朱建國(guó)， 李海歌， 曹鵬

·綜述·

克羅恩病多模態(tài)磁共振成像

朱建國(guó)， 李海歌， 曹鵬

克羅恩病是一種消化道的慢性炎癥，多發(fā)生于腸道，以往對(duì)該病的診斷和隨訪多依賴于內(nèi)鏡和實(shí)驗(yàn)室檢查。隨著影像技術(shù)的發(fā)展，諸多的磁共振成像技術(shù)被用于克羅恩病的臨床研究，這些成像技術(shù)豐富了對(duì)克羅恩病的研究手段，能夠從微結(jié)構(gòu)和微循環(huán)的角度討論克羅恩病，拓寬了研究視野。本文在概括前人研究的基礎(chǔ)上，就不同磁共振成像技術(shù)的原理、實(shí)際應(yīng)用、問(wèn)題不足做一綜述，并對(duì)未來(lái)的發(fā)展方向提出展望。

Crohn??； 多模態(tài)； 磁共振成像

腸道克羅恩病(Crohn's disease,CD)是一種原因不明的慢性、反復(fù)發(fā)作的消化道炎性病變，多見于青少年，跳躍性分布是該病的特征。以往對(duì)CD的診斷和隨訪主要依賴于內(nèi)鏡、微生物和血清學(xué)檢查。隨著技術(shù)的發(fā)展，影像學(xué)越來(lái)越多地被用于監(jiān)控CD病情、觀察并發(fā)癥、評(píng)估療效。上個(gè)世紀(jì)九十年代開始，磁共振(magnetic resonance,MR)憑其高組織分辨率、無(wú)輻射、非侵入性的優(yōu)勢(shì)，逐步應(yīng)用于CD的研究。在軟硬件水平的提高基礎(chǔ)上，多種磁共振成像技術(shù)被應(yīng)用于CD的臨床研究，其中以磁共振腸道造影(magnetic resonance enterography/enteroclysis,MRE)，磁共振彌散加權(quán)(diffusion weighted magnetic resonance,DW-MR)、磁共振動(dòng)態(tài)增強(qiáng)(dynamic contrast enhanced magnetic resonance,DCE-MR)技術(shù)相對(duì)成熟，使用最為廣泛。近年來(lái)，磁化傳遞(magnetization transfer,MT)、超微超順磁氧化鐵粒子增強(qiáng)磁共振[ultrasmall super paramagnetic iron oxide-(USPIO-) enhanced MR]以及正電子發(fā)射型計(jì)算機(jī)斷層-磁共振成像(positron emission computed tomography-MR,PET-MR)等成像技術(shù)也開始應(yīng)用臨床。上述多模態(tài)MR成像技術(shù)有助于觀察病灶分布、病變形態(tài)并能從細(xì)胞學(xué)、微循環(huán)和組織代謝角度分析CD的病理改變，豐富了對(duì)CD 的研究手段。本文就多模態(tài)MR成像技術(shù)在CD中的研究情況做一綜述。

MRE的應(yīng)用研究

根據(jù)檢查前的準(zhǔn)備方式不同，MRE分口服法(enterography)和經(jīng)導(dǎo)管灌入法(enteroclysis)兩種。兩者的共同之處都是使用1000～2000 mL對(duì)比劑充盈腸道[1]，不同之處在于前者是在MR掃描前60 min分次口服對(duì)比劑，后者首先經(jīng)鼻向十二指腸遠(yuǎn)端-空腸近端插入小腸導(dǎo)管，經(jīng)導(dǎo)管以100 mL/min的速度直接向小腸內(nèi)注入對(duì)比劑。兩者的目的均為MR掃描前用對(duì)比劑充分充盈腸道，既能防止萎陷的腸管掩蓋病變、產(chǎn)生誤診，又能減少腸腔氣體，避免磁敏感偽影。相對(duì)于MR enteroclysis，MR enterography操作簡(jiǎn)便，但攝入的量有限，擴(kuò)張腸道的效果不如MR enteroclysis； MR enteroclysis的缺點(diǎn)是需要插入十二指腸導(dǎo)管，對(duì)操作者有技術(shù)要求，患者需忍受一定的痛苦。對(duì)比劑的應(yīng)用以雙相對(duì)比劑居多[2]，即在T1WI為低信號(hào)，T2WI為高信號(hào)，包括甲基纖維素水混合液、聚乙烯醇溶液、等滲甘露醇等。Zhu等[3]研究2.5%甘露醇溶液味微甘易被患者接受，且為等滲溶液，不被腸道吸收，充盈腸道效果最為理想。充盈腸道后的MR檢查應(yīng)選用快速序列屏氣掃描，如T1WI二維的快速擾相梯度回波(fast spoiled gradient recalled echo,FSPGR)、三維的肝臟容積快速掃描(liver acceleration volume acquisition,LAVA)、容積式內(nèi)插法掃描(volumetric interpolated breath-hold examination,VIBE)，T2WI的單次激發(fā)快速自旋回波(single shot fast spin echo,SSFSE)或半傅立葉采集單次激發(fā)快速自旋回波(half-fourier acquisition single shot turbo spin echo,HASTE)、真實(shí)穩(wěn)態(tài)進(jìn)動(dòng)快速成像(true fast imaging with steady precession,trueFISP)。達(dá)到縮短掃描時(shí)間，避免呼吸運(yùn)動(dòng)偽影和減少腸蠕動(dòng)偽影目的。

小腸是結(jié)腸鏡觀察的盲區(qū)，繼發(fā)腸道狹窄和腸瘺則是腸鏡檢查的禁忌癥，MRE可以無(wú)創(chuàng)、無(wú)侵入性的觀察整個(gè)腸道情況。Samuel等[4]比較MRE和膠囊腸鏡對(duì)小腸CD病灶檢出情況，發(fā)現(xiàn)兩種方法敏感性相似，但MRE的特異性要顯著高于膠囊腸鏡。Maccioni等[5]以膠囊腸鏡和結(jié)腸鏡為標(biāo)準(zhǔn)，評(píng)估MRE在全腸道CD病灶的檢出情況，認(rèn)為MRE具有與腸鏡相同的檢查效果。Oussalah等[6]通過(guò)定量分析認(rèn)為MRE對(duì)腸壁潰瘍的顯示具有89%的特異度，甚至超過(guò)腸鏡。Maglinte等[7]提出腸道CD分為4個(gè)階段：炎癥活動(dòng)、腸瘺穿孔、纖維性狹窄、修復(fù)再生。MRE可以結(jié)合腸壁及腸系膜的信號(hào)特征，對(duì)CD的活動(dòng)性做出判斷。CD的腸壁厚度超過(guò)3 mm，且炎癥越重，腸壁越厚[8]；T2WI脂肪抑制序列，腸壁信號(hào)的強(qiáng)度亦和炎癥反應(yīng)程度相關(guān)[9]；腸壁強(qiáng)化的程度和強(qiáng)化方式也能提示炎癥活動(dòng)[10]；腸系膜血管增粗、“梳齒征”(comb sign)和短徑>1 cm的腸系膜淋巴結(jié)也是提示CD活動(dòng)的征象[11]。在此基礎(chǔ)上先后產(chǎn)生了3項(xiàng)MRE評(píng)分標(biāo)準(zhǔn)：克羅恩病活動(dòng)性評(píng)分(Crohn's disease activity score,CDAS)， 急性炎癥評(píng)分(acute inflammation score,AIS)、磁共振小腸成像全球評(píng)分(MRE global score,MEGS)。經(jīng)過(guò)和臨床資料、血清標(biāo)記物的對(duì)比分析證實(shí)， MR評(píng)分能夠反應(yīng)CD的活動(dòng)程度，具有70%以上的特異度和敏感度[9，12]。腸壁間條狀長(zhǎng)T2信號(hào)和聚集呈“星狀”(star shaped)的腸袢是腸瘺形成的典型表現(xiàn)[13]。Schil等[14]研究76例CD患者手術(shù)證實(shí)， 不同放射科醫(yī)師對(duì)腸瘺診斷一致性達(dá)0.895(觀察者間一致性分析)。Ordas等[15]研究48例CD患者在藥物治療12周后，采用MRE評(píng)估潰瘍愈合情況，準(zhǔn)確率達(dá)90%。Peyrin-Biroulet等[16]的研究認(rèn)為在藥物治療2周后，MRE就能觀察到腸粘膜的恢復(fù)情況。

腸管蠕動(dòng)、呼吸運(yùn)動(dòng)會(huì)形成移動(dòng)偽影，空氣等腸內(nèi)容物導(dǎo)致磁敏感偽影。偽影的產(chǎn)生不僅降低圖像質(zhì)量，影響診斷。胰高血糖素和丁基東莨菪堿是目前使用較多的注射藥物，可以在一定程度上減輕腸管運(yùn)動(dòng)偽影的影響，但不能完全消除[17]。注射藥物的種類、劑量，注射途徑和時(shí)間都沒(méi)有統(tǒng)一標(biāo)準(zhǔn)，并且有不良反應(yīng)的風(fēng)險(xiǎn)[18]?？诜?duì)比劑充盈腸道可以排除腸氣，減輕磁敏感偽影，但對(duì)比劑向腸壁的外滲，表現(xiàn)為T2WI信號(hào)增高，形成假陽(yáng)性結(jié)果[2]。高場(chǎng)強(qiáng)(3.0T)能縮短掃描時(shí)間、提高時(shí)間分辨率，減輕運(yùn)動(dòng)偽影的影響，但磁敏感偽影的干擾效應(yīng)更加突出，圖像變形、扭曲，質(zhì)量下降[19]。

DW-MRI的應(yīng)用研究

DW-MR基于水分子的布朗運(yùn)動(dòng)，無(wú)需注入對(duì)比劑即可得到細(xì)胞構(gòu)成、細(xì)胞膜完整性等分子水平的信息。通過(guò)測(cè)量表觀擴(kuò)散系數(shù)(Apparent diffusion coefficient,ADC)，達(dá)到定量分析[20]。DW-MR起初廣泛應(yīng)用于神經(jīng)系統(tǒng)研究，隨著軟硬件水平的提高，梯度回波序列、多通道線圈和并行成像等技術(shù)開發(fā)利用，使DW-MR運(yùn)用于CD的研究成為可能。

炎癥越重，腸壁DW-MR信號(hào)越高、ADC值越低，其原因是由于炎癥導(dǎo)致的灌注增加、炎細(xì)胞浸潤(rùn)共同限制了水分子的彌散[21]。根據(jù)這一理論，Stanescu-Siegmund[22]認(rèn)為CD病變段腸壁的ADC值低于正常腸段，以1.56×10-3mm2/s作為截?cái)帱c(diǎn)，診斷CD的敏感度和特異度分別為97.4%、99.2%。Hordonneau[23]和Zhu等[24]認(rèn)為ADC能定量評(píng)估CD炎癥反應(yīng)程度。Schmid-Tannwald等[25]應(yīng)用DW-MRI對(duì)24例CD患者的144段病變腸管進(jìn)行研究，發(fā)現(xiàn)以1.41×10-3mm2/s作為ADC值截?cái)帱c(diǎn)可以有效區(qū)分腸壁的急性和慢性炎癥活動(dòng)。Li[26]采用多b值DW-MRI對(duì)47例CD患者進(jìn)行研究，認(rèn)為以1.17×10-3mm2/s為界判別病變靜止期和活動(dòng)期，具有100%敏感度。研究表明，病程10年以上CD患者中1/3都會(huì)發(fā)生腸道狹窄，早期以炎性狹窄為主，后期向纖維性狹窄轉(zhuǎn)化，因此狹窄性質(zhì)的判定決定治療方案[27]。Zhu等[24]研究表明以1.11×10-3mm2/s作為ADC值截?cái)帱c(diǎn)對(duì)狹窄性質(zhì)的判斷有幫助。通過(guò)與內(nèi)鏡對(duì)照，一項(xiàng)為期3年的隨訪研究[28]顯示DW-MR對(duì)療效評(píng)估的敏感度為94.12% ，特異度為73.91%。Buisson等[29]使用腫瘤壞死因子抑制劑治療CD，觀察治療前后腸壁ADC值的變化，認(rèn)為治療前腸壁ADC值<1.96×10-3mm2/s，其療效更好。

目前，磁場(chǎng)強(qiáng)度和b值是DW-MR應(yīng)用于CD研究的兩個(gè)關(guān)鍵因素。相對(duì)于1.5T，3.0T場(chǎng)強(qiáng)能夠提高疾病診斷的特異性，其不足之處在于受磁敏感偽影影響，圖像質(zhì)量下降[19]。DW-MR掃描參數(shù)b值的選取尚無(wú)統(tǒng)一標(biāo)準(zhǔn)，ADC值的測(cè)量受預(yù)設(shè)b值大小的影響，b值越大，對(duì)檢出病灶特異性強(qiáng)，但信號(hào)噪聲比和對(duì)比噪聲比同時(shí)下降[30]。Oto等[31]早期選用b=600 s/mm2。目前多數(shù)學(xué)者[11,32]還是采用b=800 s/mm2，認(rèn)為在此條件下圖像質(zhì)量和檢出病灶的敏感性都相對(duì)較高。Feng等[30]通過(guò)分析對(duì)比噪聲和信號(hào)噪聲比，建議采用b=1500 s/mm2，認(rèn)為對(duì)CD病灶檢出率90.32%，診斷敏感度81.18%、特異度95.10%，但這只是一組31例患者的小樣本研究，有待繼續(xù)討論。

DCE-MRI的應(yīng)用研究

DCE-MRI是一種基于對(duì)比劑藥物代謝動(dòng)力學(xué)的MRI成像方法，其采用快速T1加權(quán)序列追蹤經(jīng)靜脈注射、隨后通過(guò)組織的低分子量對(duì)比劑，依據(jù)每個(gè)體素的信號(hào)改變提取反映組織血流動(dòng)力學(xué)的信息，非侵入性觀察、分析組織微循環(huán)功能狀態(tài)[33]。炎癥刺激會(huì)導(dǎo)致微血管生成和血管通透性增加，注入對(duì)比劑后，對(duì)比劑分子通過(guò)高通透性的不成熟新生血管向血管外細(xì)胞外間隙(extravascular extracellular space,EES)擴(kuò)散[34-35]。DCE-MR在對(duì)比劑注入血管前、中、后連續(xù)采集圖像，分析對(duì)比劑分子在血管內(nèi)和EES間隙分布信息，獲取藥物代謝動(dòng)力學(xué)參數(shù)[36]。為了擬合出對(duì)比劑分子時(shí)間變化濃度曲線，真實(shí)反映藥物代謝情況，時(shí)間分辨率是DCE-MR成像的關(guān)鍵。Ziech等[37]認(rèn)為相對(duì)低場(chǎng)強(qiáng)，3.0T MR能將時(shí)間分辨率降低到0.82s，既保證了定量參數(shù)的可靠性，又能一定程度克服運(yùn)動(dòng)偽影對(duì)圖像的影響。DCE-MR獲得的功能參數(shù)包括半定量和定量參數(shù)，半定量參數(shù)如增強(qiáng)率(rate of enhancement)、初始上升斜率(Initial slope of increase,ISI)；定量參數(shù)包括容積轉(zhuǎn)運(yùn)常數(shù)(volume transfer coefficient reflecting vascular permeability,Ktrans)、返流常數(shù)(flux rate constant,Kep)、血管外細(xì)胞外間隙容積分?jǐn)?shù)(extracellular volume ratio reflecting vascular permeability,Ve)、血漿容量(plasma volume fractions,Vp)。相對(duì)而言，半定量參數(shù)的可靠性和穩(wěn)定性不如定量參數(shù)，和實(shí)驗(yàn)室及病理學(xué)標(biāo)記物的相關(guān)性也更差，不能直接反應(yīng)生理病理改變[38]；而定量參數(shù)反應(yīng)血管內(nèi)皮、毛細(xì)血管床容積等定量信息更準(zhǔn)確，臨床使用更廣[39-42]。

Zhu等[3]的研究發(fā)現(xiàn)DCE-MR定量參數(shù)Ktrans、Kep和Ve與炎癥反應(yīng)的血清學(xué)標(biāo)記物C反應(yīng)蛋白濃度呈線性相關(guān)，對(duì)此解釋為炎癥刺激高通透性的不成熟血管生成，對(duì)比劑分子易于擴(kuò)散到EES間隙。Jeroen等[43]以20例患者手術(shù)切除的50個(gè)腸段的病理為基礎(chǔ)，認(rèn)為DCE-MR的參數(shù)[最大強(qiáng)化(maximum enhancement,ME)]和ISI有助于鑒別狹窄的性質(zhì)。

動(dòng)脈輸入函數(shù)(arterial input function,AIF)是獲取DCE-MRI定量參數(shù)(Ktrans、Kep、Ve和Vp)的前提，并決定定量參數(shù)的穩(wěn)定性和可靠性。受年齡、性別、身體機(jī)能等多因素影響，加之對(duì)時(shí)間分辨率的高要求，AIF的穩(wěn)定性不夠理想。學(xué)者[44]提出以其他模型取代AIF，但這僅是通過(guò)7.0T MR動(dòng)物實(shí)驗(yàn)得出的結(jié)論；還有學(xué)者[38]提出個(gè)體化AIF的概念，并在膠質(zhì)瘤的臨床分級(jí)研究中得以實(shí)施，類似研究是否能應(yīng)用于腸道CD有待檢驗(yàn)。

前景和展望

多模態(tài)MR成像技術(shù)相互融合、新技術(shù)推廣和研究領(lǐng)域拓展將是未來(lái)腸道CD研究的方向。

各種成像模式各有優(yōu)劣，相互結(jié)合能提高對(duì)CD的診斷效能，綜合不同的定量參數(shù)，能從更全面的角度解釋CD的病理改變。Schmid-Tannwald等[45]對(duì)25例CD的研究表明DW-MR結(jié)合T2WI能提高對(duì)腸瘺、竇道的檢出率。Hordonneau等[23]在MR評(píng)分中增加了ADC的評(píng)價(jià)系數(shù)，提高了對(duì)CD活動(dòng)性的評(píng)估能力。Zhu等[3]將DCE-MR和DW-MR結(jié)合，對(duì)CD進(jìn)行研究，發(fā)現(xiàn)Ktrans和ADC對(duì)CD都有較高的診斷價(jià)值，同時(shí)Ktrans和ADC之間也具備統(tǒng)計(jì)相關(guān)性，據(jù)此認(rèn)為可以從微循環(huán)和微結(jié)構(gòu)的角度解釋CD的病理變化過(guò)程。

新興的MR成像技術(shù)也具備CD研究的潛能，受限于設(shè)備條件和經(jīng)濟(jì)因素，這些新技術(shù)處于實(shí)驗(yàn)階段，尚未臨床普及。MT基于自由水分子和結(jié)合水分子之間的差異，產(chǎn)生圖像對(duì)比，并能測(cè)算結(jié)合大分子的濃度。MT脈沖序列施加前、后需要加入2D或3D的梯度平面回波序列，目的是飽和結(jié)合性水分子的信號(hào)，致使含有高濃度的大分子的組織具有高的MT比[46-47]。膠原沉積被視為腸壁纖維化的標(biāo)志，因MT具有檢測(cè)大分子膠原的能力，借以判斷腸壁纖維化的程度，此結(jié)論已得到動(dòng)物實(shí)驗(yàn)研究[46]和臨床研究證實(shí)[47]。USPIO粒子是一組能夠使血管和免疫細(xì)胞雙重現(xiàn)象的MRI對(duì)比劑。由于粒子表面涂有葡聚糖涂層，當(dāng)靜脈內(nèi)給藥后，血管首先顯影，隨后炎癥部位浸潤(rùn)的巨噬細(xì)胞吞噬USPIO顆粒，導(dǎo)致USPIO積聚于巨噬細(xì)胞活躍的區(qū)域，顯示炎癥和感染病灶[48-49]。在炎癥部位積聚的USPIO粒子能降低T2*弛豫時(shí)間，從而使得信號(hào)發(fā)生改變[50]，因此USPIO粒子對(duì)于細(xì)微的炎癥活動(dòng)都有較高的敏感性，并能定量評(píng)估炎癥活動(dòng)程度[51]，該觀點(diǎn)已被實(shí)驗(yàn)[52]和臨床研究[53]證實(shí)。此外，相對(duì)于釓對(duì)比劑，USPIO粒子腎毒性更小、使用更安全[54]。氟-18易于積聚在高葡萄糖攝取和利用的炎細(xì)胞內(nèi)，因此被視為炎癥反應(yīng)的標(biāo)記物。PET-MR可以先后或者同時(shí)采集PET、MR圖像，是對(duì)單純MRE圖像的有益補(bǔ)充，其次PET-MR能夠通過(guò)氟-18攝取配準(zhǔn)，改善腸道MR的結(jié)構(gòu)圖像[55]。

CD具有病程長(zhǎng)、易反復(fù)、難治愈的臨床特點(diǎn)，影響全身代謝功能，屬于系統(tǒng)性疾病[56-57]。部分患者會(huì)出現(xiàn)抑郁、情緒反復(fù)、大腦反應(yīng)異常、癲癇發(fā)作等癥狀[58]。最新研究表明可以通過(guò)慢性迷走神經(jīng)刺激治療CD，5例患者(5/7)經(jīng)過(guò)6個(gè)月治療，出現(xiàn)不同程度臨床癥狀減輕、生物學(xué)和內(nèi)鏡指證緩解[59]。Stovicek等[60]發(fā)現(xiàn)治療前后部分CD患者腦結(jié)構(gòu)發(fā)生改變。研究[61]認(rèn)為可以通過(guò)腦功能成像評(píng)估CD患者治療后腹痛癥狀改善情況。據(jù)此，我們認(rèn)為CD患者的腦功能研究具有理論基礎(chǔ)和臨床意義，研究尚未深入，值得進(jìn)一步探討。

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R574; R05; R445.2

A

1000-0313(2017)10-1070-05

2016-09-09

2017-01-23)

210011 南京，南京醫(yī)科大學(xué)第二附屬醫(yī)院醫(yī)學(xué)放射科(朱建國(guó)、李海歌)；201203 上海，通用電氣藥業(yè)(上海)有限公司(曹鵬)

朱建國(guó)(1978-)，男，江蘇鎮(zhèn)江人，博士，副主任醫(yī)師，主要從事神經(jīng)系統(tǒng)及消化系統(tǒng)影像診斷工作。

南京醫(yī)科大學(xué)科技發(fā)展基金重點(diǎn)項(xiàng)目支持(2015NJMUZD035)

10.13609/j.cnki.1000-0313.2017.10.017