[摘要]"目的
基于磁共振成像(MRI)后處理技術(shù),對(duì)雙重病理(DP)致耐藥性顳葉癲癇(TLE)患者腦區(qū)結(jié)構(gòu)變化特征進(jìn)行自動(dòng)精細(xì)腦分割及腦區(qū)數(shù)據(jù)定量分析。
方法"選擇2017年1月—2023年12月我院DP致TLE患者35例設(shè)為T(mén)LE-DP組,并選擇同期32例健康成年人為對(duì)照組。收集兩組受試者的MRI圖像資料,進(jìn)行自動(dòng)精細(xì)腦分割及腦區(qū)數(shù)據(jù)定量分析。比較兩組受試者各腦區(qū)的體積、體積分?jǐn)?shù)、皮質(zhì)厚度、皮質(zhì)表面積及皮質(zhì)曲率,使用受試者工作特征(ROC)曲線及曲線下面積(AUC)評(píng)估上述指標(biāo)對(duì)DP致TLE的診斷效能。
結(jié)果"自動(dòng)精細(xì)腦分割及腦區(qū)數(shù)據(jù)定量分析顯示,兩組受試者30個(gè)腦區(qū)體積、12個(gè)腦區(qū)體積分?jǐn)?shù)、2個(gè)腦區(qū)皮質(zhì)厚度、11個(gè)腦區(qū)皮質(zhì)表面積、3個(gè)腦區(qū)皮質(zhì)曲率,以及21個(gè)海馬亞區(qū)體積和1個(gè)海馬亞區(qū)體積分?jǐn)?shù)差異顯著(t=-2.151~3.882,P<0.05)。ROC曲線分析顯示,部分腦區(qū)體積、腦區(qū)皮質(zhì)表面積和海馬亞區(qū)體積對(duì)DP致TLE診斷效能較高(AUC>0.7)。
結(jié)論"基于MRI后處理技術(shù)的自動(dòng)精細(xì)腦分割及腦區(qū)數(shù)據(jù)定量分析對(duì)DP致TLE患者的診斷價(jià)值較高。
[關(guān)鍵詞]"癲癇,顳葉;圖像處理,計(jì)算機(jī)輔助;磁共振成像;皮質(zhì)發(fā)育畸形;海馬;硬化
[中圖分類號(hào)]"R742.1
[文獻(xiàn)標(biāo)志碼]"A
Structural features of brain regions in temporal lobe epilepsy with dual pathology: An analysis based on MRI postprocessing technology
KONG Yu, LIU Ruihan, YAO Lei, WANG Shuzhen, LIU Chunzhao, KONG Qingxia
(College of Materials Science and Engineering, Qingdao University, Qingdao 266071, China)
[ABSTRACT]Objective To perform automatic fine brain segmentation and brain region quantitative analysis based on magnetic resonance imaging (MRI) postprocessing technology, and to investigate the structural features of brain regions in drug-resis-
tant temporal lobe epilepsy (TLE) with dual pathology (DP).
Methods Thirty-five TLE patients with DP treated at our hospital from January 2017 to December 2023 were selected as TLE-DP group, and 32 healthy adults from the same period were selected as control group. The MRI images of the two groups were collected for automatic fine brain segmentation and brain region quantitative analysis. The volume, volume fraction, cortical thickness, cortical surface area, and cortical curvature of each brain region were compared between the two groups. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the above parameters for the efficacy of diagnosis of TLE with DP.
Results Automatic fine brain segmentation and brain region quantitative analysis indicated that the volume of 30 brain regions, volume fraction of 12 brain regions, cortical thickness of 2 brain regions, cortical surface area of 11 brain regions, cortical curvature of 3 brain regions, volume of 21 hippocampal subregions, and volume fraction of 1 hippocampal subregion were significantly different between the two groups (t=-2.151-3.882,Plt;0.05). The ROC curve analysis showed that the volume and the cortical surface area of some brain regions and the vo-
lume of some hippocampal subregions were effective in the diagnosis of TLE with DP (AUCgt;0.7).
Conclusion Automatic fine brain segmentation and brain region quantitative analysis based on MRI postprocessing technology are of high diagnostic value in TLE patients with DP.
[KEY WORDS] Epilepsy, temporal lobe; Image processing, computer-assisted; Magnetic resonance imaging; Malformations of cortical development; Hippocampus; Sclerosis
顳葉癲癇(temporal lobe epilepsy,TLE)是最常見(jiàn)的耐藥性癲癇,外科手術(shù)是其最有效的治療方法。手術(shù)治療的目的除最大程度控制癲癇發(fā)作,還應(yīng)盡量減少TLE引發(fā)的患者神經(jīng)以及心理的損傷[1-2]。雙重病理(DP)致TLE是指癲癇患者除存在海馬硬化(HS)外,還存在第二個(gè)導(dǎo)致癲癇的主要病灶,如腦腫瘤、腦血管畸形、腦膠質(zhì)瘢痕、邊緣性/Rasmussen腦炎或局灶性腦皮質(zhì)發(fā)育畸形(FCD)等,其中FCD最為常見(jiàn)[3]。有研究發(fā)現(xiàn)DP是導(dǎo)致患者癲癇手術(shù)失敗及影響預(yù)后重要因素之一[4-9]。癲癇的發(fā)生常與不同腦區(qū)及亞區(qū)的結(jié)構(gòu)改變有關(guān),主要表現(xiàn)為腦深部灰質(zhì)體積或形態(tài)改變及腦區(qū)的皮
質(zhì)厚度、表面積或折疊模式改變等。MRI是癲癇診
療中的基本檢查,傳統(tǒng)MRI檢出海馬早期的細(xì)微的病變或識(shí)別海馬外致癇灶具有一定困難[10],且人工判讀MRI圖像對(duì)于腦形態(tài)改變的診斷存在一定主觀性。腦形態(tài)改變定量分析是基于MRI圖像后處理軟件,測(cè)量顱腦內(nèi)部結(jié)構(gòu)的體積、表面積等以分析腦形態(tài)改變。該分析方法可作為診斷TLE的重要影像學(xué)分析方法。腦分割則是將MRI圖像中腦組織劃分成多個(gè)不重疊的腦區(qū)或腦亞區(qū),是進(jìn)行腦形態(tài)改變定量分析的前提[11]。腦分割方法分為人工腦分割和自動(dòng)腦分割,自動(dòng)腦分割包括基于腦圖譜的腦分割、基于人工智能深度學(xué)習(xí)的腦分割和精細(xì)腦分割。目前對(duì)于精細(xì)腦分割的研究較少,本研究使用上海聯(lián)影醫(yī)療科技有限公司開(kāi)發(fā)的人工智能全腦定量分析軟件,對(duì)結(jié)構(gòu)MRI圖像進(jìn)行自動(dòng)精細(xì)腦分割及各腦區(qū)數(shù)據(jù)定量分析,進(jìn)而分析DP致TLE患者各腦區(qū)結(jié)構(gòu)特征的改變,指導(dǎo)臨床制定該類患者的個(gè)體化診療計(jì)劃。
1"資料與方法
1.1"一般資料
回顧性分析2017年1月—2023年12月就診于濟(jì)寧醫(yī)學(xué)院附屬醫(yī)院癲癇診療中心的35例耐藥性TLE患者的資料?;颊哐芯考{入標(biāo)準(zhǔn):①依據(jù)《中國(guó)成人局灶性癲癇規(guī)范化診治指南(2022)》[12]確診為T(mén)LE者;②有TLE發(fā)作的典型臨床表現(xiàn)及與之對(duì)應(yīng)的腦電圖證據(jù)者;③行標(biāo)準(zhǔn)前內(nèi)側(cè)顳葉切除術(shù)(ATL)且術(shù)后病理診斷為DP者;④術(shù)前有高分辨MRI癲癇序列成像結(jié)果,術(shù)后行顱腦MRI或者CT檢查者。排除標(biāo)準(zhǔn):①既往有顱腦手術(shù)史者;②MRI成像質(zhì)量差或臨床資料不完整者;③DP與TLE灶非同側(cè)者。將上述患者設(shè)為T(mén)LE-DP組,另選擇同期行MRI檢查的32例健康成年人設(shè)為對(duì)照組。收集兩組受試者的年齡、性別、MRI圖像(T1WI 3D MPRAGE序列以及高分辨頭顱橫斷面及冠狀面的T1WI、T2WI、T2WI-FLAIR序列)結(jié)果,以及TLE-DP組患者的首次癲癇發(fā)作年齡、發(fā)作年限、發(fā)作類型、腦電圖結(jié)果及術(shù)后病理診斷結(jié)果。
1.2"圖像分析
將每位受試者的MRI圖像導(dǎo)入上海聯(lián)影醫(yī)療科技有限公司所研發(fā)的人工智能MRI圖像后處理軟件[11]進(jìn)行自動(dòng)精細(xì)腦分割,輸出結(jié)果如下:顳葉可分為22亞區(qū)(包括雙側(cè)海馬、海馬旁回、杏仁核、內(nèi)嗅皮質(zhì)、梭狀回、顳極、顳上回、顳中回、顳下回、顳上回坡部和顳橫回),額葉20亞區(qū),頂葉12亞區(qū),枕葉8亞區(qū),扣帶回8亞區(qū),島葉2亞區(qū),皮質(zhì)下灰質(zhì)12亞區(qū),以及腦白質(zhì)、腦室、小腦及其他結(jié)構(gòu),共計(jì)106亞區(qū)。所有分割結(jié)果均由3位經(jīng)驗(yàn)超過(guò)十年的神經(jīng)影像學(xué)診斷醫(yī)師進(jìn)行復(fù)核。繼續(xù)使用該軟件通過(guò)腦區(qū)數(shù)據(jù)定量分析測(cè)量每位受試者腦區(qū)的體積、體積分?jǐn)?shù)、腦皮質(zhì)厚度、表面積及皮質(zhì)曲率,以及海馬亞區(qū)體積、體積分?jǐn)?shù)等。
1.3"統(tǒng)計(jì)學(xué)處理
采用SPSS 26.0軟件對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析,符合正態(tài)分布的計(jì)量資料以±s表示,兩組間比較采用兩獨(dú)立樣本t檢驗(yàn),使用受試者工作特征(ROC)曲線評(píng)估MRI圖像后處理軟件對(duì)DP致TLE的診斷效能。以P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。
2"結(jié)""果
2.1"兩組受試者M(jìn)RI圖像腦區(qū)數(shù)據(jù)定量分析結(jié)果比較
TLE-DP組35例患者,男12例,女23例;平均(29.29±1.91)歲;首次癲癇發(fā)作年齡(15.86±2.03)歲;發(fā)作年限(13.40±1.62)年;所有患者中局灶性發(fā)作32例,全面性發(fā)作3例;左側(cè)TLE 19例,右側(cè)TLE 16例。視頻腦電圖顯示15例患者左側(cè)腦區(qū)異常放電,15例患者右側(cè)腦區(qū)異常放電,5例患者存在多腦區(qū)異常放電。所有患者均行ATL治療,術(shù)后病理診斷均為HS合并FCD。對(duì)照組32例受試者,男17例,女15例;平均(26.53±1.54)歲。兩組受試者30個(gè)腦區(qū)體積、12個(gè)腦區(qū)體積分?jǐn)?shù)、2個(gè)腦區(qū)皮質(zhì)厚度、11個(gè)腦區(qū)皮質(zhì)表面積、3個(gè)腦區(qū)皮質(zhì)曲率,及21個(gè)海馬亞區(qū)體積和1個(gè)海馬亞區(qū)體積分?jǐn)?shù)差異顯著(t=-2.151~3.882,P<0.05)。見(jiàn)表1、2。
2.2"ROC曲線評(píng)估各腦區(qū)指標(biāo)對(duì)DP致TLE的診斷效能
通過(guò)ROC曲線計(jì)算各腦區(qū)指標(biāo)對(duì)DP致TLE診斷效能的曲線下面積(AUC),結(jié)果顯示在腦區(qū)體積中右側(cè)丘腦、胼胝體中部、左側(cè)腹側(cè)間腦、右側(cè)腹側(cè)間腦及右側(cè)顳下回,腦區(qū)皮質(zhì)表面積中左側(cè)顳下回,海馬亞區(qū)體積中右側(cè)海馬前下托、左側(cè)海馬尾、右側(cè)海馬頭、右側(cè)齒狀回、右側(cè)海馬體、右側(cè)海馬傘、右側(cè)海馬CA4亞區(qū)、右側(cè)海馬尾、左側(cè)海馬體、右側(cè)海馬CA3亞區(qū)、右側(cè)海馬CA1亞區(qū)、左側(cè)海馬CA4亞區(qū)、左側(cè)海馬CA3亞區(qū)及右側(cè)海馬杏仁核過(guò)渡區(qū)對(duì)DP致TLE均有較高診斷效能(AUC=0.701~0.759)。見(jiàn)圖1。
3"討""論
既往研究發(fā)現(xiàn),與單純HS致TLE相比,DP致TLE患者術(shù)后癲癇復(fù)發(fā)的風(fēng)險(xiǎn)更高,可能需要接受二次手術(shù)來(lái)改善癲癇發(fā)作的情況[7,13]。反之,當(dāng)僅存一個(gè)致癇灶時(shí),采取限制性手術(shù)可確保癲癇發(fā)作得到控制的同時(shí)減少患者神經(jīng)及精神損傷[1,14-15]。因此,精準(zhǔn)定位致癇灶是癲癇術(shù)前評(píng)估的重要部分,其直接影響手術(shù)預(yù)后[16]。探測(cè)致癇灶最常用的方法是發(fā)現(xiàn)患者腦形態(tài)學(xué)改變,MRI是各癲癇中心術(shù)
前評(píng)估腦形態(tài)結(jié)構(gòu)改變的常規(guī)腦成像方法?;?/p>
MRI圖像的腦精細(xì)分割和定量分析等后處理技術(shù)可更準(zhǔn)確地提供患者病變腦區(qū)的信息。最初的自動(dòng)腦分割技術(shù)主要基于MRI中T1WI信號(hào)強(qiáng)度將腦分割為三種不同的組織,即灰質(zhì)、白質(zhì)和腦脊液[17]。由于大腦結(jié)構(gòu)的復(fù)雜性,僅基于MRI圖像信號(hào)強(qiáng)度的腦分割并不準(zhǔn)確,形態(tài)、位置或方向等更多的信息需要添加到分割算法中?;谏疃葘W(xué)習(xí)的自動(dòng)腦分割技術(shù)在特定腦區(qū)分割中具備較高的計(jì)算效率和穩(wěn)定性,但對(duì)大量不同腦區(qū)同時(shí)分割時(shí)腦區(qū)間界限劃分準(zhǔn)確性稍低。本研究所使用的自動(dòng)精細(xì)腦分割和定量分析軟件可通過(guò)多方位測(cè)算和局部修正,實(shí)現(xiàn)對(duì)各腦區(qū)界限的精準(zhǔn)劃分[11,18]。
在本研究中,TLE-DP組較對(duì)照組受試者出現(xiàn)多腦區(qū)體積減小,以顳葉(海馬、海馬旁回、顳上回、顳中回和顳下回)為著。既往研究發(fā)現(xiàn)海馬體積減小與HS病程進(jìn)展有關(guān),即年輕或處于病變?cè)缙诘腄P致TLE患者M(jìn)RI中海馬結(jié)構(gòu)正常,病理檢查僅表現(xiàn)為少量神經(jīng)細(xì)胞缺失[10],而年長(zhǎng)或者病程長(zhǎng)者M(jìn)RI圖像多表現(xiàn)為海馬體積萎縮,病理檢查多見(jiàn)大量神經(jīng)細(xì)胞缺失和膠質(zhì)細(xì)胞增生。本研究進(jìn)一步對(duì)TLE-DP組受試者海馬亞區(qū)體積進(jìn)行分析,發(fā)現(xiàn)多個(gè)海馬亞區(qū)體積減小,以CA1~4亞區(qū)和海馬前下托體積縮小為著,該結(jié)果可能對(duì)于評(píng)估DP致TLE中HS分型及患者語(yǔ)言記憶受損程度具有參考價(jià)值[19]。以往研究指出DP起病較早,在人腦發(fā)育階段即出現(xiàn)腦形態(tài)結(jié)構(gòu)的異常改變[20-21]。本研究中TLE-DP組受試者腦體積減小幾乎累及了大部分顳葉腦區(qū)及部分顳葉外腦區(qū),由此可推斷DP所影響的腦區(qū)中顳葉改變最大,是DP致TLE引發(fā)較明顯記憶、認(rèn)知和語(yǔ)言功能障礙的主要原因,這與既往研究結(jié)果一致[6]。大量研究報(bào)道稱丘腦是參與TLE形成的神經(jīng)環(huán)路中的重要神經(jīng)核團(tuán),并與顳葉海馬、
顳上回、顳中回、梭狀回等存在神經(jīng)連接[22-24]。本研究中TLE-DP組受試者丘腦體積明顯減小,提示TLE患者丘腦區(qū)存在明顯損傷,丘腦與顳葉神經(jīng)連接強(qiáng)度減弱,協(xié)同性減低。本研究中TLE-DP組受試者大腦皮質(zhì)厚度異常表現(xiàn)為顳上回皮質(zhì)增厚,這與DP中FCD的分布位置相符合,且從結(jié)果推斷TLE-DP組受試者以FCD Ⅱ型為主,其病理表現(xiàn)為病變區(qū)皮質(zhì)厚度增加,灰白質(zhì)交界區(qū)模糊,病變區(qū)和皮質(zhì)下白質(zhì)可見(jiàn)膠質(zhì)增生和脫髓鞘改變[25-26]。既往研究指出DP中FCD可發(fā)生在大腦任何部位,以額顳葉最多見(jiàn),其中FCDⅡ型在MRI上典型影像學(xué)表現(xiàn)為皮質(zhì)增厚,但FCD Ⅰ型在MRI上多表現(xiàn)為陰性結(jié)果,因此僅通過(guò)腦皮質(zhì)厚度判斷FCD具有一定局限性。另外,本研究發(fā)現(xiàn)部分腦區(qū)體積、腦區(qū)皮質(zhì)表面積和海馬亞區(qū)體積對(duì)DP致TLE的診斷效能較高,因此我們強(qiáng)調(diào)癲癇患者應(yīng)盡早行MRI檢查,通過(guò)自動(dòng)精細(xì)腦分割及腦區(qū)數(shù)據(jù)定量分析篩查DP致TLE高風(fēng)險(xiǎn)患者,并定位致癇灶[27-28]。
本研究存在一定局限性,首先本研究為單中心、回顧性研究,納入病例總數(shù)偏少,可能存在選擇偏倚;其次本研究?jī)H篩選了DP致TLE患者及健康受試者進(jìn)行對(duì)比研究,未將單純HS致TLE患者與DP致TLE患者進(jìn)行對(duì)比。后續(xù)我們還會(huì)進(jìn)行多中心研究擴(kuò)大樣本量,用以篩選DP致TLE的影像組學(xué)特征。
綜上所述,自動(dòng)精細(xì)腦分割技術(shù)可對(duì)腦MRI數(shù)據(jù)實(shí)現(xiàn)高速、準(zhǔn)確提取,并可自動(dòng)化輸出各腦區(qū)結(jié)構(gòu)定量數(shù)據(jù),對(duì)DP致TLE患者的診斷及致癇灶定位具有較高價(jià)值。
倫理批準(zhǔn)和知情同意:本研究涉及的所有試驗(yàn)均已通過(guò)濟(jì)寧醫(yī)學(xué)院附屬醫(yī)院科學(xué)倫理委員會(huì)的審核批準(zhǔn)(文件號(hào)2023-07-C010)。所有試驗(yàn)過(guò)程均遵照《赫爾辛基宣言》的條例進(jìn)行。受試對(duì)象或其親屬已經(jīng)簽署知情同意書(shū)。
作者聲明:孔鈺、劉瑞寒、劉春朝、孔慶霞參與了研究設(shè)計(jì);孔鈺、劉瑞寒、姚磊、王淑貞參與了論文的寫(xiě)作和修改。所有作者均閱讀并同意發(fā)表該論文,且均聲明不存在利益沖突。
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(本文編輯"范睿心"厲建強(qiáng))