張如志 陳 偉 夏 睿 郜發(fā)寶
心臟MR延遲強化在急性心肌梗死的應(yīng)用及研究現(xiàn)狀
張如志 陳 偉*夏 睿*郜發(fā)寶*
急性心肌梗死(AMI)梗死心肌、心肌活性和微血管梗阻(MVO)的定量評價對于AMI病人的危險程度分級、治療決策的制定、治療效果的評價以及預(yù)后評估具有重要意義。心臟MR延遲強化(LGE-CMR)具有較高的時間及空間分辨力,可用于AMI梗死心肌、心肌活性和MVO的定量評價,并且具有較好的可重復(fù)性和較高的準(zhǔn)確性。就LGE-CMR在AMI的應(yīng)用及研究現(xiàn)狀進(jìn)行綜述。
急性心肌梗死;心臟MR延遲強化;心肌活性;微血管梗阻
急性心肌梗死(acute myocardial infarction,AMI)在全球有較高的發(fā)病率和死亡率,是致人類死亡的主要原因之一[1-2]。梗死心肌、活性心肌和微血管梗阻(microvascular obstruction,MVO)的定量評價對于AMI病人的危險程度分級、治療決策的制定、治療效果的評價以及預(yù)后評估具有重要意義[3-4]。心臟MR成像技術(shù)憑借其較高的時間和空間分辨力,可綜合提供心臟的解剖、功能、代謝等方面的信息[5],具有較好的可重復(fù)性和較高的準(zhǔn)確性,已經(jīng)成為臨床前和臨床研究中檢測AMI的有效手段?;卺彽男呐KMR延遲強化(late gadolinium-enhanced cardiac magnetic resonance,LGE-CMR)技術(shù)能夠提供梗死心肌病理學(xué)方面的信息,可用于梗死心肌、活性心肌和MVO的定量評價,并以此評價AMI后病人的心功能,預(yù)測心臟不良事件發(fā)生[2,6]。
常用的MR對比劑為順磁性對比劑,如Gd-DTPA,它以縮短T1為主[7],提高人體正常組織與病變組織間信號強度差異,從而最大限度發(fā)揮MRI軟組織分辨力高的優(yōu)勢。Gd-DTPA為細(xì)胞外間質(zhì)對比劑,在正常心肌,由于心肌細(xì)胞排列緊密,Gd-DTPA不能通過完整的細(xì)胞膜,其分布空間較小[7]。發(fā)生AMI后,由于缺血缺氧,梗死區(qū)域心肌細(xì)胞的細(xì)胞膜完整性遭到破壞;微血管內(nèi)皮細(xì)胞損傷導(dǎo)致其通透性增加,從而引起心肌間質(zhì)水腫。這兩個因素會導(dǎo)致Gd-DTPA在這些區(qū)域的分布增加[8-9]。另一方面,梗死區(qū)域由于冠狀動脈血流量減低、毛細(xì)血管及功能性毛細(xì)血管密度的改變導(dǎo)致Gd-DTPA動力學(xué)發(fā)生異常改變,即Gd-DTPA流入流出該區(qū)域時間延長。因此,心肌梗死區(qū)有較多的對比劑聚集,發(fā)生延遲強化[10]。
2.1 LGE-CMR定量評價AMI梗死心肌及其臨床價值 LGE-CMR具有較高的空間分辨力,不僅可用于AMI的定性診斷,還可對AMI的梗死心肌進(jìn)行定量評價。LGE評價的AMI梗死心肌范圍與組織病理染色所檢測的一致,這已經(jīng)被大量的基礎(chǔ)研究所證實。Thomas等[11]通過運用心臟MRI、單光子發(fā)射 體 層 成 像 (single-photon emission computed tomography,SPECT)和正電子發(fā)射體層成像(positron emission tomography,PET)對AMI模型大鼠進(jìn)行研究后發(fā)現(xiàn),LGE評價的梗死范圍比SPECT和PET更為準(zhǔn)確,與氯化三苯基四氮唑(triphenyltetrazolium chloride,TTC)染色的一致性最好。Luo等[12]通過對缺血30 min和永久缺血的大鼠心肌梗死模型研究發(fā)現(xiàn),無論是短暫性缺血還是永久缺血,LGE評價的梗死大小均與TTC染色所顯示的一致。Feng等[13]通過對兔子再灌注心肌梗死模型的研究證實,LGE顯示的梗死核心面積與活體靜注EB(Evans blue)染色所顯示的梗死核心面積無差異。
有研究[14-15]顯示,LGE所顯示的梗死大小與左室重塑直接相關(guān),是ST段抬高心肌梗死 (ST-segment elevation myocardial infarction,STEMI)病人心功能惡化和心臟不良事件獨立的預(yù)測因素。Wu等[14]通過對122例24 h內(nèi)接受了經(jīng)皮冠狀動脈介入術(shù)(percutaneous coronary intervention,PCI)治療的急性STEMI病人研究后發(fā)現(xiàn),梗死大小與最初的收縮末期容積指數(shù)(end-systolic volume index,ESVI)、舒張末期容積指數(shù) (end-diastolic volume index, EDVI)和射血分?jǐn)?shù)(ejection fraction,EF)呈直線相關(guān),這些參數(shù)均與不良預(yù)后(包括死亡、復(fù)發(fā)心肌梗死和心肌衰竭)相關(guān)。然而,梗死大小是其中唯一的不良后果的重要預(yù)測因素。梗死面積最小的病人射血分?jǐn)?shù)增加 (0.49~0.53),而舒張期容積指數(shù)則不變。相反,梗死面積最大的病人雖然也有射血分?jǐn)?shù)的改善,但卻是以舒張期容積指數(shù)的明顯增加(86~ 95 mL/m2)為前提。Larose等[15]通過對103例接受了血管成形術(shù)的急性STEMI病人研究后指出,與梗死透壁程度、MVO和可挽救心肌 (myocardial salvage)相比,LGE所顯示的梗死大小與左室射血分?jǐn)?shù)的改變緊密相關(guān),左室梗死超過23%準(zhǔn)確地預(yù)測了隨后的左室功能失調(diào)。Izquierdo等[16]通過對440例STEMI病人進(jìn)行平均2年的隨訪研究后,證實心律失常性心臟不良事件(包括出院后的突然死亡、持續(xù)性心室性心動過速和心室纖維性顫動)與LGE所評價的較大的梗死范圍相關(guān),梗死灶大?。╣/m2)≥23.5 g/m2者更易發(fā)生心臟不良事件。總之,LGE評價的梗死大小與AMI病人的心功能和不良臨床結(jié)果相關(guān),可以用來預(yù)測AMI病人心肌梗死后的心功能和不良心臟事件。
2.2 LGE-CMR在評價心肌活性中的價值 很多臨床研究[7]包括Meta分析已經(jīng)證實,對AMI病人及時行血管重建治療可降低其年死亡率,其原因在于仍有活性心肌存在。因此,活性心肌的評價對于AMI病人治療決策的制定和預(yù)后至關(guān)重要[17]。很多無創(chuàng)的成像方法均可用于評價心肌活性,但LGE-CMR是其中非常準(zhǔn)確的方法[17]。LGE-CMR可通過與其他心臟MR方法聯(lián)合用于活性心肌的評價。
心肌挽救指數(shù)(myocardiumsalvageindex,MSI)是評價活性心肌的一個重要參數(shù),可作為AMI壞死心肌和再灌注治療療效評價的重要預(yù)測指標(biāo)[13]。冠狀動脈阻塞后其所支配區(qū)域發(fā)生缺血,此區(qū)域稱為危險區(qū)(area at risk,AAR),包含了不可逆性心肌損傷區(qū),也稱梗死核心(myocardium infarction core,MIC),以及可逆性心肌損傷區(qū),又稱可挽救區(qū)(salvageable zone,SZ)。MSI可通過以下公式計算得到:MSI=SZ/ AAR=(AAR-MIC)/AAR。Kim等[18]研究發(fā)現(xiàn),LGE所顯示的強化大小和形狀與不可逆損傷區(qū)一致,并指出延遲強化不會發(fā)生在可逆性損傷區(qū)。LGE-CMR可通過與T2WI聯(lián)合來分別確定MIC和AAR,從而計算出MSI[13]。另外,LGE-CMR也可與電影MRI聯(lián)合來區(qū)分AMI的梗死區(qū)(強化并伴有收縮異常)、可逆性區(qū)域(無強化但是有收縮異常)和正常心?。o強化并且功能正常)[18]。
梗死透壁程度是反映AMI后心肌活性的另一間接參數(shù)。冠狀動脈阻塞后,其所支配的心肌發(fā)生缺血,造成心肌細(xì)胞結(jié)構(gòu)和功能的損傷,如果血流沒有及時恢復(fù),缺血區(qū)的心肌將發(fā)生壞死,并由心內(nèi)膜下向心包膜下發(fā)展[19]。換句話說,透壁程度小就預(yù)示著有較多的活性心肌存在[20],病人就更有可能通過臨床治療獲益。有研究者[21-22]對犬AMI模型研究后發(fā)現(xiàn),AMI后早期血流的恢復(fù)和收縮功能的改善與LGE所顯示的強化透壁程度的下降有關(guān),隨后他們在AMI病人證實了LGE所顯示的梗死透壁程度可以預(yù)測收縮功能的改善。因此,LGE-CMR可通過評價梗死透壁程度間接地對心肌活性做出評估,并以此指導(dǎo)臨床治療和預(yù)測預(yù)后。
2.3 LGE-CMR對MVO的評價及其意義 MVO是AMI中的一種常見的現(xiàn)象[23],它往往存在于心肌持續(xù)缺血的區(qū)域,包括組織水腫、血小板堵塞、中性粒細(xì)胞黏附和毛細(xì)血管內(nèi)紅細(xì)胞淤積等多個過程[10,24]。這些病理過程可能會因再灌注治療早期階段的再灌注損傷而加劇[25]。MVO導(dǎo)致血流灌注減少,對比劑不能到達(dá)此區(qū)域。因此,MVO在LGE上顯示為高信號強化的梗死區(qū)內(nèi)的低信號無強化區(qū)域[23]。
MVO與解剖學(xué)上定義的無復(fù)流 (no-reflow)區(qū)相一致[26]。Iwakura等[27]認(rèn)為無復(fù)流現(xiàn)象的發(fā)展與心肌損傷的嚴(yán)重程度、危險區(qū)的大小和梗死區(qū)支配動脈的閉塞程度有關(guān)。MVO與梗死范圍擴大、心肌功能降低、左心室重構(gòu)以及不良的臨床結(jié)果密切相關(guān)[28]。因此,對MVO進(jìn)行準(zhǔn)確的評價對于AMI病人的預(yù)后評估有重要意義。有研究[23]指出,LGE顯示的MVO與冠狀動脈內(nèi)多普勒超聲所見一致,而且LGE對MVO的檢測更加敏感,他們通過多變量回歸分析發(fā)現(xiàn),與梗死大小和透壁壞死相比,MVO的范圍是與早期的收縮期逆流和舒張期減速速率相關(guān)的獨立因素。Vicente等[29]通過運用LGE和心肌顯色分級對39例PCI術(shù)后的AMI病人的MVO進(jìn)行評價后指出,相對于心肌顯色分級,LGE評價MVO有更高的準(zhǔn)確性,MVO是左室重構(gòu)的重要預(yù)測因素。Hadamitzky等[30]通過對281例STEMI病人的隨訪研究發(fā)現(xiàn),相比LGE和SPECT評價的梗死區(qū)域而言,LGE評價的MVO是AMI病人更重要的臨床風(fēng)險遠(yuǎn)期預(yù)測因素。另一方面,對MVO的評價有助于識別成功實施PCI后的高危AMI病人,可以促進(jìn)實施額外干預(yù)措施的決策制定。從理論上講,微血管灌注的改善有益于梗死治療、心室重構(gòu)和側(cè)支循環(huán)的建立。通過LGE評價MVO除了可以選擇能進(jìn)行輔助治療的病人之外,它對于評價新的治療方法的效果也是非常有效的[23]。
2.4 LGE對心內(nèi)膜下梗死的檢測及其他應(yīng)用 在臨床上,有很多AMI病人的梗死位于心內(nèi)膜下且較局限(心室壁內(nèi)側(cè)1/3),這類梗死稱為心內(nèi)膜下心肌梗死,其他檢查方法如SPECT由于空間分辨力有限,對這一類梗死的檢出敏感性較低。LGE有較高的組織對比度和空間分辨力,可清楚地顯示心內(nèi)膜下梗死,是目前檢測心內(nèi)膜下梗死的最敏感的方法[31-32]。由于空間分辨力低,SPECT不易區(qū)分透壁性心肌梗死和心內(nèi)膜下心肌梗死[33]。因此,對于梗死范圍較大的心內(nèi)膜下心肌梗死,SPECT可能會得出不支持行血管重建術(shù)的診斷,而LGE對心內(nèi)膜下梗死更準(zhǔn)確的評價則有助于AMI病人選擇治療方案[20]。
有的AMI病人梗死范圍較小,超聲心動圖和SPECT較難檢出,如果這類病人發(fā)生心臟破裂,其位置的檢測也較困難。LGE憑借其較高的分辨力,可檢測心臟破裂和預(yù)測即將發(fā)生的心臟破裂[34]。另外,LGE也可用于檢測附壁血栓。Lanzillo等[35]通過運用LGE-CMR對36例STEMI病人研究后發(fā)現(xiàn),LGE可準(zhǔn)確地檢測AMI后的附壁血栓,并指出梗死的位置、再灌注時間、射血分?jǐn)?shù)和左室收縮末期容積是左室附壁血栓形成的重要預(yù)測因素。
盡管LGE-CMR是目前評價AMI比較常用的方法,但是其準(zhǔn)確性與可靠性也會受到很多因素的影響,需要在操作過程中加以注意。首先,LGE定量評價梗死大小和MVO可能并非完全準(zhǔn)確,主要由以下幾方面的原因造成。①對比劑的非特異性。有研究[13]顯示,LGE檢測的梗死核心范圍比EB染色所顯示的梗死核心稍大,這可能是由于Gd-GTPA的非特異性這一固有特性所造成。②對比劑的劑量。有文獻(xiàn)[36]報道高劑量的對比劑(≥0.2 mmol/kg)對于急慢性心肌梗死的檢測比低劑量的更加準(zhǔn)確,當(dāng)對比劑劑量為0.3 mmol/kg時,LGE檢測AMI的敏感度為99%。③對比劑注入后的影像采集時間會影響測量結(jié)果。有研究[37]發(fā)現(xiàn),針對不同缺血時間(分別為30 min和2 h)的AMI大鼠,其最佳影像采集時間明顯不同,分別為注射對比劑后約26 min和16 min。也有研究[38]指出,當(dāng)對比劑劑量≥0.2 mmol/kg時,在對比劑注入后10~30 min之間采集的影像是沒有顯著差異的。④增強時不同MR序列的選擇雖然不會直接影響強化范圍的大小,但會影響影像質(zhì)量和強化程度,從而會影響對強化的判斷[37]。⑤反轉(zhuǎn)時間(inversion time,TI)。通過調(diào)整反轉(zhuǎn)時間可以增加影像對比和梗死檢出敏感性[39]。⑥部分容積效應(yīng)會導(dǎo)致LGE高估梗死區(qū)[18]。其次,LGE評價心內(nèi)膜下的梗死的可靠性也存在質(zhì)疑。傳統(tǒng)的LGE影像所顯示的梗死和心腔血同為高信號,它們之間較低的對比度可能會影響心內(nèi)膜下梗死的檢出[40]。另一方面,Gd-GTPA進(jìn)入人體后主要經(jīng)腎代謝以原型排出,因此不能用于伴有嚴(yán)重腎功能衰竭的AMI病人[41]。因此,LGE-CMR評價AMI時,應(yīng)根據(jù)不同的受試者和掃描設(shè)備,調(diào)整合理的對比劑劑量、掃描時間及TI值,從而才能夠更加準(zhǔn)確地評價AMI。
針對傳統(tǒng)LGE-CMR的不足,新對比劑的應(yīng)用和MR序列的優(yōu)化可在一定程度上解決相關(guān)問題。已開始應(yīng)用于AMI的診斷。由于釓對比劑分子質(zhì)量相對較大(為微摩爾水平),故與SPECT或PET相比,CMR檢測心肌梗死的敏感性較低。超順磁性的氧化鐵超微顆粒 (ultrasmall superparamagnetic particles of iron oxide,USPIO)的應(yīng)用可增加心臟MR檢測梗死心肌的敏感性[6]。USPIO的分子直徑較?。s為30 nm),可自由進(jìn)出毛細(xì)血管,并且被網(wǎng)狀內(nèi)皮系統(tǒng)的炎癥細(xì)胞(主要是巨噬細(xì)胞)吞噬[42]?;A(chǔ)和臨床研究已證實,它進(jìn)入體內(nèi)后會到達(dá)AMI的炎癥區(qū)域,通過改變炎癥心肌組織的T2*以增加其與正常心肌的對比[6,42]。因此,作為一種新的MR對比劑,USPIO對于AMI的評價具有廣闊的前景。LGE盡管分辨力很高,但是由于梗死組織和心腔血之間缺乏對比,仍然可能遺漏部分心內(nèi)膜下梗死。多對比延遲增強 (multicontrast delayed enhancement,MCODE)技術(shù)在一次屏氣下可獲得同一心動周期時刻的心臟T2加權(quán)影像和T1加權(quán)LGE影像,心肌組織(包括正常和梗死心肌)通過T2加權(quán)與心腔血液相區(qū)分,T2加權(quán)影像和LGE影像的聯(lián)合可更好地顯示心內(nèi)膜下梗死。Bandettini等[40]通過運用MCODE技術(shù)對73例病人(包括心肌缺血、AMI、慢性MI和其他疾病)進(jìn)行評價后發(fā)現(xiàn),MCODE序列檢測梗死的敏感度、特異度和準(zhǔn)確度分別為100%、88%和96%,可以發(fā)現(xiàn)傳統(tǒng)LGE不能發(fā)現(xiàn)的心內(nèi)膜下梗死,降低梗死檢出假陰性率。
綜上所述,LGE-CMR憑借其較高的時間和空間分辨力,可對AMI的梗死心肌以及MVO進(jìn)行定量評價,并可通過與其他方法的聯(lián)合用于可挽救心肌的評價。通過運用LGE-CMR對AMI病人的梗死范圍大小、心肌活性和MVO進(jìn)行評價可有效地指導(dǎo)臨床治療和預(yù)測預(yù)后。LGE-CMR相對于其他方法的優(yōu)勢還在于它能檢出其他方法較難檢出的小梗死灶,區(qū)分透壁梗死和心內(nèi)膜下心肌梗死,并且可以有效地檢出AMI后的附壁血栓和心臟破裂。LGE-CMR盡管存在不足,但目前仍是無創(chuàng)評價AMI的常用手段,并且隨著新對比劑的運用和MR序列的不斷優(yōu)化,它應(yīng)用于AMI評價的前景將越來越廣闊。
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(收稿2014-07-16)
Current application and research status of late gadolinium-enhanced cardiac magnetic resonance in the evaluation of acute myocardial infarction
ZHANG Ruzhi,CHEN Wei,XIA Rui,GAO Fabao.Molecular Imaging Laboratory,Department of Radiology,West China Hospital,Sichuan University,Chengdu 610041,China
The accurate quantifications of infarcted myocardium,myocardial viability and microvascular obstruction (MVO)are essential for patients with acute myocardial infarction (AMI)including dangerous degree classification,treatment decisions making,evaluation of therapeutic effect and prognosis evaluation.Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR)imaging is available for quantitative evaluation of infarcted myocardium,viable myocardium and MVO due to its high spatial and temporal resolution.It has good repeatability and high accuracy in the application of AMI evaluation.In this paper,we reviewed the current application and research status of LGE-CMR in AMI.
Acute myocardial infarction;Late gadolinium-enhanced cardiac MR;Myocardial viability;Microvascular obstruction
10.3874/j.issn.1674-1897.2015.01.Z0106
610041成都,四川大學(xué)華西醫(yī)院放射科 分子影像中心
郜發(fā)寶,E-mail:gaofabao@yahoo.com
*審校者
國家自然科學(xué)基金重點項目(81130027),國家科技部十二五支撐計劃(2012BAI23B08)