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      功能MRI鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)及放射性腦損傷的影像學(xué)研究進(jìn)展

      2017-03-23 18:41:21劉志成顏林楓孫穎志崔光彬
      磁共振成像 2017年9期
      關(guān)鍵詞:假性腦損傷膠質(zhì)瘤

      劉志成, 顏林楓,孫穎志,崔光彬

      高級(jí)別膠質(zhì)瘤(gliomas)是中樞神經(jīng)系統(tǒng)最常見(jiàn)的原發(fā)性惡性腫瘤,呈高度侵襲性生長(zhǎng),預(yù)后較差。臨床治療以最大范圍的切除病灶并輔以術(shù)后放化療為主。近年來(lái)隨著術(shù)后放療以及新型化療藥物的應(yīng)用,高級(jí)別膠質(zhì)瘤患者的預(yù)后略有改善,但中位生存期仍只有14個(gè)月[1-2]。對(duì)術(shù)后接受單純放療或同步放化療的膠質(zhì)瘤患者進(jìn)行MRI追蹤隨訪,??砂l(fā)現(xiàn)在術(shù)區(qū)出現(xiàn)新的強(qiáng)化灶或原有強(qiáng)化灶范圍增大,這種影像學(xué)改變既可以是膠質(zhì)瘤術(shù)后復(fù)發(fā),也可能是放化療導(dǎo)致的放射性腦損傷所致(radiation-induced brain injury)。然而二者的治療策略卻截然不同,腫瘤復(fù)發(fā)需要再次手術(shù)或其他進(jìn)一步治療,而放射性腦損傷則無(wú)需進(jìn)一步干預(yù)處理,常常能自行消退或長(zhǎng)期保持穩(wěn)定。病理組織活檢是鑒別腦膠質(zhì)瘤術(shù)后復(fù)發(fā)和放射性腦損傷的金標(biāo)準(zhǔn),但組織活檢有創(chuàng)性限制了其臨床應(yīng)用。因此,早期應(yīng)用無(wú)創(chuàng)的影像學(xué)方法鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)與放射性腦損傷,對(duì)選擇合適的治療方案和提高患者預(yù)后具有重要的臨床意義。

      1 放射性腦損傷概況

      放射性腦損傷主要包括早期的假性進(jìn)展(pseudoprogression)和晚期的放射性壞死(radiation necrosis)[3-6]。假性進(jìn)展被認(rèn)為是由放化療引起一種亞急性的療效反應(yīng),主要包括無(wú)菌性炎癥反應(yīng)、腦組織的術(shù)后改變、局部腦缺血以及放療的亞急性損傷[7]。一般好發(fā)于同步放化療結(jié)束后6個(gè)月內(nèi),其中約一半的病人發(fā)生在放化療結(jié)束后3個(gè)月[8]。假性進(jìn)展的發(fā)生率約為20%~30%,但不同的文獻(xiàn)報(bào)道并不一致[7,9-10],Sanghera等[11]進(jìn)行了一次大樣本的研究,搜集了104例膠質(zhì)母細(xì)胞瘤患者,MRI增強(qiáng)掃描提示26%患者在放療后病灶進(jìn)展,但其中約32%患者后被證實(shí)為假性進(jìn)展。臨床已證實(shí)在放療結(jié)合TMZ同步化療的高級(jí)別膠質(zhì)瘤患者中,假性進(jìn)展的發(fā)生率明顯高于接受單純放療的患者[12]。腫瘤組織中O6-甲基鳥(niǎo)嘌呤-DNA-甲基轉(zhuǎn)移酶(MGMT)啟動(dòng)子甲基化程度高的患者假性進(jìn)展的發(fā)生率也更高[13]。放射性壞死主要發(fā)生在同步放化療后6~18個(gè)月或數(shù)年不等,是由放射治療等造成的慢性療效反應(yīng)[4]。其潛伏期長(zhǎng)短及發(fā)生率與接受的放射劑量、次數(shù)及聯(lián)合化療等有關(guān)。雖然放射性壞死與假性進(jìn)展的發(fā)生時(shí)間及病理生理機(jī)制不盡相同[9],但是在病理上均表現(xiàn)為炎性細(xì)胞滲出和組織細(xì)胞壞死,無(wú)腫瘤細(xì)胞生長(zhǎng)[14]。

      目前關(guān)于膠質(zhì)瘤患者放化療后出現(xiàn)放射性腦損傷的生物學(xué)機(jī)制尚未完全闡明,觀點(diǎn)較一致的假說(shuō)是多種治療因素(主要為放、化療)可以引起血管內(nèi)皮細(xì)胞損傷、壞死,造成血管內(nèi)皮細(xì)胞緊密連接開(kāi)放,血腦屏障功能破壞、通透性增強(qiáng),在MRI增強(qiáng)掃描上出現(xiàn)類(lèi)似腫瘤復(fù)發(fā)的影像學(xué)表現(xiàn)[15-16]。

      2 常規(guī)MRI影像學(xué)檢查對(duì)鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)及放射性腦損傷的局限性

      目前,MRI平掃及增強(qiáng)掃描是評(píng)估高級(jí)別膠質(zhì)瘤療效及復(fù)發(fā)情況最重要的影像學(xué)指標(biāo),根據(jù)使用最為廣泛的Macdonald標(biāo)準(zhǔn),當(dāng)增強(qiáng)掃描提示強(qiáng)化灶增大超過(guò)25%即可考慮為腫瘤復(fù)發(fā)。但是,隨著對(duì)MR成像技術(shù)研究的深入和大量臨床病例的觀察,MR增強(qiáng)掃描強(qiáng)化灶大小已經(jīng)不能成為準(zhǔn)確判斷腫瘤復(fù)發(fā)與否以及評(píng)估療效的依據(jù)。

      頭顱增強(qiáng)MRI顯示的病灶大小,只反映了血腦屏障破壞后通透性增強(qiáng)的范圍,而不能代表腫瘤體積的大小。對(duì)于膠質(zhì)瘤術(shù)后接受了同步放化療的患者,除了腫瘤細(xì)胞本身對(duì)血腦屏障的破壞之外,非腫瘤性因素也可以導(dǎo)致局部血腦屏障破壞通透性增加,在增強(qiáng)掃描上表現(xiàn)為強(qiáng)化灶增大或新強(qiáng)化灶,類(lèi)似于腫瘤進(jìn)展,但并非腫瘤進(jìn)展,而是對(duì)治療的反應(yīng)[17]。

      由于已經(jīng)意識(shí)到MRI增強(qiáng)掃描在評(píng)估膠質(zhì)瘤放化療效果以及腫瘤進(jìn)展的局限性,國(guó)際上已提出較完善的評(píng)估膠質(zhì)瘤療效的RANO標(biāo)準(zhǔn),其明確指出在完成同步放化療后的前12周,當(dāng)增強(qiáng)掃描顯示病灶較上一次增大或出現(xiàn)新增強(qiáng)化灶時(shí),只有當(dāng)強(qiáng)化灶出現(xiàn)在放療照射野外或組織活檢中找到腫瘤細(xì)胞,才能考慮復(fù)發(fā),因此,常規(guī)MRI及增強(qiáng)掃描在新的診斷標(biāo)準(zhǔn)中仍不能達(dá)到準(zhǔn)確診斷。近年來(lái),多種磁共振功能成像方法在高級(jí)別膠質(zhì)瘤術(shù)后復(fù)發(fā)的診斷和鑒別診斷中發(fā)揮了越來(lái)越重要的作用,為早期診斷膠質(zhì)瘤術(shù)后復(fù)發(fā)提供了有力的依據(jù)。

      3 功能磁共振影像評(píng)估高級(jí)別膠質(zhì)瘤術(shù)后復(fù)發(fā)和放射性腦損傷的臨床應(yīng)用

      3.1 磁共振擴(kuò)散加權(quán)成像(DWI)

      磁共振擴(kuò)散加權(quán)成像(diffusion weighted imaging,DWI)技術(shù)可以通過(guò)測(cè)量表觀擴(kuò)散系數(shù)(apparent diffusion coefficient,ADC)值無(wú)創(chuàng)定量地評(píng)估人體組織中水分子微觀運(yùn)動(dòng)。在人體組織中,水分子的擴(kuò)散運(yùn)動(dòng)主要包括細(xì)胞外、細(xì)胞內(nèi)、跨細(xì)胞膜運(yùn)動(dòng)及微循環(huán)灌注,因此,組織內(nèi)任何結(jié)構(gòu)和生理狀態(tài)的變化均會(huì)改變組織的擴(kuò)散系數(shù)ADC值。腫瘤組織由于腫瘤細(xì)胞的異常增殖,細(xì)胞密度高,細(xì)胞外間隙減小,組織結(jié)構(gòu)對(duì)水分子擴(kuò)散的限制作用明顯,水分子的擴(kuò)散受限,ADC值較正常組織降低。相反地,壞死組織,大量細(xì)胞崩解、壞死,結(jié)構(gòu)較松散,ADC值相對(duì)增大。目前應(yīng)用DWI鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)和治療后改變的臨床研究較多,但結(jié)果不一。Prager等[18]研究發(fā)現(xiàn)病變平均ADC值大于1.313×10-3mm2/s時(shí),診斷假性進(jìn)展的敏感性和特異性達(dá)到98.3%和100.0%。然而,也有學(xué)者認(rèn)為平均ADC值在鑒別診斷中不具有診斷價(jià)值[19]。研究結(jié)果不同可能與手工放置感興趣區(qū)等因素有關(guān),因?yàn)椴糠衷鰪?qiáng)病灶區(qū)可能既有復(fù)發(fā)的腫瘤成分,又有屬于療效反應(yīng)的組織成分,單點(diǎn)或多點(diǎn)的手工放置感興趣區(qū)很容易造成片面的診斷。為了減少取樣誤差,目前通常是分析整個(gè)病變ADC值來(lái)代替手工放置感興趣區(qū),通過(guò)ADC直方圖可以得到峰度、偏度、平均數(shù)以及百分位數(shù)等參數(shù)。Chu等[20]通過(guò)在同步放化療結(jié)束后2個(gè)月內(nèi),對(duì)疑似為膠質(zhì)瘤術(shù)后復(fù)發(fā)或假性進(jìn)展的患者進(jìn)行高/低b (3000 s/mm2、1000 s/mm2) DWI檢查,獲取整個(gè)強(qiáng)化病變的ADC值分布,并計(jì)算累積頻率ADC直方圖上第5百分位數(shù)值,研究發(fā)現(xiàn),無(wú)論是高或低b值DWI,膠質(zhì)瘤術(shù)后復(fù)發(fā)組ADC第5百分位數(shù)均顯著低于假性進(jìn)展組,差異有統(tǒng)計(jì)學(xué)意義,并且當(dāng)b=3000 s/mm2,診斷的準(zhǔn)確率更高。Song等[21]研究也證實(shí)累積頻率ADC直方圖上第5百分位數(shù)在鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)與假性進(jìn)展中顯示出了較好的診斷效能,其敏感度和特異度均可達(dá)到90%。也有研究顯示ADC直方圖上的峰度、偏度在鑒別腫瘤復(fù)發(fā)與假性進(jìn)展中不具有統(tǒng)計(jì)學(xué)意義[22]。Zhang等[23]通過(guò)對(duì)以往的獨(dú)立研究結(jié)果進(jìn)行系統(tǒng)的綜合分析,提出ADC值有助于鑒別二者,并建議DWI檢查應(yīng)該作為常規(guī)MRI序列的一種重要補(bǔ)充。雖然ADC值有助于鑒別二者,但也必須指出膠質(zhì)瘤術(shù)后的膠質(zhì)增生、纖維瘢痕以及組織水腫會(huì)影響ADC值的測(cè)量結(jié)果,限制了其臨床應(yīng)用價(jià)值[24]。擴(kuò)散張量成像(diffusion tensorimaging,DTI)是DWI的延伸,能夠通過(guò)其參數(shù)各向異性分?jǐn)?shù)(fractional anisotropy,F(xiàn)A),定量評(píng)估組織中水分子運(yùn)動(dòng)的各向異性。目前,常用于白質(zhì)纖維束的追蹤以及評(píng)估放化療后腦白質(zhì)損傷、恢復(fù)的情況以及白質(zhì)纖維束的完整性。有研究發(fā)現(xiàn)在假性進(jìn)展中,腦白質(zhì)纖維束被大大破壞,相比腫瘤復(fù)發(fā)FA值更低,因此,研究認(rèn)為DTI有助于鑒別膠質(zhì)母細(xì)胞瘤術(shù)后復(fù)發(fā)與假性進(jìn)展[25]。但由于受設(shè)備、序列及b值選擇不同的影響,現(xiàn) DTI應(yīng)用于早期診斷膠質(zhì)瘤術(shù)后復(fù)發(fā)的研究較少。基于體素內(nèi)不相干運(yùn)動(dòng)(intravoxelinoherentmotion,IVIM)的磁共振擴(kuò)散加權(quán)成像,在無(wú)需使用對(duì)比劑下,可以對(duì)腫瘤內(nèi)微循環(huán)灌注和水分子擴(kuò)散信息進(jìn)行量化,已逐步應(yīng)用于全身多類(lèi)腫瘤的研究[26-27]。Kim等[28]對(duì)51例經(jīng)病理證實(shí)為膠質(zhì)瘤術(shù)后復(fù)發(fā)(31例)及治療后改變(20例)的患者進(jìn)行IVIM-DWI掃描,得到灌注相關(guān)參數(shù)(f)、擴(kuò)散參數(shù)(D)和ADC值,并計(jì)算累積頻率直方圖上第90百分位數(shù)和第10百分位數(shù)的參數(shù)值,分別標(biāo)記為f90,D10,ADC10。結(jié)果發(fā)現(xiàn)膠質(zhì)瘤術(shù)后復(fù)發(fā)組f90明顯高于治療后改變組,而D10、ADC10在膠質(zhì)瘤術(shù)后復(fù)發(fā)組明顯低于治療后改變組。通過(guò)ROC曲線分析顯示f90能較好的鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)與治療后改變,敏感性為87.1%,特異性達(dá)到95.0%。

      3.2 磁共振灌注成像(PWI)

      磁共振灌注成像(perfusion imaging,PWI)技術(shù)主要用于檢測(cè)病變血管內(nèi)、外或跨血管的血流灌注信息,與MRI增強(qiáng)掃描提供的信息不同。在增強(qiáng)上明顯強(qiáng)化的病灶未必是血供豐富或者說(shuō)高灌注的病灶;而在增強(qiáng)上沒(méi)有強(qiáng)化的病變也未必是血供不豐富或者說(shuō)低灌注的病變。這種增強(qiáng)和灌注上的不一致在顱內(nèi)腫瘤性病變中更明顯。目前,不少研究認(rèn)為腫瘤病變的新生血管形成程度是決定腫瘤良惡性重要的指標(biāo),而PWI是量化腫瘤血管形成程度最重要的無(wú)創(chuàng)評(píng)價(jià)方法。因此,PWI對(duì)于鑒別膠質(zhì)瘤術(shù)后增強(qiáng)病灶是治療后改變還是腫瘤復(fù)發(fā)具有重要臨床意義。目前臨床上常用的磁共振灌注成像主要包括動(dòng)態(tài)磁敏感對(duì)比增強(qiáng)MRI (dynamic susceptibility contrast MRI,DSCMRI)、動(dòng)態(tài)對(duì)比增強(qiáng)MRI成像(dynamic contrast enhanced MRI,DCE-MRI)和動(dòng)脈自旋標(biāo)記成像(arterial spin labeling,ASL)。

      DSC-MRI是臨床上最常用的MRI灌注成像技術(shù),基于單室血流動(dòng)力學(xué)模型,利用時(shí)間-信號(hào)強(qiáng)度曲線,計(jì)算出腦血容量(cerebral blood volume,CBV)、腦血流量(cerebral blood flow,CBF)、平均通過(guò)時(shí)間(mean transittime,MTT)和達(dá)峰時(shí)間(time to peak,TTP)等反映血流動(dòng)力學(xué)的參數(shù),可以對(duì)目標(biāo)區(qū)域內(nèi)微血管結(jié)構(gòu)與功能進(jìn)行定量評(píng)估,不少研究顯示相對(duì)腦血容量(relative cerebral blood volume,rCBV)在鑒別膠質(zhì)瘤術(shù)后復(fù)發(fā)和治療后改變中具有良好的診斷效能。Prager等[18]研究認(rèn)為膠質(zhì)瘤術(shù)后復(fù)發(fā)組rCBV明顯高于治療后改變組,當(dāng)rCBV>1.27時(shí)診斷膠質(zhì)瘤術(shù)后復(fù)發(fā)的敏感度和特異度分別為86.5%和83.3%。Blasel等[29]研究顯示rCBVmax在膠質(zhì)瘤術(shù)后復(fù)發(fā)組中為3.40±1.25,而在治療后改變組中為2.21±0.62,兩組的差異有統(tǒng)計(jì)學(xué)意義。有研究證實(shí)rCBV直方圖上第90百分位數(shù)取閾值為2.892時(shí),診斷膠質(zhì)瘤術(shù)后復(fù)發(fā)的敏感度和特異度分別為83.9%和95.0%[28]。也有研究認(rèn)為rCBV直方圖參數(shù)在鑒別診斷中不具有診斷價(jià)值[21]。為了盡量縮小由于對(duì)比劑滲出導(dǎo)致CBV測(cè)量值影響,也有不少研究利用治療前后rCBV的變化趨勢(shì)進(jìn)行鑒別診斷。Boxerman等[30]通過(guò)對(duì)膠質(zhì)瘤同步放化療前基線rCBV與復(fù)查rCBV圖進(jìn)行分析,并計(jì)算前后差值,發(fā)現(xiàn)治療后改變組的rCBV縱向比較明顯降低,平均差值為-0.84,而膠質(zhì)瘤術(shù)后復(fù)發(fā)組rCBV縱向比較明顯升高,平均差值為0.84。Mangla等[31]研究也發(fā)現(xiàn)同步放化療結(jié)束后1個(gè)月,復(fù)發(fā)組rCBV上升41%,而治療后改變組rCBV下降12%。DSC-MRI因采集速度快,后處理簡(jiǎn)單,已被廣泛應(yīng)用于膠質(zhì)瘤術(shù)前分級(jí)以及顱內(nèi)腫瘤的鑒別診斷,但其也存在一些缺陷,其使用的rCBV、rCBF等半定量參數(shù)難以做到絕對(duì)定量,易受大血管和骨質(zhì)的磁敏感偽影影響。另外,DSC-MRI是在血腦屏障完整的前提下提出的單室模型,忽視了血腦屏障的通透性。有文獻(xiàn)證實(shí)在血腦屏障破壞的腦腫瘤中,DSC灌注成像并不能真實(shí)地反映病變的灌注水平,并指出這可能與對(duì)比劑在感興趣區(qū)的滲透導(dǎo)致無(wú)法建立有效的磁敏感對(duì)比差別有關(guān)[32]。

      DCE-MRI亦屬于灌注成像范疇,其主要是利用時(shí)間-信號(hào)強(qiáng)度曲線計(jì)算半定量和定量參數(shù),以反映組織灌注及微血管通透性。由于不同系統(tǒng)之間背景信號(hào)有差異使得半定量參數(shù)在不同MR掃描中不易比較,因此美國(guó)國(guó)家癌癥研究院推薦將定量參數(shù)作為研究的重點(diǎn)[33]。其定量參數(shù)主要包括轉(zhuǎn)移常數(shù)(Ktrans)、速率常數(shù)(Kep)、血管外細(xì)胞外容積分?jǐn)?shù)(Ve)及血漿容積分?jǐn)?shù)(Vp);其中,Ktrans主要反映微血管通透性,Ve反映血管外或細(xì)胞外空間容量,Vp反映血管內(nèi)或血漿內(nèi)空間容量。Yun等[34]對(duì)膠質(zhì)母細(xì)胞瘤放、化療后第一次復(fù)查出現(xiàn)新發(fā)強(qiáng)化灶或強(qiáng)化灶增大的33例患者進(jìn)行DCE-MRI檢查,結(jié)果發(fā)現(xiàn)復(fù)發(fā)組的Ktrans和Ve平均值均高于假性進(jìn)展組。Ktrans和Ve均反映對(duì)比劑漏出至血管外間隙的能力,研究認(rèn)為兩個(gè)參數(shù)不同可能是由腫瘤復(fù)發(fā)和假性進(jìn)展的組織學(xué)差異所致。腫瘤復(fù)發(fā)時(shí),不成熟腫瘤血管大量增殖,并且腫瘤細(xì)胞浸潤(rùn)嚴(yán)重破壞血腦屏障,血管通透性明顯增高,大分子對(duì)比劑可以順利通過(guò),而假性進(jìn)展可能是放化療導(dǎo)致的血管內(nèi)皮細(xì)胞損傷,血管通透性?xún)H輕度增高。Thomas等[35]研究發(fā)現(xiàn)復(fù)發(fā)組Ktrans和Vp均高于假性進(jìn)展組,Ktrans值和Vp值具有較高的診斷效能,當(dāng)Vp<3.7時(shí),診斷為假性進(jìn)展的敏感度和特異度分別為85%和79%,當(dāng)Ktrans>3.6時(shí),診斷為復(fù)發(fā)的敏感度和特異度分別為69%和79 %。國(guó)內(nèi)學(xué)者錢(qián)的研究也證實(shí)了DCE-MRI有助于鑒別真性進(jìn)展與假性進(jìn)展[36]。盡管隨著MRI設(shè)備及后處理技術(shù)的不斷發(fā)展,DCE-MRI的實(shí)用性和可行性大大提高,但該技術(shù)也面臨一些挑戰(zhàn),現(xiàn)階段各研究機(jī)構(gòu)所推薦的圖像掃描和后處理方法欠統(tǒng)一,不同后處理模型測(cè)量的結(jié)果不穩(wěn)定,難以橫向比較,并且各種疾病與之相適應(yīng)的分析模型也有待多中心研究證實(shí)。

      ASL技術(shù)是一種無(wú)需使用對(duì)比劑的磁共振灌注成像技術(shù),已得到了臨床的廣泛認(rèn)可,目前主要應(yīng)用于腦部疾病的臨床診斷及功能研究[37-38]。Ye等[39]對(duì)證實(shí)為膠質(zhì)瘤術(shù)后復(fù)發(fā)(16例)與放射性壞死(5例)的患者進(jìn)行ASL和DSC檢查并分別測(cè)定血流動(dòng)力學(xué)參數(shù)rCBV,結(jié)果發(fā)現(xiàn)術(shù)后復(fù)發(fā)組ASL和DSC的rCBV均明顯高于放射性壞死組,腫瘤復(fù)發(fā)組ASL-rCBV和DSC-rCBV分別為4.45±2.72,3.38±2.08,放射性壞死組ASL-rCBV和DSC-rCBV分別為1.22±0.61,1.09±0.55,兩組之間均有明顯統(tǒng)計(jì)學(xué)差異,并且ASL-rCBV與DSC-rCBV呈明顯正相關(guān)。Choi等[40]研究也證實(shí)ASL有利于鑒別復(fù)發(fā)與假性進(jìn)展。雖然ASL將自由擴(kuò)散的水作為內(nèi)源性示蹤劑,不易受血腦屏障破壞的影響,但ASL掃描時(shí)間長(zhǎng),分辨率及信噪比低,并且對(duì)運(yùn)動(dòng)偽影較敏感,這些缺點(diǎn)一定程度上限制了其臨床運(yùn)用[41]。

      3.3 磁共振波譜分析(MRS)

      磁共振波譜分析(magnetic resonance spectroscopy,MRS)通過(guò)定量檢測(cè)組織內(nèi)代謝產(chǎn)物的含量,可以無(wú)創(chuàng)反映組織局部代謝情況。臨床上常用的是氫質(zhì)子波譜分析(1H-MRS) ,常用于檢測(cè)的代謝產(chǎn)物包括N-乙酰天冬氨酸(NAA) 、肌酸(Cr) 、膽堿(Cho) 、磷酸肌酸(PCr) 、脂質(zhì)(Lip) 、乳酸(Lac)等。其中,NAA是神經(jīng)元的標(biāo)志物,峰值降低反映神經(jīng)元損傷或數(shù)量減少。Cho與磷脂的合成分解與髓鞘形成有關(guān),細(xì)胞增殖旺盛Cho峰升高。Cr是能量?jī)?chǔ)存利用的主要代謝物,組織壞死時(shí)Cr降低。

      Anbarloui等[42]研究發(fā)現(xiàn)術(shù)后復(fù)發(fā)組平均Cho/NAA和Cho/Lipid (2.72,2.78)均明顯高于放射性壞死組(1.46,0.6),兩組間有顯著統(tǒng)計(jì)學(xué)差異,當(dāng)Cho/NAA大于1.8或Cho/Lipid大于1時(shí),對(duì)兩者鑒別的敏感度為84%,特異度為75%,準(zhǔn)確度為81%,作者認(rèn)為膠質(zhì)瘤術(shù)后復(fù)發(fā)時(shí)細(xì)胞增生活躍,正常的神經(jīng)元細(xì)胞破壞,NAA值降低和Cho值升高,放射性壞死時(shí),細(xì)胞崩解、壞死,NAA峰及Cho峰均下降。Elias等[43]研究認(rèn)為Cho/NAA值大于1.2時(shí),敏感度為86%,特異度為90%。MRS進(jìn)行鑒別診斷亦存在一些缺陷,MRS容易受顱骨、腦脊液及病變內(nèi)出血、鈣化、壞死成分信號(hào)影響,當(dāng)病變位置距腦表或者腦室較近時(shí),MRS鑒別能力較差;感興趣區(qū)的選擇也會(huì)影響MRS結(jié)果,體素框一般依病變大小而定,當(dāng)病變太小時(shí),MRS鑒別能力較差。另外,Wang等[25]指出當(dāng)放射性壞死合并炎性改變及膠質(zhì)細(xì)胞增生時(shí)也可出現(xiàn) Cho峰升高,此時(shí)利用Cho比值鑒別也較困難。

      3.4 磁共振氨基質(zhì)子轉(zhuǎn)移(APT)成像

      磁共振氨基質(zhì)子轉(zhuǎn)移(amideproton transfer,APT)成像是一種基于化學(xué)交換飽和轉(zhuǎn)移(chemical exchange saturation transfer,CEST)機(jī)制的成像方法,可以通過(guò)參數(shù)APT加權(quán)(APT weighted,APTw)信號(hào)強(qiáng)度來(lái)反映生物組織中內(nèi)源性游離蛋白和肽類(lèi)的含量以及氨基質(zhì)子的交換速率。APTw信號(hào)強(qiáng)度隨內(nèi)源性游離蛋白和肽類(lèi)含量的增加而升高。APT-MRI在中樞神經(jīng)系統(tǒng)應(yīng)用廣泛,可有效鑒別低級(jí)別與高級(jí)別膠質(zhì)瘤,研究顯示高級(jí)別膠質(zhì)瘤APTw信號(hào)強(qiáng)度顯著高于低級(jí)別膠質(zhì)瘤[44]。并且APT-MRI有助于評(píng)估膠質(zhì)瘤的療效以及鑒別高級(jí)別膠質(zhì)瘤術(shù)后復(fù)發(fā)與假性進(jìn)展。

      Ma等[45]研究發(fā)現(xiàn)真性進(jìn)展的平均APTw信號(hào)強(qiáng)度(2.75%±0.42%)明顯要高于假性進(jìn)展(1.56%±0.42%),兩組之間有明顯統(tǒng)計(jì)學(xué)差異,取平均APTW信號(hào)強(qiáng)度為2.42%作為臨界值,敏感度和特異度分別為85.0%和100%,文中指出二者APTw差異明顯,可能和組織病理有關(guān),真性進(jìn)展細(xì)胞密度和細(xì)胞分裂活躍,細(xì)胞內(nèi)游離蛋白和肽類(lèi)的含量增高,導(dǎo)致APTw信號(hào)強(qiáng)度顯著升高。Park等[46]通過(guò)分析膠質(zhì)瘤治療前后,感興趣區(qū)內(nèi)APT磁化轉(zhuǎn)移率不對(duì)稱(chēng)值與Cho/Cr及Cho/NAA比值,結(jié)果顯示APT磁化轉(zhuǎn)移率不對(duì)稱(chēng)值與相應(yīng)病灶內(nèi)Cho/ Cr呈中度相關(guān),與Cho/ NAA呈輕度相關(guān)。在膠質(zhì)瘤分級(jí)中APT-MRI與MRS診斷效能相似,在鑒別腫瘤進(jìn)展和假性進(jìn)展中準(zhǔn)確度高于MRS。

      4 展望

      膠質(zhì)瘤術(shù)后復(fù)發(fā)和治療后改變的鑒別直接關(guān)系到患者治療方式的選擇和預(yù)后。組織病理學(xué)檢查是鑒別二者的“金標(biāo)準(zhǔn)”,但其有創(chuàng)性限制了其臨床運(yùn)用,磁共振增強(qiáng)掃描長(zhǎng)期動(dòng)態(tài)隨訪觀察能有效鑒別腫瘤復(fù)發(fā)以及治療后改變,但缺乏時(shí)效性。DWI、PWI、MRS以及APT成像能從多角度、多方面反映組織的功能和代謝等信息,有助于鑒別腫瘤復(fù)發(fā)和治療后改變,但盡管這些檢查應(yīng)用了最先進(jìn)的技術(shù),由于各自技術(shù)上缺陷以及術(shù)后復(fù)發(fā)、治療后改變組織異質(zhì)性極高,其鑒別的敏感性和特異性仍需要大樣本多中心研究進(jìn)行科學(xué)評(píng)估。有研究利用基于像素的容積加權(quán)多參數(shù)聚類(lèi)(VVMC)方法處理MR成像數(shù)據(jù),并與單參數(shù)測(cè)量ADC和rCBV等診斷效能進(jìn)行比較;結(jié)果顯示VVMC觀察者間一致性最高,與單參數(shù)測(cè)量方法相比較,VVMC值鑒別膠質(zhì)母細(xì)胞瘤放化療后假性進(jìn)展及早期進(jìn)展診斷效能更高[47]。國(guó)內(nèi)有研究學(xué)者發(fā)現(xiàn),單參數(shù)測(cè)量值rCBVmax)和ADCmin早期診斷膠質(zhì)瘤復(fù)發(fā)的準(zhǔn)確度僅分別為82.7%和76.9%,兩者聯(lián)合應(yīng)用的準(zhǔn)確度可提高至90.4%[48]。因此,針對(duì)各種檢查手段的優(yōu)缺點(diǎn),聯(lián)合應(yīng)用多種功能影像學(xué)檢查或圖像融合技術(shù)是提高診斷準(zhǔn)確性的途徑和趨勢(shì)。

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