來源：中國卒中雜志

【摘要】 識別動(dòng)脈粥樣硬化斑塊及其易損性能有效地預(yù)測高危人群，減低心腦血管臨床事件的發(fā)生。磁共振作為一項(xiàng)無創(chuàng)檢查手段，可以觀察斑塊的形態(tài)和易損性，并進(jìn)行綜合評價(jià)。本文就磁共振成像技術(shù)對動(dòng)脈粥樣硬化斑塊的形態(tài)功能學(xué)檢查做一簡要綜述。

【關(guān)鍵詞】 動(dòng)脈粥樣硬化；斑塊；磁共振；血管壁

【DOI】 10.3969/j.issn.1673-5765.2014.02.012

心腦血管病已經(jīng)逐漸成為威脅人類生命健康的“頭號殺手”。在心腦血管臨床事件中，動(dòng)脈粥樣硬化斑塊破裂和血栓形成是主要的發(fā)病機(jī)制。研究發(fā)現(xiàn)，近70%的急性心血管事件是由斑塊破裂造成的[1]。

傳統(tǒng)的評價(jià)易損斑塊的臨床指標(biāo)仍停留在對管腔狹窄程度的評估方面。但由于存在血管的正性重構(gòu)（positive remodeling），即斑塊占血管的橫截面積小于40％時(shí)斑塊所在處的動(dòng)脈代償性擴(kuò)張[2]，造成了管腔顯影對斑塊識別的局限性。Ballotta等[3]學(xué)者研究發(fā)現(xiàn)即使有癥狀的輕度頸動(dòng)脈狹窄的患者，斑塊內(nèi)也存在著不同程度的潰瘍、斑塊破裂、出血及表面血栓形成。Dong等[4]對一組沒有頸動(dòng)脈狹窄但有高危因素的人群（n=46）進(jìn)行磁共振（magnetic resonance，MR）血管壁成像檢查，發(fā)現(xiàn)67.4％的患者存在脂質(zhì)斑塊，8.7％的患者斑塊具有內(nèi)出血，4.3%的患者斑塊破裂。Libby[1]研究發(fā)現(xiàn)急性心血管事件的元兇超過2/3發(fā)生于非顯著狹窄性病變。這些研究均表明單純地只對管腔的狹窄程度進(jìn)行評價(jià)有可能低估了病變自身的危險(xiǎn)性。

既能夠顯示管腔狹窄，又能顯示斑塊形態(tài)及功能的成像技術(shù)，如MRI已成為當(dāng)前的研究熱點(diǎn)。MR血管壁成像結(jié)合黑血及亮血技術(shù)，可以提供血管組織結(jié)構(gòu)、管壁厚度、斑塊成分等信息。這將給臨床提供除狹窄以外的一種檢查手段和評判指標(biāo)。同時(shí)對那些狹窄程度不是很重的高危病人提供更多的診斷信息。本文對MR血管壁成像即斑塊負(fù)荷、斑塊成分識別進(jìn)行一簡要綜述。

1 斑塊負(fù)荷定性、定量研究

動(dòng)脈壁內(nèi)皮損傷及脂質(zhì)的沉積是目前公認(rèn)的動(dòng)脈粥樣硬化始動(dòng)因素。由于血管內(nèi)皮細(xì)胞功能受損，血液中低密度脂蛋白顆粒進(jìn)入血管壁，繼而被巨噬細(xì)胞所吞噬形成脂質(zhì)條紋（fatty streak），血管壁反應(yīng)性地增厚[5]。因此，早期的動(dòng)脈硬化表現(xiàn)為血管壁增厚。研究證實(shí)MR不僅可以清楚地探測血管壁，準(zhǔn)確測量血管壁的厚度[6]，而且不同的MR機(jī)型、不同掃描、不同閱片者之間都有很好的一致性（可重復(fù)性）[7-9]。另外，Underhill等[10]發(fā)現(xiàn)MRI測量頸動(dòng)脈管壁與超聲也有很好的一致性（r=0.93，P＜0.001）。2000年，F(xiàn)ayad等[11]成功地在8位健康志愿者及5例冠狀動(dòng)脈粥樣硬化性心臟病患者中得到了二維黑血冠狀動(dòng)脈管壁圖像，并發(fā)現(xiàn)冠狀動(dòng)脈粥樣硬化性心臟病患者的冠狀動(dòng)脈管壁較正常人增厚。2002年，Kim等[12]在12位健康志愿者及冠狀動(dòng)脈粥樣硬化性心臟病患者中得到了三維的右冠狀動(dòng)脈近中段管壁圖像。Desai等[13]對健康志愿者進(jìn)行右冠狀動(dòng)脈近中段三維管壁成像，并在1個(gè)月后進(jìn)行重復(fù)成像。對兩次檢查所顯示的冠狀動(dòng)脈管壁長度、管壁厚度由不同的觀察者進(jìn)行觀察，結(jié)果顯示同一觀察者前后兩次判斷及不同觀察者間都具有良好的一致性。

2 斑塊成分定性、定量研究

隨著病程的發(fā)展，脂紋表層沉積大量膠原纖維，平滑肌細(xì)胞（smooth muscle cell）增生并分泌大量細(xì)胞外間質(zhì)（extracellular matrix），構(gòu)成薄厚不一的纖維帽（fibrous cap）。纖維帽下細(xì)胞外脂質(zhì)、富含細(xì)胞內(nèi)脂質(zhì)的巨噬細(xì)胞和泡沫細(xì)胞以及脂紋則構(gòu)成了脂核（lipid core）。脂核進(jìn)一步發(fā)展可出現(xiàn)壞死（lipid-rich necrotic core）、斑塊內(nèi)微血管出血（intraplaque hemorrhage）、鈣化（calcification）和斑塊內(nèi)微血管化（mircovessels）。MR多對比成像技術(shù)可以可靠地評價(jià)斑塊內(nèi)成分并進(jìn)行定性、定量分析（信號特點(diǎn)見表1）。

2.1 脂核和纖維帽 多種MR加權(quán)成像［T1加權(quán)圖像（T1 weighted images，T1WI），T2加權(quán)圖像（T2 weighted images，T2WI）/質(zhì)子密度加權(quán)圖像（proton density weighted images，PDWI），時(shí)間飛躍（time of flight，TOF）］可以顯示脂質(zhì)核心（圖1）。與胸鎖乳突肌信號相比，脂核在T1WI和TOF上為等信號，T2WI為低信號。Fabiano等[14]用MR掃描離體斑塊，發(fā)現(xiàn)其敏感性為92%，特異性為74%。在活體，與病理相對照，MR敏感性為92%，特異性為65%[15]。Cai等[16]對纖維帽進(jìn)行了定量分析，發(fā)現(xiàn)MRI與病理有很好的相關(guān)性（最大纖維帽厚度：r=0.78，P＜0.001；長度：r=0.73，P＜0.001；面積：r=0.73，P＜0.001）。如給予對比劑行增強(qiáng)掃描，可以顯示脂核和纖維帽更多的信息[17-18]。對比劑可使纖維組織的信號提高79.5%，而脂核的信號下降28.6%[17]。強(qiáng)化的纖維帽和未強(qiáng)化的脂核形成了良好的對比，從而更容易勾勒出脂核的邊界而得到準(zhǔn)確的定量測量結(jié)果（圖1）。Wasserman等[18]還發(fā)現(xiàn)與T2WI相比，對比劑增強(qiáng)后T1WI可提升脂核與纖維帽間的對比噪聲比約2倍。Maintz等[19]嘗試采用增強(qiáng)三維T1WI冠狀動(dòng)脈管壁成像（Navigator-gated Free-breathing and Cardiac-triggered T1-weighted Inversion-recovery and Fat-suppressed 3D black-blood Gradient-echo Sequence），探討MR延遲強(qiáng)化評價(jià)冠狀動(dòng)脈斑塊的價(jià)值。Yeon等[20]選擇6位健康志愿者和14例冠狀動(dòng)脈粥樣硬化性心臟病患者進(jìn)行延遲強(qiáng)化MR冠狀動(dòng)脈管壁成像，發(fā)現(xiàn)具有動(dòng)脈硬化斑塊的冠狀動(dòng)脈節(jié)段延遲強(qiáng)化信號明顯高于正常節(jié)段。

2.2 斑塊內(nèi)微血管出血 斑塊內(nèi)出血來自斑塊內(nèi)未成熟血管的紅細(xì)胞滲漏[21]。盡管斑塊內(nèi)出血導(dǎo)致斑塊破裂的機(jī)制還不十分清楚，但其可加速脂核的形成[22]。新近發(fā)表的研究表明，斑塊內(nèi)出血對斑塊的發(fā)展進(jìn)程以及轉(zhuǎn)歸也起著至關(guān)重要的作用。Sun等[23]對一組狹窄程度在50%～75%的無癥狀患者進(jìn)行了54個(gè)月的隨訪，發(fā)現(xiàn)隨訪期間出現(xiàn)斑塊內(nèi)出血的患者，斑塊生長速度明顯高于斑塊內(nèi)未出血的患者［（34.2±9.0）mm3/year vs （5.3±7.2）mm3/year］。由于正鐵血紅蛋白可以不同程度地縮短T1弛豫時(shí)間從而在T1加權(quán)像上呈現(xiàn)高信號，表現(xiàn)為在T1WI和TOF上為高信號，早期出血在T2WI為低信號，晚期的則為等或高信號（圖2）。此信號特點(diǎn)與病理相對照，敏感性為85%～95%，特異性為70%～77%[24]。Moody等[25]用三維重T1加權(quán)磁化強(qiáng)度預(yù)備梯度回波序列（magnetizationprepared rapid acquisition gradient-echo，MP-RAGE）觀察出血，其敏感性為84%，特異性為84%。Ota等[26]在高場強(qiáng)（3.0T）MR設(shè)備進(jìn)行探究，發(fā)現(xiàn)其敏感性為80%，特異性為97%。而利用MR血管壁成像對冠狀動(dòng)脈內(nèi)血栓的顯示敏感性為91%，特異性達(dá)到了88%[27]。新近研發(fā)的顯示出血的序列（simultaneous noncontrast angiography and intraplaque hemorrhage，SNAP）不僅很好地顯示出血病灶自身，并可以清晰地顯示管腔情況，為臨床提供了更加直觀的信息[28]。

2.3 鈣化 鈣化在MR的T1WI、T2WI、TOF均表現(xiàn)為低信號（圖3）。Fabiano等[14]報(bào)道MR探測鈣化的準(zhǔn)確性為98%，特異性為99%。Saam等[15]用MR測量了鈣化的大小，與病理有很好的一致性（r=0.74，P＜0.001）。

盡管鈣化經(jīng)常在斑塊內(nèi)出現(xiàn)，但其是否導(dǎo)致斑塊的不穩(wěn)定性尚無定論。一些研究表明出現(xiàn)大量鈣化與增加斑塊破裂的危險(xiǎn)性呈正相關(guān)[29-33]，而另一些研究則提示鈣化有助于斑塊的穩(wěn)定[34-36]。最近，研究者開始提出鈣化出現(xiàn)的位置有可能影響斑塊的穩(wěn)定性。Li等[37-38]利用生物力學(xué)模型研究顯示，如果鈣化出現(xiàn)在薄纖維帽內(nèi)，則纖維帽的最大剪切力相應(yīng)增加47.5%。相反，如果鈣化出現(xiàn)在脂核或遠(yuǎn)離纖維帽的位置，剪切力則沒有增加。

2.4 斑塊內(nèi)微血管化形成 細(xì)胞內(nèi)微血管化的形成一方面是供給斑塊營養(yǎng)的來源，另一方面也是傳導(dǎo)、運(yùn)輸炎性細(xì)胞、炎性因子的渠道。Moreno等[39]發(fā)現(xiàn)微血管的數(shù)目不僅和炎性細(xì)胞的數(shù)量相關(guān)，也和斑塊破裂有關(guān)。Mofidi等[40]也發(fā)現(xiàn)微血管的數(shù)目和斑塊內(nèi)出血相關(guān)。目前有兩種MR技術(shù)探測斑塊內(nèi)微血管化。一種是利用動(dòng)態(tài)增強(qiáng)（dynamic contrast enhanced MRI，DCE-MRI）技術(shù)。這種技術(shù)最初被應(yīng)用于腫瘤微血管化的研究。在斑塊內(nèi)部，利用這種技術(shù)同樣可以觀察微血管的數(shù)目和通透性[41-42]。有研究證實(shí)，血漿容量分?jǐn)?shù)（fractional plasma volume，Vp）與微血管的面積相關(guān)[43]，而對比劑的透過常數(shù)（transfer constant，Ktrans）與微血管的通透性相關(guān)[41]。另一種應(yīng)用，超順磁性氧化鐵（ultrasmall super-paramagnetic ironoxide，USPIO）顆粒作為分子影像對比劑也用于斑塊成分及穩(wěn)定性的研究。USPIO顆?？梢酝ㄟ^受損的內(nèi)皮細(xì)胞進(jìn)入斑塊內(nèi)，并被巨噬細(xì)胞所吞噬，表現(xiàn)為信號缺失。Trivedi等[44]發(fā)現(xiàn)這種局部信號的缺失出現(xiàn)在75%的易損斑塊中，而只有7%在穩(wěn)定斑塊中。

總之，在體MR多對比成像技術(shù)可以作為有效的方法定性、定量地診斷頸動(dòng)脈斑塊，識別易損斑塊特征，并對斑塊的轉(zhuǎn)歸或發(fā)展進(jìn)行動(dòng)態(tài)監(jiān)測。這項(xiàng)技術(shù)已漸漸成熟走向臨床，對卒中高?；颊叩脑缙谧R別，臨床的早期干預(yù)治療提供可靠的影像依據(jù)。

參考文獻(xiàn)

 1 Libby P. Coronary artery injury and the biology of atherosclerosis inflammation, thrombosis, and stabilization[J]. Am J Cardiol, 2000, 86:3J-8J.

 2 Glagov S , Weisenberg E , Zarins CK , et al. Compensatory enlargement of human atherosclerotic coronary arteries[J]. N Engl J Med, 1987, 316:1371-1375.

 3 Ballotta E, Angelini A, Mazzalai F, et al. Carotid endarterectomy for symptomatic low-grade carotid stenosis[J]. J Vasc Surg, 2014, 59:25-31.

 4 Dong L, Underhill HR, Yu W, et al. Geometric and compositional appearance of atheroma in an angiographically normal carotid artery in patients with atherosclerosis[J]. AJNR Am J Neuroradiol, 2010, 31:311-316.

 5 Hansson G. Inf lammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med, 2005, 352:1685-1695.

 6 Zhang S, Cai J, Luo Y, et al. Measurement of carotid wall volume and maximum area with contrastenhanced 3D MRimaging:initial observations[J]. Radiology, 2003, 228:200-205.

 7 Kang X, Polissar NL, Han C, et al. Analysis of the measurement precision of arterial lumen and wall areas using high-resolution MRI[J]. Magn Reson Med, 2000, 44:968-972.

 8 Alizadeh Dehnavi R, Doornbos J, Tamsma JT, et al. Assessment of the carotid artery by MRI at 3T:a study on reproducibility[J]. J Magn Reson Imaging, 2007, 25:1035-1043.

 9 Vidal A, Bureau Y, Wade T, et al. Scan-rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T[J]. Phys Med Biol, 2008, 53:6821-6835.

10 Underhill H, Ker wi n W, Hatsu kami T, et al. Automated measurement of mean wall thickness in the common carotid artery by MRI:a comparison to intima-media thickness by B-mode ultrasound[J]. J Magn Reson Imaging, 2006, 24:379-387.

11 Fayad ZA, Fuster V, Fallon JT, et al. Noninvasive in vivo human coronary artery lumen and wall imaging using black-blood magnetic resonance imaging[J]. Circulation, 2000, 102:506-510.

12 Kim W Y, Stuber M, Bornert P, et al. Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease[J]. Circulation, 2002, 106:296-299.

13 Desai MY, Lai S, Barmet C, et al. Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging[J]. Eur Heart J, 2005, 26:2320-2324.

14 Fabiano S, Mancino S, Stefanini M, et al. Highresolutionmulticontrast-weighted MR imaging from human carotid endarterectomy specimens to assess carotid plaque components[J]. Eur Radiol, 2008, 18:2912-2921.

15 Saam T, Ferguson MS , Yarnykh VL , et al . Quantitative evaluation of carotid plaque composition by in vivo MRI[J]. Arterioscler Thromb Vasc Biol, 2005, 25:234-239.

16 Cai J, Hatsukami TS, Ferguson MS, et al. In vivo quantitative measurement of intact fibrous cap and lipid-rich necrotic core size in atherosclerotic carotid plaque:comparison of high-resolution, contrast-enhanced magnetic resonance imaging and histology[J]. Circulation, 2005, 112:3437-3444.

17 Yuan C, Kerwin WS, Ferguson MS, et al.Contrastenhanced high resolution MRI for atherosclerotic carotid artery tissue characterization[J]. J Magn Reson Imaging, 2002, 15:62-67.

18 Wasserman BA, Smith WI, Trout HH, et al. Carotid artery atherosclerosis:in vivo morphologic characterization with gadolinium-enhanced doubleoblique MR imaging initialresults[J]. Radiology, 2002, 223:566-573.

19 Maintz D, Ozgun M, Hoffmeier A, et al. Selective coronary artery plaque visualizati on and differentiation by contrast-enhanced inversion prepared MRI[J]. Eur Heart J, 2006, 27:1732-1736.

20 Yeon SB, Sabir A, Clouse M, et al. Delayed-enhancement cardiovascular magnetic resonance coronary artery wall imaging comparison with multislice computed tomography and quantitative coronary angiography[J]. J Am Coll Cardiol, 2007, 50:441-447.

21 Kockx M , Cromheeke K , Knaapen M , e t al. Phagocy tosis and macrophage act ivat ion associated with hemorrhagic microvessels in human atherosclerosis[J]. Arterioscler Thromb Vasc Biol, 2003, 23:440-446.

22 Virmani R , Kolodgie F, Burke A , et al . Atherosclerotic plaque progression and vulnerability to rupture:angiogenesis as a source of intraplaque hemorrhage[J]. Arterioscler Thromb Vasc Biol, 2005, 25:2054-2061.

23 Sun J, Underhill HR, Hippe DS, et al. Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage:a long-term time course study[J]. JACC Cardiovasc Img, 2012, 5:798-804.

24 Chu B, Kampschulte A, Ferg uson MS, et al. Hemorrhage in the atherosclerotic carotid plaque:a high-resolution MRI study[J]. Stroke, 2004, 35:1079-1084.

25 Moody A , Murphy R , Morgan P, et al . Characterization of complicated carotid plaque with magnetic resonance direct thrombus imaging in patients with cerebral ischemia[J]. Circulation, 2003, 107:3047-3052.

26 Ota H, Yarnykh VL, Ferguson MS, et al. Carotid intraplaque hemor rhage imaging at 3.0-T MR imaging:comparison of the diagnostic performance of three T1-weighted sequences[J]. Radiology, 2010, 254:551-563.

27 Jansen CH, Perera D, Makowski MR , et al. Detection of intracoronary thrombus by magnetic resonance imaging in patients with acute myocardial infarction[J]. Circulation, 2011, 124:416-424. 

28 Wang J, B?rnert P, Zhao H, et al. Simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging for carotid atherosclerotic disease evaluation[J]. Magn Reson Med, 2013, 69:337-345.

29 Stary H. Natural history of calcium deposits in atherosclerosis progression and regression[J]. Z Kardiol, 2000, 89:28-35.

30 Mintz G, Pichard A, Popma J, et al. Determinants and correlates of target lesion calcium in coronary artery disease:a clinical, angiographic and intravascular ultrasound study[J]. J Am Coll Cardiol, 1997, 29:268-274.

31 Raggi P, Callister T, Cooil B, et al. Identification of patients at increased risk of first unheralded acute myocardial infarction by electron-beam computed tomography[J]. Circulation, 2000, 101:850-855.

32 Taylor A, Burke A, O'Malley P, et al. A comparison of the Framingham risk index, coronary artery calcifi cation, and culprit plaque morphology in sudden cardiac death[J]. Circulation, 2000, 101:1243-1248.

33 Schmermund A, Erbel R. Unstable coronary plaque and its relation to coronary calcium[J]. Circulation, 2001, 104:1682-1687.

34 Huang H, Virmani R, Younis H, et al. The impact of calcification on the biomechanical stability of atherosclerotic plaques[J]. Circulation, 2001, 103:1051-1056.

35 Cheng G, Loree H, Kamm R, et al. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation[J]. Circulation, 1993, 87:1179-1187.

36 Alderman E, Corley S, Fisher L, et al. Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff[J]. J Am Coll Cardiol, 1993, 22:1141-1154.

37 Li Z, Howarth S, Tang T, et al. Does calcium deposition play a role in the stability of atheroma? Location may be the key[J]. Cerebrovasc Dis, 2007, 24:452-459.

38 Li Z , U-K i ng-I m J, Tang T, et al. I mpact of calcification and intraluminal thrombus on the computed wall st resses of abdom i nal aor t ic aneurysm[J]. J Vasc Surg, 2008, 47:928-935.

39 Moreno P, Pur ushothaman K, Fuster V, et al. Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta:implications for plaque vulnerability[J]. Circulation, 2004, 110:2032-2038.

40 Mofidi R, Crotty T, McCarthy P, et al. Association between plaque instabilit y, angiogenesis and symptomatic carotid occlusive disease[J]. Br J Surg, 2001, 88:945-950.

41 Kerwin W, O'Brien K , Ferguson M , e t a l . Inf lammation in carotid atherosclerotic plaque:a dynamic contrast-enhanced MR imaging study[J]. Radiology, 2006, 241:459-468.

42 Kerwin W, Oikawa M, Yuan C, et al. MR imaging of adventitial vasa vasorum in carotid atherosclerosis[J]. Magn Reson Med, 2008, 59:507-514.

43 Kerwin W, Hooker A, Spilker M, et al. Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque[J]. Circulation, 2003, 107:851-856.

44 Trivedi R, U-King-Im J, Graves M, et al. In vivo detect ion of macrophages in human carotid atheroma:temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI[J]. Stroke, 2004, 35:1631-1635.

【點(diǎn)睛】

傳統(tǒng)的單純對管腔狹窄程度的評價(jià)造成了管腔顯影對斑塊識別的局限性。MR血管壁成像結(jié)合黑血及亮血技術(shù)，可以提供血管組織結(jié)構(gòu)、管壁厚度、斑塊成分等信息。這將給臨床提供除狹窄以外的一種檢查手段和評判指標(biāo)。