孛茹婷，姬廣海，劉嶺嶺，吳玉華，邱銀萍，楊文君，李艷，陳志強(qiáng)*

1.寧夏醫(yī)科大學(xué)，銀川 750004

2.寧夏醫(yī)科大學(xué)總醫(yī)院新生兒科，銀川 750004

3.寧夏醫(yī)科大學(xué)生育力保持教育部重點(diǎn)實(shí)驗(yàn)室，銀川 750004

4.寧夏醫(yī)科大學(xué)總醫(yī)院放射科，銀川750004

彌漫性高信號(hào)(diffuse excessive high signal intensity，DEHSI)是在T2WI以正常無髓鞘化白質(zhì)為參考，在雙側(cè)腦室周圍及皮層下白質(zhì)(white matter，WM)表現(xiàn)為信號(hào)增高的一種象[1]。相關(guān)研究[2]表明，DEHSI可能導(dǎo)致患兒認(rèn)知及精神障礙，相關(guān)神經(jīng)發(fā)育落后所致的運(yùn)動(dòng)及語言功能障礙等。近年來磁共振成像技術(shù)的飛速發(fā)展，使得其在新生兒中樞神經(jīng)系統(tǒng)疾病的診斷中得到了廣泛應(yīng)用，為DEHSI的早期診斷及預(yù)后評(píng)估提供了依據(jù)。

1 資料與方法

1.1 臨床資料

選取2013年1月至2014年6月寧夏醫(yī)科大學(xué)總醫(yī)院新生兒科124例新生兒為研究對(duì)象，包括37例適于胎齡早產(chǎn)兒和87例正常足月兒。所有新生兒均無神經(jīng)功能障礙和窒息史；經(jīng)臨床、實(shí)驗(yàn)室及影像學(xué)相關(guān)檢查，存在DEHSI并排除先天代謝性疾病、先天性畸形、顱內(nèi)感染及其它腦損傷等疾??；所有研究對(duì)象均有臨床隨訪復(fù)查，由兒科一名經(jīng)驗(yàn)豐富的副主任醫(yī)師在矯正胎齡的條件下對(duì)患兒的粗大運(yùn)動(dòng)發(fā)育商(gross motor development quotience，GMDQ)、精細(xì)運(yùn)動(dòng)發(fā)育商(fine motor development quotience，F(xiàn)MDQ)、語言發(fā)育商(language development quotience，LDQ)、適應(yīng)性發(fā)育商(adaptive development quotience，ADQ)、個(gè)人-社交發(fā)育商(personal-social development quotience，PSDQ)等進(jìn)行評(píng)價(jià)(根據(jù)Gesell發(fā)育量表)[3]。本研究經(jīng)醫(yī)院倫理委員會(huì)批準(zhǔn)，檢查前均取得受試者家屬同意，并與之簽訂知情同意書。

1.2 檢查方法

采用GE Signa Twin Speed 1.5 T MR掃描儀，在研究對(duì)象熟睡時(shí)掃描，不能入睡者給予5%水合氯醛50 mg/kg口服鎮(zhèn)靜。檢查需在一名護(hù)士或醫(yī)師陪同下進(jìn)行，并注意患兒的保暖、聽力保護(hù)及生命體征的觀察。所有研究對(duì)象均接受常規(guī)MRI檢查(掃描參數(shù)：T1fl air：TR 1784 ms，TE 21.5 ms，矩陣 288×192；T2WI：TR 5400 ms，TE 111.1 ms，矩陣320×224；T2flair：TR 7800 ms，TE 146.5 ms，矩陣 320×224；所有序列層厚5 mm，層間距0.5 mm，F(xiàn)OV 24 cm×18 cm)。

1.3 磁共振成像分類

MRI圖像分別由兩位高年資放射科醫(yī)師獨(dú)立閱片評(píng)價(jià)，意見不一致時(shí)經(jīng)協(xié)商統(tǒng)一意見。根據(jù)影像學(xué)表現(xiàn)將DEHSI定性分類如下：正常：腦白質(zhì)區(qū)無高信號(hào)；輕度：腦室前后角旁稍高信號(hào)；中度：腦室前后角旁無邊界的彌漫性高信號(hào)；重度：所有白質(zhì)區(qū)彌漫性高信號(hào)[4-5]。分別測(cè)量不同分度額葉T2信號(hào)值。

1.4 統(tǒng)計(jì)學(xué)方法

采用SPSS 20.0軟件包對(duì)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析，計(jì)量資料以±s表示，本組資料中DEHSI與臨床指標(biāo)、矯正年齡后(1個(gè)月、3個(gè)月、5個(gè)月)患兒復(fù)查時(shí)Gesell評(píng)分的相關(guān)性采用Spearman相關(guān)分析。對(duì)矯正年齡后(1個(gè)月、3個(gè)月、5個(gè)月)嬰兒正常組與輕度、中重度DEHSI 的Gesell評(píng)分采用單因素方差分析，以P＜0.05為差異具有統(tǒng)計(jì)學(xué)意義。

表1 不同信號(hào)組間的一般情況(±s)Tab.1 Each grade of DEHSI in infant of the characteristics(±s)

表1 不同信號(hào)組間的一般情況(±s)Tab.1 Each grade of DEHSI in infant of the characteristics(±s)

Group Without DEHSI(n=37)Mild DEHSI(n=37)Moderate-severe DEHSI(n=50)Total(n=124)Signal values 1271.43±249.52 1478.53±197.01 1536.31±245.14 1440.03±257.46 Postnatal age(days)17.68±14.91 8.86±7.80 8.32±6.06 11.27±10.73 Gestational age(weeks)38.81±1.78 38.05±2.05 37.04±3.03 37.87±2.53 Weight(g)3062.03±560.72 3081.22±602.61 2862.86±809.58 2987.44±685.59 Head girth(cm)33.96±2.07 33.82±2.17 32.95±2.79 33.51±2.44

2 結(jié)果

2.1 DEHSI的分布

124例受試者中正常無DEHSI 37例，輕度DEHSI 37例，中度DEHSI 35例，重度DEHSI 15例。由于重度病例相對(duì)較少，結(jié)合文獻(xiàn)[6]分類將DEHSI分為3組：無DEHSI、輕度DEHSI、中重度DEHSI(圖1)，其T2信號(hào)值(±s)分別為(1271.43±249.52)、(1478.53±197.01)和(1536.31±245.14)，見表1。

圖1 T2WI上DEHSI分度圖。A：腦白質(zhì)區(qū)無高信號(hào)，男，7 d，36+5 w；B：腦室前后角旁稍高信號(hào)，可見邊界(箭頭處),男，3天，35+4 w；C：所示白質(zhì)區(qū)均呈彌漫性高信號(hào)，腦室前后角旁無邊界，男，7 d，35+2 w。右額葉ROI面積約(30±1)mm2Fig.1 Samples of different grades of DEHSI are viewed on T2WI.A:No DEHSI throughout the white matter,male,7 days,36+5 weeks; B:High signal intensity is visible only within the crossroads(arrow),male,3 days,35+4 weeks; C:Widespread high signal intensity is visible in the entire cerebral white matter,male,7 days,35+2 weeks.The ROI of the signal value is measured in the right frontal area,the area is about(30±1)mm2.

2.2 圍產(chǎn)期臨床特點(diǎn)與DEHSI的關(guān)系

124例受試者平均胎齡(37.9±2.5)w；MRI掃描時(shí)平均生后年齡(11.3±10.7)d；平均體重(2987.4±685.6)g；平均頭圍(33.5±2.4)cm(表1)。胎齡、體重和頭圍之間互呈正相關(guān)(胎齡與體重、胎齡與頭圍、體重與頭圍分別為r=0.616、0.573、0.817，P均＜0.05)。生后年齡、胎齡、頭圍均與DEHSI程度呈負(fù)相關(guān)(r=－0.266、－0.303、－0.200，P均＜0.05)。DEHSI程度與T2信號(hào)值之間呈正相關(guān)(r=0.429，P＜0.05)。生后年齡與T2信號(hào)值呈負(fù)相關(guān)(r=－0.191，P＜0.05)，見表2。

表2 患兒DEHSI與其臨床特點(diǎn)的相關(guān)性Tab.2 The correlation between DEHSI and clinical index

2.3 關(guān)于矯正年齡后1個(gè)月、3個(gè)月、5個(gè)月之間神經(jīng)行為評(píng)估的關(guān)聯(lián)

124名研究對(duì)象臨床復(fù)查情況：矯正年齡后1個(gè)月64例，3個(gè)月85例，5個(gè)月43例；1個(gè)月和3個(gè)月均進(jìn)行臨床復(fù)查的嬰兒43例，3個(gè)月和5個(gè)月均進(jìn)行臨床復(fù)查的嬰兒39例。矯正年齡后5個(gè)月的嬰兒的預(yù)后評(píng)估：中重度DEHSI患兒中評(píng)分低于85分[7]者所占比例高于無及輕度DEHSI患兒(8/43 =18.6%vs 0%)，而且評(píng)分低于85分的患兒中，早產(chǎn)兒(7/8 =87.5%)遠(yuǎn)遠(yuǎn)多于足月兒(1/8=12.5%)；適應(yīng)性異常2例(4.7%)，粗大運(yùn)動(dòng)異常8例(18.6%)，精細(xì)運(yùn)動(dòng)異常3例(7.0%)，個(gè)人-社交異常2例(4.7%)，表明Gesell評(píng)分低于85分的患兒主要表現(xiàn)為粗大運(yùn)動(dòng)延遲。采用單因素方差分析對(duì)矯正年齡后5個(gè)月嬰兒正常組與輕度、中重度DEHSI的Gesell評(píng)分進(jìn)行評(píng)估，其中正常組和中重度DEHSI的Gesell評(píng)分相比較，ADQ、GMDQ、FMDQ、LDQ和PSDQ等5項(xiàng)指標(biāo)差異有統(tǒng)計(jì)學(xué)意義(P均＜0.05)；輕度和中重度DEHSI的Gesell評(píng)分相比較，只有ADQ差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)，見表3。DEHSI與矯正年齡后1個(gè)月患兒復(fù)查時(shí)Gesell評(píng)分中僅LDQ呈負(fù)相關(guān)(r=0.024，P＜0.05)； DEHSI與矯正年齡后5個(gè)月患兒復(fù)查時(shí)Gesell評(píng)分中ADQ、GMDQ、FMDQ、LDQ、PSDQ指標(biāo)與DEHSI均呈負(fù)相關(guān)(r=－0.423、－0.499、－0.553、－0.317、－0.453，P均＜0.05)見表4。

3 討論

胎兒在母體處于動(dòng)態(tài)發(fā)育過程，胎兒的體重、頭圍等呈上升曲線，目前衡量新生兒生長(zhǎng)發(fā)育的標(biāo)志很多，如體重、頭圍等。本組數(shù)據(jù)證實(shí)，隨著胎齡的增加，體重與頭圍呈增長(zhǎng)趨勢(shì)。此外，胎兒出生以后宮外環(huán)境暴露時(shí)間增加是DEHSI程度減低的相關(guān)因素，從而促進(jìn)嬰兒成熟度增高[8]。Counsell等[9]認(rèn)為嬰兒腦白質(zhì)DEHSI是成熟延遲的表現(xiàn)，而非永久性白質(zhì)損傷。未成熟少突膠質(zhì)細(xì)胞在預(yù)產(chǎn)期前最后3個(gè)月極其脆弱[10-11]，因此這一時(shí)期未成熟少突膠質(zhì)細(xì)胞受損是最常見的早產(chǎn)兒腦損傷形式[12-14]。一些研究表明，DEHSI可能提示認(rèn)知發(fā)育不良[2]。DEHSI在T2WI顯示為腦室周圍及皮層下腦白質(zhì)的高信號(hào)，這種現(xiàn)象也可通過微觀結(jié)構(gòu)的變化來解釋，延遲成熟或組織損傷時(shí)軸突和細(xì)胞外水分子的變化可能是T2WI信號(hào)變化的原因[15]。早產(chǎn)兒的白質(zhì)損傷主要表現(xiàn)為髓鞘化過程中50%～90%少突神經(jīng)膠質(zhì)和軸突及膠質(zhì)細(xì)胞成分的枯竭[16]。文獻(xiàn)[17]報(bào)道，DEHSI可能代表少突膠質(zhì)細(xì)胞和/或軸突異常。DEHSI中神經(jīng)元的降低與未成熟少突膠質(zhì)細(xì)胞損傷及其演變過程中進(jìn)入軸突障礙有關(guān)[13]。

表3 DEHSI 3組間5項(xiàng)Gesell評(píng)分的單因素方差分析Tab.3 One-way ANOVA analysis in gesell scores(5 indexes)among the three groups of DEHSI

表4 矯正年齡后1個(gè)月、3個(gè)月、5個(gè)月大的嬰兒DEHSI與預(yù)后相關(guān)性Tab.4 The relationship between DEHSI and Gesell scores at 1,3,5 month corrected age in infants

近年來，隨著新生兒監(jiān)護(hù)水平不斷提高及疾病診治策略的日益完善，新生兒死亡率已明顯降低，但新生兒腦損傷致殘仍普遍存在。本組數(shù)據(jù)發(fā)現(xiàn)DEHSI的發(fā)生率約占3/4，與之前國外的研究結(jié)果一致[18]。DEHSI是國外醫(yī)學(xué)界研究的熱點(diǎn)，國內(nèi)鮮有報(bào)道。文獻(xiàn)[19]報(bào)道，新生兒腦白質(zhì)信號(hào)異常與神經(jīng)發(fā)育結(jié)局不良有一定相關(guān)性。本研究表明，嬰兒在矯正年齡后5個(gè)月的神經(jīng)行為結(jié)果與DEHSI呈顯著負(fù)相關(guān)，隨著DEHSI的信號(hào)強(qiáng)度增加，Gesell評(píng)分越低，預(yù)后越差。此外，早產(chǎn)兒神經(jīng)發(fā)育延遲發(fā)生率高于足月兒，中重度DEHSI與神經(jīng)發(fā)育結(jié)局有一定相關(guān)性，且主要表現(xiàn)在粗大運(yùn)動(dòng)發(fā)育延遲。DEHSI主要表現(xiàn)在雙側(cè)腦室旁的額葉、頂葉、枕葉及雙側(cè)半卵圓中心，而額葉是控制人體軀體運(yùn)動(dòng)功能的神經(jīng)中樞，同時(shí)也負(fù)責(zé)語言功能。由于特定的白質(zhì)纖維有助于建立大腦功能信息網(wǎng)的傳輸，起源于大腦皮質(zhì)中央前回、額葉及頂葉皮質(zhì)區(qū)的皮質(zhì)脊髓束是大腦皮質(zhì)至脊髓前角運(yùn)動(dòng)神經(jīng)元的運(yùn)動(dòng)纖維束[20]，主要支配軀干肌和四肢骨骼肌的運(yùn)動(dòng)，而額葉皮層和丘腦由丘腦前輻射鏈接，因此額葉對(duì)認(rèn)知和執(zhí)行能力發(fā)揮重要作用[21]。新生兒腦組織少突膠質(zhì)細(xì)胞的損傷可能改變皮質(zhì)脊髓束和丘腦前輻射的擴(kuò)散指數(shù)，這也從細(xì)胞學(xué)及解剖學(xué)層面解釋了DEHSI的發(fā)生及運(yùn)動(dòng)和認(rèn)知功能缺陷產(chǎn)生的原因[22]。

本組結(jié)果表明，無及輕度DEHSI與神經(jīng)行為的結(jié)果沒有直接的關(guān)聯(lián)，但是中重度DEHSI可能因白質(zhì)損傷和相關(guān)的軸突病變而與嬰兒不良神經(jīng)發(fā)育結(jié)局有關(guān)。Dyet等[23]研究認(rèn)為腦白質(zhì)DEHSI可預(yù)測(cè)矯正年齡后18～36個(gè)月的輕度發(fā)育延遲，中重度DEHSI會(huì)有較差的認(rèn)知發(fā)展。本研究結(jié)果亦證實(shí)這一點(diǎn)。DEHSI的細(xì)胞學(xué)及解剖學(xué)基礎(chǔ)尚存爭(zhēng)議，因此DEHSI能否代表輕度腦白質(zhì)損傷或成熟延遲有待進(jìn)一步證實(shí)[15]。筆者認(rèn)為，DEHSI微觀結(jié)構(gòu)的變化改變了腦白質(zhì)組織[24]，它可能預(yù)測(cè)短期神經(jīng)發(fā)育的結(jié)果。

本研究的局限性：(1)T2WI信號(hào)可能受到的磁場(chǎng)非均勻性影響，磁場(chǎng)不均勻性與DEHSI信號(hào)強(qiáng)度混淆。(2)因?yàn)楣P者回顧性分析1個(gè)月、3個(gè)月、5個(gè)月年齡之間復(fù)查神經(jīng)發(fā)育測(cè)試的嬰兒，使得這項(xiàng)研究可能存在選擇偏倚。另外，由于隨訪時(shí)間相對(duì)較短，仍需延長(zhǎng)隨訪時(shí)間繼續(xù)觀察。(3)本研究仍需擴(kuò)大樣本量進(jìn)一步隨訪以完善神經(jīng)系統(tǒng)發(fā)育的評(píng)估。隨著新生兒重癥監(jiān)護(hù)的進(jìn)步，神經(jīng)影像學(xué)或病理學(xué)檢查對(duì)腦白質(zhì)損傷的認(rèn)識(shí)明顯轉(zhuǎn)變[25]。MRI診斷彌漫性腦室周圍白質(zhì)損傷可能在新生兒早期診斷及預(yù)后評(píng)估中產(chǎn)生影響，準(zhǔn)確地揭示DEHSI嚴(yán)重程度的模式和量化，識(shí)別潛在高危早產(chǎn)兒并行神經(jīng)保護(hù)和早期干預(yù)治療是解決問題并受益的關(guān)鍵。

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