黃海波，黃桂雄*，陳毓秀，李大創(chuàng)，孫熙勇，管俊，覃明

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腎臟磁共振梯度多回波-R2*成像可行性研究

黃海波1，黃桂雄1*，陳毓秀2，李大創(chuàng)1，孫熙勇3，管俊1，覃明1

[摘要]目的 探討磁共振腎臟梯度多回波R2*成像可行性。材料與方法 應(yīng)用3.0 T MR系統(tǒng)梯度多回波序列，分別掃描專用水模(含氯化錳鹽酸混合液小瓶15只)、原位正常腎51例(A組)和移植正常腎22例(B組)志愿者，次月重復(fù)掃描專用水模、原位正常腎組，原始DICOM數(shù)據(jù)導(dǎo)入CMRtools軟件測算獲得水模各小瓶及腎皮髓質(zhì)R2*值。結(jié)果 水模R2*與其濃度直線相關(guān)(r=0.999，P=0.000)，通過直線回歸分析，得到R2*與PhC擬合直線斜率為0.008，截距為–0.050。實(shí)際與預(yù)測水模濃度組內(nèi)相關(guān)系數(shù)(ICC)為0.999，重復(fù)掃描水模R2*ICC為1，重復(fù)掃描水模R2*差值與總體0比較無統(tǒng)計(jì)學(xué)意義(P＞0.05)。原位和移植腎組間性別與年齡無統(tǒng)計(jì)學(xué)意義(P＞0.05)；原位腎雙側(cè)R2*無統(tǒng)計(jì)學(xué)差異(P＞0.05)；原位腎皮髓質(zhì)重復(fù)測量R2*ICC分別為0.847和0.915，差值與總體0無統(tǒng)計(jì)學(xué)意義(P＞0.05)。移植與原位正常腎R2*無統(tǒng)計(jì)學(xué)差異(P＞0.05)，腎髓質(zhì)R2*顯著高于皮質(zhì)，差異有統(tǒng)計(jì)學(xué)意義(P＜0.05)。結(jié)論 磁共振梯度多回波R2*成像評(píng)價(jià)腎氧合狀態(tài)具有可行性，可為更多腎臟R2*成像推廣應(yīng)用提供依據(jù)。

[關(guān)鍵詞]腎臟；磁共振成像；診斷技術(shù)和方法

廣西科學(xué)研究與技術(shù)開發(fā)計(jì)劃項(xiàng)目(編號(hào)：桂科攻1298003-8-6)

作者單位：

1.解放軍第303醫(yī)院影像科，南寧，530021

2.武警陜西總隊(duì)醫(yī)院MR室，西安，710054

3.解放軍第303醫(yī)院移植科，南寧，530021

黃桂雄，E-mail: 303hgx@163.com

接受日期：2015-11-09

黃海波, 黃桂雄, 陳毓秀, 等.腎臟磁共振梯度多回波-R2*成像可行性研究.磁共振成像, 2016, 7(1): 62–67.

Feasibility of multiple-echo GRE-R2*to renals at 3.0 T MRI

Huang Hai-bo1, Huang Gui-xiong1*, Chen Yu-xiou2, Li Da-chuang1, Sun Xi-yong3, Guan Jun1, Qin Ming1

1Department of Medical Imaging, 303rd Hospital of PLA, Nanning 530021, China

2MR Room of Shanxi CAPF Hospital, Nanning 530003, China

3Department of Transplantation, 303rd Hospital of PLA, Nanning 530021, China

*Correspondence to: Huang GX, E-mail: 303hgx@163.com

Received 28 Sep 2015, Accepted 9 Nov 2015

ACKNOWLEDGMENTS Guangxi Scientific and Technological Plan (No.GUIKEGONG1298003-8-6).

Abstract Objective: To explore the feasibility of multiple-echo GRE- R2*to renals at 3.0 T MRI.Materials and Methods: A MR phantom which includes fifteen vials containing 0.2—3.2 mmol/L manganese chloride in hydrochloric acid solution, 51 healthy vonlunteers (Group A) with kidneys in-situ and 22 normal renals (Group B) transplanted were scanned by 3.0 T MRI, repeated protocols to the phantom and group A with kidneys in-situ one month later.Both phantom and in-vivo renals R2*were quantified by a well-trained physician using a CMR tools after MRI.Results: Phantom R2*was linearly correlated with its concentration in vials (r=0.999, P=0.000).Through the regressions procedure,a slope of 0.008 and an intercept of –0.050 were found.No statistic differences were found for R2*value between the first and second scanning on phantom (P＞0.05), The real and predicted concentration of phantom, R2*repeated scanning on phantom have a highly reliability respectively (ICCconcentration=1, ICCR2*=0.999).No statistic differences were found for gender and age between group A and B(P＞0.05).No statistic differences were found for the cortical and medullary R2*between left and right renal (P＞0.05).No statistic differences were found for kidneys R2*in group A between the first and second scanning (P＞0.05), It showed a well reliability respectively (ICCcortex=0.847, ICCmedullation=0.915).No statistic differences were found for renal R2*between group A and B (P＞0.05).However, renal R2*was dramatically higher in medullation than in cortex and there was statistic difference (P＜0.05).Conclusions: With CMRtools, multiple-echo GRE protocol is feasible for evaluating oxygenation in kidneys at 3.0 T MRI, it could provide a reliable evidence for clinic application to renals.

Key words Kidney; Magnetic resonance imaging; Diagnostic techniques and procedures

腎實(shí)質(zhì)氧合狀態(tài)在腎疾病發(fā)生、發(fā)展中具有重要作用，Pedersen等[1]和Neugarten等[2]運(yùn)用微電極的方法證實(shí)R2*與腎內(nèi)氧分壓具有良好一致性即R2*增高代表脫氧血紅蛋白或脫氧/含氧血紅蛋白比例增加，是直接測量腎臟氧分壓的方法，但因創(chuàng)傷較大不適用于活體腎。而血氧水平依賴磁共振功能成像(blood oxygenation level-dependent magnetic resonance functional imaging，BOLD-fMRI)是利用內(nèi)源性脫氧血紅蛋白引起局部微觀磁場不均勻、改變質(zhì)子自旋去相位而導(dǎo)致表觀自旋-自旋弛豫率(R2*=1000/T2*)變化的一種無創(chuàng)性氧代謝評(píng)價(jià)的MR技術(shù)[3]，1996年P(guān)rasad等[4]首先將其應(yīng)用于腎臟以來，BOLD fMRI信號(hào)強(qiáng)度與腎組織氧合關(guān)系通過氧敏感光纖探針直接測量組織氧分壓已得到證實(shí)[2]，目前不斷進(jìn)展的缺血性腎損傷、腫瘤、糖尿病、腎移植等研究[5-9]認(rèn)為BOLDMRI評(píng)價(jià)氧代謝具有重要作用。然而BOLDMRI因需專用序列與特殊軟件僅限于少數(shù)科研機(jī)構(gòu)才能實(shí)施，筆者擬通過調(diào)整梯度多回波序列掃描水模與人活體腎臟，應(yīng)用軟件CMRtools測算R2*，探索弛豫率成像評(píng)價(jià)腎氧合狀態(tài)可行性。

1　 材料與方法

1.1資料

專用的標(biāo)準(zhǔn)水模(澳大利亞Ferriscan公司提供)一個(gè)，內(nèi)含有濃度(0.2～3.2) mmol/L氯化錳鹽酸溶液小瓶15只。

選取我院2012年3月至2014年5月申請腎掃描原位正常腎51例(A組，男35例、女16例，年齡18～55歲，平均34.9±10.9歲)和移植正常腎22例(B組，男16例、女6例，年齡16～57歲，平均35.9±11.4歲)為志愿者入組研究。分組標(biāo)準(zhǔn)：禁水12 h，排除已知可改變腎氧合狀態(tài)藥物(襟利尿劑、乙酰唑胺、碘對(duì)比劑、一氧化氮合成酶抑制劑等)近期使用及原繼發(fā)性血色病外，原位腎尚滿足無相關(guān)臨床癥狀，血肌酐、尿素氮及超聲無陽性指征；髂窩移植正常腎滿足術(shù)后2周至6個(gè)月，余標(biāo)準(zhǔn)同原位腎。研究實(shí)驗(yàn)獲我院倫理委員會(huì)批準(zhǔn)，志愿者知情并簽署同意書。

1.2設(shè)備與方法

Philips Achieva 3.0 T TX MR掃描儀，掃描前水模靜置磁體室2 h以上。水模掃描應(yīng)用SENSE HEAD 8 coils，腎掃描使用SENSE XL TORSO 16 coils配合呼吸門控，掃描前嚴(yán)格勻場和(或)參考掃描，梯度多回波_R2*成像參數(shù)設(shè)置：TR 200 ms，F(xiàn)A=20°，層數(shù)=1，水模序列為TE (ms)=1.2/2.1/3.1/4.0/5.0/5.9/6.9/8.6/9.7/10.6/11.6，腎序列為TE(ms)=9.2/13.2/17.2/21.2/25.2/29.2/33.2/37.2/41.2/45.2/49.2/53.2，腎R2*成像(呼氣末屏氣)掃描冠狀及橫斷位，掃描前常規(guī)橫斷與冠狀位T1WI、T2WI成像并以此參考確定腎門區(qū)，詳細(xì)序列設(shè)置見表1，完成掃描保存原始數(shù)據(jù)。

1.3數(shù)據(jù)處理

水模、腎掃描DICOM數(shù)據(jù)由受過良好培訓(xùn)醫(yī)師使用CMRtools軟件處理獲得R2*值。水模ROI位于小瓶內(nèi)，腎臟測量選擇冠狀位皮髓質(zhì)對(duì)比良好梯度回波像，取5～10個(gè)ROI (10～20 mm2)且避開偽影，取三次測量平均值，軟件自動(dòng)計(jì)算T2*或R2*值(=1000/)。

1.4統(tǒng)計(jì)學(xué)

表1　腎臟掃描序列參數(shù)設(shè)置(冠狀面+ 橫軸面)Tab.1 Protocol parameters for renal coronal&transverse scanning

表2　水模及原位右腎皮髓質(zhì)R2*重復(fù)測量表(Hz)Tab.2 R2*values repeated of phantom and right renal cortex & medullation (Hz)

圖1　 為水模首次和重復(fù)掃描CMRtools測量圖。首次(A)與1個(gè)月后(B) R2*(1000/T2*)分別為146.4 Hz與144.7 Hz，波動(dòng)小于4%，說明重復(fù)性高 圖2 為水模小瓶R2*與PhC間散點(diǎn)圖。實(shí)線為兩者間擬合直線，虛線為95% CI 圖3，4 為原位腎首次與重復(fù)掃描、移植腎CMRtools處理圖與R2*(Hz)值。原位腎首次掃描(圖3A～D) 左右皮髓質(zhì)分別為17.43、27.78、17.66、26.23；重復(fù)掃描右腎結(jié)果(圖3E，F(xiàn))分別為18.88、27.59；移植腎皮髓質(zhì)(圖4A，B)分別為17.75、26.90。原位腎雙側(cè)、重復(fù)掃描、移植腎與原位腎間比較均無明顯差異，腎重復(fù)掃描波動(dòng)小于7%，由此可見，掃描序列具有很好重復(fù)性Fig.1 Model R2*(1000/T2*) of the first and repeated measured by CMRtools were 146.8 Hz (A) and 158.4 Hz (B) respectively, it follows that model R2*fluctuation was below 2% and has a dramatically highly reliability.Fig.2 Scatter plots of R2*against PhC with the linear fit (solid line) and the 95% CI (dashed line).Fig.3, 4 Measured by CMRtools, the cortical and medullary R2*(Hz) on left and right kidney in-situ were 17.43 (Fig.3A), 27.78 (Fig.3B), 17.66 (Fig.3C), 26.23 (Fig.3D) for the first quantitative respectively, the repeated after one month were 18.88 (Fig.3E), 27.59 (Fig.3F) respectively.while the transplanted were 17.75 (Fig.4A), 26.90 (Fig.4B) respectively.No statistic differences were found for R2*not only between both side kidneys in-situ, the repeated scanning, but the transplanted and in-situ renals as well.It follows that renal R2*fluctuation was below 7% and therefore with CMRtools, the protocol has a high reliability.

2　 結(jié)果

水模小瓶Mncl2濃度為1.41±0.95 (0.20～3.20) mmol/L，兩次掃描測量見表2，水模與其濃度呈直線相關(guān)(r=0.999，P=0.000)，擬合直線斜率為0.008，截距為–0.05，建議回歸方程PhC=0.008–0.05，R2=0.998 (F=4899.247，P=0.000)，預(yù)測濃度為1.41±0.95 (0.21～3.15) mmol/L，與實(shí)際濃度高度一致(ICC=0.999)，重復(fù)掃描高度一致(ICC=1)，差值均數(shù)與總體0比較無統(tǒng)計(jì)學(xué)意義(P＞0.05)，如圖1，2。

原位腎和移植腎組間性別與年齡無統(tǒng)計(jì)學(xué)意義(χ2性別=0.123，t年齡=0.342，P性別/年齡=0.726/0.734)；原位左腎皮髓質(zhì)分別為17.70±0.66 (16.26～19.26) Hz、29.88±2.42 (25.77～38.59) Hz，原位右腎兩次掃描見表2，雙側(cè)比較無統(tǒng)計(jì)學(xué)差異(t皮質(zhì)/髓質(zhì)=–0.539/–0.786，P皮質(zhì)/髓質(zhì)=0.591/0.434)，髓質(zhì)明顯高于皮質(zhì)，皮髓質(zhì)差值(11.82± 3.21) Hz與總體0差異有統(tǒng)計(jì)學(xué)意義(t=26.275，P=0.000)；右腎兩次掃描差值均數(shù)與總體0無統(tǒng)計(jì)學(xué)意義(P＞0.05)并具有高度一致性(ICC皮質(zhì)/髓質(zhì)=0.847/0.915；移植腎皮髓質(zhì)分別為17.85±0.99 (16.08～19.43) Hz、29.75±3.35 (25.77～41.19) Hz，與原位右腎無統(tǒng)計(jì)學(xué)差異(t皮質(zhì)/髓質(zhì)=–0.972/–0.370，P皮質(zhì)/髓質(zhì)=0.334/0.712)(圖3，4)。

3　 討論

腎臟血流量約占心輸出量1/4，約90%供應(yīng)分布于皮質(zhì)，僅約10%供應(yīng)髓質(zhì)[10]，皮質(zhì)氧分壓約50 mm Hg (1 mm Hg=0.133 kPa)，而髓質(zhì)僅為10～20 mm Hg，腎髓質(zhì)低氧合、高負(fù)荷特點(diǎn)使BOLD MRI評(píng)價(jià)腎氧合狀態(tài)成為理想手段并已經(jīng)實(shí)驗(yàn)研究肯定[11-12]。梯度多回波_與BOLD_成像具有相同原理，為多回波穩(wěn)態(tài)自由進(jìn)動(dòng)(SSFP)采集信號(hào)，反映脫氧血紅蛋白、含鐵血黃素、Mn元素等順磁性物質(zhì)周圍局部磁場不均勻性增加、質(zhì)子加速失相而產(chǎn)生自旋-自旋弛豫()或弛豫率()變化的MRI序列[3]。CMRtools是一種開源軟件，可通過網(wǎng)絡(luò)下載或少量付費(fèi)獲得，主要應(yīng)用于原發(fā)血色病、地中海貧血、鐮狀細(xì)胞病等鐵沉積MR定量檢測，軟件實(shí)用與有效性已在肝臟、心肌等鐵沉積臨床與動(dòng)物實(shí)驗(yàn)中證實(shí)且在一定范圍內(nèi)有替代活檢趨勢[13-15]。

研究按順磁性物質(zhì)特點(diǎn)設(shè)置標(biāo)準(zhǔn)水模與活體腎臟掃描兩種梯度多回波序列(回波數(shù)=12)：水模Mncl2濃度較高應(yīng)用TEmin/max=1.2 ms/11.7 ms，回波間隙0.9 ms，而腎臟脫氧血紅蛋白含量相對(duì)很小使用TEmin/max=9.2 ms/53.2 ms，回波間隙為4.0 ms，掃描(1000/)數(shù)據(jù)全部應(yīng)用CMRtools測算。實(shí)驗(yàn)結(jié)果顯示：水模與腎掃描原始圖像基本滿足定量評(píng)價(jià)，擬合曲線R2均大于0.99(圖1，3，4)，證明數(shù)據(jù)結(jié)果具有很高可信度。水模與其小瓶內(nèi)Mncl2濃度(PhC)直線相關(guān)(r=0.999)，這與龍莉玲等[16]的研究高度一致(圖2)。直線回歸方程斜率與截距分別為0.008和–0.050，決定系數(shù)R2=0.998，方程預(yù)測與實(shí)際Mncl2濃度(ICC=0.999)、重復(fù)掃描(ICC=1.0)均具有高度一致性。雙側(cè)原位腎皮質(zhì)-皮質(zhì)、髓質(zhì)-髓質(zhì)間無顯著性差異，這是重復(fù)掃描僅評(píng)價(jià)右腎重復(fù)性和移植腎只與右腎比較的基礎(chǔ)與依據(jù)，腎重復(fù)掃描皮髓質(zhì)具有良好一致性(ICC皮質(zhì)/髓質(zhì)=0.847/0.915)，同時(shí)原位與正常移植腎亦未見明顯差異，但腎髓質(zhì)明顯高于皮質(zhì)，這與多數(shù)BOLD-研究報(bào)道[17-20]基本一致且高于1.5 T MR 報(bào)道定量數(shù)據(jù)[21-22]，文獻(xiàn)[23]認(rèn)為，髓質(zhì)PaO2＜40 mm Hg，其氧含量輕微變動(dòng)即會(huì)引起脫氧血紅蛋白濃度或脫氧/氧合血紅蛋白比例很大變化，而皮質(zhì)(PaO2＞50 mm Hg)血紅蛋白處于解離曲線上段，氧含量輕微變化不會(huì)以髓質(zhì)相似程度影響脫氧血紅蛋白濃度，本研究實(shí)驗(yàn)足于反映腎皮髓質(zhì)脫氧血紅蛋白的分布特點(diǎn)。說明通過CMRtools數(shù)據(jù)處理，梯度多回波-成像可滿足原位腎、髂窩移植腎臨床應(yīng)用要求，具備腎臟氧含量評(píng)價(jià)科學(xué)性、可行性與創(chuàng)新性，筆者推薦可在未裝備高級(jí)掃描序列與專業(yè)軟件的高場強(qiáng)磁共振上推廣應(yīng)用。

筆者分析原始圖像及軟件發(fā)現(xiàn)，正常腎圖像質(zhì)量良好、皮髓質(zhì)分界(Cortico-medullary differentiation，CMD)隨回波延長逐漸對(duì)比清晰，第八個(gè)回波37.2 ms時(shí)可獲得良好CMD以定位腎皮髓質(zhì)區(qū)放置ROI，這正好與正常髓質(zhì)橫向弛豫T2*值接近。部分原位左腎、髂窩移植腎出現(xiàn)的輕微磁敏感偽影在一定程度上影響整體腎臟評(píng)價(jià)，原因可能為與右腎相比，左腎、移植腎更毗鄰腸道，而腸道氣體與腎臟磁敏感性差異增大所致，通過軸位成像以及減少腸道氣體可減輕或抑制該偽影。此外，筆者還發(fā)現(xiàn)CMRtools只能依賴灰階對(duì)比而無法提供偽彩圖輔助定位皮髓質(zhì)，同時(shí)軟件不能拆分不同層面多回波圖像導(dǎo)致序列每次屏氣僅采集一層，多層掃描則需多次定位、重復(fù)序列執(zhí)行，這必然延長掃描時(shí)間、降低嚴(yán)重患者依從性，此外單層掃描可能會(huì)導(dǎo)致雙側(cè)評(píng)估一致性降低，因?yàn)橥ㄟ^一側(cè)腎門的定位可能會(huì)在對(duì)側(cè)前后偏離、重疊部分皮質(zhì)導(dǎo)致部分容積效應(yīng)，這有可能引起左右腎測量誤差加大。

志謝 廣西醫(yī)科大學(xué)統(tǒng)計(jì)教研室主任黃高明教授、解放軍第303醫(yī)院信息中心藍(lán)華分別對(duì)本研究給予的統(tǒng)計(jì)學(xué)指導(dǎo)和圖像后處理

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DOI:10.12015/issn.1674-8034.2016.01.012

文獻(xiàn)標(biāo)識(shí)碼：A

中圖分類號(hào)：R445.2；R692

收稿日期：2015-09-28

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基金項(xiàng)目：