microstructural parameters using limited spectrally edited diffusion, IMPULSED)序列获得的细胞大小值可反映细胞大小的特征,细胞大小值与癌组织内T细胞浸润程度成反比,可早期预测PD-1抑制剂疗效[47]。以上这些定量参数有望早期预测PD-1抑制剂疗效,但需要进一步研究其机制,并在更多病例中验证,以获得早期预测免疫治疗疗效的定量标志物。

6 探索和揭示发病机制的重要方法与工具

       对于出现视力或听力下降及耳鸣等症状的患者,DTI、DKI、DSI及ASL等序列获得的定量参数是研究视觉传导通路和听觉传导通路及相关脑结构异常的重要指标,通过这些参数发现了重要脑区结构与功能的损害与代偿性重组改变,为先天性盲、青光眼、弱视、语前聋、耳鸣的机制研究提供了重要的信息和依据[3,6, 7,10,15, 16, 17, 18, 19,24,48],其已成为探索这些疾病发病机制的重要方法与工具。定量MRI研究结果表明原发开角型青光眼(primary open-angle glaucoma, POAG)是一种神经退行性病变,视觉传导通路及视路以外的广泛脑区的结构、功能、血流灌注及代谢等都发生了改变,且与POAG患者病情严重程度相关[15, 16, 17, 18, 19],回答和验证了以前发病机制不能解释的重要问题,为POAG早期诊断和治疗提供新的思路。成人弱视患者的枕、颞叶皮质区域的低频振幅分数(fractional amplitude of low-frequency fluctuations, fALFF)值和局部一致性(regional homogeneity, ReHo)值发生明显改变,提示这些区域激活及ReHo发生了改变,并可能参与了视力损害的视觉信息处理功能代偿过程[48]

7 总结与未来发展前景展望

       综上所述,源于DCE、DWI、MRS和ASL以及基于MRI影像组学获得的MRI定量参数,为头颈部疾病显示与评估、鉴别诊断、分期与分级、活动性、疗效评估与预测、预后预测以及发生机制研究提供了重要的客观依据,有助于提升诊疗效果。头颈部定量MRI研究存在的主要问题:(1)大多数为单中心研究,样本量较小;(2)大部分为回顾性研究;(3)大部分研究为单模态或单序列获得的结果,缺少多参数联合的结果;(4)扫描参数和后处理要求不统一;(5)部分序列扫描和/或后处理时间较长;(6)缺乏统一的诊断、评估和预测标准。希望未来通过组建医工交叉多学科团队,对现有参数和结果系统性综述和分析,并针对存在的问题严格做好设计及确定纳入和排除标准,确定统一的诊断、评估和预测标准,以患者为中心、以临床问题为导向,开展全国多中心大样本量前瞻性研究,进一步提升定量MRI在头颈部疾病诊疗中的价值,并在临床推广应用,提高诊疗水平,保障人民健康。

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