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摘要: 胰腺癌是最主要的胰腺肿瘤, 其5年生存率不足5%, 早期发现、有效评估及采取恰当的治疗十分关键。自1984年磁共振扩散加权成像(diffusion weighted imaging, DWI)首次被报道以来, 其临床研究和应用价值日益凸显。DWI作为磁共振成像检查序列之一, 为胰腺癌的诊断、鉴别诊断及治疗效果评价等提供重要信息。本文对DWI技术及其在胰腺癌中的应用进行综述。Abstract: Pancreatic cancer is the most common pancreatic tumor, with a 5-year survival rate of less than 5%. Therefore, early detection, effective evaluation and appropriate treatment are critical to the disease. Since diffusion weighted imaging (DWI) was first reported in 1984, it has become more and more important in clinical research and applications. As part of the sequence of magnetic resonance imaging, DWI provides important information for the diagnosis and differential diagnosis of pancreatic cancer, as well as for the evaluation of therapeutic effects. This article reviews the technology of DWI and its application in the diagnosis of pancreatic cancer.
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胰腺癌是一种恶性程度高,诊断和治疗均困难的消化道肿瘤,约90%为起源于腺管上皮的胰腺导管腺癌,其早期隐匿,多数患者就诊时病变已处于进展期,仅15%左右适合手术,约80%患者确诊后1年内死亡,5年生存率不足5%[1]。我国胰腺癌发病率仍呈逐年上升趋势[2],早期发现、准确评估及恰当治疗十分关键。磁共振扩散加权成像(diffusion weighted imaging, DWI)可无创测量活体组织内水分子扩散运动,提供了异于常规磁共振成像(magnetic resonance imaging,MRI)(如T1和T2加权成像)的组织对比,更重要的是其还可获得定量参数以间接评估器官或组织的病理改变,目前已广泛应用于胰腺疾病的诊断、鉴别诊断及治疗效果评价中[1, 3]。本文对DWI技术及其在胰腺癌中的应用进行综述。
1. 扩散加权成像原理
Stejskal-Tanner序列是DWI最基本的脉冲序列[4],利用两个对称的扩散敏感梯度脉冲来实现水分子扩散的测量,扩散程度用扩散敏感因子b值表征。液体分子扩散的快慢常用扩散系数(diffusion,D)表示;因生理运动与血液流动等因素均会影响DWI信号强度,活体组织DWI信号的变化并非由单纯的水分子扩散运动引起,因此临床上常用一个较低b值(<100 s/mm2)和一个较高b值(>500 s/mm2) DWI,基于单指数模型计算表观扩散系数(apparent diffusion coefficient,ADC)代替D表征组织中水分子扩散的快慢。
DWI单指数模型假设每个体素内的扩散成分单一、水分子自由运动,ADC近似为体素内各种成分的平均值,其优点是模型简单、计算快速;缺点是假设过于理想,不能反映组织内多种成分。随着DWI研究的深入,研究者们相继提出了多个b值DWI方法,试图将组织内不同成分分离出来或提出新参数反映组织内微观结构信息。这些模型包括体素内不相干运动模型(intravoxel incoherent motion, IVIM)[5]、拉伸指数模型[6]和扩散峰度模型[7]等。因腹部DWI受运动和磁敏感效应影响显著,限制了高b值DWI成像,胰腺多b值DWI应用最为成熟的模型是基于双指数分析的IVIM,可获得组织内水分子扩散及微循环灌注双重信息。
2. 胰腺扩散加权成像技术及定量分析
2.1 胰腺扩散加权成像技术
平面回波成像技术(single-shot echo plane imaging, SS-EPI)成功将DWI推向临床,该技术显著缩短成像时间和降低图像的运动伪影。采集胰腺DWI数据时,通常通过屏气、呼吸门控或自由呼吸方式进行扫描[8]。(1)屏气DWI:优点是成像时间短,可有效减少呼吸运动伪影,但获得图像信噪比(signal to noise,SNR)较低,同时对患者的屏气能力也有较高要求。(2)呼吸门控DWI:常用的方式有基于腹带的呼吸监控、膈肌导航技术和肝内相位导航3种,均需监控被试者呼吸并在适当位置激发和接收信号。基于呼吸门控的DWI可通过增加累加次数提高图像SNR,往往需要较长的扫描时间。(3)自由呼吸DWI:可权衡扫描时间和图像SNR,但受运动伪影影响显著。就DWI图像质量及定量参数的可重复性而言,行胰腺DWI时推荐选择哪种成像方法尚无定论[9]。
基于SS-EPI的胰腺DWI临床上最为常用,但人体内偏共振效应和磁敏感伪影增加了SS-EPI读出时间(填充K空间的时间),相位误差积累随之增大,胰腺DWI图像分辨率有限,有研究报道小视野技术可用于提高胰腺DWI分辨率(平面分辨率约1.25 mm×1.25 mm)及减小图像变形以更好显示组织和病变细节[10-12]。与SS-EPI相比,小视野DWI方法通常需要较长时间才能达到符合临床诊断的图像质量,其临床应用价值需进一步探讨。
病变组织内复杂的微观结构影响水分子扩散,在DWI图像上通常表现出异常的信号特征。除组织本身特性外,DWI信号受b值影响较大,当b值较低时(<200 s/mm2),DWI图像具有明显的T2效应,即对于弛豫时间T2较长的组织在DWI图像上表现出与病变组织类似的信号特征;当b值较高时,虽然T2效应及血流灌注的影响明显降低,图像可更加敏感和准确反映组织内水分子的扩散,但同时图像的SNR降低、变形且伪影增大,故临床DWI扫描常选用的高b值范围为500~1500 s/mm2[13]。胰腺DWI临床检查中,优化DWI的b值具有重要意义。Fukukura等[14]推荐b值为1500 s/mm2。Taouli等[9]最新发布的体部DWI指南中推荐,用非0低b值(<100 s/mm2)的DWI图像代替脂肪抑制的T2用于局灶性胰腺结节的诊断,用3个b值(0,150,1000 s/mm2)计算ADC用于胰腺结节的诊断,用9~11个b值(0~1000 s/mm2)的IVIM参数用于胰腺癌与局灶性胰腺炎的鉴别诊断。
扩散梯度场强的大小决定水分子扩散引起的DWI信号的相位离散程度,其施加的方向亦影响DWI图像及定量参数[15]。由于人体组织内水分子扩散并非各向同性,建议采用3个垂直方向施加扩散梯度场采集DWI数据[9],从而获得平均的DWI图像及参数图。
2.2 胰腺扩散加权成像定量分析
DWI定量分析中,在ADC图上画感兴趣区(region of interest,ROI)可测量组织的ADC均值,用于疾病诊断、鉴别诊断和疗效评价[5, 9]。常用的ROI方法有3种:整体容积法、单一层面法和小样本法[16]。(1)整体容积法:指在肿瘤的每个连续层面沿病灶的边缘画ROI,并将多层测量值的均值作为最终结果;(2)单一层面法:指在肿瘤显示的最大层面上沿着肿瘤边缘勾画ROI测量ADC均值;(3)小样本法:指在肿瘤实性部分选择一个或多个ROI进行测量,并将测量结果的均值作为测量值,其简单易行,是目前ADC测量中最常用的方法,但数据测量的重复性不高,如腹部脏器ADC均值变化率近30%[17]。尽管尚无规范的ROI方法推荐,但多项DWI研究建议在肿瘤组织上尽量勾画较大ROI用于测量ADC均值[1]。Ma等[16]探究了3种ROI方法在胰腺癌与正常胰腺鉴别诊断中的价值,结果小样本法测量的胰腺癌ADC一致性最低,但诊断效能最高[18];该小组在另外两项研究中报道,推荐的胰腺癌ADC测量的ROI尺寸为214 mm2[19-20]。关于胰腺癌IVIM定量参数ROI分析方法的研究尚未见报道,其将成为未来研究的重要内容之一。
基于ROI测量参数平均值是常用的数据分析方法,但该方法丢弃了组织异质性信息,而肿瘤的异质性通常与放化疗抵抗相关。基于ROI直方图分析方法可用于肿瘤异质性评价,该方法对评估肿瘤进展、有效干预治疗和判断患者预后等具有重要意义[21],Ma等[22]发现ADC直方图百分数(b值为0和800 s/mm2)有助于鉴别胰腺癌和肿块型慢性胰腺炎;Pereira等[23]发现ADC直方图可对胰腺神经内分泌肿瘤进行分级。随着图像后处理技术的发展,基于ADC直方图的分析将在DWI研究中发挥重要的作用。
3. 扩散加权成像在胰腺癌诊断中的应用价值
DWI作为常规胰腺MRI检查序列的补充,在胰腺癌诊断中具有重要意义,如多项研究表明胰腺癌ADC显著小于正常胰腺组织[24-31];DWI联合常规增强MRI(敏感性97%,特异性92%)对小尺寸胰腺癌(<3 cm)的诊断效能显著高于常规增强MRI(敏感性75.5%,特异性87.5%)[32];DWI有利于胰腺癌分期,特别是诊断<10 mm肝转移病灶的敏感性和特异性皆显著高于CT[33]。
胰腺癌内部不均匀性明显,DWI显示胰腺癌的能力低于T1增强图像[25],Fukukura等[24]和Legrand等[25]发现约47%和25%的胰腺癌在DWI上不表现高信号特征。既往报道的胰腺癌ADC变化较大[(0.78~ 2.32)×103 mm2/s][34],ADC用于胰腺实性肿瘤(如胰腺癌、实性假乳头状瘤、神经内分泌肿瘤等)的鉴别诊断价值有限[27, 35],且ADC鉴别诊断胰腺癌和慢性肿块性胰腺炎的报道并不一致[3]。关于胰腺癌ADC均值和病理相关性研究的结果亦相互矛盾:Wang等[26]发现胰腺癌ADC和肿瘤分化程度呈正相关,而Rosenkrantz等[28]和Hayano等[36]未发现二者相关性,本研究组前期研究发现胰腺癌分化程度越低或分期越高,D值越小,但差异无统计学意义[37]。从DWI图像特征来看,本研究组基于305例胰腺癌DWI数据分析发现,仅约37%的胰腺癌在DWI上表现高信号特征。尽管胰腺癌明显异质性是造成DWI信号不均及ADC值变化较大的主要原因,但通过规范的扫描参数、数据处理与测量方法及标准水模的校准等可进一步提高DWI在胰腺癌诊断的精确性,该项工作需通过多中心研究来实现。
IVIM-DWI在鉴别正常胰腺组织、胰腺癌及其他胰腺肿块的准确性高于常规DWI和ADC[38]。Concia等[39]和Kang等[40]发现胰腺癌f值显著低于慢性胰腺炎和胰腺内分泌肿瘤,Lee等[27]发现胰腺癌的D值显著高于肿块型慢性胰腺炎,Klauss等[38]发现胰腺癌的f值显著低于肿块型慢性胰腺炎、D值与胰腺癌纤维化程度相关[41],本研究组亦发现胰腺癌分化程度越低或分期越高,D值越小[37]。关于IVIM在胰腺癌中的应用需进一步评价定量参数的一致性及可重复性。
在胰腺疾病直方图分析研究中,Ma等[22]发现ADC直方图百分数(b值为0和800 s/mm2)有助于鉴别胰腺癌和肿块型慢性胰腺炎,但未探究峰度、偏度、熵和均一性等指标对二者的鉴别价值。尽管IVIM-DWI诊断胰腺癌准确性较常规DWI和ADC更高[27, 38],但胰腺癌IVIM-DWI直方图研究迄今未见报道,需进一步探究该方法在评价胰腺癌异质性中的作用。DWI还可用于评估胰腺癌化疗效果[42]和可切除性胰腺癌辅助放化疗反应的评价[43]。但该方面研究较少,需进一步探究。
4. 小结
DWI作为临床MRI检查方法的重要补充,其在胰腺癌诊断、鉴别诊断应用中发挥着重要作用。但规范的扫描方法及定量参数分析方法可进一步提高DWI在胰腺癌诊断及治疗评价中的精度,该方面工作尚需进一步探究;另外,DWI直方图分析可用于肿瘤异质性评价,对个性化诊疗方案的制定具有重要意义,也将成为胰腺癌DWI研究的热点。
利益冲突 无 -
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