張欽城,王廣文,郭岳霖,鄭曉紅,陳薇*
彌散峰度成像對急性腦梗死半暗帶診斷價值的臨床研究
張欽城1,王廣文2,郭岳霖3,鄭曉紅1,陳薇1*
目的探討磁共振彌散峰度成像技術(diffusion kurtosis imaging,DKI)對急性腦梗死半暗帶診斷、病情嚴重度判斷、療效觀察的臨床價值。材料與方法急性腦梗死43例,分為三組:超急性期(13例)、急性期(14例)、亞急性期(16例),行頭顱MRI、DTI、DKI、T2-FLAIR掃描,測量MK、MD圖的病灶面積及MK、MD值,以病灶對側正常鏡像區(qū)作為對照,經(jīng)對比及分析后,進行統(tǒng)計學分析。結果(1)三組MK圖異常信號區(qū)表現(xiàn)為不均勻、邊緣清晰的高信號,MD圖異常信號區(qū)則相反。(2)三組病灶區(qū)MK值升高、MD值下降與鏡像區(qū)比較有顯著性差異。(3)三組MK圖病灶面積明顯小于MD圖。二者重疊部分為匹配區(qū),非重疊部分為不匹配區(qū)。不匹配區(qū)出現(xiàn)率:超急性期組86.4%,急性期組92.8%,亞急性期組75%。(4)三組病灶區(qū)?MK明顯大于?MD。(5)三組病灶側匹配區(qū)的MK、MD值和?MK、?MD變化明顯大于不匹配區(qū)。(6)三組MK、MD面積和MK、MD值與腦梗死病情嚴重程度(NIHSS評分)呈顯著正相關和正相關。(7) 14例復查T2-FLAIR病灶:①同首次MK圖比較:10例基本一致,提示療效佳,4例明顯變大,提示療效差;②與首次MD圖比較:10例變小,提示療效佳,2例基本一致,提示穩(wěn)定,2例明顯變大,提示效果差。結論DKI可顯示急性腦梗死壞死區(qū)和缺血區(qū),對半暗帶有診斷價值;能評估病情嚴重程度;動態(tài)監(jiān)測可評價治療效果。
顱內栓塞和血栓形成;急性?。淮殴舱癯上?/p>
目前,腦血管疾病已成為威脅人類健康的三大疾病之一[1]。腦梗死發(fā)病率占全部腦血管病的75%,急性腦梗死占急性腦血管疾病的60%~80%[2]。最關鍵而有效的治療在于有效治療時間窗內早期溶栓治療,盡早恢復缺血半暗帶(ischemia penumbra,IP)腦組織的供血。不同的研究結果顯示IP存在的時間長短不一:有認為缺血后3~6 h[3],最近有研究可達到24 h,甚至48 h[4-7]。很多在睡眠中起病或無法確定起病的具體時間。因此應用缺血半暗帶的影像學改變指導超時間窗的溶栓治療已經(jīng)成為臨床研究熱點。
彌散張量成像(diffusion tensor imaging,DTI)的參數(shù)平均彌散系數(shù)(mean diffusivity,MD)反映組織細胞毒性水腫的范圍,顯示腦梗死缺血的范圍;彌散峰度成像(diffusion kurtosis imaging,DKI)的參數(shù)平均峰度(mean kurtosis,MK)則對細胞內細胞骨架結構的崩裂與線粒體水腫敏感,顯示壞死的區(qū)域?;謴推赥2-FLAIR異常信號區(qū)代表腦梗死的最終壞死區(qū)。本研究對急性腦梗死患者進行DTI、DKI、T2-FLAIR聯(lián)合檢查,為半暗帶的診斷、病情評估、療效判斷提供客觀依據(jù)。
搜集2014年10月至2015年12月在汕頭大學醫(yī)學院第二附屬醫(yī)院神經(jīng)內科住院治療的急性腦梗死患者43例,平均年齡63.9歲。其中男26例,平均年齡63.9歲;女17例,平均年齡64歲。記錄患者姓名、性別、年齡、發(fā)病時間、是否吸煙、合并有高血壓和糖尿病及心臟病等腦梗死危險因素、入出院時的美國國立衛(wèi)生研究院腦卒中量表評分(National Institutes of Health Stroke Scale,NIHSS)。
納入標準:(1)符合2010年中國急性缺血性腦卒中診治指南中缺血性腦卒中的診斷標準[2]:①急性起??;②局灶性神經(jīng)功能缺損,少數(shù)為全面神經(jīng)功能缺損;③癥狀和體征持續(xù)24 h以上;④排除非血管性腦部病變;⑤頭顱CT或磁共振排除腦出血和其他病變,有責任缺血灶。(2)常規(guī)MRI及DWI檢查明確為急性腦梗死。(3)首發(fā)急性腦梗死,可有陳舊性腔隙性腦梗死。(4)發(fā)病時間≤72 h。排除標準:(1)頭顱CT和(或)MRI檢查有腦出血、顱內感染、占位性病變、腦變性疾病、腦外傷等其他顱腦疾?。?2)合并非神經(jīng)系統(tǒng)的嚴重疾病,如心肺肝腎功能衰竭、血液系統(tǒng)疾病、嚴重電解質紊亂等;(3)發(fā)病時間大于72 h;(4)發(fā)病1個月復查發(fā)現(xiàn)首次腦梗死部位附近有新(再)發(fā)腦梗死者(影響T2-FLIAR檢測結果)。分組:根據(jù)患者發(fā)病時間[8],分為超急性期組(發(fā)病時間≤6 h)13例、急性期組(發(fā)病時間>6 h≤24 h)14例、亞急性期組(發(fā)病時間>24 h≤72 h) 16例。14例(超急性期組6例、急性期組4例、亞急性期組4例)患者到發(fā)病1個月時(恢復期)復查頭顱磁共振T2-FLIAR。
所有受檢者和(或)其家屬均對本研究知情同意簽署知情同意書;本研究獲得本院倫理委員會審核批準。
所有患者發(fā)病后均行頭顱CT檢查,排除腦出血;在發(fā)病72 h內均行頭顱T1WI、T2WI等常規(guī)序列掃描及DWI、DTI、DKI檢查。14例發(fā)病1個月時做T2-FLAIR檢查。
檢查前確認所有受檢患者無MRI檢查禁忌證。囑患者仰臥于檢查床上,以頭足位進入主磁場,將頭部置于線圈正中,用海綿固定好頭部,以避免頭部移動。
采用美國通用公司(GE)生產的Signa Excite HDxT 3.0 T磁共振機,用標準8通道頭線圈作發(fā)射及接收線圈。
(1)常規(guī)MR掃描序列及參數(shù):常規(guī)MR掃描包括軸面T1WI、T2WI、矢狀面T2WI。掃描參數(shù):常規(guī)SE序列T1-FLAIR (TR 2162 ms,TE 20.6 ms),矩陣320×256,F(xiàn)OV 240 mm×180 mm,層厚7 mm,層距1.5 mm;T2-FLAIR (TR 4420 ms,TE 112.1 ms),矩陣384×256,F(xiàn)OV 240 mm×180 mm,層厚7 mm,層距1.5 mm。(2) DWI序列及參數(shù):采用SE-EPI序列,TR 6000 ms,TE 98.6 ms,矩陣128×128,F(xiàn)OV 240 mm×240 mm,層厚7 mm,層距1.5 mm,共30層,NEX為2。(3) DTI、DKI掃描:采用梯度回波單次激發(fā)的回波平面成像序列(GRE-EPI序列),層厚:5 mm,間隔:0.5 mm,TR 4500 ms,TE 98.6 ms,F(xiàn)OV 240 mm×240 mm,矩陣128×128,體素大小為2 mm×2 mm×3 mm,進行DKI掃描,掃描層數(shù)18層,NEX為1,掃描時間3 min 5 s,擴散敏感梯度場施加的方向為15個,每個方向的b值均有三個值(0、1000、2000 s/mm2)。DKI掃描同時獲得DTI的MD和MK圖像及數(shù)值。圖像面積單位:mm2,MD值的單位為μm2/ms。(4) T2-FLAIR掃描:采用FLAIR Fast序列,TR 8602 ms,TE 122 ms,矩陣為288×160,F(xiàn)OV 240 mm×240 mm,層厚7 mm,層間距1.5 mm。
將掃描的DKI 序列原始DICOM 數(shù)據(jù)傳輸至在GE ADW4.6工作站,使用GE 醫(yī)療集團提供的Functool 9軟件包的處理軟件進行圖像處理。(1)選擇基底節(jié)層面進行閾值設定,設定以保留最高信噪比為原則,設定上限達到盡量保留全腦實質范圍并去除非腦組織,下限剛好消除背景噪聲;(2)填上MR 掃描的參數(shù)b (0,1000,2000 s/mm2)及b0的數(shù)目后,計算機自動計算生成DKI的MK參數(shù)圖及DTI的MD參數(shù)圖;(3)所有病例進行手繪感興趣區(qū)(region of interest,ROI),多發(fā)病灶者選擇大面積的病灶。測量時注意盡量避開腦溝、腦室區(qū)域。根據(jù)掃描MK圖、MD圖信號異常區(qū)的實際面積(mm2)大小,將MK圖信號異常區(qū)與MD圖信號異常區(qū)的重疊部位設為匹配區(qū),不重疊部位設為不匹配區(qū),采用ROI法。分別測量病灶側匹配區(qū)和不匹配區(qū)以及對側與病灶相對應的鏡像區(qū)(包括匹配區(qū)和不匹配)的MK值和MD值(分別測量3次、取平均值)。記錄首次MK和MD圖像上異常信號區(qū)域面積(mm2)、MK值和MD值(μm2/ms)、?MK和?MD*;14例發(fā)病1個月時復查T2-FLAIR異常信號面積(mm2)。根據(jù)各參量的均值,計算腦梗死區(qū)域各變量的變化率。*?MK、?MD為MK及MD值的變化幅度,其計算公式:參量變化率=|X病灶側-X鏡像側|/X鏡像側×100%(X代表不同的擴散參量)。
面積的測量:使用GE ADW4.6工作站及GE 醫(yī)療集團提供的Functool 9軟件包的面積測量工具對MD圖、MK圖及T2-FLAIR圖中病灶的異常信號區(qū)進行人工勾畫、測量面積。具體操作是:由2名主治資格以上的影像科醫(yī)師在單盲和標準窗寬窗位下勾畫、測量MRI參數(shù)圖的異常信號面積,然后取兩者平均值作為最終數(shù)據(jù)。
應用SPSS 22.0進行統(tǒng)計分析。(1)病灶區(qū)與鏡像區(qū)MK值和MD值的比較、病灶匹配區(qū)與不匹配區(qū)的MK值和MD值的比較、病灶區(qū)MK面積與MD面積的比較、病灶匹配區(qū)與不匹配區(qū)?MK(MK的變化幅度)和?MD (MD的變化幅度)的比較、病灶區(qū)?MK與?MD的比較、復查T2-FLAIR病灶面積與首次MK病灶面積和MD病灶面積的比較均采用t檢驗。(2) MK病灶面積和MD病灶面積、病灶側MK值升高和MD值下降與病情NIHSS評分的相關性采用Spearman相關分析。(3)以P<0.05為差異有統(tǒng)計學意義。
超急性期組、急性期組、亞急性期組三組MK圖病灶區(qū)表現(xiàn)為高信號、不均勻、邊緣清晰,MD圖病灶區(qū)均表現(xiàn)為低信號、較均勻、邊緣模糊(圖1)。
MK圖病灶區(qū)面積(217.26±320.807) mm2明顯小于MD圖病灶區(qū)面積(398.21±586.762) mm2,P<0.01。大部分MK圖病灶區(qū)小于MD圖病灶區(qū),MK圖病灶區(qū)=MD圖病灶區(qū)部分為匹配區(qū),MD圖病灶區(qū)大于MK圖病灶區(qū)部分為不匹配區(qū)。不匹配區(qū)的出現(xiàn)率超急性期組86.4% (11/13)、急性期組92.8% (13/14)、亞急性期組75% (12/16)(圖1,2)。
病灶匹配區(qū)和不匹配區(qū)MK值顯著高、MD值顯著低于鏡像區(qū)正常組織(P值均<0.01;表1)。提示與正常組織比較,腦梗死病灶區(qū)顯示出MK值和MD值的變化。
三組的病灶(匹配區(qū)和不匹配區(qū)) ?MK與?MD比較均有顯著性差異(P值均<0.01;表2)。提示MK值異常幅度顯著大于MD值異常幅度。
三組的病灶MK值和MD值、?MK和?MD,匹配區(qū)與不匹配區(qū)比較有顯著性差異(P值均<0.01;表3,4)。提示MK值和MD值變化、MK值和MD值異常幅度匹配區(qū)重于不匹配區(qū)。
?MK和?MD與NIHSS評分呈正相關,r值分別為0.345和0.343,P值均<0.05;MK面積和MD面積與NIHSS評分呈顯著正相關,r值分別為0.618和0.735,P值均<0.01。提示 ?MK和?MD、MK面積及MD面積能夠呈現(xiàn)腦梗死病情的嚴重程度。
14例(三組分別為6例、4例、4例)發(fā)病1月時復查的T2-FLAIR圖像病灶面積,(1)與首次MK病灶面積比較:10例基本一致提示壞死區(qū)沒有擴大、治療效果好;4例明顯增大提示壞死區(qū)擴大。(2)與首次MD病灶面積比較:10例明顯縮小提示缺血半暗帶恢復、治療效果好;2例基本一致提示壞死區(qū)沒有擴大、效果好;2例明顯增大提示壞死區(qū)擴大(圖3~5)。提示重復檢查評估治療效果。
圖1 女,81歲,發(fā)病5 h。A:MK圖異常病灶區(qū),為不均勻性高信號,邊緣清晰;MK圖病灶面積為832 mm2;MK面積明顯小于MD,有明顯不匹配區(qū)。B:MD圖異常病灶區(qū),為均勻低信號區(qū),邊緣模糊;MD圖病灶面積為2361 mm2 圖2 男,80歲,發(fā)病12 h。A:MD圖病灶面積為91 mm2。B:MK圖病灶面積為88 mm2。MK與MD面積基本相同,無明顯不匹配區(qū) 圖3 男,57歲,發(fā)病24 h。A:首次MD圖異常面積為191 mm2。B:首次MK圖異常面積為53 mm2。C:復查T2-FLAIR最終梗死面積為50 mm2。復查T2-FLAIR面積基本與首次MK面積相等,小于首次MD面積,提示梗死面積無增大,治療效果好Fig. 1 A case of 81-year-old women, 5 hours from stroke onset. A: MK showed a hyperintense lesion with significant intense contrast different and clear boundary. The area of MK lesion was 832 mm2. The areas of MK lesion were much smaller than MD lesion, and there was significant MD/MK mismatch. B:MD showed a hypointense lesion without significant intense contrast different and fuzzy boundaries. The area of MD lesion was 2361 mm2. Fig. 2 A case of 80-year-old man, 12 hours from stroke onset. A: The area of MD lesion was 91 mm2. B: The area of MK lesion was 88 mm2. The areas of MK and MD lesions were similar, and there was no significant MD/MK mismatch. Fig. 3 A case of 57-year-old man, 24 hours from stroke onset. A: The area of MD lesion at the first visit was 191 mm2. B: The area of MK lesion at the first visit was 53 mm2. C: The area of T2-FLAIR at the final visit was 50 mm2. The areas of followup T2-FLAIR lesion and the MK lesion at the first visit were similar, and much smaller than MD lesion at the first visit. It suggested that no expansion of the original lesion and therapeutic effect was good.
圖4 男,66歲,發(fā)病24 h。A:首次MD圖異常面積為130 mm2。B:首次MK圖異常面積為41 mm2。C:復查T2-FLAIR最終梗死面積為72 mm2。復查T2-FLAIR面積大于首次MK面積,小于首次 MD面積,提示梗死區(qū)增大(但未超過原來缺血區(qū)) 圖5 女,50歲,發(fā)病8 h。A:首次MD圖異常面積為75 mm2。B:首次MK圖異常面積為42 mm2。C:復查T2-FLAIR最終梗死面積為93 mm2。復查T2-FLAIR面積大于首次MK面積,大于MD面積,提示最終梗死面積大于原來梗死區(qū)并增大到整個半暗帶區(qū)以外,腦梗死病情進展Fig. 4 A case of 66-year-old man, 24 hours from stroke onset. A: The area of MD lesion at the first visit was 130 mm2. B: The area of MK lesion at the first visit was 41 mm2. C: The area of T2-FLAIR at the final visit was 72 mm2. The areas of follow-up T2-FLAIR lesion were bigger than the MK lesion at the first visit, and smaller than MD lesion at the first visit. It suggested that there was some expansion of the original lesion. Fig. 5 A case of 50-year-old women,8 hours from stroke onset. A: The area of MD lesion at the first visit was 75 mm2. B: The area of MK lesion at the first visit was 42 mm2. C: The area of T2-FLAIR at the final visit was 93 mm2. The areas of follow-up T2-FLAIR lesion were bigger than the MK and MD lesion at the first visit. It suggested that there was a significant expansion of the original lesion and associated with poor outcomes.
表1 病灶側匹配區(qū)與不匹配區(qū)MK值和MD值的比較Tab. 1 Comparison of the MK value and the MD value of the lesion side matching area and the mismatched region
表2 各組MK變化幅度(?MK)與MD變化幅度(?MD)的比較Tab.2 Comparison of ?MK and ?MD of the groups
腦梗死實質是由于血管閉塞、腦血流量(cerebral blood flow,CBF)下降而引起的腦細胞形態(tài)和功能的改變甚至死亡。1977年Abtrup等[9]首次提缺血半暗帶(ischemia penumbra,IP)的概念:即介于正常腦組織與梗死組織之間的局部低灌注、功能異常、結構保持完整,恢復正常血流后功能可恢復的區(qū)域。所以盡快恢復IP的血流供應,成為早期腦梗死治療的主要手段。
腦血管梗死、供血減少、局部腦組織缺血缺氧,細胞膜上的Na+-K+-ATP泵功能障礙,細胞內外離子失衡、細胞內水鈉潴留、細胞腫脹[10-11],細胞質流動性減少、胞外間隙變小扭曲,導致水分子擴散受限,MD值下降,圖像顯示為較均勻的低信號,所以梗死缺血區(qū)顯示為MD圖低信號區(qū)、MD值下降,MD圖低信號區(qū)面積大小顯示缺血區(qū)的范圍。而腦組織缺血缺氧時,細胞內的結構先發(fā)生變化:能量依賴性細胞骨架崩潰、微管及其他的細胞成分分解斷裂、細胞內粘度增加、細胞壞死[12],局部結構復雜性增加,MK值升高、圖像顯示為不均勻高信號。腦梗死壞死區(qū)顯示MK圖高信號、MK值升高,MK圖高信號區(qū)面積大小顯示壞死區(qū)的范圍。MD和MK不匹配區(qū)(即缺血半暗帶)代表的是細胞損傷程度較輕的可逆性的缺血損傷組織,而MD和MK匹配的異常信號區(qū)則代表細胞損傷嚴重的不可逆的缺血損傷組織。
本研究三組MK圖病灶異常信號表現(xiàn)為不均勻邊緣清晰的高信號,MD圖病灶異常信號表現(xiàn)為均勻邊緣模糊的低信號,這和Grinberg等[13]和Hui等[14]的實驗結果相一致,提示MK值和MD值的改變可以顯示出腦梗死的病灶情況:MK圖顯示壞死區(qū)、MD圖顯示缺血區(qū),MK圖與MD圖的不匹配區(qū)顯示半暗帶區(qū);三組病灶的匹配區(qū)MK值和MD值、?MK和?MD明顯大于不匹配區(qū),提示匹配區(qū)(壞死區(qū))異常程度重于不匹配區(qū)(缺血半暗帶),這和張順等[8]的研究結果基本一致;三組共14例1個月后復查T2-FLAIR,與DKI、DTI檢測前后結合對比,能夠評價治療效果,這和Hui等[14]和Cheung[15]等的研究結果也基本一致。
但是,DKI掃描時間過長,降低了腦梗死患者掃描的成功率;快速DKI序列雖然在動物MRI上取得肯定性研究成果,但臨床MRI的快速DKI序列與后處理技術尚未普及;3D纖維束跟蹤DTI技術也已相當成熟,但其技術性仍有待進一步完善。另外,部分患者來診時已過了超急性期、急性期,未能把每個病例都完成三個期的影像動態(tài)監(jiān)測;本研究病例數(shù)較少,可擴大樣本量,更加細化地觀察腦梗死的影像學特點。
本研究結果表明,DKI檢測可分別顯示急性腦梗死壞死區(qū)和缺血區(qū),對半暗帶有診斷價值;能夠評估病情嚴重程度;動態(tài)監(jiān)測可評價治療效果。
表3 匹配區(qū)、不匹配區(qū)MK值和MD值的比較Tab.3 Comparison of the MK value and the MD value of the matching area and not matching area
表4 匹配區(qū)、不匹配區(qū)MK變化幅度(?MK)與MD變化幅度(?MD)的比較Tab.4 Comparison of ?MK and ?MD of the matching area and not matching area
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Clinical study of magnetic resonance diffusion kurtosis imaging technology on half dark with acute cerebral infarction diagnosis value
ZHANG Qin-cheng1, WANG Guang-wen2, GUO Yue-lin3, ZHENG Xiao-hong1, CHEN Wei1*
1Department of Neurology, the Second Affiliated Hospital, Medical Academy of Shantou University, Shantou 515041, China
2Department of Neurology, Maoming People's Hospital of Guangdong Province,Maoming 525000, China
3Department of Medical Imaging, the Second Affiliated Hospital, Medical Academy of Shantou University, Shantou 515041, China
Objective:The purpose of this study was to analyze the clinical value of diffusional kurtosis imaging on diagnosis, prognosis and observation of curative effect of ischemic penumbra.Materials and Methods:Forty-three patients were divided into superacute stage group (n=13), acute stage group (n=14) and subacute group (n=16). All the patients were examined with conventional MRI, DTI, DKI and T2-FLAIR, measured the area of abnormal signal of MK and MD maps. MK values and MD values of the corresponding parts of the mirror side were used as controls. These data were used for statistical analysis.Results:(1) The MD maps of our three groups in the lesion side showed relatively homogeneous low signal with fuzzy edge, in comparison, the MK maps showed heterogeneous high signal with clear edge. (2) In the lesion, the increase in the MK value, decrease in the MD value was different from that of the reference side (P<0.01). (3) The lesion area (mm2)in the MK map was obviously smaller than that in the MD map, with their difference being the mismatch area. The mismatch occurrence rate were 86.4%, 92.8%, 75.0%respectively in superacute, acute and subacute group. (4) ?MK was apparently greater than ?MD in the lesion. (5) MK, MD, ?MK,?MD value in the match area varied a lot more than that of the mismatch area. (6) The lesion area in the MK and MD map and the MK and MD value positively correlated to the severity of ischemia evaluated by NHISS. (7) Fourteen cases were followed up with T2-FLAIR: ① Compared with the primitive MK map: ten cases showed almost the same lesion area, indicating good curative effect, 4 cases showed severely enlarged lesion area, indicating poor clinical outcome. ② Compared with the primitive MD map:ten cases showed smaller lesion area, indicating good curative effect, 2 cases showed the same lesion area, indicating stable clinical state, 2 cases showed significantly enlarged lesion area, indicating poor clinical outcome. Conclusions: DKI was able to differentiate infarct and ischemic area separately in ischemia, and it played an important role in detecting penumbra. Moreover, it could be used to evaluate the severity of ischemia and the curative effect if the patients were followed up with this technique in the long term.
Intracranial embolism and thrombosis; Acute disease; Magnetic resonance imaging
1. 汕頭大學醫(yī)學院第二附屬醫(yī)院神經(jīng)內科,汕頭 515041
2. 廣東省茂名市人民醫(yī)院神經(jīng)內科,茂名 525000
3. 汕頭大學醫(yī)學院第二附屬醫(yī)院影像科,汕頭 515041
陳薇,E-mail:chw7203@126.com
2017-03-12
接受日期:2017-06-06
R445.2;R743.33
A
10.12015/issn.1674-8034.2017.07.002
張欽城, 王廣文, 郭岳霖, 等. 彌散峰度成像對急性腦梗死半暗帶診斷價值的臨床研究. 磁共振成像, 2017, 8(7):486-492.
*Correspondence to: Chen W, E-mail: chw7203@126.com
Received 12 Mar 2017, Accepted 6 June 2017