腦血管磁共振管壁成像：從不同的視角探索新的臨床路徑

趙錫海

腦血管易損斑塊破裂隨即引發(fā)的血栓栓塞，是缺血性卒中的主要病理學(xué)基礎(chǔ)。因此，早期識別腦血管易損斑塊是缺血性卒中防控的關(guān)鍵。引起腦血管事件的責(zé)任病灶既可以發(fā)生于顱內(nèi)動脈，也可位于顱外頸動脈。有證據(jù)表明，不同種族之間易損斑塊在不同血管床的發(fā)生率存在一定的差異，亞洲人群顱內(nèi)動脈易損斑塊可能是缺血性卒中的主要病因，而美國白種人的缺血性卒中更多是由于顱外動脈易損斑塊所致（表1）[1-14]。由此可見，顱內(nèi)動脈可能是國人篩查易損斑塊的主要血管床。

現(xiàn)階段，通過各種血管成像手段［如超聲、計算機斷層掃描血管成像（computed tomography angiography，CTA）和磁共振血管成像（magnetic resonance angiography，MRA）］等測量管腔狹窄程度，仍然是評價腦動脈粥樣硬化病變嚴(yán)重性的主要指標(biāo)。然而，僅通過管腔信息判斷斑塊的易損性存在明顯的低估現(xiàn)象。研究顯示，超過20%的癥狀性輕度狹窄的頸動脈（狹窄＜50%）存在易損斑塊[15-16]，甚至某些易損斑塊并不引起管腔變化（狹窄=0%）[17]。這是因為粥樣硬化病變在發(fā)生、發(fā)展過程中存在“正性重構(gòu)效應(yīng)”，即病變向血管壁外膨脹性生長，而不引起管腔嚴(yán)重狹窄（圖1）[18]。這種正性重構(gòu)效應(yīng)廣泛存在于全身各個血管床，包括顱內(nèi)動脈和顱外頸動脈。因此，單純測量管腔狹窄并不能客觀反映粥樣硬化病變的嚴(yán)重性。

表1 腦血管病患者顱內(nèi)外動脈易損斑塊發(fā)生率的人群差異

注：粥樣硬化斑塊向血管外膨脹性生長，僅造成管腔輕度狹窄，狹窄程度：（D2-D1）/D2×100%=35%

病理學(xué)上，粥樣硬化易損斑塊主要表現(xiàn)為動脈管壁形態(tài)與成分的變化。易損斑塊通常表現(xiàn)為較大的斑塊負(fù)荷（厚度、面積或體積）、大脂質(zhì)核薄纖維帽、斑塊內(nèi)出血、纖維帽破裂或炎癥反應(yīng)及新生血管[19]。管腔狹窄只是粥樣硬化病變進(jìn)展產(chǎn)生的間接征象?；谝陨鲜聦?，評價易損斑塊的技術(shù)關(guān)鍵是如何敏感識別動脈管壁的成分特征，而不是單純測量管腔狹窄程度。

磁共振高分辨率管壁成像技術(shù)，是目前評價頸動脈易損斑塊最為可靠的無創(chuàng)性影像學(xué)手段。這一技術(shù)的核心是應(yīng)用特殊的磁共振血流抑制技術(shù)（即黑血技術(shù)）抑制管腔流動的血液信號，同時結(jié)合脂肪抑制技術(shù)，獲得動脈管壁與管腔血流和管壁周圍脂肪間隙之間鮮明的信號對比，從而實現(xiàn)對動脈管壁的直接成像。此外，該技術(shù)還采用多對比度成像方法來識別斑塊成分[20-22]，即時間飛躍法血管成像（timeof-flight，TOF）、T1加權(quán)像（T1weighted imaging，T1WI）、T2加權(quán)像（T2weighted imaging，T2WI）和磁化準(zhǔn)備快速回波序列（magnetization prepared rapid acquisition gradient echo sequences，MP-RAGE），利用不同物質(zhì)在不同對比度圖像上表現(xiàn)特征的差異性，來準(zhǔn)確識別斑塊內(nèi)各種成分，從而評價斑塊的易損性（圖2）。與病理學(xué)對照研究證實，磁共振高分辨率管壁成像技術(shù)幾乎能準(zhǔn)確識別所有易損斑塊的特征[21-22]。

圖2 頸動脈磁共振多對比度管壁成像

近年來，隨著磁共振成像技術(shù)的快速發(fā)展，管壁成像亦由原來的二維成像發(fā)展為三維成像。如表2所示，傳統(tǒng)的二維多對比度管壁成像存在耗時長、覆蓋范圍小、層面間分辨率低、迂曲血管存在部分容積效應(yīng)等缺點。近來，有學(xué)者研究開發(fā)出三維管壁成像序列用于評價腦血管易損斑塊，如運動敏感驅(qū)動快速梯度回波（motion-sensitizing driven equilibrium rapid gradient echo sequence，MERGE）[23]、非增強血管成像與斑塊內(nèi)出血同時成像序列（simultaneous noncontrast angiography and intraplaque hemorrhage，SNAP）[24]和等體素快速自旋回波采集序列（volume isotropic TSE acquisition，VISTA）/快速自旋回波（sampling perfection with application-optimized contrasts by using different flip angle evolutions，SPACE）[25]。三維成像序列具有掃描速度快、覆蓋范圍大等優(yōu)點，大大提高了成像效率，并且使顱內(nèi)外腦血管壁一站式成像成為可能。應(yīng)用三維管壁成像技術(shù)，能夠直觀顯示腦動脈粥樣硬化病變的大小、形態(tài)以及位置分布，尤其對多發(fā)病變的顯示更具優(yōu)勢（圖3）。

通過磁共振管壁成像，可以獲得豐富的腦動脈粥樣硬化病變的量化信息，為臨床診斷、治療方案的選擇、療效評價及預(yù)防提供重要依據(jù)。管壁厚度、管壁面積、管壁體積及標(biāo)準(zhǔn)化管壁指數(shù)［管壁面積/（管壁面積+管腔面積）×100%］等是斑塊負(fù)荷的常用測量指標(biāo)，這些反映粥樣硬化病變大小的參數(shù)與斑塊的易損性具有一定的相關(guān)性。通過管壁成像定性和定量評價斑塊成分特征（如鈣化、脂質(zhì)核、斑塊內(nèi)出血、纖維帽破裂等），對于斑塊易損性的判斷、腦血管事件風(fēng)險的預(yù)測、決策臨床治療方案以及他汀類藥物治療效果的評價具有重要意義。纖維帽破裂、斑塊內(nèi)出血和較大的

表2 二維和三維管壁成像的對比

圖3 三維管壁成像技術(shù)（MERGE）對腦血管粥樣硬化病變的顯示

脂質(zhì)核（脂質(zhì)核占據(jù)＞40%的管壁面積）并伴有薄纖維帽是典型的易損斑塊特征。此外，通過磁共振動態(tài)增強技術(shù)測得的管壁高傳輸常數(shù)（transfer constant，Ktrans）或血漿容積分?jǐn)?shù)（fractional plasma volume，Vp）反映的是局部炎癥反應(yīng)和新生血管化的程度，存在這一特征的斑塊同樣具有一定的破裂風(fēng)險[26]。一系列前瞻性研究證實，纖維帽破裂、斑塊內(nèi)出血和

脂質(zhì)核大小是腦血管事件的有效預(yù)測指標(biāo)（表3）[27-32]。管壁成像獲得的斑塊特征信息還可以用于決策臨床治療方案。Yamada等[33]研究發(fā)現(xiàn)，頸動脈出血性斑塊進(jìn)行支架植入術(shù)圍術(shù)期發(fā)生靜默腦梗死的概率是61%，這一比例明顯高于內(nèi)膜剝脫術(shù)（13%）。由于磁共振管壁成像是一項具有高度可重復(fù)性的技術(shù)，現(xiàn)已被廣泛應(yīng)用于監(jiān)測他汀類藥物治療粥樣硬化病變療效的方面[34-35]。

磁共振管壁成像能夠精準(zhǔn)識別腦動脈粥樣硬化易損斑塊，并可對其進(jìn)行全面的定性和定量分析，充分利用管壁成像獲得的斑塊信息可能會改變腦血管病的臨床路徑。首先，對于腦動脈粥樣硬化病變嚴(yán)重性的評價，不應(yīng)僅局限于測量管腔狹窄程度，需要重點關(guān)注病變局部管壁的成分特征；其次，在臨床決策再血管化治療方案環(huán)節(jié)，充分考慮斑塊的成分特征（如有無斑塊內(nèi)出血）有可能會降低圍術(shù)期并發(fā)癥，從而增加患者獲益；再次，對他汀類藥物治療效果評價傳統(tǒng)的做法局限于監(jiān)測血脂水平的變化，而不是直接觀察靶血管粥樣硬化病變有無進(jìn)展或退縮。由于磁共振管壁成像能夠直接顯示和準(zhǔn)確定量斑塊內(nèi)脂質(zhì)核成分，為臨床觀察藥物療效提供了有效的監(jiān)測手段；最后，磁共振管壁成像能夠?qū)δX動脈粥樣硬化病變的破裂風(fēng)險進(jìn)行分層分析，這將為制訂腦血管病的預(yù)防策略提供重要依據(jù)。當(dāng)然，磁共振管壁成像獲得的信息能否改變臨床路徑，還需要開展大規(guī)模前瞻性研究以提供更多的循證醫(yī)學(xué)證據(jù)。

表3 磁共振斑塊特征預(yù)測腦血管事件

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