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的血栓栓塞，是缺血性卒中的主要病理學基礎。因此，早期識別腦血管易損斑塊是缺血性卒中防控的關鍵。引起腦血管事件的責任病灶既可以發生于顱內動脈，也可位于顱外頸動脈。有證據表明，不同種族之間易損斑塊在不同血管床的發生率存在一定的差異，亞洲人群顱內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，顱內動脈可能是國人篩查易損斑塊的主要血管床。

現階段，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重性的主要指標。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生、發展過程中存在“正性重構效應”，即病變向血管壁外膨脹性生長，而不引起管腔嚴重狹窄（圖1）[18]。這種正性重構效應廣泛存在于全身各個血管床，包括顱內動脈和顱外頸動脈。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重性。

表1 腦血管病患者顱內外動脈易損斑塊發生率的人群差異

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%

病理學上，粥樣硬化易損斑塊主要表現為動脈管壁形態與成分的變化。易損斑塊通常表現為較大的斑塊負荷（厚度、面積或體積）、大脂質核薄纖維帽、斑塊內出血、纖維帽破裂或炎癥反應及新生血管[19]。管腔狹窄只是粥樣硬化病變進展產生的間接征象。基于以上事實，評價易損斑塊的技術關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，是目前評價頸動脈易損斑塊最為可靠的無創性影像學手段。這一技術的核心是應用特殊的磁共振血流抑制技術（即黑血技術）抑制管腔流動的血液信號，同時結合脂肪抑制技術，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，從而實現對動脈管壁的直接成像。此外，該技術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加權像（T1weighted imaging，T1WI）、T2加權像（T2weighted imaging，T2WI）和磁化準備快速回波序列（magnetization prepared rapid acquisition gradient echo sequences，MP-RAGE），利用不同物質在不同對比度圖像上表現特征的差異性，來準確識別斑塊內各種成分，從而評價斑塊的易損性（圖2）。與病理學對照研究證實，磁共振高分辨率管壁成像技術幾乎能準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的快速發展，管壁成像亦由原來的二維成像發展為三維成像。如表2所示，傳統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等缺點。近來，有學者研究開發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、覆蓋范圍大等優點，大大提高了成像效率，并且使顱內外腦血管壁一站式成像成為可能。應用三維管壁成像技術，能夠直觀顯示腦動脈粥樣硬化病變的大小、形態以及位置分布，尤其對多發病變的顯示更具優勢（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、療效評價及預防提供重要依據。管壁厚度、管壁面積、管壁體積及標準化管壁指數［管壁面積/（管壁面積+管腔面積）×100%］等是斑塊負荷的常用測量指標，這些反映粥樣硬化病變大小的參數與斑塊的易損性具有一定的相關性。通過管壁成像定性和定量評價斑塊成分特征（如鈣化、脂質核、斑塊內出血、纖維帽破裂等），對于斑塊易損性的判斷、腦血管事件風險的預測、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（MERGE）對腦血管粥樣硬化病變的顯示

脂質核（脂質核占據＞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，通過磁共振動態增強技術測得的管壁高傳輸常數（transfer constant，Ktrans）或血漿容積分數（fractional plasma volume，Vp）反映的是局部炎癥反應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險[26]。一系列前瞻性研究證實，纖維帽破裂、斑塊內出血和

脂質核大小是腦血管事件的有效預測指標（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]研究發現，頸動脈出血性斑塊進行支架植入術圍術期發生靜默腦梗死的概率是61%，這一比例明顯高于內膜剝脫術（13%）。由于磁共振管壁成像是一項具有高度可重復性的技術，現已被廣泛應用于監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識別腦動脈粥樣硬化易損斑塊，并可對其進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重性的評價，不應僅局限于測量管腔狹窄程度，需要重點關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節，充分考慮斑塊的成分特征（如有無斑塊內出血）有可能會降低圍術期并發癥，從而增加患者獲益；再次，對他汀類藥物治療效果評價傳統的做法局限于監測血脂水平的變化，而不是直接觀察靶血管粥樣硬化病變有無進展或退縮。由于磁共振管壁成像能夠直接顯示和準確定量斑塊內脂質核成分，為臨床觀察藥物療效提供了有效的監測手段；最后，磁共振管壁成像能夠對腦動脈粥樣硬化病變的破裂風險進行分層分析，這將為制訂腦血管病的預防策略提供重要依據。當然，磁共振管壁成像獲得的信息能否改變臨床路徑，還需要開展大規模前瞻性研究以提供更多的循證醫學證據。

表3 磁共振斑塊特征預測腦血管事件

1 Huang YN, Gao S, Li SW, et al. Vascular lesions in Chinese patients with transient ischemic attacks[J].Neurology, 1997, 48:524-525.

2 Leung SY, Ng TH, Yuen ST, et al. Pattern of cerebral atherosclerosis in Hong Kong Chinese. Severity in intracranial and extracranial vessels[J]. Stroke, 1993,24:779-786.

3 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.

4 Zhao H, Zhao X, Liu X, et al. Association of carotid atherosclerotic plaque features with acute ischemic stroke:a magnetic resonance imaging study[J]. Eur J Radiol, 2013, 82:e465-e470.

5 Guo Y, Jiang X, Chen S, et al. Aortic arch and intra-/extracranial cerebral arterial atherosclerosis in patients suffering acute ischemic strokes[J]. Chin Med J (Engl),2003, 116:1840-1844.

6 Gorelick PB, Wong KS, Bae HJ, et al. Large artery intracranial occlusive disease:a large worldwide burden but a relatively neglected frontier[J]. Stroke, 2008,39:2396-2399.

7 Kim YD, Choi HY, Cho HJ, et al. Increasing frequency and burden of cerebral artery atherosclerosis in Korean stroke patients[J]. Yonsei Med J, 2010, 51:318-325.

8 Ko Y, Park JH, Yang MH, et al. Signif i cance of aortic atherosclerotic disease in possibly embolic stroke:64-multidetector row computed tomography study[J]. J Neurol, 2010, 257:699-705.

9 Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebral arteries:intracranial versus extracranial[J]. Neuroepidemiology, 2003, 22:37-40.

10 Sacco RL, Kargman DE, Gu Q, et al. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study[J]. Stroke, 1999, 26:14-20.

11 Wityk RJ, Lehman D, Klag M, et al. Race and sex differences in the distribution of cerebral atherosclerosis[J]. Stroke, 1996, 27:1974-1980.

12 Russo C, Jin Z, Rundek T, et al. Atherosclerotic disease of the proximal aorta and the risk of vascular events in a population-based cohort:the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study[J]. Stroke, 2009,40:2313-2318.

13 Di Tullio MR, Russo C, Jin Z, et al. Aortic arch plaques and risk of recurrent stroke and death[J]. Circulation,2009, 119:2376-2382.

14 Sacco RL, Khatri M, Rundek T, et al. Improving global vascular risk prediction with behavioral and anthropometric factors. The multiethnic NOMAS(Northern Manhattan Cohort Study)[J]. J Am Coll Cardiol, 2009, 54:2303-2311.

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

16 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.

17 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.

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

19 Naghavi M, Libby P, Falk E, et al. From vulnerable plaque to vulnerable patient:a call for new def i nitions and risk assessment strategies:Part I[J]. Circulation,2003, 108:1664-1672.

20 Yuan C, Mitsumori LM, Ferguson MS, et al. In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques[J].Circulation, 2001, 104:2051-2056.

21 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.

22 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.

23 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.

24 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.

25 Fan Z, Zhang Z, Chung YC, et al. Carotid arterial wall MRI at 3T using 3D variable-f l ip-angle turbo spin-echo(TSE) with fl ow-sensitive dephasing (FSD)[J]. J Magn Reson Imaging, 2010, 31:645-654.

26 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.

27 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.

28 Sadat U, Teng Z, Young VE, et al. Association between biomechanical structural stresses of atherosclerotic carotid plaques and subsequent ischaemic cerebrovascular events--a longitudinal in vivo magnetic resonance imaging-based fi nite element study[J]. Eur J Vasc Endovasc Surg, 2010, 40:485-491.

29 Kwee RM, van Oostenbrugge RJ, Mess WH, et al. MRI of carotid atherosclerosis to identify TIA and stroke patients who are at risk of a recurrence[J]. J Magn Reson Imaging, 2013, 37:1189-1194.

30 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.

31 Hosseini AA, Kandiyil N, Macsweeney ST, et al.Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke[J]. Ann Neurol, 2013, 73:774-784.

32 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.

33 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.

34 Underhill HR, Yuan C, Zhao XQ, et al. Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients:a high-resolution magnetic resonance imaging trial[J]. Am Heart J, 2008, 155:584.e1-8.

35 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.