地中海貧血患者肝臟T2*、血清鐵蛋白預(yù)測(cè)心肌鐵過(guò)載價(jià)值研究

李大創(chuàng)，黃海波*，尹曉林，周亞麗，管俊，覃明，黃桂雄

地中海貧血患者肝臟T2*、血清鐵蛋白預(yù)測(cè)心肌鐵過(guò)載價(jià)值研究

李大創(chuàng)1，黃海波1*，尹曉林2，周亞麗2，管俊1，覃明1，黃桂雄1

目的定量評(píng)估地中海貧血(thalassemia，TM)患者心肌和肝臟鐵沉積，探討肝臟T2*、血清鐵蛋白(serum ferritin，SF)預(yù)測(cè)心鐵過(guò)載價(jià)值。材料與方法應(yīng)用3.0 T磁共振梯度多回波序列掃描基因確診并滿足要求的地中海貧血患者113例，測(cè)量其心肌和肝臟T2*值，所有受試者掃描前后7 d、間隔1 w實(shí)驗(yàn)室兩次檢測(cè)血清鐵蛋白。對(duì)心肌T2*、肝臟T2*、SF分度診斷并應(yīng)用秩相關(guān)分析3者間的關(guān)系，采用受試者工作特征曲線(receiver operating characteristic curve，ROC曲線)，評(píng)價(jià)肝臟T2*＜0.70 ms、SF＞2500 μg/L時(shí)預(yù)測(cè)心鐵過(guò)載及SF＞300 μg/L預(yù)測(cè)肝鐵過(guò)載診斷效能及最佳閾值。結(jié)果113例TM患者的鐵沉積分度診斷如下：心肌正常94例，輕度6例，中度10例，重度3例；肝臟正常13例，輕度31例，中度29例，重度25例，極重度15例；血清鐵蛋白正常1例，輕度48例，中度17例，重度35例，極重度12例。秩相關(guān)分析顯示心肌T2*-肝臟T2*(rs=0.267，P=0.004)、心肌T2*-SF (rs=-0.63，P=0.000)、肝臟T2*-SF (rs=-0.641，P=0.000)三者間輕中度相關(guān)但無(wú)規(guī)律性。以心肌T2*＜10 ms診斷心鐵沉積異常，肝臟T2*＜0.70 ms、SF＞2500 μg/L預(yù)測(cè)心鐵過(guò)載準(zhǔn)確性分別為0.788和0.833，敏感度分別為80.0%、73.3%，特異性分別為70.4%、63.3%；以肝臟T2*＜3.57 ms診斷肝鐵過(guò)載，SF＞300 μg/L預(yù)測(cè)肝鐵過(guò)載ROC曲線下面積為0.719，敏感度為94.0%，特異性為15.4%。結(jié)論在一定范圍內(nèi)，MRI T2*掃描可直接定量體內(nèi)器官鐵沉積，心鐵過(guò)載、肝鐵沉積、SF三者間輕中度相關(guān)但無(wú)規(guī)律性；以肝臟T2*、血清鐵蛋白預(yù)測(cè)心肌鐵異常價(jià)值較低，而血清鐵蛋白預(yù)測(cè)肝鐵過(guò)載尚不可靠。

地中海貧血；磁共振成像；血清鐵蛋白；心?。昏F過(guò)載

地中海貧血(thalassemia，TM)為常染色體缺陷導(dǎo)致的一或多種珠蛋白數(shù)量不足或缺乏，造成紅細(xì)胞易被破壞的溶血性貧血。張之南等[1]將其分為α型、β型和遺傳性胎兒血紅蛋白持續(xù)存在綜合征(hereditary persistence of fetal hemoglobin，HPFH)，α-TM和β-TM進(jìn)一步分重型、中間型、輕型與靜止型。因重型α-TM死于宮內(nèi)或早產(chǎn)，輕型、靜止型和HPFH常不需處理，而中間型及β-重型TM常由于反復(fù)輸血而引起鐵沉積和內(nèi)臟損害，心力衰竭為其死亡的最重要因素[2]。

多項(xiàng)研究[3-5]證實(shí)，磁共振成像(magnetic resonance imaging，MRI)可在一定范圍內(nèi)準(zhǔn)確評(píng)價(jià)水?；蛐蔫F、肝鐵濃度，現(xiàn)有少數(shù)以1.5 T MR文獻(xiàn)[3，6]認(rèn)為以SF、肝鐵預(yù)測(cè)心鐵沉積不可靠或準(zhǔn)確度中等偏低。此外，磁共振在心肌微血管阻塞、心功能及細(xì)胞間質(zhì)容積分?jǐn)?shù)等評(píng)估亦具有重要意義[7]。然而，超高場(chǎng)強(qiáng)下和基因確診的中間型及β-重型TM中體內(nèi)SF、肝鐵對(duì)心鐵沉積診斷效能及SF預(yù)測(cè)肝鐵過(guò)載的研究鮮有報(bào)告，筆者就此探討TM體內(nèi)肝臟T2*、血清鐵蛋白預(yù)測(cè)心肌鐵過(guò)載價(jià)值，以期為臨床提供相關(guān)依據(jù)。

1 材料與方法

1.1 材料

隨機(jī)選取2014年6月至2015年7月我院血液科117例TM患者磁共振心肌、肝臟T2*掃描，掃描前后7 d、間隔1 w完成兩次實(shí)驗(yàn)室血清鐵蛋白檢測(cè)及記錄其平均值。納入標(biāo)準(zhǔn)：(1)基因診斷血紅蛋白H病、中間型或重型β-TM；(2)反復(fù)多次輸(全)血且達(dá)到10 U (1 U=200 ml)、未進(jìn)行規(guī)律去鐵治療。排除標(biāo)準(zhǔn)：SF資料不完整、嚴(yán)重心律失常、幽閉恐懼、交流困難及其他原因不能完成MRI有效序列。試驗(yàn)獲我院倫理委員會(huì)批準(zhǔn)，志愿者或其家屬知情并簽署同意書。

1.2 設(shè)備與方法

Philips 3.0 T MR掃描儀、體部16通道線圈，頭先進(jìn)仰臥位、呼氣后屏氣和/或心舒中末期采集受試者肝門上一層肝實(shí)質(zhì)、心室中部短軸位T2*序列圖像，肝臟T2*成像前掃描冠狀、橫斷位T2WI及橫斷位T1WI (參數(shù)略)，心肌T2*成像前掃描左室標(biāo)準(zhǔn)橫斷位-兩腔心-四腔心電影序列(參數(shù)略)并確定短軸位層面，MRI T2*參數(shù)設(shè)置：TR=200 ms，F(xiàn)A=20°，肝臟12回波序列TEmin/max(ms)=0.6～1.3/7.8～16.0，心肌8回波序列TEmin/max(ms)=1.1/12.6，回波間隙為默認(rèn)最小設(shè)置，余參數(shù)見(jiàn)表1。

1.3 數(shù)據(jù)處理

SF數(shù)據(jù)來(lái)自實(shí)驗(yàn)室檢測(cè)兩次平均值且前后檢測(cè)變化不大于10%，肝臟、心肌T2*值由受良好培訓(xùn)的醫(yī)師使用CMRtools和/或結(jié)合Excel處理獲得。心肌感興趣區(qū)(region of interest，ROI)位于室間隔，肝臟取左右葉實(shí)質(zhì)4～5個(gè)ROI (30～50 mm2)且避開(kāi)偽影及肉眼可見(jiàn)膽管、血管，曲線擬合度要求不小于0.99，取3次平均值。

1.4 體內(nèi)鐵沉積標(biāo)準(zhǔn)參照文獻(xiàn)[8-9]及水模實(shí)驗(yàn)[5]擬定

心肌(單位：ms)：0級(jí)(正常)：T2*≥10.0，1級(jí)(輕度)：7.0≤T2*＜10.0，2級(jí)(中度)：5.0≤T2*＜7.0，3級(jí)(重度)：T2*＜5.0；肝臟(單位：ms)：0級(jí)(正常)：T2*≥3.57，1級(jí)(輕度)：1.41≤T2*＜3.57，2級(jí)(中度)：0.70≤T2*＜1.41，3級(jí)(重度)：0.47≤T2*＜0.70，4級(jí)(極重度)：T2*＜0.47；血清鐵蛋白(單位：μg/L)：0級(jí)(正常)：SF男性≤300、女性≤200，1級(jí)(輕度)：0級(jí)＜SF≤1500，2級(jí)(中度)：1500＜SF≤2500，3級(jí)(重度)：2500＜SF≤5000，4級(jí)(極重度)：SF≥5000。

1.5 統(tǒng)計(jì)方法

表1MRI T2*序列掃描參數(shù)Tab.1Parameters of MRI T2*protocols

2 結(jié)果

117例患者剔除2例嚴(yán)重心率失常，1例不能配合，1例擬合度未達(dá)標(biāo)，共納入113例，男61例、女52例，年齡(21.6±13.8)歲(5.0～68.0歲)，成功率為96.6%(113/117)。其中鐵沉積情況：(1)肝臟正常13例，輕度31例，中度29例，重度25例，極重度15例；(2)心肌正常94例，輕度6例，中度10例，重度3例；(3)血清鐵蛋白正常1例，輕度48例，中度17例，重度35例，極重度12例。

多回波T2*WI滿足定量要求，心肌T2*測(cè)量均由CMRtools完成，肝T2*計(jì)算由CMRtools完成70例(約61.9%)，另外43例需協(xié)同Excel測(cè)算(約38.1%)。心肌T2*、肝臟T2*、SF中位數(shù)分別為21.81(1.88～36.17) ms、1.00(0.36～10.36) ms、1591.0(200.0～14673.0) μg/L，心肌T2*-肝臟T2*(rs=0.267，P=0.004)、心肌T2*-SF (rs=-0.463，P=0.000)、肝臟T2*-SF (rs=-0.641，P=0.000)輕中度相關(guān)但無(wú)規(guī)律性(圖1～3)。

心肌T2*＜10 ms為標(biāo)準(zhǔn)診斷心鐵異常，以肝T2*＜0.70 ms、SF＞2500 μg/L預(yù)測(cè)心鐵過(guò)載準(zhǔn)確性分別為0.788和0.833，敏感度分別為80.0%和73.3%，特異性分別為70.4%和63.3%；以肝T2*＜3.57 ms診斷肝鐵過(guò)載，SF＞300 μg/L預(yù)測(cè)肝鐵過(guò)載準(zhǔn)確性為0.719，敏感度為94.0%，特異性為15.4%(圖4)。

3 討論

圖1女，17歲，脾切除術(shù)后重型β-TM患者，Cardiac T2*=6.67 ms (A)，Liver T2*=6.22 ms (B)，SF=1479.0 μg/L，提示心鐵與肝鐵、SF 三間者均不一致圖2男，40歲，中間型TM病例，Cardiac T2*=7.38 ms (A)，Liver T2*=1.33 ms (B)，SF=2566 μg/L，顯示心肌與肝鐵、SF不平行，肝鐵與SF水平相一致Fig. 1A 17-year-old female patient with β-TM major after surgery of spleen, of cardiac T2*(A), liver T2*(B), SF were 6.67 ms, 6.22 ms, 1479.0 μg/L, respectively. No agreements amongst cardiac T2*, liver T2*, SF were found.Fig. 2A 40-year-old male subject with TMinter, of cardiac T2*(A), liver T2*(B), SF were 7.38 ms, 1.33 ms, 2566.0 μg/L, respectively. It demonstrates that no accordance between MIC with LIC, and SF as well, but LIC matches SF.

地中海貧血反復(fù)輸血患者紅細(xì)胞被吞噬后，體內(nèi)產(chǎn)生鐵沉積將不可避免地影響肝臟、心臟等功能，其中心力衰竭為患者的致命因素，因此心臟與肝臟體內(nèi)鐵含量精準(zhǔn)、早期監(jiān)測(cè)對(duì)改善生活品質(zhì)、提高患者存活期具有重要意義，不僅預(yù)防心鐵和肝鐵過(guò)載發(fā)生、加劇，還可逆轉(zhuǎn)早期心肌病及早中期肝纖維化。肝臟作為體內(nèi)儲(chǔ)存鐵的主要部位[10]已經(jīng)證實(shí)且MRI定量技術(shù)也已經(jīng)被認(rèn)可為心鐵和肝鐵沉積診斷的可靠手段[11-12]及心功能評(píng)估的金標(biāo)準(zhǔn)[7]，可替代穿刺活檢以降低創(chuàng)傷、出血、膽瘺等發(fā)生率，同時(shí)提高準(zhǔn)確性、可重復(fù)性、受檢者耐受性及指導(dǎo)臨床去鐵治療[13]。

體內(nèi)鐵定量MRI原理[14]主要是應(yīng)用自旋或梯度多回波序列采集信號(hào)，反映細(xì)胞內(nèi)鐵離子、含鐵血黃素等順磁性物質(zhì)造成質(zhì)子周圍磁環(huán)境波動(dòng)、加速質(zhì)子失相位，采取一定函數(shù)模型計(jì)算其時(shí)間與信號(hào)變化斜率即可獲得自旋-自旋弛豫值(T2或T2*)，順磁性物質(zhì)濃度越大、組織弛豫值越低，根據(jù)此原理可重復(fù)、無(wú)創(chuàng)性測(cè)量心鐵和肝鐵濃度。龍莉玲等[4]證實(shí)在一定范圍內(nèi)，使用3.0 T MRI定量肝鐵沉積具有可行性，肝鐵沉積(liver iron concentration，LIC)與R2(即1/T2)高度相關(guān)(r=0.948，P＜0.05)。彭鵬等[3，6]以肝鐵濃度＞15 mg/g預(yù)測(cè)輸血依賴患者心鐵沉積準(zhǔn)確性為0.771，敏感度為42.2%，特異度為89.7%[3]。而以SF＞2500 μg/L或LIC＞15 mg/g預(yù)測(cè)β-重型TM心鐵過(guò)載準(zhǔn)確性分別為0.652和0.775，敏感度分別為90.9%和100%，特異度分別為16.0%和20%[6]。

圖3113例TM中心肌-肝T2*(A)、心肌T2*-SF (B)、肝臟T2*-SF (C)之間散點(diǎn)圖。A：113例TM中心肌-肝T2*散點(diǎn)圖，rs=0.267，P=0.004，R2=0.005；B：113例TM中心肌T2*-SF散點(diǎn)圖，rs=-0.463，P=0.000，R2=0.274；C：113例TM中肝臟T2*-SF散點(diǎn)圖，rs=-0.641，P=0.000，R2=0.146圖4ROC圖：以肝T2*＜0.70 ms (A)、SF＞2500 μg/L (B)為界值，肝鐵沉積預(yù)測(cè)心鐵過(guò)載準(zhǔn)確性分別為0.788和0.833，敏感度分別為80.0%和73.3%，特異性分別為70.4%和63.3%；以SF＞300 ug/L (C)為閾值，SF預(yù)測(cè)肝鐵過(guò)載準(zhǔn)確性為0.719，敏感度為94.0%，特異性為15.4%Fig. 3Scatter plots of hepatic T2*(A), SF (B) against cardiac T2*, and SF (C) against hepatic T2*with the linear fit (solid line), for 113 TM patients. A: Scatter plot of cardiac-hepatic T2*for patients, rs=0.267, P=0.004, R sq linear=0.005; B: Scatter plot of cardiac T2*-SF for patients, rs=-0.463, P=0.000, R sq linear=0.274; C: Scatter plot of hepatic T2*-SF for patients, rs=-0.641, P=0.000, R sq linear=0.146.Fig. 4ROC curve: with an area under the ROC curve of liver T2*＜0.70 ms (A), SF＞2500 μg/L (B) as diagnosis critical points, the sensibilities were 80.0% and 73.3%, the specificities were 70.4% and 63.3%, and the accuracies were 0.788 and 0.833 in the prediction of cardiac excess iron. Moreover, with an area under the ROC curve of SF＞300 μg/L (C) as diagnosis critical points, the sensibility was 94.0%, the specificity was 15.4%, the accuracy was 0.719 in the prediction of liver iron deposition.

本研究納入基因確診的113例TM被試應(yīng)用3.0 T MR前瞻性掃描，結(jié)果顯示，中間型與β-重型TM體內(nèi)心肌T2*與肝臟T2*、SF均呈輕度相關(guān)且無(wú)明顯規(guī)律，以肝臟T2*＜0.70 ms、SF＞2500 μg/L預(yù)測(cè)心鐵過(guò)載準(zhǔn)確性分別為0.788和0.833，敏感度分別為80.0%、73.3%，特異性分別為70.4%、63.3%；以SF＞300 μg/L預(yù)測(cè)肝鐵過(guò)載ROC曲線下面積為0.719，敏感度為94.0%，特異性為15.4%。提示診斷效能中等偏低，敏感性和特異性均難于達(dá)到醫(yī)學(xué)定量檢測(cè)要求，因此筆者認(rèn)為以肝鐵、血清鐵蛋白預(yù)測(cè)心鐵或以血清鐵蛋白預(yù)測(cè)肝鐵均尚不十分可靠，這些結(jié)果與彭鵬等[3，6]報(bào)道基本一致，而兩者不全相同之處在于筆者應(yīng)用3.0 T超高場(chǎng)強(qiáng)MR儀并選擇基因診斷的113例中間型與β-重型TM受試者進(jìn)行研究，這是本實(shí)驗(yàn)的創(chuàng)新點(diǎn)，后者則以1.5 T設(shè)備為基礎(chǔ)研究58例反復(fù)輸血治療的TM或103例β-重型TM患者。由此可見(jiàn)，不同病例選擇可能導(dǎo)致診斷效能不完全一致，因?yàn)榛颊呋蚍中?、輸血量和頻率、輸血開(kāi)始年齡與時(shí)間長(zhǎng)短、是否去鐵治療及治療規(guī)律性、有無(wú)脾切史等均將影響體內(nèi)鐵嚴(yán)重程度與分布，而對(duì)于不同型號(hào)、廠商或場(chǎng)強(qiáng)MR掃描儀，肝鐵、血清鐵蛋白預(yù)測(cè)心鐵過(guò)載或血清鐵蛋白預(yù)測(cè)肝鐵含量?jī)r(jià)值尚未達(dá)到醫(yī)學(xué)精確影像定量要求(即準(zhǔn)確性、敏感度與特異性均超過(guò)85%)卻可能是相似的，故筆者建議，鑒于MRI已經(jīng)成為鐵定量的最可靠手段，臨床上應(yīng)盡可能采用行之有效的MRI T2*技術(shù)定量肝或心鐵過(guò)載，以替代有創(chuàng)性心肌或肝組織活檢減少并發(fā)癥，避免使用血清鐵蛋白預(yù)測(cè)心鐵或肝鐵含量和心功能變化，同時(shí)也不應(yīng)該以肝鐵來(lái)預(yù)測(cè)心鐵或心功能，此外，在療效評(píng)估和要求反復(fù)檢測(cè)時(shí)MRI T2*技術(shù)也可發(fā)揮積極作用。

實(shí)驗(yàn)數(shù)據(jù)收集還發(fā)現(xiàn)，TM被試鐵過(guò)載嚴(yán)重64例僅憑CMRtools計(jì)算難于獲得準(zhǔn)確結(jié)果，此時(shí)還須結(jié)合Excel測(cè)算肝臟T2*，證明超高場(chǎng)強(qiáng)MR儀對(duì)少量鐵檢出敏感的同時(shí)存在低估嚴(yán)重病例鐵含量的缺陷，這是鐵沉積超高強(qiáng)場(chǎng)實(shí)際應(yīng)用需要提醒的注意事項(xiàng)。對(duì)于問(wèn)題的解決方法，研究中依據(jù)T2WI和T1WI預(yù)判肝鐵過(guò)載程度，正常和輕中度異常者應(yīng)用TEmin/max(ms)=1.3/16.8、黑肝現(xiàn)象明顯病例(提示含鐵量高)則采用TEmin/max(ms)=0.6/7.8序列掃描，在處理中如發(fā)現(xiàn)CMRtools曲線擬合未達(dá)0.99時(shí)協(xié)同Excel測(cè)量即可，此亦為研究創(chuàng)新發(fā)現(xiàn)之處。黃海波等[5]報(bào)道認(rèn)為，3.0 T MR優(yōu)化首回波T2*序列可顯著增加定量掃描準(zhǔn)確度，根據(jù)Wood等[15]報(bào)告，一般組織可測(cè)量最小T2值大約為最短TE的5/7即越小首回波值可檢測(cè)更大鐵濃度閾值。

需要指出的是，業(yè)內(nèi)標(biāo)準(zhǔn)肝臟和心肌T2*參考值目前均基于1.5 T掃描獲得[8-9]，而廣泛認(rèn)可的3.0 T鐵過(guò)載標(biāo)準(zhǔn)尚未確定，故此實(shí)驗(yàn)心鐵分度初定約為1.5 T參考值的1/2，肝鐵沉積則依據(jù)本中心M R掃描儀水模實(shí)驗(yàn)結(jié)果即PhC=7.008R2*+0.036[5]，這也是此次研究將肝T2*直接代表鐵濃度而未轉(zhuǎn)換為L(zhǎng)IC的重要原因。

綜上所述，實(shí)驗(yàn)被試體內(nèi)心肌T2*與肝臟T2*、SF均呈輕度相關(guān)且無(wú)明顯規(guī)律，臨床上以肝鐵、血清鐵蛋白預(yù)測(cè)心鐵或以血清鐵蛋白預(yù)測(cè)肝鐵均尚不十分可靠、診斷效能中等偏低。研究不足之處及展望：MR可直接精確定量心肌、肝臟鐵沉積，但以下因素將對(duì)結(jié)果產(chǎn)生影響：言語(yǔ)不理解、呼吸不配合、嚴(yán)重心律失常等，同時(shí)嚴(yán)重肝鐵掃描CMRtools計(jì)算肝T2*不準(zhǔn)確。此外，幽閉恐怖、神經(jīng)刺激、金屬置入等導(dǎo)致技術(shù)應(yīng)用受限，受最小回波限制與磁敏感影響，3.0 T鐵含量閾值小于1.5 T機(jī)型。但隨著軟硬件性能提高，這些因素當(dāng)可逐步解決，MRI精確鐵定量與療效評(píng)定將迎來(lái)新的高度并為科研和臨床提供更可信的依據(jù)。

[References]

[1] Zhang ZN, Sheng D. Diagnositc and effect-therapying criteria of hematopathy (Ver.3). Beijing: Science Press, 2007: 29-34.張之南, 沈悌. 血液病診斷與療效標(biāo)準(zhǔn). 3版. 北京: 科學(xué)出版社, 2007: 29-34.

[2] Lekawanvijit S, Chattipakorn N. Iron overload thalassemiccardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol, 2009, 25(4): 213-218.

[3] Peng P, Huang ZK, Long LL, et al. The relationship between heart and liver iron in thalassemia: A quantitative analysis using MRI. Zhonghua Fang She Xue Za Zhi, 2012, 46(3): 244-247.彭鵬, 黃仲奎, 龍莉玲, 等. 地中海貧血患者心臟、肝臟鐵沉積的MRI定量研究. 中華放射學(xué)雜志, 2012, 46(3): 244-247.

[4] Long LL, Peng P, Huang ZK, et al. Liver iron quantification by 3.0 T MRI: calibration on a rabbit model. Chin J Magn Reson Imaging, 2012, 3(6): 451-455.龍莉玲, 彭鵬, 黃仲奎, 等. 鐵超負(fù)荷模型3.0 T MRI定量肝鐵沉積可行性研究. 磁共振成像, 2012, 3(6): 451-455.

[5] Huang HB, Zhou YL, Li ZZ, et al. Feasibility of multiple-echo GRE with parameters optimized protocol at 3.0 T MRI. Chin J Magn Reson Imaging, 2015, 6(7): 529-534.黃海波, 周亞麗, 李致忠, 等. 前瞻性3.0 T MRI梯度多回波序列參數(shù)優(yōu)化可行性研究. 磁共振成像, 2015, 6(7): 529-534.

[6] Peng P, Long LL, Huang ZK, et al. Correlation study between MR quantitative cardiac iron accumulated and serum ferritin, liver iron concentration in patients with β-thalassemiamajor. Zhonghua Fang She Xue Za Zhi, 2012, 46(11): 993-997.彭鵬, 龍莉玲, 黃仲奎, 等. β-重型地中海貧血MR定量心臟鐵沉積與血清鐵蛋白、肝鐵濃度相關(guān)性研究. 中華放射學(xué)雜志, 2012, 46(11): 993-997.

[7] Chen XY, Zhao SH. Progress and clinical application of cardiovascular magnetic resonance. Chin J Magn Reson Imaging, 2015, 6(2): 86-89.陳秀玉, 趙世華. 心血管磁共振臨床應(yīng)用及進(jìn)展. 磁共振成像, 2015, 6(2): 86-89.

[8] Kerk P, Roughton M, Porter JB, et al. Cardiac T2*magnetic resonance for predication of cardiac complications in thalassemia magor. Circulation, 2009, 120(20): 1961-1968.

[9] Fischer R, Harmatz PR. Non-invasive assessment of tissue iron overload. Hematology, 2009, 1(1): 215-221.

[10] Liu SX, Wang Y, Li CG, et al. A multiple-center clinical study on quantitative T2*magnetic resonance imaging of iron deposition of liver, pancreas and heart of beta-thalassemia major patients. Chin J Prac Pediatrics, 2014, 29(11): 845-848.劉四喜, 王纓, 李長(zhǎng)鋼, 等. 重型β地中海貧血患者肝臟、胰腺和心臟鐵負(fù)荷磁共振成像T2*的多中心研究. 中華實(shí)用兒科雜志, 2014, 29(11): 845-848.

[11] Zhang Q, Hou B, Wang L, et al. Significance of magnetic resonance imaging in the detection of iron overload. Natl Med J China, 2013, 93(44): 3506-3509.張倩, 侯波, 王璐, 等. 磁共振成像技術(shù)定量檢測(cè)鐵過(guò)載的臨床意義. 中華醫(yī)學(xué)雜志, 2013, 93(44): 3506-3509.

[12] Aessopos A, Fragdimitri C, Karabatsos F, et al. Cardiac magnetic resonance Imaging R2*assessmentsand analysis of historical parameters in patients with transfusion- dependent thalassemia. Haemetologica, 2007, 92(1): 131-132.

[13] Meloni A, Positano V, Ruffo GB, et al. Improvement of heart iron with preserved patterns of iron store by CMR-guided chelation therapy. Eur Heart J Cardiovasc Imaging, 2015, 16(3): 325-334.

[14] Yang ZH, Feng F, Wang XY. A guide to technique of magnetic resonance imaging. Beijing: People's Military Medical Press, 2014: 303.楊正漢, 馮逢, 王霄英. 磁共振成像技術(shù)指南. 北京: 人民軍醫(yī)出版社, 2014: 303.

[15] Wood JC, Ghugre N. Magnetic resonance imaging assessment of excess iron in thalassemia, sickle cell disease and others iron overload diseases. Hemoglobin, 2008, 32(1-2): 85-96.

Value of liver T2*and SF to predict myocardial iron concentration patients with thalassemia

LI Da-chuang1, HUANG Hai-bo1*, YIN Xiao-lin2, ZHOU Ya-li2, GUAN Jun1, QIN Ming1, HUANG Gui-xiong1

1Department of Medical Imaging, 303rdHospital of PLA, Nanning 530021, China

2Department of Haematology, 303rdHospital of PLA, Nanning 530021, China

ACKNOWLEDGMENTSThis work was part of Guangxi Natural Science Foundation of China (No. 2014GXNSFBA118187, 2015GXNSFAA139164).

Objective:To quantify the MIC, liver iron concentration (LIC) in TM patients and discuss the value of liver T2*, SF to predict the MIC.Materials and Methods:Study protocol was approved by local ethics committee; informed consent was obtained. A total of 113 TM patients diagnosed by gene were enrolled. A multiple fast-field echo (mFFE) within a single breath-hold was performed using a 3.0 Tesla MR unit to acquire 8 or 12 T2*weighted images in the heart or liver. T2*values of myocardium and liver were quantified based on mFFE T2*protocol by a well-trained physician respectively, SF was obtained twice within 7 days before and after MRI. Spearman rank correlation was applied to analyze the relationships among the MIC, LIC and SF. The ROC curve was drawn to predict the possibility of using liver T2*＜0.70 ms, SF＞2500 μg/L as an index of cardiac iron deposition, and the possibility of using SF＞300 μg/L as an index of liver iron overload.Results:A total of 113 patients, the grades of body iron deposition as following: nineteen out of 113 were found to have myocardial excess iron, including 3 severe cases, 10 moderate cases, and 6 mildcases; 100 out of 113 were found to be liver excess iron, including 15 very severe cases, 25 severe cases, 29 moderate cases, and 31 mild cases; 112 out of 113 patients were found to be abnormal SF, including 12 very severe cases, 35 severe cases, 17 moderate cases, and 48 mild cases. There was weakly or moderate correlation between myocardial T2*and liver T2*(rs=0.267, P=0.004), myocardial T2*and SF (rs=-0.463, P=0.000), as well as between liver T2*and SF (rs=-0.641, P=0.000), but no clear regularity. To predict cardiac iron deposition with myocardial T2*＜10 ms as diagnostic criteria, the accuracies, sensibilities and specificities were 76.9%, 75% and 77.1% for the index of liver T2*＜0.70 ms, 82.7%, 68.8% and 68.6% for SF＞2500 μg/L, respectively. Moreover, to predict liver excess iron with liver T2*＜3.57 ms as standard setting, the accuracy, sensibility and specificity were respectively 80.2%, 92.4% and 20.7% for the index of SF＞2500 μg/L.Conclusion:Within a certain limits, MRI T2*technique could directly quantify the MIC and LIC, there was weakly or moderate correlation among MIC, LIC and SF, but no clear regularity. Using LIC or SF as an indirect index to predict cardiac excess iron were low valuable, meanwhile, using SF to predict liver iron overload was not reliable in clinical.

Thalassemia; Magnetic resonance imaging; Serum ferritin; Myocardium; Iron overload

Huang HB, E-mail:jackie000528@163.com

Received 9 Sep 2016, Accepted 26 Oct 2016

廣西壯族自治區(qū)自然科學(xué)基金(編號(hào)：2014 GXNSFBA118187，2015GXNSFAA139164)

1.解放軍第303醫(yī)院醫(yī)學(xué)影像科，南寧530021

2.解放軍第303醫(yī)院血液科，南寧530021

黃海波，Email：Jackie000528@163. com

2016-09-09

接受日期：2016-10-26

R445.2；R556.6

A

10.12015/issn.1674-8034.2016.12.004

李大創(chuàng), 黃海波, 尹曉林, 等. 地中海貧血患者肝臟T2*、血清鐵蛋白預(yù)測(cè)心肌鐵過(guò)載價(jià)值研究. 磁共振成像, 2016, 7(12): 909-914.*