沈慧聰,李正然,常天靜,張寧,王春雪,馬軍*
老年人腦白質(zhì)病變相關(guān)性跌倒患者的腦彌散張量成像研究
沈慧聰1,李正然1,常天靜2,張寧3,4,王春雪3,4,馬軍1*
目的 定量分析老年人腦白質(zhì)病變(white matter lesions, WMLs)相關(guān)性跌倒患者的腦彌散張量成像(diffusion tensor imaging, DTI)及臨床改變,初步探索老年人跌倒風(fēng)險(xiǎn)的影像學(xué)預(yù)測(cè)指標(biāo)。材料與方法 選擇2015年6月至2016年1月期間首都醫(yī)科大學(xué)附屬北京天壇醫(yī)院60歲以上的WMLs患者,根據(jù)Tinetti平衡和步態(tài)量表劃分為跌倒風(fēng)險(xiǎn)組15人(Tinetti<25分)及對(duì)照組29人(Tinetti≥25分)。運(yùn)用基于纖維束追蹤空間統(tǒng)計(jì)分析(tract based spatial statistics, TBSS)識(shí)別跌倒風(fēng)險(xiǎn)組患者異常的腦白質(zhì)纖維束,并與簡(jiǎn)易精神狀態(tài)檢查量表(mini mental state exam,MMSE)、蒙特利爾認(rèn)知評(píng)估(montreal cognitive assessment, MoCA)量表、Tinetti平衡和步態(tài)量表(tinetti balance and gait analysis)、計(jì)時(shí)起立-步行測(cè)驗(yàn)(timed up and go test, TUGT)分別進(jìn)行相關(guān)性分析。結(jié)果 跌倒風(fēng)險(xiǎn)組的MMSE(t=2.806,P=0.008)及MoCA (t=2.890,P=0.006)量表評(píng)分低于對(duì)照組。跌倒風(fēng)險(xiǎn)組的全腦平均各向異性分?jǐn)?shù)(fractional anisotropy, FA)值低于對(duì)照組(t=2.862,P= 0.007);跌倒風(fēng)險(xiǎn)組全腦平均FA值與MMSE(r=0.533,P=0.041)及MoCA(r=0.642,P=0.010)量表呈正相關(guān)。跌倒風(fēng)險(xiǎn)組FA值減低的腦白質(zhì)纖維束為右側(cè)鉤束、胼胝體膝部、體部及壓部、雙側(cè)放射冠前部、右側(cè)放射冠上部、右側(cè)上縱束、左側(cè)扣帶回;其中跌倒風(fēng)險(xiǎn)組的胼胝體膝部、右側(cè)放射冠前部、胼胝體體部、胼胝體壓部、右側(cè)上縱束、左側(cè)扣帶回的平均FA值均與MoCA呈正相關(guān)(P值均<0.05);右側(cè)鉤束的平均FA值(r=0.562,P=0.029)與Tinetti平衡量表呈正相關(guān);右側(cè)鉤束(r=0.572,P=0.026)、胼胝體體部(r=0.538,P=0.038)、胼胝體壓部(r=0.580,P=0.023)、左側(cè)扣帶回(r=0.520,P=0.047) 的平均FA值與Tinetti步態(tài)量表呈正相關(guān);胼胝體體部(r=-0.582,P=0.023)及左側(cè)扣帶回(r=-0.538,P=0.039)的平均FA值與TUGT呈負(fù)相關(guān)。結(jié)論 跌倒風(fēng)險(xiǎn)組的全腦平均FA值及9條腦白質(zhì)纖維束平均FA值低于對(duì)照組,并與認(rèn)知、步態(tài)、平衡功能存在一定的相關(guān)性。DTI定量分析可用于識(shí)別老年人WMLs相關(guān)性跌倒患者的顱腦結(jié)構(gòu)特點(diǎn),為具有跌倒風(fēng)險(xiǎn)的WMLs患者的識(shí)別、判斷病情及預(yù)后評(píng)價(jià)提供了重要的影像學(xué)依據(jù)。
老年人;腦白質(zhì)病;意外跌倒;彌散張量成像
1Department of Radiology, Beijing Tiantan Hospital, Capital Medical University,Beijing 100050, China
2Department of Radiology, Peking University Shougang Hospital, Beijing 100144,China
3Department of Neuropsychological and Clinical Psychology, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050,China
4China National Clinical Research Center for Neurological Diseases, Beijing 100050,China
*Correspondence to: Ma J, E-mail: dr_ma@sina.com
ACKNOWLEDGMENTS This work was part of Beijing Natural Science Foundation (No. 7092027) and supported by Beijing Municipal Science & Technology Commission (NO. Z151100003915117).
北京市自然科學(xué)基金(編號(hào):7092027);首都臨床特色研究項(xiàng)目(編號(hào):Z151100004015127)
接受日期:2016-05-18
沈慧聰, 李正然, 常天靜, 等. 老年人腦白質(zhì)病變相關(guān)性跌倒患者的腦彌散張量成像研究. 磁共振成像, 2016, 7(6): 422-427.
跌倒是導(dǎo)致老年人傷殘、死亡的常見(jiàn)傷害性事件之一。2005年預(yù)防跌倒歐洲共識(shí)將跌倒概念定義為滑倒(slip)或絆倒(trip),當(dāng)事人突發(fā)、不自主、非故意的體位改變,失去平衡而使其跌落至地板、地面或更低的平面[1]。國(guó)外研究表明[2],65歲以上的老年人有30%每年至少跌倒一次,其中10%會(huì)造成嚴(yán)重?fù)p傷。我國(guó)北京某社區(qū)60歲以上的老年人1年中跌倒的發(fā)生率也高達(dá)18%,其中8.7%的老年人因跌倒受傷[3]。目前跌倒的評(píng)估手段包括記錄跌倒次數(shù)、Tinetti平衡與步態(tài)量表、簡(jiǎn)易體能狀況量表(short physical performance battery, SPPB)等[4],但僅使用單方面的評(píng)估工具無(wú)法準(zhǔn)確定量地評(píng)估跌倒風(fēng)險(xiǎn)。腦白質(zhì)病變(white matter lesions,WMLs)見(jiàn)于60歲以上的正常老年人,可引起認(rèn)知、平衡及步態(tài)功能異常甚至發(fā)生跌倒[5-7]。彌散張量成像(diffusion tensor imaging, DTI)可以定量反映活體組織水分子的擴(kuò)散信息,還能反映腦白質(zhì)的微結(jié)構(gòu)及纖維走行情況[8-9],但應(yīng)用DTI來(lái)研究老年人WHLs相關(guān)性跌倒患者的腦微觀結(jié)構(gòu)改變還未深入進(jìn)行,臨床-影像的相關(guān)性尚未確定,本研究通過(guò)定量分析老年人WHLs相關(guān)性跌倒患者的腦DTI,初步探索老年人跌倒風(fēng)險(xiǎn)的影像學(xué)預(yù)測(cè)指標(biāo)。
1.1 一般資料
收集2015年5月至2016年1月首都醫(yī)科大學(xué)附屬北京天壇醫(yī)院60歲以上的WMLs患者44人,行DTI檢查。根據(jù)Tinetti平衡和步態(tài)量表分為兩個(gè)研究組[8]:跌倒風(fēng)險(xiǎn)組(Tinetti<25)共計(jì)15人,平均(71.870±7.717)歲,其中男6人,女9人;對(duì)照組(Tinetti≥25)共計(jì)29人,平均(71.410±5.124)歲,其中男11人,女18人,男女差別無(wú)統(tǒng)計(jì)學(xué)意義(χ2= 0.018,P=0.894)。排除標(biāo)準(zhǔn):癡呆及明顯運(yùn)動(dòng)障礙,腦卒中、腫瘤、感染、免疫代謝性病等中樞神經(jīng)系統(tǒng)病變者;帕金森病及前庭病變,嚴(yán)重視力障礙、骨關(guān)節(jié)及肌肉病變者;癲癇、精神病或特殊藥物服用史;有MRI檢查禁忌者。對(duì)所有患者進(jìn)行臨床量表測(cè)評(píng),包括簡(jiǎn)易精神狀態(tài)檢查量表(mini mental state exam, MMSE)、蒙特利爾認(rèn)知評(píng)估(montreal cognitive assessment, MoCA)量表、Tinetti步態(tài)量表、Tinetti平衡量表、計(jì)時(shí)起立-步行測(cè)驗(yàn)(timed up and go test, TUGT)。
1.2 影像學(xué)檢查
采用Siemens Trio Tim 3.0 T超導(dǎo)磁共振掃描儀;使用頭部8通道相控陣頭線(xiàn)圈。DTI圖像采集使用單次激發(fā)自旋回波-平面回波序列,掃描參數(shù):TR=11000 ms,TE=94 ms,F(xiàn)OV=256 mm,矩陣128×128,NEX=1,共掃描65層,層厚2 mm,無(wú)間隔的連續(xù)掃描,b值分別為0和1000 s/mm2,在30個(gè)不同的非線(xiàn)性方向上施加梯度磁場(chǎng)。T1WI結(jié)構(gòu)像掃描參數(shù):TE=2.16 ms,TR=2300 ms,TI=900 ms,翻轉(zhuǎn)角9°,F(xiàn)OV=240 mm,矩陣256× 256,共掃描176層。
1.3 圖像后處理
使用FSL軟件,首先進(jìn)行圖像預(yù)處理:(1)頭動(dòng)及渦流校正;(2)提取B0圖,去除頭皮、顱骨,提取大腦信息(閾值=0.3);(3)運(yùn)用DTIFit工具計(jì)算獲得各向異性分?jǐn)?shù)(fractional anisotropy, FA)圖。
采用基于纖維束追蹤空間統(tǒng)計(jì)分析(tract based spatial statistics, TBSS),將TBSS工作目錄下所有被試FA做TBSS預(yù)處理;將FA圖通過(guò)非線(xiàn)性配準(zhǔn)的方式配準(zhǔn)到標(biāo)準(zhǔn)空間MNI,以FMRIB58 FA圖像當(dāng)作目標(biāo)圖像進(jìn)行配準(zhǔn);因?yàn)門(mén)BSS僅適用于檢測(cè)較大的白質(zhì)纖維束(FA值大于0.2),因此選取閾值(一般為0.2~0.8)生成所有被試者平均FA值圖像,并提取白質(zhì)纖維骨架;將配準(zhǔn)后的FA圖投射到白質(zhì)纖維骨架上,產(chǎn)生各自的FA骨架。
1.4 統(tǒng)計(jì)學(xué)分析
在白質(zhì)纖維束骨架上統(tǒng)計(jì)兩組的全腦平均FA值,經(jīng)雙樣本t檢驗(yàn),以年齡、性別為協(xié)變量,P<0.05認(rèn)為有統(tǒng)計(jì)學(xué)差異,將FA值與MMSE、MoCA做相關(guān)性分析。
利用FSL軟件中的randomiset函式對(duì)兩組進(jìn)行基于全腦纖維束體素的顯著性差異統(tǒng)計(jì)分析,以年齡和性別為協(xié)變量,置換檢驗(yàn)n=10000。采用無(wú)閾值簇群增強(qiáng)(threshold-free cluster enhancement,TFCE)FWE方法來(lái)校正多重比較中的I類(lèi)錯(cuò)誤,校正水平為P<0.05。識(shí)別異常的白質(zhì)纖維束,得出相應(yīng)FA值并與MMSE、MoCA、Tinetti平衡量表、Tinetti步態(tài)量表、TUGT做相關(guān)性分析。
跌倒風(fēng)險(xiǎn)組患者的MMSE(t=2.806,P=0.008)及MoCA(t=2.890,P=0.006)量表評(píng)分均低于對(duì)照組,跌倒風(fēng)險(xiǎn)組的全腦平均FA值低于對(duì)照組(t=2.862,P=0.007),差異具有統(tǒng)計(jì)學(xué)意義。跌倒風(fēng)險(xiǎn)組及對(duì)照組全腦平均FA值與MMSE呈正相關(guān),其中跌倒風(fēng)險(xiǎn)組r=0.533,P=0.041,所有被試r=0.518,P=0.000(圖1A)。跌倒風(fēng)險(xiǎn)組及對(duì)照組全腦平均FA值與MoCA呈正相關(guān),跌倒風(fēng)險(xiǎn)組r=0.642,P=0.010,所有被試r=0.622,P=0.000(圖1B)。
與對(duì)照組相比,跌倒風(fēng)險(xiǎn)組9條腦白質(zhì)纖維束FA值減低(圖2、3),差異具有統(tǒng)計(jì)學(xué)意義。跌倒風(fēng)險(xiǎn)組、對(duì)照組及所有被試部分腦白質(zhì)纖維束的平均FA值與MoCA量表、Tinetti步態(tài)量表、Tinetti平衡量表呈正相關(guān)(表1、2),與TUGT呈負(fù)相關(guān)(表2)。
DTI是利用組織中水分子擴(kuò)散運(yùn)動(dòng)的各向異性特征進(jìn)行成像的一種功能磁共振技術(shù),不僅反映活體組織水分子的擴(kuò)散信息,一定程度上還能反映腦白質(zhì)的微結(jié)構(gòu)及纖維走行情況,在研究腦白質(zhì)病變方面,DTI的敏感性明顯高于T2WI等常規(guī)磁共振序列[9]。TBSS是一種基于纖維束骨架的空間統(tǒng)計(jì)方法,采用非線(xiàn)性配準(zhǔn)方法對(duì)全腦白質(zhì)進(jìn)行自動(dòng)測(cè)量。
圖1 跌倒風(fēng)險(xiǎn)組及對(duì)照組全腦平均FA值與MMSE及MoCA的相關(guān)性(方格代表跌倒風(fēng)險(xiǎn)組,黑三角代表對(duì)照組)Fig. 1 The correlation between mean FA of whole brain and MMSE/MoCA scores in the fall risk group and contrast group(□ fall risk group, ▲ contrast group).
圖2 跌倒風(fēng)險(xiǎn)組FA值減低的腦白質(zhì)纖維束分布區(qū)域,綠色標(biāo)記為平均纖維束骨架,黃色表示平均FA值減低(P<0.05,TFCE-corrected)Fig. 2 Mean FA skeleton of white matter tracts, green indicates white matter skeleton, yellow indicates the reduced Mean FA (P<0.05, TFCE-corrected).
圖3 跌倒風(fēng)險(xiǎn)組與對(duì)照組相比平均FA值減低的白質(zhì)纖維束(1~9分別為右側(cè)鉤束、胼胝體膝部、右側(cè)放射冠前部、左側(cè)放射冠前部、胼胝體體部、右側(cè)放射冠上部、胼胝體壓部、右側(cè)上縱束、左側(cè)扣帶回)Fig. 3 The reduced Mean FA of white matter tracts in the fall risk group (1—9 indicate right fasciculus uncinatus, genu of corpus callosum, right anterior corona radiate, left anterior corona radiate, body of corpus callosum, right superior corona radiate, splenium of corpus callosum, right superior longitudinal fasciculus and left cingulate gyrus).
WMLs是常見(jiàn)的中老年腦影像表現(xiàn),指腦白質(zhì)斑點(diǎn)狀或斑片狀非特異性CT低密度,MRI T2WI及FLAIR高信號(hào)區(qū),病理基礎(chǔ)是髓鞘腫脹或脫失,軸突破壞,可見(jiàn)膠質(zhì)細(xì)胞增生、小血管硬化、動(dòng)脈壁纖維化及玻璃樣變性[10]。FA值是DTI 的常用參數(shù)之一,反映纖維髓鞘的完整性,當(dāng)髓鞘結(jié)構(gòu)破壞時(shí),抑制水分子擴(kuò)散的屏障作用減弱,導(dǎo)致有序的各向異性結(jié)構(gòu)喪失,F(xiàn)A值減低[11]。研究發(fā)現(xiàn),WHLs與老年人跌倒具有顯著相關(guān)性[3],而且異常的腦白質(zhì)體積越大,發(fā)生跌倒的可能性也越大[12-13]。本研究結(jié)果顯示跌倒風(fēng)險(xiǎn)組患者的全腦平均FA值明顯低于對(duì)照組,進(jìn)一步說(shuō)明了跌倒風(fēng)險(xiǎn)組老年人具有更顯著的腦白質(zhì)異常,同時(shí)說(shuō)明正常表現(xiàn)白質(zhì)區(qū)域也可能存在微觀損害。Koo等[8]研究發(fā)現(xiàn)存在跌倒風(fēng)險(xiǎn)的患者(Tinetti量表得分<25),其額頂皮質(zhì)通路、胼胝體膝部和壓部、扣帶回后部、額葉前部和眶額通路以及連接額-頂-顳葉的縱向通路均可見(jiàn)FA值減低。本研究結(jié)果與其部分一致,筆者發(fā)現(xiàn)跌倒風(fēng)險(xiǎn)組的右側(cè)鉤束、胼胝體膝部、體部及壓部、雙側(cè)放射冠前部、右側(cè)放射冠上部、右側(cè)上縱束、左側(cè)扣帶回FA值減低。
腦白質(zhì)損傷時(shí),各功能區(qū)纖維聯(lián)絡(luò)中斷,導(dǎo)致相應(yīng)的功能障礙[14-15]。WHLs可引起不同程度的認(rèn)知功能損害[1]。本研究跌倒風(fēng)險(xiǎn)組的MMSE、MoCA 評(píng)分均低于對(duì)照組,其中跌倒風(fēng)險(xiǎn)組胼胝體膝部、體部及壓部、右側(cè)放射冠前部、右側(cè)上縱束、左側(cè)扣帶回的平均FA值與MoCA呈正相關(guān)。胼胝體是連接雙側(cè)大腦半球最大的連合纖維,是雙側(cè)大腦半球之間情感、認(rèn)知及其他功能等信息傳遞、整合的重要通道。胼胝體膝部與認(rèn)知功能、調(diào)制情緒刺激和多種記憶功能有關(guān)[16]。前放射冠參與了一系列認(rèn)知過(guò)程,包括執(zhí)行功能,在姿勢(shì)控制與跌倒風(fēng)險(xiǎn)的認(rèn)知控制中起到關(guān)鍵性作用[17]。上縱束是人腦最大的聯(lián)絡(luò)纖維,是連接額葉與顳、頂葉最重要的纖維束[18],輕度認(rèn)知障礙患者(mild cognitive impairment, MCI)的認(rèn)知功能減退可能與上縱束微觀結(jié)構(gòu)受損有關(guān)[19]。扣帶束是邊緣系統(tǒng)最重要的腦白質(zhì)纖維束,其中扣帶回被認(rèn)為是默認(rèn)網(wǎng)絡(luò)的核心區(qū)域[20],與情節(jié)記憶功能密切相關(guān),而情節(jié)記憶與認(rèn)知功能存在相關(guān)性,是MCI最早期也是最明顯的神經(jīng)心理改變[19]。
表1 跌倒風(fēng)險(xiǎn)組及對(duì)照組腦白質(zhì)纖維束平均FA值與MoCA量表的相關(guān)性Tab. 1 The correlation between mean FA of white matter tracts and MoCA scores in the fall risk group and contrast group
表2 跌倒風(fēng)險(xiǎn)組白質(zhì)纖維束平均FA值與Tinetti步態(tài)量表、Tinetti平衡量表、TUGT的相關(guān)性Tab. 2 The correlation between mean FA of white matter tracts and Tinetti Gait Analysis, Tinetti Balance Analysis and TUGT in the fall risk group
WHLs可引起平衡、步態(tài)功能異常[21],進(jìn)而增加跌倒風(fēng)險(xiǎn)[22-23]。Tinetti步態(tài)和平衡量表通過(guò)測(cè)試患者的步態(tài)和平衡功能預(yù)測(cè)老年人跌倒的危險(xiǎn)性[8]。本研究結(jié)果顯示右側(cè)鉤束的平均FA值與Tinetti平衡量表呈正相關(guān);右側(cè)鉤束、胼胝體體部、胼胝體壓部、左側(cè)扣帶回的平均FA值與Tinetti步態(tài)量表呈正相關(guān)。TUGT常用于測(cè)定老年病人的平衡功能及體能,對(duì)跌倒有預(yù)測(cè)作用[24],TUGT值越大,提示運(yùn)動(dòng)能力越差。本研究結(jié)果顯示胼胝體體部及左側(cè)扣帶回的平均FA值與TUGT呈負(fù)相關(guān)。Koerte等[25]研究認(rèn)為經(jīng)胼胝體的運(yùn)動(dòng)纖維束損傷可能與運(yùn)動(dòng)控制和協(xié)調(diào)能力減弱有關(guān)。胼胝體壓部與運(yùn)動(dòng)執(zhí)行功能密切相關(guān),對(duì)運(yùn)動(dòng)能力下降具有最佳的預(yù)測(cè)效果。胼胝體壓部白質(zhì)纖維受損導(dǎo)致視空間信息在大腦半球的整合障礙,進(jìn)而影響運(yùn)動(dòng)功能[26]。鉤束是傳導(dǎo)額葉執(zhí)行控制功能的主要纖維束之一,有研究認(rèn)為WHLs與運(yùn)動(dòng)損害的關(guān)系是通過(guò)對(duì)執(zhí)行功能的影響介導(dǎo)的[12, 27]。
總之,本研究顯示,跌倒風(fēng)險(xiǎn)組的全腦平均FA值及9條腦白質(zhì)纖維束平均FA值低于對(duì)照組,并與認(rèn)知、步態(tài)、平衡功能存在一定的相關(guān)性。DTI定量分析可用于識(shí)別老年人WMLs相關(guān)性跌倒患者的顱腦結(jié)構(gòu)特點(diǎn),為具有跌倒風(fēng)險(xiǎn)的WMLs患者的識(shí)別、判斷病情及預(yù)后評(píng)價(jià)提供了重要的影像學(xué)依據(jù)。
致謝:感謝中國(guó)科學(xué)院自動(dòng)化研究所劉勇博士在圖像處理中給予的大力幫助!
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A study of white matter lesions in older people with fall risk using diffusion tensor imaging
SHEN Hui-cong1, LI Zheng-ran1, CHANG Tian-jing2, ZHANG Ning3,4,WANG Chun-xue3,4, MA Jun1*
20 Apr 2016, Accepted 18 May 2016
Objective: To analyze the diffusion tensor imaging (DTI) and clinical characteristic of the aged who had white matter lesions with fall risks, quantify the fall risk index and provide a basis for fall precautions. Materials and Methods: People aged more than 60 years old with brain white matter lesions from Beijing Tiantan Hospital, Capital Medical University, were included in study, according to the Tinetti Balance and Gait Analysis, 15 patients were divided into experimental group (Tinetti<25) and 29 contrast group (Tinetti≥25). The significantly different white matter fiber tracts were identified by Tract Based Spatial Statistics (TBSS) and were also made correlation analysis with MoCA, MMSE, Tinetti Gait Analysis, Tinetti Balance Analysis and TUGT. Results: There was statistic significance in the score of MMSE (t=2.806, P=0.008) and MoCA (t=2.890, P=0.006)between two groups with white matter lesions. In subjects with risk of falls, the mean FA of whole brain was lower than that of contrast group (t=2.862, P=0.007), and was positively correlated with MMSE (r=0.533, P=0.041) and MoCA (r=0.642, P=0.010). Significantly abnormal FA clusters (representing loss of WM integrity) of patients with risk of falls were seen in the right fasciculus uncinatus, genu, body and splenium of corpus callosum, both anterior corona radiate, right superior corona radiate, right superior longitudinal fasciculus and left cingulate gyrus. The mean FA of corpus callosum-genu, right superior corona radiate,body of corpus callosum, splenium of corpus callosum, right superior longitudinal fasciculus and left cingulate gyrus were positively correlated with MoCA scores in those with risk of falls(P<0.05). The mean FA of right fasciculus uncinatus (r=0.562,P=0.029) was positively correlated with Tinetti Balance Analysis. The mean FA of right fasciculus uncinatus (r=0.572, P=0.026),body of corpus callosum (r=0.538, P=0.038), splenium of corpus callosum (r=0.580, P=0.023) and left cingulate gyrus (r=0.520,P=0.047) were positively correlated with Tinetti Gait Analysis. The mean FA of body of corpus callosum (r=-0.582, P=0.023)and left cingulate gyrus (r=-0.538, P=0.039) were negatively correlated with TUGT. Conclusion: In subjects with risk of falls,the mean FA of whole brain and some white matter fiber tracts decreased, these differences were correlated with cognition,balance and gait. Therefore, DTI can identify the structural changes in brain of those with risk of falls and quantify the fall risk index.
Aged; Leukoencephalopathies; Accidental falls; Diffusion tensor imaging
1. 首都醫(yī)科大學(xué)附屬北京天壇醫(yī)院放射科,北京 100050
2. 北京大學(xué)首鋼醫(yī)院放射科,北京100144
3. 首都醫(yī)科大學(xué)附屬北京天壇醫(yī)院神經(jīng)精神醫(yī)學(xué)與臨床心理科、神經(jīng)內(nèi)科,北京 100050
4. 首都醫(yī)科大學(xué)附屬北京天壇醫(yī)院國(guó)家神經(jīng)系統(tǒng)疾病臨床研究中心,北京100050
馬軍,E-mail:dr_ma@sina.com
2016-04-20
R445.2;R742
A
10.12015/issn.1674-8034.2016.06.005