李超偉，鮑海華，孔德民，李偉霞，員強(qiáng)

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基于體素形態(tài)學(xué)測(cè)量技術(shù)對(duì)高原地區(qū)正常成人腦結(jié)構(gòu)的研究

李超偉，鮑海華*，孔德民，李偉霞，員強(qiáng)

[摘要]目的 基于體素形態(tài)學(xué)測(cè)量(VBM)技術(shù)，分析久居高原地區(qū)(＞3000 m) 正常成人腦結(jié)構(gòu)體積的變化。材料與方法 選取兩組正常成人參與本次研究，其中包括高原組[男8例，女8例，平均年齡(21.81 ± 2.07)歲]和與之年齡、受教育年限相匹配的平原組[男7例、女13例，平均年齡(21.85 ± 1.90)歲]，對(duì)每個(gè)被試行全腦掃描，獲取3D-T1結(jié)構(gòu)圖像，利用VBM方法對(duì)全腦灰、白質(zhì)圖像進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果 與平原組比較，高原組正常成人左側(cè)后扣帶回、顳上回灰質(zhì)體積增加；右側(cè)島葉灰質(zhì)體積減低；白質(zhì)體積增加區(qū)域?yàn)樽髠?cè)丘腦、右側(cè)額上回、左側(cè)豆?fàn)詈?、左?cè)枕葉。結(jié)論 利用VBM技術(shù)對(duì)MRI結(jié)構(gòu)圖像分析，能夠客觀顯示高原地區(qū)相對(duì)平原地區(qū)正常成人腦部特定區(qū)域體積的變化，從而全面的評(píng)價(jià)高原長(zhǎng)期低氧對(duì)腦結(jié)構(gòu)的影響。

[關(guān)鍵詞]腦；人體測(cè)量術(shù)；高原；磁共振成像

國(guó)家自然科學(xué)基金(編號(hào)：81060117)；青海省科技廳國(guó)際合作項(xiàng)目(編號(hào)：2012-H-807)

作者單位：

青海大學(xué)附屬醫(yī)院影像中心，西寧810001

鮑海華，E-mail: baohelen2@sina.com

接受日期：2015-11-11

李超偉, 鮑海華, 孔德民, 等.基于體素形態(tài)學(xué)測(cè)量技術(shù)對(duì)高原地區(qū)正常成人腦結(jié)構(gòu)的研究.磁共振成像, 2016, 7(1): 1–5.

Study of brain structure in nomal plateau area adult with voxel-based morphometry

LI Chao-wei, BAO Hai-hua*, KONG De-min, Li Wei-xia, YUAN Qiang

The Affiliated Hospital of Qinghai University, Medical Imaging Center, Xining 810001, China

*Correspondence to: Bao HH, E-mail: baohelen2@sina.com

Received 17 Oct 2015, Accepted 11 Nov 2015

ACKNOWLEDGMENTS National Natural Science Foundation of China(No.81060117).International cooperation project of science and Technology Department of Qinghai Province (No.2012-H-807).

Abstract Objective: The aim of the study was to investigate the brain structure volumes alterations in born and raised high altitude (HA) (＞3000 m) normal adult by using voxel-based morphometry method (VBM).Materials and Methods: Two groups of adults participated in the study, including an HA group [8 males and 8 females, mean age=(21.81±2.07) years] and an age- and education-matched sea level (SL) group [7 males and 13 females, mean age=(21.85±1.90) years].3D-T1 structural images of all subjects who were underwent the whole brain scan were acquired.Then we used the VBM method to compare the whole brain GM and WM images differences between HA group and SL group.Results: HA acclimatization (vs.SL) showed increased gray matter volume in the left posterior cingulate, the left superior temporal gyrus,decreased GM volumes was found in the right insular lobe in highland group and we also found increased WM volumes in left thalamus, the right superior frontal gyrus, the lentiform nucleus, the left occipital lobe.Conclusions: The VBM method was applied to the analysis of the magnetic resonance structural images and it could objectively display the volume changes of specific brain areas in HA group and could get us a comprehensive evaluation of the impact of altitude hypoxia on brain structure.

Key words Brain; Anthropometry; Altitude; Magnetic resonance imaging

青藏高原號(hào)稱“世界屋脊”，是我國(guó)面積最大，海拔最高，居住人口最多的高原地區(qū)。缺氧是高原環(huán)境影響人體的最關(guān)鍵的因素之一。近年來(lái)，有關(guān)高原低氧對(duì)腦部影響的文獻(xiàn)報(bào)道比較多，例如對(duì)慢性高原病患者腦部的病理生理及神經(jīng)影像學(xué)表現(xiàn)進(jìn)展[1]做一綜述；研究發(fā)現(xiàn)，慢性高原病患者灰質(zhì)體積增加的腦區(qū)為右側(cè)舌回、后扣帶回、雙側(cè)海馬及左側(cè)顳下回[2]；平原移居至青藏高原地區(qū)并適應(yīng)生活2年的正常成人的不同腦區(qū)灰、白質(zhì)結(jié)構(gòu)發(fā)生變化[3]；也有學(xué)者發(fā)現(xiàn)，長(zhǎng)期生活在海拔2600～4200 m地區(qū)的正常成人下達(dá)平原地區(qū)1年的腦灰白質(zhì)結(jié)構(gòu)發(fā)生改變[4]。但是久居高原從未下達(dá)平原地區(qū)的正常成人的腦結(jié)構(gòu)的變化尚未報(bào)道。

基于體素形態(tài)學(xué)測(cè)量(voxel-based morphometry, VBM)技術(shù)是一種全自動(dòng)化、客觀進(jìn)行全腦形態(tài)分析的技術(shù)，能夠定量和全面的評(píng)估大腦結(jié)構(gòu)差異[5]；此技術(shù)已經(jīng)廣泛地應(yīng)用于研究多種疾病導(dǎo)致的腦形態(tài)學(xué)改變[6]。筆者應(yīng)用優(yōu)化的VBM技術(shù)，對(duì)高原及平原地區(qū)正常成人進(jìn)行全腦結(jié)構(gòu)的形態(tài)學(xué)測(cè)量，分析全腦結(jié)構(gòu)變化。

1　 材料與方法

1.1臨床資料

1.1.1研究對(duì)象

搜集兩組正常成人參與本次研究，并均為漢族人；高原組共計(jì)16例，來(lái)自兩代以上均出生并長(zhǎng)期居住在高原地區(qū)[居住海拔高度平均為(3628.88±295.72) m]的正常成人，其中男8 例，女8例，年齡18～24歲，平均(21.81±2.07)歲；受教育時(shí)間平均(11.69±0.48)年。平原組共計(jì)20例，其中男7例，女13例，平均年齡(21.85±1.90)歲，居住海拔高度平均為(391.72±373.24) m；受教育時(shí)間平均(13.50±3.56)年。兩組的平均年齡和受教育時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義(P值分別為0.96和0.59)。所有受檢者在檢查時(shí)均就讀于青海大學(xué)醫(yī)學(xué)院，到青海后1周內(nèi)進(jìn)行MRI檢查，檢查前均了解了檢查內(nèi)容和意義并簽署知情同意書，并由青海省倫理委員會(huì)批準(zhǔn)。

1.1.2納入標(biāo)準(zhǔn)和排除標(biāo)準(zhǔn)

納入標(biāo)準(zhǔn)：(1)常規(guī)頭顱MRI掃描無(wú)其他腦實(shí)質(zhì)病變；(2)患者無(wú)MRI檢查的相關(guān)禁忌證；(3)臨床各項(xiàng)檢查確認(rèn)無(wú)精神異常等；(4)均為右利手。排除標(biāo)準(zhǔn)：(1)有慢性高原??；(2)被確診的腦神經(jīng)失調(diào)；(3)過(guò)去有腦部損傷致意識(shí)喪失。

1.2MRI檢查方法

應(yīng)用3.0 T超導(dǎo)MR成像系統(tǒng)(PHILIPS)，標(biāo)準(zhǔn)頭顱8通道相控陣線圈完成所有掃描序列；研究對(duì)象首先進(jìn)行常規(guī)頭部MR成像獲得T1WI和T2WI；同時(shí)采用超快速場(chǎng)回波(TFE)序列獲取3D-T1結(jié)構(gòu)像，TR 7.5 ms，TE 3.7 ms，層厚2 mm，層間隔–1 mm，矩陣256 × 256，激發(fā)角度7°，掃描全腦將連續(xù)獲得176層矢狀面圖像；所有的掃描均由同一名資深影像科醫(yī)師操作完成。

1.3數(shù)據(jù)處理及統(tǒng)計(jì)分析

將所有被試的原始數(shù)據(jù)導(dǎo)入個(gè)人電腦工作站，采用統(tǒng)計(jì)參數(shù)圖(SPM8)的嵌套軟件VBM8 toolbox進(jìn)行數(shù)據(jù)處理；計(jì)算和處理圖像矩陣在Matlab平臺(tái)上運(yùn)行；數(shù)據(jù)處理包括：(1)對(duì)頭位偏差大的圖像進(jìn)行位置校正；(2)每個(gè)被試3D-T1圖像分割成灰質(zhì)、白質(zhì)、腦脊液后，將所有被試者的MR圖像都配準(zhǔn)至模板圖像，進(jìn)行空間標(biāo)準(zhǔn)化處理；(3)采用半高全寬為8 mm的三維高斯核進(jìn)行圖像平滑，并對(duì)處理后的結(jié)果進(jìn)行統(tǒng)計(jì)分析。采用兩樣本t檢驗(yàn)進(jìn)行比較(檢驗(yàn)參數(shù)t＞3.7459，P＜0.05；校正)，選取相鄰像素(voxels)大于389個(gè)以上的組塊(cluster)才視為有差異的腦區(qū)，將檢驗(yàn)結(jié)果疊加到T1結(jié)構(gòu)圖的模板上，分析研究對(duì)象全腦結(jié)構(gòu)體積的變化。

表1　高原組與平原組腦區(qū)相比灰質(zhì)增加的統(tǒng)計(jì)分析結(jié)果Tab.1 The statistic analysis results of increased gray matter voxels in HA group contrasted with SL group

2　 結(jié)果

VBM分析顯示高原地區(qū)正常成年人與平原組相比：(1)高原組較平原組的左側(cè)后扣帶回、左側(cè)顳上回灰質(zhì)體積增加(表1，圖1)；(2)高原組較平原組的右側(cè)島葉灰質(zhì)體積減低(表2，圖1)；(3)高原組較平原組的左側(cè)丘腦、右側(cè)額上回、左側(cè)豆?fàn)詈?、左?cè)枕葉白質(zhì)體積增加(表3，圖2)。

圖1　 高原組與平原組相比灰質(zhì)體積有差異的腦區(qū)的統(tǒng)計(jì)參數(shù)圖。紅色代表HA正常成人腦區(qū)相對(duì)于SL正常成人腦區(qū)灰質(zhì)體積增加的區(qū)域，包括：左側(cè)后扣帶回；左側(cè)顳上回；藍(lán)色代表HA正常成人腦區(qū)相對(duì)于SL正常成人腦區(qū)灰質(zhì)體積減少的區(qū)域：右側(cè)島葉 (統(tǒng)計(jì)閾值設(shè)定為P＜0.05，cluster size＞389，校正) 圖2 高原組與平原組相比白質(zhì)體積有差異腦區(qū)的統(tǒng)計(jì)參數(shù)圖。紅色代表HA正常成人腦區(qū)相對(duì)于SL正常成人腦區(qū)白質(zhì)體積增加的區(qū)域，包括：左側(cè)丘腦、右側(cè)額上回、左側(cè)豆?fàn)詈?、左?cè)枕葉 (統(tǒng)計(jì)閾值設(shè)置為P＜0.05，cluster size＞389，校正)Fig.1 The statistical parametric map showed difference between HA group and SL group in gray matter volume.Compared with SL group, red display the increased regions of GM volume in HA group, include left posterior cingulate, the left superior temporal gyrus and blue display the reduced regions in the right insular lobe.The statistical threshold is set to P＜0.05, cluster size＞389, corrected.Fig.2 The statistical parametric map showed difference between HA group and SL group in white matter volume.Compared with SL group, red display the increased regions of WM volume in HA group, include in left thalamus, the right superior frontal gyrus, the lentiform nucleus, the left occipita lobe.The statistical threshold is set to P＜0.05, cluster size＞389, corrected.

表 2 高原組與平原組腦區(qū)相比灰質(zhì)減低的統(tǒng)計(jì)分析結(jié)果Tab.2 The statistic analysis results of decreased gray matter voxels in HA group contrasted with SL group

表 3 高原組與平原組腦區(qū)相比白質(zhì)減低的統(tǒng)計(jì)分析結(jié)果Tab.3 The statistic analysis results of increased white matter voxels in HA group contrasted with SL group

3　 討論

一個(gè)世紀(jì)以來(lái)，從臨床方面對(duì)腦缺氧后的生理學(xué)、組織解剖學(xué)、神經(jīng)化學(xué)等進(jìn)行了大量的宏觀和微觀研究；但從影像學(xué)的角度上報(bào)道較少。

研究表明高海拔環(huán)境(低溫，低壓，紫外線，寒冷，脫水)下的土著居民和移民在呼吸道和心血管方面產(chǎn)生了適應(yīng)性的改變，這直接與氧氣的運(yùn)輸有關(guān)[7-10]。大腦是人體的控制中心，通過(guò)其傳入反饋，心血管和呼吸道系統(tǒng)的適應(yīng)性改變作用于大腦，也可能引起相應(yīng)腦結(jié)構(gòu)的改變[11]。另一方面，中樞神經(jīng)系統(tǒng)是高度氧化的，它不可避免的遭受含氧量低的壓力。血紅蛋白濃度以及動(dòng)脈血氧飽和度的變化使大腦血流的氧輸送發(fā)生改變，最后導(dǎo)致腦結(jié)構(gòu)的積累性改變[12-14]。許多研究者對(duì)高原地區(qū)居民的研究主要注重于腦葡萄糖代謝率[13]和腦自身調(diào)節(jié)[15-16]。但到目前為止，高原地區(qū)的居民腦部結(jié)構(gòu)的適應(yīng)性改變?nèi)匀徊磺宄?/p>

目前研究表明，高海拔適應(yīng)與大腦結(jié)構(gòu)的改變有關(guān)，包括某些區(qū)域皮層灰質(zhì)體積和白質(zhì)結(jié)構(gòu)的改變；根據(jù)Zatorre等[17]的研究發(fā)現(xiàn)，正常成人灰質(zhì)增加可能與以下幾個(gè)方面有關(guān)：神經(jīng)細(xì)胞的增加、膠質(zhì)細(xì)胞再生、突觸發(fā)生及血管生成。然而，灰質(zhì)的減少可能與缺氧新陳代謝副產(chǎn)物和低氧環(huán)境下谷氨酸能神經(jīng)細(xì)胞釋放的谷氨酸鹽增多有關(guān)[18]。本研究結(jié)果示，高海拔地區(qū)正常成人較平原組左側(cè)后扣帶回、顳上回灰質(zhì)體積增加；前腦島葉灰質(zhì)體積減少；說(shuō)明高原正常成人的此腦區(qū)對(duì)缺氧極為敏感。

后扣帶回是默認(rèn)網(wǎng)絡(luò)中心節(jié)點(diǎn)之一，是情節(jié)處理和工作記憶的重要構(gòu)成部分；顳上回是視聽(tīng)覺(jué)中樞的一部分。登山運(yùn)動(dòng)員[18-22]、生活在適度海拔高度的世居者[23]以及高海拔移民的后代[24-25]中有短期記憶，視覺(jué)結(jié)構(gòu)，程序?qū)W習(xí)，工作記憶的減弱并且反應(yīng)時(shí)間的增加情況，該區(qū)域灰質(zhì)增加也可能解釋上述機(jī)制，到目前為止為什么發(fā)生及怎樣發(fā)生還不完全清楚。

島葉皮層已被證明與心血管疾病控制有關(guān)[26-28]，前腦島在呼吸困難中起重要作用[29]，呼吸困難常常發(fā)生在對(duì)高海拔低氧的適應(yīng)過(guò)程中。最近，Paulus等[30]提出一種假設(shè)：前腦島在高海拔環(huán)境中處理自身平衡穩(wěn)定是必需的；有氧代謝能力與右側(cè)前腦島灰質(zhì)有很強(qiáng)的相關(guān)性[31]，高海拔地區(qū)居民在生長(zhǎng)發(fā)育期間需氧容量降低[32-33]，因而島葉灰質(zhì)體積減少。所以，筆者推測(cè)居民在適應(yīng)于高海拔會(huì)有前腦島部灰質(zhì)的減少。

白質(zhì)由神經(jīng)纖維構(gòu)成，位于大腦皮質(zhì)與基底核之間。彌散張量成像是研究腦白質(zhì)的方法之一，但本文章采用基于VBM方法測(cè)量腦白質(zhì)體積的研究。本研究結(jié)果顯示，白質(zhì)體積增加區(qū)域?yàn)樽髠?cè)丘腦、右側(cè)額上回、左側(cè)豆?fàn)詈恕⒆髠?cè)枕葉。丘腦與腦內(nèi)許多結(jié)構(gòu)有著豐富的纖維連接，并且是腦的中繼站，起著過(guò)濾器的作用，通過(guò)排除多余或者無(wú)關(guān)的刺激來(lái)傳遞重要的或相關(guān)的信息。前額葉的主要功能是記憶、判斷、分析、思考、操作，人類完成高級(jí)認(rèn)知任務(wù)主要與前額葉有關(guān)。左側(cè)豆?fàn)詈伺c右側(cè)運(yùn)動(dòng)和神經(jīng)傳導(dǎo)有關(guān)。枕葉為視覺(jué)皮質(zhì)中樞，以上白質(zhì)的改變可能與情感的調(diào)節(jié)、認(rèn)知功能、地處高原環(huán)境、基因和生活環(huán)境等有關(guān)。

我們初步探討了長(zhǎng)期低氧對(duì)高原地區(qū)正常成人腦結(jié)構(gòu)的影響，證明了高海拔適應(yīng)性與腦部結(jié)構(gòu)改變有關(guān)；但本研究樣本量較小，沒(méi)有設(shè)計(jì)認(rèn)知功能測(cè)試，本研究中對(duì)結(jié)果的解釋主要依靠其他學(xué)者的研究結(jié)果。今后， 筆者將擴(kuò)大樣本量，行腦認(rèn)知功能測(cè)驗(yàn)等，為高原地區(qū)正常成人腦結(jié)構(gòu)改變提供更多證據(jù)；增進(jìn)我們對(duì)高原長(zhǎng)期低氧改變腦結(jié)構(gòu)的全面認(rèn)識(shí)。

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DOI:10.12015/issn.1674-8034.2016.01.001

文獻(xiàn)標(biāo)識(shí)碼：A

中圖分類號(hào)：R445.2；R322.81

收稿日期：2015-10-17

通訊作者：

基金項(xiàng)目：