江國(guó)權(quán),方興根,徐善水,張連富
·綜述General review·
顱內(nèi)動(dòng)脈瘤破裂的血流動(dòng)力學(xué)和形態(tài)學(xué)因素
江國(guó)權(quán),方興根,徐善水,張連富
隨著計(jì)算機(jī)斷層攝影血管成像(CTA)、磁共振血管成像(MRA)等影像技術(shù)的廣泛應(yīng)用,越來(lái)越多的無(wú)癥狀性顱內(nèi)動(dòng)脈瘤被檢測(cè)出來(lái),如何從中鑒別出高破裂風(fēng)險(xiǎn)的動(dòng)脈瘤成為治療的關(guān)鍵,本文就近年來(lái)動(dòng)脈瘤破裂的危險(xiǎn)因素做一總結(jié)。
顱內(nèi)動(dòng)脈瘤;血流動(dòng)力學(xué);形態(tài)學(xué)
顱內(nèi)未破裂動(dòng)脈瘤的發(fā)病率為2%~3%[1],而我國(guó)35~75歲年齡段成年人的發(fā)病率則高達(dá)7%[2]。這些未破裂動(dòng)脈瘤中大部分不發(fā)生破裂,只有一小部分發(fā)生破裂。有學(xué)者統(tǒng)計(jì)破裂的動(dòng)脈瘤僅占全部動(dòng)脈瘤的1%~2%[3]。但是一旦動(dòng)脈瘤破裂,后果非常嚴(yán)重,病死率可高達(dá)50%[4]。因此如何從中判斷出具有高破裂風(fēng)險(xiǎn)的動(dòng)脈瘤并及時(shí)對(duì)其進(jìn)行干預(yù)成為動(dòng)脈瘤治療的關(guān)鍵。本文就如何判別高破裂風(fēng)險(xiǎn)的動(dòng)脈瘤,從血流動(dòng)力學(xué)因素、形態(tài)學(xué)因素及其他因素等方面進(jìn)行闡述。
血流動(dòng)力學(xué)與動(dòng)脈瘤的發(fā)生、發(fā)展以及破裂密切相關(guān)。目前了解,影響動(dòng)脈瘤發(fā)生發(fā)展的血流動(dòng)力學(xué)因素主要有:壁面切應(yīng)力(wall shear stress,WSS)、切應(yīng)力震蕩指數(shù)(oscillatory shear index,OSI)、壁面切應(yīng)力梯度(wall shear stress gradient,WSSG)、沖擊域大小、血流模式以及血流速度。
1.1 WSS
血流的沖擊對(duì)血管壁會(huì)形成3種不同方向的生理壓力:WSS、跨壁壓(transmural pressure)、機(jī)械性伸縮力(mechanical stretch)。其中WSS被認(rèn)為是血流動(dòng)力學(xué)因素中影響顱內(nèi)動(dòng)脈瘤形成、發(fā)展和破裂的主要因素[5-6]。由于血液具有黏性,當(dāng)血流通過(guò)血管壁時(shí)便會(huì)產(chǎn)生摩擦形成WSS。WSS對(duì)維持細(xì)胞的正常形態(tài)具有重要作用。研究認(rèn)為維持細(xì)胞正常形態(tài)的WSS需要大約2 Pa左右,過(guò)低的WSS會(huì)導(dǎo)致上皮細(xì)胞間隙破壞、抗氧化和抗炎介質(zhì)調(diào)節(jié)失常,使得內(nèi)皮細(xì)胞壁重塑,甚至細(xì)胞變性、凋亡[7]。但是過(guò)高的WSS對(duì)動(dòng)脈瘤也是不利??偨Y(jié)起來(lái),目前WSS在動(dòng)脈瘤的破裂中的作用機(jī)制有2種觀點(diǎn):高血流理論和低血流理論。前者認(rèn)為過(guò)高的WSS會(huì)導(dǎo)致局部血管壁退化、擴(kuò)張甚至膨脹,進(jìn)而形成動(dòng)脈瘤或者導(dǎo)致動(dòng)脈瘤的生長(zhǎng)[8-9]。后者認(rèn)為低WSS可導(dǎo)致動(dòng)脈瘤壁發(fā)生退行性變,局部壁面WSS的不足導(dǎo)致動(dòng)脈瘤破裂[10-11]。
1.2 OSI和WSSG
OSI代表一個(gè)區(qū)域隨時(shí)間變化與WSS相對(duì)的方向改變的速度,它是預(yù)測(cè)血管疾病的有用的血流動(dòng)力學(xué)參數(shù)。OSI值的大小代表流動(dòng)振蕩水平的大小,即流動(dòng)方向和強(qiáng)度改變的程度。OSI越高,該處流體在周期內(nèi)的流動(dòng)方向越不穩(wěn)定,隨時(shí)間越頻繁變化甚至出現(xiàn)回流;相反,OSI越低,該處流動(dòng)越穩(wěn)定,變化越小。研究認(rèn)為高OSI與動(dòng)脈瘤破裂明顯相關(guān)[12]。
WSSG是表示壁面切應(yīng)力變化大小的系數(shù)。Valencia等[13]發(fā)現(xiàn),高WSSG下高振幅WSS變化會(huì)引起內(nèi)皮細(xì)胞疲勞和損傷,從而導(dǎo)致內(nèi)皮細(xì)胞功能紊亂和血管病理性重塑,并進(jìn)一步誘發(fā)動(dòng)脈瘤。
1.3 沖擊域大小
Hoi等[14]首先定義了“沖擊域”這一概念,它是指射入的血流作用于動(dòng)脈瘤壁的主要區(qū)域。沖擊域的大小與動(dòng)脈瘤的破裂密切相關(guān)。原因在于沖擊域內(nèi)血流速度會(huì)發(fā)生明顯改變,同時(shí)血流方向也會(huì)發(fā)生明顯變化,造成該區(qū)域動(dòng)脈壁壓力明顯高于其他區(qū)域,從而導(dǎo)致該區(qū)域管壁更易發(fā)生破裂。研究認(rèn)為未破裂動(dòng)脈瘤內(nèi)有相對(duì)廣的血流沖擊域,破裂前的動(dòng)脈瘤則有更為局限的沖擊區(qū)域[15-16]。
1.4 血流模式
血流模式是影響動(dòng)脈瘤發(fā)展變化的重要因素。它主要分為側(cè)壁性動(dòng)脈瘤血流模式和頂端動(dòng)脈瘤血流模式兩種。側(cè)壁性動(dòng)脈瘤:血流從瘤頸口下游側(cè)流向動(dòng)脈瘤瘤內(nèi),并沿著瘤周壁回流至載瘤動(dòng)脈中,再?gòu)牧鲱i口上游流出,形成一個(gè)主要渦流。該模式造成血流動(dòng)力學(xué)的特點(diǎn)是:流入道血流速度、動(dòng)壓及流入道側(cè)壁的壁面WSS最高,流出道次之,瘤頂部最低,且動(dòng)脈瘤壁面WSS、動(dòng)壓與血流速度呈正相關(guān)[17]。頂端動(dòng)脈瘤:血流從流入動(dòng)脈直接沖擊動(dòng)脈瘤,然后沿動(dòng)脈瘤周壁回流至兩條流出動(dòng)脈,形成兩側(cè)兩個(gè)主要渦流(圖1)。由于血流由入口動(dòng)脈直接進(jìn)入動(dòng)脈瘤,造成血流直接沖擊瘤頂。此外由于血流阻力驟然增加,血流動(dòng)能轉(zhuǎn)換瘤內(nèi)壓力,導(dǎo)致瘤內(nèi)壓增加,血流速度減慢,瘤內(nèi)WSS下降。因此該模式的血流動(dòng)力學(xué)特點(diǎn)是:瘤內(nèi)低血流速度,高壓力和低WSS[11]。
1.5 血流速度
圖1 動(dòng)脈瘤的血流模式(圖中箭頭方向?yàn)檠鞯姆较颍?/p>
血流速度作為血流動(dòng)力學(xué)上的重要參數(shù),對(duì)動(dòng)脈瘤的影響是多方面的,主要從2方面影響動(dòng)脈瘤。一方面可通過(guò)影響WSS影響動(dòng)脈瘤的發(fā)展: Ujiie等[18]對(duì)大腦前動(dòng)脈-前交通動(dòng)脈交界處血流動(dòng)力學(xué)的研究發(fā)現(xiàn),均一流速的血流對(duì)前交通動(dòng)脈管壁的切應(yīng)力幾乎為零,而血流速度不均一時(shí)可觀察到交叉血流和血流停滯點(diǎn),停滯點(diǎn)附近的WSS顯著增高。另一方面它可通過(guò)影響沖擊域的大小影響動(dòng)脈瘤的進(jìn)展:Castro等[19]發(fā)現(xiàn)動(dòng)脈瘤瘤體內(nèi)血流速度越快,瘤體WSS越高,受沖擊的區(qū)域越小,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)也越高。
形態(tài)學(xué)因素是影響動(dòng)脈瘤發(fā)生、發(fā)展及破裂的重要因素。目前描述形態(tài)學(xué)因素指標(biāo)較多,本文將其分為2方面——二維形態(tài)學(xué)參數(shù)和三維形態(tài)學(xué)參數(shù)進(jìn)行歸納。二維形態(tài)學(xué)參數(shù)是指那些能被直接采集到,不需要進(jìn)行三維重建的參數(shù),主要包括動(dòng)脈瘤的大小、位置、AR值、SR值、載瘤動(dòng)脈曲度半徑、血管角以及動(dòng)脈瘤角度。三維形態(tài)學(xué)參數(shù)是指通過(guò)三維重建得到的參數(shù),主要有:波動(dòng)指數(shù)、橢圓度指數(shù)、非球形指數(shù)以及體積瘤頸比。
2.1 二維形態(tài)學(xué)參數(shù)
動(dòng)脈瘤的大小是影響動(dòng)脈瘤發(fā)生、發(fā)展、破裂的重要因素。以前認(rèn)為5~10 mm的動(dòng)脈瘤容易破裂,>10mm或<5mm的不易破裂。但是越來(lái)越多的研究表明,動(dòng)脈瘤越大其破裂風(fēng)險(xiǎn)越高。UCAS[20]計(jì)算不同大小的動(dòng)脈瘤年破裂率,比較動(dòng)脈瘤破裂風(fēng)險(xiǎn)的大小。結(jié)果如下:<7 mm的動(dòng)脈瘤不易破裂,5~6mm的動(dòng)脈瘤與3~4mm動(dòng)脈瘤破裂風(fēng)險(xiǎn)無(wú)明顯差別,平均年破裂率為1.13%,但是動(dòng)脈瘤>7mm時(shí),動(dòng)脈瘤的破裂風(fēng)險(xiǎn)與動(dòng)脈瘤的大小呈正相關(guān)。7~9 mm的動(dòng)脈瘤平均年破裂率為3.35%;10~24 mm的動(dòng)脈瘤平均年破裂率為9.09%;25 mm或者更大的動(dòng)脈瘤平均年破裂率更高為76.26%。另外,動(dòng)脈瘤越大越容易生長(zhǎng):<8 mm的動(dòng)脈瘤,年生長(zhǎng)率為6.9%,8~12 mm為25%,>12 mm為83%[21]。增長(zhǎng)的動(dòng)脈瘤破裂風(fēng)險(xiǎn)為2.4%,比不增長(zhǎng)的動(dòng)脈瘤0.2%的破裂風(fēng)險(xiǎn)高出20多倍[22]。
動(dòng)脈瘤的位置也是影響動(dòng)脈瘤變化的重要因素。盡管有學(xué)者認(rèn)為后循環(huán)動(dòng)脈瘤破裂風(fēng)險(xiǎn)高于前循環(huán),但越來(lái)越多的研究證實(shí)前交通動(dòng)脈瘤跟其他位置動(dòng)脈瘤相比更易發(fā)生破裂[23-25]。
AR值(aspect ratio,AR)是動(dòng)脈瘤的瘤體高與瘤頸寬的比值,瘤體高是指瘤頂?shù)搅鲱i的最大垂直距離[26]。動(dòng)脈瘤破裂風(fēng)險(xiǎn)與AR值呈正相關(guān)性,AR值越高,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)就越大。Tateshima等[27]研究認(rèn)為AR的閾值應(yīng)為1.6,因?yàn)楫?dāng)AR>1.6后,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)顯著增加。
SR值(size ratio,SR)是瘤體長(zhǎng)與載瘤動(dòng)脈血管直徑的比值,瘤體長(zhǎng)是指瘤頂至瘤頸的中心點(diǎn)最長(zhǎng)距離,不一定是垂直距離(圖2)。它最先由Dhar等[23]提出,也與動(dòng)脈瘤的破裂成正相關(guān)性。但其閾值,目前尚有爭(zhēng)議。Dhar等[23]認(rèn)為其閾值為2,他們發(fā)現(xiàn)75%的破裂動(dòng)脈瘤的SR>2,而83%的未破裂動(dòng)脈的SR≤2。而Rahman等[28]認(rèn)為SR的閾值應(yīng)為3。
動(dòng)脈瘤內(nèi)的血流動(dòng)力學(xué)會(huì)隨著載瘤動(dòng)脈曲度半徑的變化而變化。Hoi等[14]研究發(fā)現(xiàn)隨著載瘤動(dòng)脈曲度半徑的增加,在瘤頸遠(yuǎn)側(cè)段的沖擊域、wss顯著增強(qiáng)。Avolio等[29]應(yīng)用計(jì)算機(jī)流體動(dòng)力學(xué)(computational fluid dynamics,CFD)技術(shù)研究發(fā)現(xiàn)瘤體大小和形態(tài)相當(dāng),在不同曲度血管上的動(dòng)脈瘤,其血流速度明顯高于直行血管壁動(dòng)脈瘤。
載瘤動(dòng)脈軸線與瘤頸平面所形成的夾角為血管角(vessel angle,VA),即出口動(dòng)脈與入口動(dòng)脈夾角(圖2)。VA的大小與瘤內(nèi)壓力及WSS變化密切相關(guān)。VA越大,動(dòng)脈瘤內(nèi)血液流出阻力越大,瘤內(nèi)血流速度越小,而瘤內(nèi)壓力越大,WSS越??;VA越小,動(dòng)脈瘤內(nèi)血液流出阻力越小,瘤內(nèi)血流速度越大,而瘤內(nèi)壓力相對(duì)越小,WSS相對(duì)越大[30-31]。瘤體長(zhǎng)軸與瘤頸平面形成的夾角為動(dòng)脈瘤角度(aneurysm angle,AA)(圖2)。Dhar等[23]發(fā)現(xiàn)在AA與動(dòng)脈瘤破裂呈正相關(guān)性,AA越大,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)越大。Lin等[32]更認(rèn)為動(dòng)脈瘤的破裂與VA、AA均密切相關(guān)。
2.2 三維形態(tài)學(xué)參數(shù)
近年來(lái),隨著三維重建技術(shù)的日益成熟,對(duì)動(dòng)脈瘤瘤體三維結(jié)構(gòu)形態(tài)的研究越來(lái)越多,用于描述其形態(tài)結(jié)構(gòu)的參數(shù)也在不斷完善。目前描述動(dòng)脈瘤瘤體自身結(jié)構(gòu)形態(tài)的三維參數(shù)主要有:波動(dòng)指數(shù)、橢圓度指數(shù)、非球形指數(shù)。
圖2 動(dòng)脈瘤的形態(tài)學(xué)示意圖
波動(dòng)指數(shù)(undulation index,UI)反映動(dòng)脈瘤瘤體凹陷程度的指標(biāo)。其公式如下[33]:
式中VCH是在動(dòng)脈瘤瘤體凸起部分的體積,V是動(dòng)脈瘤瘤體總體積。UI隨著VCH的減小而逐漸增大,即動(dòng)脈瘤由飽滿變扁平時(shí),破裂風(fēng)險(xiǎn)增加。
橢圓度指數(shù)(elipticity index,EI)反映動(dòng)脈瘤瘤體橢圓化程度的指標(biāo)。其公式如下[33]:
式中VCH是在動(dòng)脈瘤瘤體凸起部分的體積,SCH是動(dòng)脈瘤瘤體凸起部分的表面積。EI隨著VCH和SCH比值的減少而增大,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)也在增加。當(dāng)EI為0時(shí),即動(dòng)脈瘤瘤體呈完全規(guī)則球形時(shí),EI最小,破裂風(fēng)險(xiǎn)也最小。
非球形指數(shù)(nonsphericity index,NSI)是對(duì)EI和UI的概括總結(jié),它是反映動(dòng)脈瘤瘤體凹陷和橢圓化程度的指標(biāo)。其公式為[34]:
式中,V為動(dòng)脈瘤瘤體的體積;S為瘤體的表面積。NSI也是隨著V和S的比值的減小而增大的,NSI越大,動(dòng)脈瘤破裂的風(fēng)險(xiǎn)越大。
此外,體積瘤頸比(volume to neck ratio,VNR)也是三維形態(tài)學(xué)的重要參數(shù),在預(yù)測(cè)動(dòng)脈瘤破裂風(fēng)險(xiǎn)參數(shù)中,其重要性不亞于AR,實(shí)際上VNR和AR具有線性關(guān)系,因?yàn)樗鼈兌际欠从沉鲶w大小與瘤頸大小程度的指標(biāo)。研究發(fā)現(xiàn)動(dòng)脈瘤體積越大,瘤頸越窄,流入動(dòng)脈瘤內(nèi)的血流越慢,而低速血流容易導(dǎo)致動(dòng)脈瘤的生長(zhǎng)和破裂[35]。
2.3 其他因素
顱內(nèi)血管先天發(fā)育異常是導(dǎo)致動(dòng)脈瘤的發(fā)生、發(fā)展、破裂的重要因素。因?yàn)檠茏儺悤?huì)引起血流動(dòng)力學(xué)的改變,而血流動(dòng)力學(xué)的改變又可導(dǎo)致動(dòng)脈瘤發(fā)生改變。以前交通動(dòng)脈復(fù)合體為例,因?yàn)榇颂幯茏儺愝^多,大腦前動(dòng)脈A1段常發(fā)生缺如,當(dāng)A1段發(fā)生缺如時(shí),同側(cè)的頸內(nèi)動(dòng)脈只供應(yīng)該側(cè)的大腦中動(dòng)脈,因此其血流量減少,而對(duì)側(cè)的頸內(nèi)動(dòng)脈需要供應(yīng)其側(cè)的大腦中動(dòng)脈及雙側(cè)的大腦前動(dòng)脈,導(dǎo)致其血流量增加,從而引起血流動(dòng)力學(xué)改變[36]。Alnaes等[37]發(fā)現(xiàn),大腦前動(dòng)脈A1段變異與前交通動(dòng)脈瘤關(guān)系密切,以左側(cè)A1段優(yōu)勢(shì)多見(jiàn),而前交通動(dòng)脈瘤也以偏左側(cè)多見(jiàn)。種種跡象表明先天性血管發(fā)育異常是預(yù)測(cè)動(dòng)脈瘤破裂的不可忽略的因素。
動(dòng)脈瘤瘤內(nèi)壓力也是預(yù)測(cè)動(dòng)脈瘤破裂的重要參數(shù),對(duì)動(dòng)脈瘤生長(zhǎng)及破裂的影響是隨著動(dòng)脈瘤的生長(zhǎng)而增加,這解釋了臨床上所觀察到動(dòng)脈瘤生長(zhǎng)在初期較慢而到一定階段加快并易于發(fā)生破裂的現(xiàn)象[38]。但是由于缺乏足夠的病理狀態(tài)下瘤壁的生物力學(xué)參數(shù),目前對(duì)于特定的動(dòng)脈瘤尚無(wú)法準(zhǔn)確計(jì)算瘤壁內(nèi)壓力。
此外如性別、吸煙、高血壓、相關(guān)的結(jié)締組織病、動(dòng)脈瘤病史和家族史[39],在判斷動(dòng)脈瘤破裂風(fēng)險(xiǎn)時(shí),也是不可忽略的因素。
上述各種評(píng)估動(dòng)脈瘤破裂的參數(shù)及因素較多且繁雜,目前只是將它們作為預(yù)測(cè)動(dòng)脈瘤破裂風(fēng)險(xiǎn)的重要因素,為臨床治療提供參考,尚未形成統(tǒng)一的標(biāo)準(zhǔn)。需要我們進(jìn)一步研究和探索。
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The effect of hem odynam ic and m orphological factors on the rupture of intracranial aneurysm s
JIANG Guo-quan,F(xiàn)ANG Xing-gen,XU Shan-shui,ZHANG Lian-fu.Department of Neurosurgery,Affiliated Yijishan Hospital,Wannan Medical College,Wuhu,Anhui Province 241001,China
FANG Xing-gen,E-mail:fangxinggen@gmail.com
Along with the wide use of CT angiography and MR angiography in the clinical practice,more and more asymptomatic intracranial aneurysms have been detected.Clinically,it is of the first importance to identify these aneurysms that carry high risks to probably develop rupture as for these patients suitable treatment can be promptly adopted so as to ensure a satisfactory result.This paper aims tomake a brief review about hemodynamic and morphological risk factors that may cause the rupture of intracranial aneurysms.(JIntervent Radiol,2014,23:1109-1113)
intracranial aneurysm;hemodynamics;morphology
R578.1
A
1008-794X(2014)-12-1109-05
2014-06-04)
(本文編輯:李欣)
10.3969/j.issn.1008-794X.2014.12.023
弋磯山醫(yī)院人才引進(jìn)基金(YR201105)
241001蕪湖皖南醫(yī)學(xué)院附屬弋磯山醫(yī)院神經(jīng)外科
方興根E-mail:fangxinggen@gmail.com