趙錫海，宋焱，李飛宇，苑純，4

卒中現(xiàn)已成為我國(guó)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(guó)目前亟待解決的公共健康問(wèn)題之一。缺血性卒中（ischemic stroke，IS）的主要責(zé)任病變是腦動(dòng)脈粥樣硬化易損斑塊。因此，早期識(shí)別頸動(dòng)脈易損斑塊并對(duì)其進(jìn)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(dòng)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(dòng)脈斑塊的負(fù)荷和成分特征，被認(rèn)為是現(xiàn)階段識(shí)別頸動(dòng)脈易損斑塊的最佳無(wú)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(dòng)脈易損斑塊特征，對(duì)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(jí)預(yù)防均具有重要價(jià)值。隨著MR斑塊成像技術(shù)的進(jìn)一步發(fā)展，其臨床應(yīng)用前景會(huì)更為廣闊。

1 MR斑塊成像識(shí)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(shí)別易損斑塊并對(duì)其進(jìn)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(dòng)脈血管床，如顱內(nèi)動(dòng)脈和顱外頸動(dòng)脈等。Wong等[1]研究發(fā)現(xiàn)，中國(guó)人群IS患者中46.6%存在顱內(nèi)大動(dòng)脈狹窄，而西方人群IS多為顱外頸動(dòng)脈易損斑塊所致。此外，一項(xiàng)小樣本研究顯示，國(guó)人癥狀性頸動(dòng)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(dòng)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(duì)中國(guó)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(jì)算機(jī)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(cè)量動(dòng)脈管腔狹窄程度，以此判斷病變的嚴(yán)重性。然而，由于動(dòng)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(dòng)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(wú)癥狀頸動(dòng)脈中，6%～8%存在易損斑塊。因此，學(xué)者建議對(duì)動(dòng)脈管壁進(jìn)行直接成像，通過(guò)識(shí)別斑塊內(nèi)部的成分特征評(píng)價(jià)斑塊的易損性。

MR斑塊成像技術(shù)在評(píng)價(jià)腦血管易損斑塊方面具有重要價(jià)值。與組織病理學(xué)對(duì)照研究顯示，MR二維、高分辨率斑塊成像幾乎能夠識(shí)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(duì)頸動(dòng)脈進(jìn)行成像，與二維技術(shù)相比，其縱向覆蓋范圍可以擴(kuò)大至250 mm，且掃描時(shí)間明顯縮短[12]。對(duì)于顱內(nèi)動(dòng)脈易損斑塊成像，多數(shù)學(xué)者沿用顱外頸動(dòng)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(dòng)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(dòng)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(hào)對(duì)比，對(duì)其管壁成像具有一定的挑戰(zhàn)。目前有學(xué)者研究開(kāi)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(dòng)脈易損斑塊成像的未來(lái)發(fā)展方向。

早期識(shí)別易損斑塊對(duì)于IS的預(yù)防具有重要意義。大量橫斷面研究證實(shí)，斑塊內(nèi)出血、纖維帽破裂、表面潰瘍、大脂質(zhì)核等頸動(dòng)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(duì)于無(wú)癥狀人群，頸動(dòng)脈斑塊內(nèi)出血、纖維帽破裂、大脂質(zhì)核等斑塊特征對(duì)于腦血管事件具有一定的預(yù)測(cè)價(jià)值[26-28]。一系列前瞻性研究顯示，頸動(dòng)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(xiǎn)[29-31]。

應(yīng)用常規(guī)手段對(duì)IS患者進(jìn)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(lái)有學(xué)者對(duì)32例頸動(dòng)脈存在偏心性斑塊（＜50%狹窄）的隱源性卒中患者進(jìn)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(shí)，一部分隱源性卒中患者其主動(dòng)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(guò)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(dòng)脈狹窄治療指南》，癥狀性頸動(dòng)脈重度狹窄的患者需要進(jìn)行頸動(dòng)脈內(nèi)膜剝脫術(shù)（carotid endarterectomy，CEA）或頸動(dòng)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(gè)主要指征。DSA是頸動(dòng)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(shì)在于可以清晰、動(dòng)態(tài)地觀察主動(dòng)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(duì)動(dòng)脈粥樣硬化病變的評(píng)估主要是判斷血管狹窄程度，而對(duì)斑塊形態(tài)學(xué)特點(diǎn)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(dòng)脈MR斑塊成像能夠較為準(zhǔn)確地識(shí)別頸動(dòng)脈斑塊潰瘍[38]。有學(xué)者[39]就磁共振成像（magnetic resonance imaging，MRI）和DSA對(duì)頸動(dòng)脈粥樣硬化患者手術(shù)適應(yīng)證的選擇能力進(jìn)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(shí)，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(shí)，MRI對(duì)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(dòng)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(duì)于頸動(dòng)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(zhēng)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(guò)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(guò)分析斑塊與胸鎖乳突肌的信號(hào)干擾比值（signal to interference ratio，SIR），發(fā)現(xiàn)當(dāng)SIR≥1.25時(shí)，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(hào)強(qiáng)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(duì)于這種類型的斑塊適宜選擇CEA。如果該結(jié)論能通過(guò)大樣本的前瞻性研究得到進(jìn)一步證實(shí)，則可借助MR成像對(duì)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(cè)頸動(dòng)脈斑塊他汀類藥物治療療效

對(duì)于頸動(dòng)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(wú)創(chuàng)、無(wú)X線電離輻射、可重復(fù)性好等優(yōu)勢(shì)，是目前評(píng)價(jià)頸動(dòng)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(dòng)脈斑塊的療效，經(jīng)過(guò)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(dòng)脈斑塊在單獨(dú)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(dú)使用依澤替米貝并沒(méi)有抑制斑塊的進(jìn)展，而在聯(lián)合使用他汀藥物的患者中，MR上測(cè)得的斑塊體積在2年內(nèi)沒(méi)有進(jìn)展。在Kawahara等[44]的研究中，應(yīng)用MR斑塊成像監(jiān)測(cè)胸主動(dòng)脈和腹主動(dòng)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(dú)使用阿托伐他汀。有研究者對(duì)接受了半年他汀治療的動(dòng)脈粥樣硬化患者同時(shí)應(yīng)用超聲和MR評(píng)估頸動(dòng)脈斑塊的治療效果，結(jié)果發(fā)現(xiàn)，超聲測(cè)得的頸動(dòng)脈內(nèi)中膜厚度在治療前后并無(wú)顯著性變化，而MR測(cè)得的斑塊體積則明顯縮小，提示MR檢查在評(píng)價(jià)他汀類藥物療效方面可能比超聲更有優(yōu)勢(shì)[45]。

近些年來(lái)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(xiàng)利用MR監(jiān)測(cè)他汀類藥物長(zhǎng)期治療頸動(dòng)脈粥樣硬化病變的研究中，研究者發(fā)現(xiàn)，經(jīng)過(guò)3年的治療，頸動(dòng)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(huì)對(duì)未來(lái)臨床制訂他汀類藥物長(zhǎng)期治療計(jì)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(guò)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(dòng)脈斑塊對(duì)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(dòng)態(tài)增強(qiáng)MR技術(shù)觀察頸動(dòng)脈斑塊炎癥在他汀類藥物治療前后的變化，經(jīng)過(guò)1年的治療，Ktrans值明顯下降。這一點(diǎn)提示他汀類藥物可能會(huì)降低斑塊新生血管化的程度[48]。

盡管MR斑塊成像對(duì)動(dòng)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(duì)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。

1 Wong KS, Li H, Chan YL, et al. Use of transcranial Doppler ultrasound to predict outcome in patients with intracranial large-artery occlusive disease[J]. Stroke,2000, 31:2641-2647.

2 Saam T, Cai JM, Cai YQ, et al. Carotid plaque composition differs between ethno-racial groups:An MRI pilot study comparing mainland Chinese and American Caucasian patients[J]. Arterioscler Thromb Vasc Biol, 2005, 25:611-616.

3 Falk E, Shah PK, Fuster V. Coronary plaque disruption[J]. Circulation, 1995, 92:657-671.

4 Saam T, Underhill HR, Chu B, et al. Prevalence of American Heart Association type VI carotid atherosclerotic lesions identified by magnetic resonance imaging for different levels of stenosis as measured by duplex ultrasound[J]. J Am Coll Cardiol, 2008, 51:1014-1021.

5 Zhao X, Underhill HR, Zhao Q, et al. Discriminating carotid atherosclerotic lesion severity by luminal stenosis and plaque burden:A comparison utilizing high-resolution magnetic resonance imaging at 3.0 tesla[J]. Stroke, 2011, 42:347-353.

6 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.

7 Cai JM, Hatsukami TS, Ferguson MS, et al.Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging[J]. Circulation, 2002, 106:1368-1373.

8 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.

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

10 Kerwin WS, O'Brien KD, Ferguson MS, et al.Inflammation in carotid atherosclerotic plaque:A dynamic contrast-enhanced MR imaging study[J].Radiology, 2006, 241:459-468.

11 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.

12 Balu N, Yarnykh VL, Chu B, et al. Carotid plaque assessment using fast 3D isotropic resolution blackblood MRI[J]. Magn Reson Med, 2011, 65:627-637.

13 Swartz RH, Bhuta SS, Farb RI, et al. Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI[J]. Neurology, 2009, 72:627-634.

14 Li ML, Xu WH, Song L, et al. Atherosclerosis of middle cerebral artery:Evaluation with high-resolution MR imaging at 3T[J]. Atherosclerosis, 2009, 204:447-452.

15 Niizuma K, Shimizu H, Takada S, et al. Middle cerebral artery plaque imaging using 3-tesla high-resolution MRI[J]. J Clin Neurosci, 2008, 15:1137-1141.

16 Xu WH, Li ML, Gao S, et al. In vivo high-resolution MR imaging of symptomatic and asymptomatic middle cerebral artery atherosclerotic stenosis[J].Atherosclerosis, 2010, 212:507-511.

17 Xu WH, Li ML, Gao S, et al. Plaque distribution of stenotic middle cerebral artery and its clinical relevance[J]. Stroke, 2011, 42:2957-2959.

18 Xu WH, Li ML, Gao S, et al. Middle cerebral artery intraplaque hemorrhage:Prevalence and clinical relevance[J]. Ann Neurol, 2012, 71:195-198.

19 Qiao Y, Steinman DA, Qin Q, et al. Intracranial arterial wall imaging using three-dimensional high isotropic resolution black blood MRI at 3.0 tesla[J]. J Magn Reson Imaging, 2011, 34:22-30.

20 Natori T, Sasaki M, Miyoshi M, et al. Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging[J]. J Stroke Cerebrovasc Dis, 2013, [Epub ahead of print].

21 Parmar JP, Rogers WJ, Mugler JP, et al. Magnetic resonance imaging of carotid atherosclerotic plaque in clinically suspected acute transient ischemic attack and acute ischemic stroke[J]. Circulation, 2010, 122:2031-2038.

22 Homburg PJ, Rozie S, van Gils MJ, et al.Atherosclerotic plaque ulceration in the symptomatic internal carotid artery is associated with nonlacunar ischemic stroke[J]. Stroke, 2010, 41:1151-1156.

23 Sadat U, Weerakkody RA, Bowden DJ, et al. Utility of high resolution MR imaging to assess carotid plaque morphology:A comparison of acute symptomatic,recently symptomatic and asymptomatic patients with carotid artery disease[J]. Atherosclerosis, 2009,207:434-439.

24 Yuan C, Zhang SX, Polissar NL, et al. Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke[J]. Circulation, 2002, 105:181-185.

25 Saam T, Cai J, Ma L, et al. Comparison of symptomatic and asymptomatic atherosclerotic carotid plaque features with in vivo MR imaging[J]. Radiology, 2006,240:464-472.

26 Takaya N, Yuan C, Chu B, et al. Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events:A prospective assessment with MRI--initial results[J]. Stroke, 2006, 37:818-823.

27 Singh N, Moody AR, Gladstone DJ, et al. Moderate carotid artery stenosis:MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men[J]. Radiology,2009, 252:502-508.

28 Mono ML, Karameshev A, Slotboom J, et al. Plaque characteristics of asymptomatic carotid stenosis and risk of stroke[J]. Cerebrovasc Dis, 2012, 34:343-350.

29 Kurosaki Y, Yoshida K, Endo H, et al. Association between carotid atherosclerosis plaque with high signal intensity on T1-weighted imaging and subsequent ipsilateral ischemic events[J]. Neurosurgery, 2011,68:62-67; discussion 67.

30 Yamada N, Higashi M, Otsubo R, et al. Association between signal hyperintensity on T1-weighted MR imaging of carotid plaques and ipsilateral ischemic events[J]. AJNR Am J Neuroradiol, 2007, 28:287-292.

31 Lindsay AC, Biasiolli L, Lee JM, et al. Plaque features associated with increased cerebral infarction after minor stroke and TIA:A prospective, case-control, 3-T carotid artery MR imaging study[J]. JACC Cardiovasc Imaging, 2012, 5:388-396.

32 Amarenco P. Underlying pathology of stroke of unknown cause (cryptogenic stroke)[J]. Cerebrovasc Dis, 2009, 27 Suppl 1:97-103.

33 Freilinger TM, Schindler A, Schmidt C, et al.Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke[J]. JACC Cardiovasc Imaging, 2012, 5:397-405.

34 Stone DA, Hawke MW, LaMonte M, et al. Ulcerated atherosclerotic plaques in the thoracic aorta are associated with cryptogenic stroke:A multiplane transesophageal echocardiographic study[J]. Am Heart J, 1995, 130:105-108.

35 中華醫(yī)學(xué)會(huì)外科學(xué)分會(huì)血管外科學(xué)組. 顱外段頸動(dòng)脈狹窄治療指南[J]. 中國(guó)實(shí)用外科雜志, 2008, 28:913-915.

36 Streifler JY, Eliasziw M, Fox AJ, et al. Angiographic detection of carotid plaque ulceration. Comparison with surgical observations in a multicenter study.North American Symptomatic Carotid Endarterectomy Trial[J]. Stroke, 1994, 25:1130-1132.

37 Rothwell PM, Gibson R, Warlow CP. Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis.On behalf of the European Carotid Surgery Trialists'collaborative group[J]. Stroke, 2000, 31:615-621.

38 Yu W, Underhill HR, Ferguson MS, et al. The added value of longitudinal black-blood cardiovascular magnetic resonance angiography in the cross sectional identification of carotid atherosclerotic ulceration[J]. J Cardiovasc Magn Reson, 2009, 11:31.

39 Song Y, Chen M, Zhou C, et al. Comparison of cardiovascular MRI and DSA in the selection of stent-treatment for carotid atherosclerosis patients[J].Zhonghua Yi Xue Za Zhi, 2011, 91:1625-1629.

40 Henry M, Henry I, Klonaris C, et al. Benefits of cerebral protection during carotid stenting with the percusurge guardwire system:Midterm results[J]. J Endovasc Ther, 2002, 9:1-13.

41 Yamada K, Yoshimura S, Kawasaki M, et al. Embolic complications after carotid artery stenting or carotid endarterectomy are associated with tissue characteristics of carotid plaques evaluated by magnetic resonance imaging[J]. Atherosclerosis, 2011, 215:399-404.

42 Corti R, Fayad ZA, Fuster V, et al. Effects of lipidlowering by simvastatin on human atherosclerotic lesions:A longitudinal study by high-resolution,noninvasive magnetic resonance imaging[J].Circulation, 2001, 104:249-252.

43 West AM, Anderson JD, Meyer CH, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline[J]. Atherosclerosis,2011, 218:156-162.

44 Kawahara T, Nishikawa M, Furusawa T, et al. Effect of atorvastatin and etidronate combination therapy on regression of aortic atherosclerotic plaques evaluated by magnetic resonance imaging[J]. J Atheroscler Thromb,2011, 18:384-395.

45 Migrino RQ, Bowers M, Harmann L, et al. Carotid plaque regression following 6-month statin therapy assessed by 3T cardiovascular magnetic resonance:Comparison with ultrasound intima media thickness[J]. J Cardiovasc Magn Reson, 2011, 13:37.

46 Zhao XQ, Dong L, Hatsukami T, et al. MR imaging of carotid plaque composition during lipid-lowering therapy:a prospective assessment of effect and time course[J]. JACC Cardiovasc Imaging, 2011, 4:977-986.

47 Patterson AJ, Tang TY, Graves MJ, et al. In vivo carotid plaque MRI using quantitative T2*measurements with ultrasmall superparamagnetic iron oxide particles:A dose-response study to statin therapy[J]. NMR Biomed,2011, 24:89-95.

48 Dong L, Kerwin WS, Chen H, et al. Carotid artery atherosclerosis:Effect of intensive lipid therapy on the vasa vasorum--evaluation by using dynamic contrastenhanced MR imaging[J]. Radiology, 2011, 260:224-231.