蘭慧,李康*,呂發(fā)金
偏頭痛腦結(jié)構(gòu)和功能的MRI研究進展
蘭慧1,李康1*,呂發(fā)金2
作為一原發(fā)性頭痛,偏頭痛表現(xiàn)出特征性的單側(cè)、中、重度搏動性頭痛,并且隨著日常活動的增加而加劇,也常伴隨惡心嘔吐、畏光畏聲等神經(jīng)、胃腸、自主神經(jīng)癥狀。偏頭痛給患者和社會帶來負擔(dān),例如增加患者的環(huán)境敏感性、造成殘疾甚至喪失社會生產(chǎn)的能力。近年的神經(jīng)影像學(xué)發(fā)現(xiàn)頻繁的頭痛發(fā)作引起了腦結(jié)構(gòu)與功能的改變。該文將從MRI所顯示的偏頭痛腦結(jié)構(gòu)與功能異常作一次回顧性分析研究。
偏頭痛癥;磁共振成像
偏頭痛是常見神經(jīng)內(nèi)科原發(fā)性頭痛病,通常在青春期開始發(fā)作,作為一種可致殘性疾病,女性患病明顯多于男性,在男性中居第19 位,女性中居第12位[1]。其可能的發(fā)病機制學(xué)說:血管學(xué)說、皮層擴散性抑制(CSD)學(xué)說(關(guān)鍵環(huán)節(jié))、三叉神經(jīng)血管學(xué)說(目前最為認同)、中樞神經(jīng)系統(tǒng)學(xué)說。有文獻總結(jié):偏頭痛患者的腦白質(zhì)密度增高、體積增大,部分患者有腦實質(zhì)梗死病灶[2]。隨著MRI技術(shù)的發(fā)展[3],越來越多地從各個角度揭示出偏頭痛患者腦結(jié)構(gòu)和功能的異常,幫助人們更好地理解偏頭痛的發(fā)病機制。筆者主要從常規(guī)MRI、VBM、DTI、ReHo、ALFF這些MRI技術(shù)以及方法回顧偏頭痛患者的顱腦損害。
1.1 常規(guī)(magnetic resonance imaging,MRI)
偏頭痛長期以來被認為是一種良性腦功能疾病,后續(xù)逐漸在MRI圖像上發(fā)現(xiàn)腦結(jié)構(gòu)異常,表現(xiàn)為腦白質(zhì)異常(white matter abnormalities,WMAs)[4-5],即在T1WI等或稍低、T2WI高,F(xiàn)IAIR高的信號[6]。國內(nèi)最新研究,張陽等[7]對比觀察偏頭痛患者和正常人的顱腦MRI,研究顯示偏頭痛患者WMAs發(fā)生率明顯更高,且有先兆者高于無先兆者。有學(xué)者對偏頭痛進行隨訪9年的縱向研究,發(fā)現(xiàn)女性偏頭痛患者深部腦白質(zhì)病灶發(fā)病率更高。從以上研究可見偏頭痛病程、發(fā)作頻率、女性、先兆都是WMAs發(fā)生的獨立危險因素,可衡量腦損傷嚴重程度。相關(guān)研究統(tǒng)計報道額葉、腦干和小腦WMAs發(fā)生率最高[8],又進一步統(tǒng)計出約57.5%~86.5%偏頭痛患者在腦干的黑質(zhì)、紅核、中腦導(dǎo)水管周圍灰質(zhì)(PAG)可發(fā)現(xiàn)病灶[9]。目前WMAs發(fā)病機制不明確,這些腦白質(zhì)病變多發(fā)生在后循環(huán)區(qū)域,這似乎與偏頭痛可能的發(fā)病機理(皮層擴散性抑制,CSD)是相吻合的。CSD可激活基質(zhì)金屬蛋白酶9,增加血腦屏障的通透性,并通過谷氨酸能神經(jīng)遞質(zhì)的興奮性毒作用及鈣調(diào)細胞凋亡引起局部腦缺血,導(dǎo)致WMAs形成[10]。也有研究認為白質(zhì)病灶代表一種微血管病變,和低灌注、微血栓、免疫炎癥、線粒體功能紊亂等相關(guān)[11-12]。
1.2 基于體素的形態(tài)學(xué)(VBM)
即在體素水平對腦MR影像進行定量分析的技術(shù)。將采集的MRI梯度回波T1加權(quán)序列像在空間標(biāo)準化后進行圖像解剖分割,并用統(tǒng)計檢驗比較分析體素間差異,定量檢測腦灰質(zhì)和白質(zhì)的密度和體積。Valet等[13]觀察到偏頭痛患者額葉前部、前扣帶回、島回的灰質(zhì)體積減小,認為是神經(jīng)元萎縮導(dǎo)致。Rocca等[14]不僅發(fā)現(xiàn)前扣帶回、島葉灰質(zhì)密度減低,而且發(fā)現(xiàn)中腦導(dǎo)水管周圍灰質(zhì)、腦橋背側(cè)區(qū)域的灰質(zhì)體積增加,密度增高,提出不僅發(fā)生了神經(jīng)元異常,也發(fā)生了膠質(zhì)細胞的增生。Jin等[15]研究發(fā)現(xiàn)偏頭痛患者相較于對照組腦的左內(nèi)側(cè)前額葉皮質(zhì)(MPFC)、背側(cè)前扣帶回(DACC),右枕葉、小腦和腦干灰質(zhì)體積下降,但是只有DACC灰質(zhì)體積與偏頭痛患者病程呈負相關(guān),這與之前偏頭痛VBM研究結(jié)果一致[16-18]。前額葉皮質(zhì)(MPFC)是偏頭痛患者顱腦異常最突出的區(qū)域,它通過認知調(diào)節(jié)機制來調(diào)節(jié)淡化疼痛感覺。Schmitz等[19]利用VBM研究還發(fā)現(xiàn)MPFC的灰質(zhì)密度下降,并且和對任務(wù)反應(yīng)時間減慢相關(guān)。背側(cè)前扣帶回(DACC)被證實參與疼痛的認知反應(yīng)、情感體驗過程。提示偏頭痛患者這些參與疼痛形成、調(diào)節(jié)以及認知反應(yīng)、情感體驗過程的區(qū)域發(fā)生了結(jié)構(gòu)的異常。CSD被認為是刺激偏頭痛患者三叉神經(jīng)疼痛傳導(dǎo)的起始因素,并且導(dǎo)致了頭痛的發(fā)生[20]。提示枕葉的灰質(zhì)體積改變可能和反復(fù)發(fā)生的CSD相關(guān)。
1.3 DTI(擴散張量成像)
其原理是根據(jù)細胞內(nèi)外水分子的自由彌散運動成像,可以顯示腦白質(zhì)結(jié)構(gòu)主要是神經(jīng)細胞軸突的走行和結(jié)構(gòu)。 常用參數(shù)包括平均彌散率(MD)、部分各向異性(FA)等,代表局部彌散張量。MD代表磁場梯度方向上水分子的彌散性,MD值的大小與組織灌注情況、水分子的運動等因素有關(guān) 。FA 代表水分子各向異性成分占整個擴散張量的比例,是評估白質(zhì)完整性的指標(biāo)。FA值下降表明白質(zhì)纖維束的完整性被破壞,而MD值增加提示該區(qū)域的水分子屏障破壞。
Kara等[21]的DTI研究發(fā)現(xiàn)只有紅核ADC值高,推測該區(qū)域發(fā)生了其他常規(guī)影像學(xué)檢測不到的血管源性水腫,但不能確定紅核的異常是頭痛發(fā)作的原因或是發(fā)作帶來的結(jié)果。最新研究發(fā)現(xiàn)偏頭痛患者雙側(cè)丘腦前輻射、左側(cè)皮質(zhì)脊髓束、右側(cè)下縱束的MD值增加[22],其中右側(cè)丘腦前輻射、左側(cè)皮質(zhì)脊髓束MD值增加和偏頭痛病程呈正相關(guān),而FA值沒有陽性差異。但有其他研究發(fā)現(xiàn)胼胝體、視輻射、前額葉、腦干、小腦FA值下降,提示這些區(qū)域的白質(zhì)纖維束完整性受損[23]。對MD增加,F(xiàn)A值下降有兩種可能解釋,由于局部缺血導(dǎo)致水分子屏障破壞或是受損腦組織的白質(zhì)纖維束的繼發(fā)性改變,即沃勒氏變性[24]。也有研究者動態(tài)觀察偏頭痛治療前后DTI結(jié)果,下降的FA值逐漸恢復(fù),提示偏頭痛患者發(fā)生了白質(zhì)損傷,但經(jīng)有效治療其損傷是可逆的,為其治療提供重要的依據(jù)。
功能MRI (fMRI)是基于血氧水平依賴(BOLD)效應(yīng)的MRI。BOLD效應(yīng),即血液中氧合血紅蛋白具有抗磁性,而脫氧血紅蛋白具有順磁性,可導(dǎo)致血管內(nèi)外出現(xiàn)非均勻性磁場,T2弛豫時間縮短,MRI信號減小[25]。當(dāng)大腦皮層受到生理刺激,局部的氧和血紅蛋白相對增加,表現(xiàn)為該腦區(qū)的T2信號增加,反映神經(jīng)元活性與血流量變化。
2.1 BOLD
Cao等[26]研究發(fā)現(xiàn)腦干的紅核和黑質(zhì)的激活與枕葉的BOLD信號增加相關(guān)。Hadjikhani等[27]觀察到先兆偏頭痛患者紋狀體外皮層V3A的BOLD信號增加。這些結(jié)果可能和局部區(qū)域血管擴張導(dǎo)致的高灌注有關(guān),與枕葉的CSD對應(yīng)的枕葉皮層的神經(jīng)血管事件一致,即先發(fā)生枕葉皮層充血,產(chǎn)生高灌注,隨后發(fā)生低灌注,并以一定速度向周圍擴散。
2.2 局部一致性(ReHo)
基于fMRI的一種研究分析方法,用于研究靜息狀態(tài)下被觀察體素與相鄰體素之間神經(jīng)元活動一致性的情況,代表腦局部活動的差異性。國內(nèi)學(xué)者張茜等[28]發(fā)現(xiàn)有先兆偏頭痛(MA)組右丘腦、右殼核、右小腦、腦干的ReHo 值顯著降低,而右枕葉的ReHo值顯著增高,殼核可能發(fā)揮了疼痛處理及調(diào)節(jié)的作用,而先兆偏頭痛患者的發(fā)病機制包括中樞敏化作用及皮質(zhì)高反應(yīng)性。當(dāng)繼續(xù)研究無先兆偏頭痛[29],觀察到右側(cè)前額葉皮質(zhì)、右側(cè)海馬、右側(cè)丘腦、右側(cè)殼核的ReHo值顯著升高,提示發(fā)作間期疼痛處理及調(diào)節(jié)區(qū)域,應(yīng)激反應(yīng)相關(guān)腦區(qū)也存在功能異常。
2.3 ALFF
即低頻振蕩振幅,基于fMRI,是從能量角度反映大腦靜息態(tài)神經(jīng)元自發(fā)活動[30]。將時間序列用快速傅立葉變換轉(zhuǎn)換為頻域,依據(jù)頻帶對每個頻率的功率譜的平方根求均數(shù),在低頻范圍內(nèi)用平均振幅計算出ALFF值。Xue等[31]發(fā)現(xiàn)偏頭痛患者左扣帶回、雙側(cè)前額葉ALFF值下降,而右丘腦ALFF值升高。疼痛是一種復(fù)雜的感覺認知,和傷害性刺激傳入及痛覺感受并非呈線性關(guān)系。而前額葉參與調(diào)節(jié)控制痛覺的形成,扣帶回、丘腦參與疼痛傳導(dǎo)路徑,ALFF值異常提示這些區(qū)域神經(jīng)元活動性及興奮性的異常改變。Wang等[32]發(fā)現(xiàn)偏頭痛患者腦橋、右側(cè)島葉ALFF增加,而雙側(cè)枕葉、右側(cè)梭狀回、雙側(cè)中央后回ALFF值卻下降。頂葉、島葉異常提示感覺運動處理過程受累。枕葉是視覺形成的區(qū)域,包括大部分視覺皮層的解剖結(jié)構(gòu)。枕葉的ALFF異??赡芎推^痛的視覺先兆相關(guān)。
2.4 基于復(fù)雜網(wǎng)絡(luò)對偏頭痛患者腦功能的連通性研究
近年來,將圖論知識聯(lián)合fMRI成為研究熱點。人腦網(wǎng)絡(luò)由節(jié)點即腦區(qū),邊界區(qū)域之間的功能連接[33]。通過檢測到圖論系數(shù)的異常,來分析偏頭痛潛在的功能連接異常。平均聚類系數(shù),代表大腦功能分離的平均程度;特征路徑長度,反映大腦功能整合能力;介數(shù)中心度,反映節(jié)點在網(wǎng)絡(luò)中的重要性;同配系數(shù),度量連節(jié)點對的關(guān)系。小世界網(wǎng)絡(luò),是一種特殊網(wǎng)絡(luò),既有隨機網(wǎng)絡(luò)較小的特征路徑長度,又有規(guī)則網(wǎng)絡(luò)較高的聚類系數(shù)[34]。哈佛醫(yī)學(xué)院的學(xué)者Mainero等[35]研究偏頭痛靜息態(tài)腦功能網(wǎng)絡(luò),推論疼痛及其他軀感形成腦區(qū)與PAG的功能連接度增強,且增強程度與疼痛發(fā)作頻次呈正相關(guān);而疼痛調(diào)節(jié)區(qū)包括額葉皮層、前扣帶回、杏仁核等與PAG的功能連接度卻顯著減低。陳敦耀等[36]研究結(jié)果顯示,偏頭痛組的聚類系數(shù)大于對照組,可能是因為反復(fù)發(fā)作頭痛、畏光等造成,所以疼痛處理區(qū)域與視覺刺激的皮層之間相互連接更強,聚集程度較大,信息傳遞效率異常偏高。
各種MRI技術(shù)及研究方法應(yīng)用于偏頭痛患者腦結(jié)構(gòu)、腦功能改變的研究,一方面致力于揭示其發(fā)病機制,另一方面為其診斷、療效評價、預(yù)后提供切實可行的影像學(xué)依據(jù)。隨著MRI功能影像學(xué)的發(fā)展,偏頭痛腦結(jié)構(gòu)和功能異常的部位更清晰統(tǒng)一,有望為臨床提供可信的偏頭痛神經(jīng)影像學(xué)診斷標(biāo)準。目前研究已揭示其結(jié)構(gòu)和功能異常與臨床病程、發(fā)作頻率有關(guān),但其異常改變形成、相互影響過程不明,有待深入研究。目前橫向研究居多,樣本量不大,研究無明顯突破性進展。今后的研究方向可適當(dāng)轉(zhuǎn)向縱向研究,做深入觀察分析,同時擴大樣本量,有望清楚地闡明偏頭痛發(fā)病機制。
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Advances in the study of brain structure and function of migraine with MRI
LAN Hui1, LI Kang1*, Lü Fa-jin2
1Department of Radiology, Chongqing Municipal People's Hospital, Chongqing 400013, China
2Department of Radiology, First Aff i liated Hospital of Chongqing Medical University, Chongqing 630014, China
ACKNOWLEDGMENTSAdvanced research projects of project cstc (No. 2014jcyjA10120). Chongqing Municipal Planning Commission of medical scientif i c research projects (No. 2012-2-187, 20142089).
As an primary headache disorder, migraine is characteri zed by moderate to severe pain, which consists of unilateral and pulsating headache attacks that are typically aggravated by physical activity ,and accompanied by nausea and vomiting, photophobia, pho nophobia and other neurological, gastrointestinal, autonomic symptoms. Causes significant individual and societal burdens as a result of pain, such as environmental sensitivity, disability and even lost prod uctivity. Recently, advanced neuroimaging has led to an evolution in our perception of migraine pathophysiology. Numerous neuroima ging studies have detected alterations in brain structure and function in patients with migraine.In this article, we will make a retrospec tive analysis of the brain structure and function of migraine, which is shown by magnetic resonance imaging.
Migraine disorders; Magnetic resonance imaging
Li K, E-mail: likangdoctor@126.com
Received 14 July 2016, Accepted 6 Oct 2016
重慶市科委基礎(chǔ)與前沿研究計劃項目(編號:cstc2014jcyjA10120);重慶市衛(wèi)計委醫(yī)學(xué)科研計劃項目(編號:2012-2-187、20142089)
1. 重慶市人民醫(yī)院放射科,重慶400013
2. 重慶醫(yī)科大學(xué)附屬第一醫(yī)院放射科,重慶 630014
李康,E-mail:likangdoctor@126.com
2016-07-14
接受日期:2016-10-06
R445.2;R724
A
10.12015/issn.1674-8034.2016.11.016
蘭慧, 李康, 呂發(fā)金. 偏頭痛腦結(jié)構(gòu)和功能的MRI研究進展. 磁共振成像, 2016, 7(11): 872-875.*