于瑾,白皛,吳士文,徐蔚海,吳衛平
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應用高分辨率磁共振成像評估腦動脈粥樣硬化斑塊的研究進展①
于瑾1,2a,白皛2b,吳士文2a,徐蔚海3,吳衛平1
[摘要]高分辨率磁共振成像(HRMRI)是一項安全、無創、經濟和可重復的檢查方法,可以精確反映動脈粥樣硬化的程度,對未來的臨床事件有較高的預測價值。其核磁掃描像素可達到亞毫米級,采用“黑血”技術,廣泛應用于動脈管壁及斑塊成分的研究。應用HRMRI評估腦動脈粥樣硬化斑塊的易損性,包括動脈重塑、斑塊負荷、斑塊內出血和強化、斑塊分布等特點,具有重要的臨床意義。
[關鍵詞]高分辨率;磁共振成像;腦動脈;動脈粥樣硬化;斑塊;綜述
[本文著錄格式]于瑾,白皛,吳士文,等.應用高分辨率磁共振成像評估腦動脈粥樣硬化斑塊的研究進展[J].中國康復理論與實踐, 2016, 22(2): 164-167.
CITED AS: Yu J, Bai X, Wu SW, et al. Progress of high-resolution magnetic resonance imaging in evaluating cerebral atherosclerotic plaques (review) [J]. Zhongguo Kangfu Lilun Yu Shijian, 2016, 22(2): 164-167.
作者單位:1.解放軍總醫院老年神經內科,北京市100853;2.武警總醫院,a.神經內科;b.南一科,北京市100039;3.中國醫學科學院北京協和醫院神經科,北京市100730。作者簡介:于瑾(1980-),女,漢族,河北保定市人,醫學碩士,主治醫師,主要研究方向:顱內動脈的高分辨率磁共振研究。通訊作者:吳衛平,男,醫學博士,主任醫師。E-mail: wuwp@vip.sina.com。
對于腦動脈粥樣硬化性疾病,理想的成像方法應該是安全、無創、經濟和可重復的,并且可以精確反映動脈粥樣硬化的程度,對未來的臨床事件有較高的預測價值。高分辨率磁共振成像(high-resolution MRI, HRMRI)能夠在常規血管影像檢查檢測到斑塊之前發現動脈粥樣硬化斑塊,提供更敏感和更客觀的信息。它是一項符合上述要求,且最具潛力的影像技術。近年來HRMRI在臨床中得到廣泛應用,發展迅速,已應用于頸動脈[1]、主動脈[2]、外周動脈[3-4],冠狀動脈[5]以及顱內血管,包括大腦中動脈[6]和基底動脈[7]。本文對近年來應用HRMRI評估腦動脈粥樣硬化斑塊的研究予以綜述。
用于血管成像的磁共振成像脈沖序列包括“亮血”和“黑血”技術。目前廣泛應用的三維時間飛躍法磁共振血管造影(three-dimension time of flight magnetic resonance angiography, 3D TOF MRA)即“亮血”技術,此技術基于血液的流入增強效應,采集時間短。然而此技術僅能評估管腔的狹窄率,隨著對管壁結構和動脈粥樣硬化斑塊成分的關注,研究人員對磁共振成像硬件和序列設計提出新的要求。
HRMRI是指核磁掃描像素達到亞毫米級,采用“黑血”技術,使用脈沖抑制血流信號,血流呈黑色低信號,而周圍組織為高信號,從而產生對比,襯托出管壁斑塊的影像。目前臨床上為了使管壁影像獲得充足的空間分辨率和對比,使用3 T 或7 T的核磁掃描機和專用的高頻線圈以獲得較高的信噪比(signal-to-noise ratio, SNR)、對比噪聲比(contrast-to-noise ratio, CNR)和信號穿透深度。動脈粥樣硬化斑塊的成分依靠磁共振成像信號強弱進行辨別,而多模式序列顯示斑塊成分更有意義[8],包括2維T1加權圖像(T1weighted imaging, T1WI),T2加權圖像(T2weighted imaging, T2WI)和質子密度加權圖像(proton density weighted imaging, PDWI)。脂質成分在T1WI、PDWI是高信號,在T2WI是低信號;纖維蛋白成分在3個序列都是高信號;鈣離子在3個序列都是低信號;血栓在3個序列也都是高信號,但比纖維蛋白的信號稍低[9]。T1WI易于觀察出血,但不能清楚地顯示外邊界。PDWI比T1WI及T2WI的圖像對比度高,可以更好地分辨管壁和管腔,而T1WI及T2WI圖像更有利于顯示斑塊的不均質成分[1]。
3D HRMRI具有各向同性體素,可以通過減少部分容積效應檢測細微的血管壁病變,同時可以更好地抑制腦脊髓液流進行任何平面的自由重建。然而,3D影像的缺點是空間分辨率不如2D影像。
1996年,Toussaint等最早提出MRI可以精確測量和分辨體內的頸動脈斑塊[10]。頸動脈因其位置表淺,不易移動,比主動脈和冠狀動脈更適合磁共振成像檢查。動物實驗和臨床研究都證實,HRMRI可以顯示頸動脈斑塊的成分和性質,對判斷斑塊的易損性具有非常高的應用價值[11-12]。
2000年,Fayad等最先建立體內冠狀動脈斑塊的MRI影像檢查方法[5]。冠狀動脈與主動脈一樣,MRI影像易受到呼吸運動和心臟跳動的影響,且冠狀動脈位置較深,走行迂曲,獲取影像更加困難。最初,完成冠狀動脈斑塊MRI影像需要屏氣采集,后在提高空間分辨率的同時成功克服心臟和呼吸的偽影,可在自由呼吸情況下完成[13]。
在外周血管的研究中,2002年Corti等在經股動脈行經皮腔內血管成形術(percutaneous transluminal angioplasty, PTA)后24 h,利用HRMRI橫斷面影像觀察到,動脈閉塞層動脈粥樣硬化斑塊嚴重破裂,形成一個形狀不規則的內腔,進一步證實球囊成形術可引起斑塊的廣泛破裂,能夠解釋侵入性治療潛在并發癥的發生機制[3]。
2005年,Klein首先證實HRMRI評估顱內動脈粥樣硬化斑塊的有效性,包括大腦中動脈和基底動脈[6-7]。2010年,Klein等采用增強HRMRI檢查,發現73%的急性腦橋深部梗死患者的基底動脈中存在斑塊,證實HRMRI可用于分析卒中的病因及發生機制,如既往認為的腦小血管病變,部分可以重新歸類為繼發于基底動脈粥樣硬化的穿支動脈閉塞[14]。
與穩定斑塊相比,易損斑塊具有較大的脂質核心、薄纖維帽、混雜的炎性細胞以及新生血管形成。臨床上頸動脈剝脫術的樣本可提供有效的組織病理學依據。Yuan等研究表明HRMRI能辨別脂質核心、斑塊出血和纖維帽,其識別的斑塊特征與組織學的結果有很好的一致性,并進一步證實不穩定纖維帽與近期發生短暫性腦缺血發作(transient ischemic attack, TIA)或卒中是一致的[1,15-17]。顱內動脈和頸動脈斑塊具有相同的病理特征。應用HRMRI評估腦動脈粥樣硬化斑塊的易損性,包括動脈重塑、斑塊負荷、斑塊內出血和強化、斑塊分布等特點,具有重要的臨床意義。
3.1動脈重塑
動脈重塑最早在冠狀動脈粥樣硬化的患者中發現,又稱為Glagov現象[18]。動脈重塑有兩種發展模式,即正性重構(positive remodeling, PR)和負性重構(negative remodeling, NR)。正性重構表現為血管向外擴張,有利于保證血管內腔的大小[19];負性重構則為血管向內收縮,會加重狹窄程度[20-21]。冠狀動脈的相關研究已顯示正性重構更多見于癥狀性患者中[22],這可能是由于正性重構在擴大管腔面積的同時增加了斑塊破裂的風險。相反負性重構因富含纖維成分而不易破裂。顱內動脈研究有相同的發現,有癥狀的大腦中動脈狹窄患者具有較高的正性重構,而無癥狀的大腦中動脈狹窄患者有更多的負性重構[23]。馬寧等利用HRMRI觀察30例基底動脈重度狹窄患者,提示與負性重構相比,正性重構占63.3%,且包含較大斑塊[24]。
3.2斑塊負荷
斑塊的面積被認為是顱內動脈卒中發生的一個危險因素[25-26]。研究表明與無癥狀的大腦中動脈狹窄患者相比,有癥狀的大腦中動脈狹窄患者具有較大的斑塊厚度。徐蔚海對照有癥狀和無癥狀大腦中動脈狹窄的管壁特點,發現患者在血管狹窄率相似的情況下,管壁面積具有統計學差異,有癥狀的患者管壁面積大,多表現為正性重構;而無癥狀的患者管壁面積較小,多表現為負性重構,提示管壁的形態學特征可能與癥狀相關[23]。
3.3斑塊內出血
頸動脈的研究顯示斑塊內出血是缺血性卒中的重要預測指標[27]。近期一項關于779例患者隨訪1個月以上的Meta分析顯示,頸動脈MRI顯示斑塊內出血作為腦卒中或TIA的預測危險率是4.59(95%CI 2.91~7.24)[28]。Ryu等發現部分大腦中動脈的斑塊在T1WI和/或T2WI圖像中可見局限性高信號,這種表現更多出現在有癥狀的患者中[26],依據頸動脈斑塊的研究結果,推測可能是一種斑塊內出血[29]。徐蔚海等對109例大腦中動脈狹窄(>70%)的患者進行回顧性研究,HRMRI發現斑塊內高信號更多見于有癥狀的患者,而較少見于無癥狀的患者(19.6% vs. 3.2%, P=0.01)[23]。這一結果與Chen等[30]對45歲以上大腦中動脈粥樣硬化性狹窄病變的尸檢結果一致。一項關于74例基底動脈狹窄(>50%)患者的研究發現,有癥狀的損害更多出現在HRMRI發現斑塊內出血陽性組中,較少見于陰性組中(80.0% vs. 48.8%, P<0.01),且斑塊內出血多出現在狹窄程度重的患者中[31]。
3.4斑塊的強化
斑塊的強化也與穩定性相關,其表明斑塊內血供增加,并且內膜的通透性增加促進造影劑從血漿進入到斑塊內。Swartz等首先報道,對于顱內動脈,即使具有多個狹窄病變,也僅僅在急性腦梗死的責任血管壁上觀察到斑塊的強化[32]。Skarpathiotakis等證實在4周內發生缺血性卒中的所有患者,其顱內責任動脈斑塊顯示病理性強化,同時發現隨著卒中事件發生時間的延長,強化逐漸減弱[33]。Vakil等提供的一項回顧性研究顯示,在有癥狀和無癥狀組之間,斑塊強化具有顯著性差異[34]。該研究中22例重度顱內動脈狹窄患者,其中70%的癥狀患者斑塊強化,8%的無癥狀患者斑塊強化。婁昕等利用增強HRMRI觀察56例癥狀性基底動脈重度狹窄患者的動脈管壁情況,結果認為狹窄近端的管壁強化程度與新發梗死和后期缺血事件相關[35]。然而,對于斑塊強化是否可以作為一個急性缺血性卒中的預測因素還存在爭議。少數患者在急性腦梗死發生數月后仍可見強化,是否表明斑塊仍處在不穩定狀態,尚需要進一步的前瞻性研究[34]。
3.5斑塊分布
研究表明鑒于顱內動脈的解剖特點,其斑塊分布研究比顱外動脈更具有臨床意義[37]。既往冠狀動脈研究發現,斑塊易形成于血管分支的對側壁[38]。徐蔚海利用3.0 T HRMRI觀察中度狹窄的大腦中動脈斑塊分布也得出類似結果,斑塊多位于腹側壁和下壁,少數位于背側壁和上壁[39]。解剖學研究顯示,大腦中動脈的穿支血管多從管壁的背側壁及上壁發出[40]。同時徐蔚海還將有癥狀和無癥狀的患者進行對比,發現斑塊更多位于血管上壁,較少位于下壁。同時對于有癥狀的一組,伴有穿支動脈梗死的患者與不伴有穿支動脈梗死的患者相比,斑塊也多位于上壁,較少位于腹側壁和下壁。因此,上壁斑塊更容易導致腦卒中,這可能是由于斑塊更易堵塞穿支血管開口而導致梗死發生。另外,脫落的栓子也容易進入穿支的開口而堵塞下游血管[41]。然而關于基底動脈的一項研究卻與既往大腦中動脈斑塊分布規律不一致。黃飚等利用3.0 T HRMRI觀察38例基底動脈狹窄≥30%的有癥狀患者最窄層斑塊的分布,發現位于腹側的斑塊最多[42]。臨床解剖發現基底動脈的穿支動脈分布于背部和側壁,腹部沒有穿支分布[43]。這一結果與解剖結構相矛盾,基底動脈的斑塊分布特點還需要進一步的相關研究。
目前,在動脈粥樣硬化斑塊的觀察研究中,HRMRI得到廣泛應用。同時,通過HRMRI可以明確斑塊位置與穿支動脈關系,指導臨床上對于缺血性卒中的病因分型和介入治療,避免支架植入后引起穿支動脈閉塞[44]。然而,HRMRI仍存在不足,首先,一些患者因為幽閉恐懼癥、體內有心臟起搏器或除顫器、動脈瘤夾等金屬物而無法進入磁共振成像環境。其次,為了分辨斑塊成分,獲取高空間分辨率需要較高的信噪比和較長的掃描成像時間。此外,HRMRI評估斑塊形態通常局限于單個斑塊或血管段,不能評估大段的動脈系統。
未來,希望能夠在臨床醫師和影像專家的共同努力下,建立一個可以定量評估斑塊成分的方法和自動化分析軟件。同時通過對斑塊的定量和定性的檢測能夠鑒定高危斑塊,明確患者的高危分層,精準預測腦血管事件的發生。
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Progress of High-resolution Magnetic Resonance Imaging in Evaluating Cerebral Atherosclerotic Plaques (review)
YU Jin1,2a, BAI Xiao2b, WU Shi-wen2a, XU Wei-hai3, WU Wei-ping1
1. Department of Geriatric Neurology, People's Liberation Army General Hospital, Beijing 100853, China; 2. a. Department of Neurology; b. Department of Cadre Ward, General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China; 3. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
Correspondence to WU Wei-ping. E-mail: wuwp@vip.sina.com
Abstract:High-resolution magnetic resonance imaging (HRMRI) is a safe, non-invasive, inexpensive, accurate and reproducible clinical imaging modality, and the results can acutely reflect the extent of atherosclerotic disease and have high predictive values for future clinical events. It uses black blood imaging techniques and can obtain sufficient sensitivity for submillimetre imaging. HRMRI has been used widely to visualize the vessel wall and differentiate the components of atherosclerotic plaques. It is of important clinical meaning to evaluate plaque vulnerability with HRMRI, which is related to the remodeling pattern, plaque burden, intraplaque hemorrhage and contrast enhancement, and plaque distribution, etc.
Key words:high-resolution; magnetic resonance imaging; cerebral arteries; atherosclerosis; plaque; review
(收稿日期:2015-11-02修回日期:2015-12-01)
DOI:10.3969/j.issn.1006-9771.2016.02.009
[中圖分類號]R543.5
[文獻標識碼]A
[文章編號]1006-9771(2016)02-0164-04