磁共振斑塊成像技術(shù)臨床應(yīng)用的現(xiàn)在與未來

趙錫海，宋焱，李飛宇，苑純，4

卒中現(xiàn)已成為我國城市居民致死性疾病的首要原因，如何有效預(yù)防與控制卒中是我國目前亟待解決的公共健康問題之一。缺血性卒中（ischemic stroke，IS）的主要責(zé)任病變是腦動脈粥樣硬化易損斑塊。因此，早期識別頸動脈易損斑塊并對其進行有效治療是卒中預(yù)防的關(guān)鍵。高分辨率磁共振（magnetic resonance，MR）斑塊成像技術(shù)自20世紀(jì)90年代研發(fā)至今，已被廣泛應(yīng)用于頸動脈易損斑塊成像的相關(guān)研究中。MR斑塊成像技術(shù)能夠準(zhǔn)確定性、定量分析頸動脈斑塊的負(fù)荷和成分特征，被認(rèn)為是現(xiàn)階段識別頸動脈易損斑塊的最佳無創(chuàng)性影像學(xué)手段。研究顯示，應(yīng)用MR斑塊成像獲得的腦動脈易損斑塊特征，對于卒中的病因?qū)W診斷、責(zé)任病變治療、預(yù)后判斷和二級預(yù)防均具有重要價值。隨著MR斑塊成像技術(shù)的進一步發(fā)展，其臨床應(yīng)用前景會更為廣闊。

1 MR斑塊成像識別腦血管易損斑塊，有效預(yù)防缺血性卒中

腦血管粥樣硬化易損斑塊破裂引發(fā)的血栓栓塞，是IS的主要病因之一。因此，早期識別易損斑塊并對其進行有效干預(yù)，有利于IS的預(yù)防。引發(fā)卒中的責(zé)任病變多發(fā)生于腦組織上游的動脈血管床，如顱內(nèi)動脈和顱外頸動脈等。Wong等[1]研究發(fā)現(xiàn)，中國人群IS患者中46.6%存在顱內(nèi)大動脈狹窄，而西方人群IS多為顱外頸動脈易損斑塊所致。此外，一項小樣本研究顯示，國人癥狀性頸動脈斑塊更多表現(xiàn)為大脂質(zhì)核、少鈣化[2]。這些中西方人群顱內(nèi)外動脈粥樣硬化發(fā)病的差異可能與遺傳、環(huán)境、飲食、他汀類藥物使用等因素有關(guān)。因此，需要針對中國人群的發(fā)病特征制訂IS的預(yù)防策略。

目前，臨床上常應(yīng)用各種血管成像技術(shù)［如超聲（ultrasound，US）、計算機斷層掃描血管造影（computed tomography angiography，CTA）、磁共振血管造影（magnetic resonance angiography，MRA）、數(shù)字減影血管造影（digital subtraction angiography，DSA）］測量動脈管腔狹窄程度，以此判斷病變的嚴(yán)重性。然而，由于動脈存在正性重構(gòu)效應(yīng)，僅依據(jù)管腔狹窄程度常低估動脈粥樣硬化病變的嚴(yán)重性[3]。近年有研究表明，多數(shù)易損斑塊僅造成管腔輕度狹窄[3-5]。Dong等[6]研究發(fā)現(xiàn)，狹窄程度為0%的無癥狀頸動脈中，6%～8%存在易損斑塊。因此，學(xué)者建議對動脈管壁進行直接成像，通過識別斑塊內(nèi)部的成分特征評價斑塊的易損性。

MR斑塊成像技術(shù)在評價腦血管易損斑塊方面具有重要價值。與組織病理學(xué)對照研究顯示，MR二維、高分辨率斑塊成像幾乎能夠識別易損斑塊的所有組織學(xué)特征，如大脂質(zhì)核薄纖維帽、斑塊內(nèi)出血、炎癥反應(yīng)與新生血管化等[7-11]。目前，有學(xué)者推薦應(yīng)用三維成像技術(shù)對頸動脈進行成像，與二維技術(shù)相比，其縱向覆蓋范圍可以擴大至250 mm，且掃描時間明顯縮短[12]。對于顱內(nèi)動脈易損斑塊成像，多數(shù)學(xué)者沿用顱外頸動脈MR斑塊成像技術(shù)[13-18]。有研究發(fā)現(xiàn)，癥狀性大腦中動脈斑塊更多表現(xiàn)為正性重構(gòu)效應(yīng)[16]，斑塊內(nèi)出血發(fā)生率達(dá)19.6%[18]。然而，由于顱內(nèi)動脈位置深在、管徑小管壁薄、部分節(jié)段走行迂曲或缺乏脂肪和腦脊液等天然信號對比，對其管壁成像具有一定的挑戰(zhàn)。目前有學(xué)者研究開發(fā)三維管壁成像技術(shù)[19-20]，以加快掃描速度、提高空間分辨率、更好抑制復(fù)雜血流，這也是顱內(nèi)動脈易損斑塊成像的未來發(fā)展方向。

早期識別易損斑塊對于IS的預(yù)防具有重要意義。大量橫斷面研究證實，斑塊內(nèi)出血、纖維帽破裂、表面潰瘍、大脂質(zhì)核等頸動脈復(fù)雜斑塊磁共振表現(xiàn)特征與腦血管癥狀密切相關(guān)[21-25]。有學(xué)者發(fā)現(xiàn)，對于無癥狀人群，頸動脈斑塊內(nèi)出血、纖維帽破裂、大脂質(zhì)核等斑塊特征對于腦血管事件具有一定的預(yù)測價值[26-28]。一系列前瞻性研究顯示，頸動脈存在斑塊內(nèi)出血或纖維帽破裂的腦血管病患者具有較高的復(fù)發(fā)風(fēng)險[29-31]。

應(yīng)用常規(guī)手段對IS患者進行篩查，仍有30%～40%的患者找不到明確原因[32]，稱為隱源性卒中。近來有學(xué)者對32例頸動脈存在偏心性斑塊（＜50%狹窄）的隱源性卒中患者進行MR管壁成像，發(fā)現(xiàn)12例（37.5%）存在易損斑塊[33]。另有研究證實，一部分隱源性卒中患者其主動脈弓存在易損斑塊[34]。這些研究結(jié)果提示我們，一部分“隱源性卒中”患者通過MR管壁成像有可能找到責(zé)任病變。

2 MR斑塊成像優(yōu)化再血管化治療方案

根據(jù)《顱外段頸動脈狹窄治療指南》，癥狀性頸動脈重度狹窄的患者需要進行頸動脈內(nèi)膜剝脫術(shù)（carotid endarterectomy，CEA）或頸動脈支架植入術(shù)（carotid artery stenting，CAS）[35]。血管的狹窄程度和斑塊纖維帽破裂是決定患者是否需要手術(shù)治療的兩個主要指征。DSA是頸動脈粥樣硬化患者手術(shù)適應(yīng)證選擇的主要影像學(xué)檢查方法。DSA檢查的優(yōu)勢在于可以清晰、動態(tài)地觀察主動脈弓至顱內(nèi)的血管床的病變情況，并可以將檢查與治療融于一體。但DSA對動脈粥樣硬化病變的評估主要是判斷血管狹窄程度，而對斑塊形態(tài)學(xué)特點及組成成分的判斷能力有限，即使可以顯示斑塊纖維帽破裂，其敏感性和特異性也較低[36-37]。

在斜矢狀位管壁成像序列的輔助下，頸動脈MR斑塊成像能夠較為準(zhǔn)確地識別頸動脈斑塊潰瘍[38]。有學(xué)者[39]就磁共振成像（magnetic resonance imaging，MRI）和DSA對頸動脈粥樣硬化患者手術(shù)適應(yīng)證的選擇能力進行了比較，發(fā)現(xiàn)MR管壁成像較DSA可以更準(zhǔn)確地判斷管腔狹窄程度，更敏感地檢出潰瘍斑塊，從而有助于協(xié)助臨床醫(yī)生準(zhǔn)確地確定患者是否需要手術(shù)治療。尤其是當(dāng)患者管腔狹窄程度為50%～70%時，是否需要手術(shù)治療更主要地取決于是否存在斑塊表面潰瘍。此時，MRI對斑塊表面潰瘍的精確檢出則有助于醫(yī)生制訂治療方案。

頸動脈MR斑塊成像可能有助于選擇再血管化治療的手術(shù)策略。對于頸動脈癥狀性重度狹窄的患者選擇CEA還是CAS手術(shù)治療一直存在爭議。有研究表明，斑塊內(nèi)的不穩(wěn)定成分（如脂質(zhì)核和斑塊內(nèi)出血），與CAS術(shù)中微栓子的形成有密切的關(guān)系[40]。因此，通過MR斑塊成像準(zhǔn)確分析易損斑塊特征，有可能預(yù)防圍術(shù)期新發(fā)梗死。Yamada等[41]通過分析斑塊與胸鎖乳突肌的信號干擾比值（signal to interference ratio，SIR），發(fā)現(xiàn)當(dāng)SIR≥1.25時，CAS手術(shù)出現(xiàn)微栓子的概率要明顯高于CEA。研究者分析認(rèn)為，這種信號強度的斑塊多為富含脂質(zhì)核或具有斑塊內(nèi)出血等成分，并提出對于這種類型的斑塊適宜選擇CEA。如果該結(jié)論能通過大樣本的前瞻性研究得到進一步證實，則可借助MR成像對斑塊成分的分析，得以指導(dǎo)手術(shù)方案的選擇，提高患者的預(yù)后。

3 MR斑塊成像監(jiān)測頸動脈斑塊他汀類藥物治療療效

對于頸動脈粥樣硬化輕中度狹窄的病變，臨床一般采用他汀類藥物治療。MR斑塊成像因其無創(chuàng)、無X線電離輻射、可重復(fù)性好等優(yōu)勢，是目前評價頸動脈斑塊藥物治療療效最為可靠的手段。Corti等[42]最早應(yīng)用MR成像觀察辛伐他汀治療頸動脈斑塊的療效，經(jīng)過2年的治療，斑塊的體積明顯縮小、管腔增大。West等[43]則應(yīng)用MR斑塊成像觀察股淺動脈斑塊在單獨使用依澤替米貝和聯(lián)合使用他汀后的變化，結(jié)果發(fā)現(xiàn)，單獨使用依澤替米貝并沒有抑制斑塊的進展，而在聯(lián)合使用他汀藥物的患者中，MR上測得的斑塊體積在2年內(nèi)沒有進展。在Kawahara等[44]的研究中，應(yīng)用MR斑塊成像監(jiān)測胸主動脈和腹主動脈斑塊體積藥物治療前后的變化，結(jié)果發(fā)現(xiàn)阿托伐他汀和羥乙磷酸鹽聯(lián)合使用的效果要優(yōu)于單獨使用阿托伐他汀。有研究者對接受了半年他汀治療的動脈粥樣硬化患者同時應(yīng)用超聲和MR評估頸動脈斑塊的治療效果，結(jié)果發(fā)現(xiàn)，超聲測得的頸動脈內(nèi)中膜厚度在治療前后并無顯著性變化，而MR測得的斑塊體積則明顯縮小，提示MR檢查在評價他汀類藥物療效方面可能比超聲更有優(yōu)勢[45]。

近些年來隨著3.0 T磁共振成像設(shè)備的廣泛應(yīng)用，除了斑塊形態(tài)外，MR還能夠準(zhǔn)確定量分析斑塊內(nèi)成分，如脂質(zhì)核、纖維帽、出血等。在一項利用MR監(jiān)測他汀類藥物長期治療頸動脈粥樣硬化病變的研究中，研究者發(fā)現(xiàn)，經(jīng)過3年的治療，頸動脈斑塊內(nèi)脂質(zhì)核的體積和比例均明顯縮小。其中治療的第一年和第二年斑塊脂質(zhì)核體積逐漸縮小，而到了第三年，脂質(zhì)核體積并未繼續(xù)縮小，這可能會對未來臨床制訂他汀類藥物長期治療計劃有所幫助[46]。此外，MR還可以使用一些特異造影劑觀察斑塊內(nèi)特定成分在藥物治療過程中的變化，如用超小順磁性超氧化鐵顆粒（ultrasmall superparamagnetic iron oxide，USPIO）觀察斑塊內(nèi)巨噬細(xì)胞的情況。Patterson等[47]研究表明，在使用阿托伐他汀治療后，頸動脈斑塊對于USPIO的攝取在12周內(nèi)出現(xiàn)了下降，提示斑塊內(nèi)炎癥反應(yīng)減弱。最近，有學(xué)者應(yīng)用動態(tài)增強MR技術(shù)觀察頸動脈斑塊炎癥在他汀類藥物治療前后的變化，經(jīng)過1年的治療，Ktrans值明顯下降。這一點提示他汀類藥物可能會降低斑塊新生血管化的程度[48]。

盡管MR斑塊成像對動脈粥樣硬化斑塊治療具有一定的指導(dǎo)意義，但患者是否具有遠(yuǎn)期獲益、能否明顯降低腦血管事件還需大規(guī)模、前瞻性研究提供循證醫(yī)學(xué)證據(jù)。尤其是對于那些輕中度狹窄但具有易損斑塊特征的粥樣硬化病變（如大脂質(zhì)核、斑塊內(nèi)出血），需要臨床加以關(guān)注。

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