田士峰
劉愛(ài)連LIU Ailian
李 燁LI Ye
陳麗華CHEN Lihua
汪禾青WANG Heqing
王逸敏WANG Yimin
韓 錚HAN Zheng
宋清偉SONG Qingwei
R2*值預(yù)估子宮內(nèi)膜樣腺癌病理分級(jí)的價(jià)值
田士峰TIAN Shifeng
劉愛(ài)連LIU Ailian
李 燁LI Ye
陳麗華CHEN Lihua
汪禾青WANG Heqing
王逸敏WANG Yimin
韓 錚HAN Zheng
宋清偉SONG Qingwei
中國(guó)醫(yī)學(xué)影像學(xué)雜志
2016年 第24卷 第11期:864-867
Chinese Journal of Medical Imaging 2016 Volume 24 (11): 864-867
目的探討增強(qiáng)T2*加權(quán)血管成像(ESWAN)序列的R2*值預(yù)估子宮內(nèi)膜樣腺癌(EA)病理分級(jí)的價(jià)值,以期準(zhǔn)確判斷EA分級(jí),指導(dǎo)臨床治療。資料與方法回顧性分析在1.5T MRI行ESWAN序列檢查并經(jīng)手術(shù)病理證實(shí)為EA的82例患者,按照病理分級(jí)分為3組,其中高分化組37例,中分化組28例,低分化組17例。由2位觀察者分別測(cè)量各組EA病灶實(shí)質(zhì)區(qū)的R2*值,檢驗(yàn)2位觀察者測(cè)量數(shù)據(jù)的一致性,分析R2*值與EA病理級(jí)別的相關(guān)性,對(duì)不同級(jí)別EA的 R2*值進(jìn)行組間兩兩比較,評(píng)估R2*值預(yù)估不同病理級(jí)別組EA的效能,并找出相應(yīng)界值。結(jié)果2位觀察者測(cè)量各組數(shù)據(jù)的一致性較高(ICC>0.75)。R2*值與EA病理級(jí)別呈弱相關(guān)(r=0.464,P<0.001),高、中、低分化組EA的R2*值分別為(12.54±2.75)Hz、(13.08±2.92)Hz、(18.71±3.80)Hz,高、低分化組間及中、低分化組間差異有統(tǒng)計(jì)學(xué)意義(P<0.001),高、中分化組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。R2*值預(yù)估低分化EA的曲線下面積為0.893,R2*值≥16.17 Hz為其界值,敏感度82.4%,特異度87.7%。結(jié)論R2*值可以作為非強(qiáng)化方式預(yù)估低分化EA的定量指標(biāo),有很好的應(yīng)用前景。
子宮內(nèi)膜腫瘤;腺癌;磁共振成像;磁敏感加權(quán)成像;病理學(xué),外科;女(雌)性
子宮內(nèi)膜癌是常見(jiàn)的女性生殖系統(tǒng)惡性腫瘤,發(fā)病率位居惡性腫瘤前十位[1],其最主要的病理類型是子宮內(nèi)膜樣腺癌(endometrial adenocarcinoma,EA)。不同分化程度的EA生物學(xué)行為不同,高、中分化EA因侵襲性弱而較少存在腫瘤淋巴管間隙浸潤(rùn)(lymph vascular space invasion,LVSI),而低分化的EA常侵及深肌層且廣泛存在LVSI[2]。LVSI是導(dǎo)致EA復(fù)發(fā)、影響預(yù)后及治療方案制定的重要因素[3]。術(shù)前通過(guò)影像學(xué)方法預(yù)估EA病理分級(jí)尤為重要,目前常用的方法是表觀擴(kuò)散系數(shù)(ADC)值[4-6]。由于EA的血供及耗氧情況較正常組織不同,因此血液代謝產(chǎn)物等順磁性物質(zhì)的濃度常出現(xiàn)變化,而表觀橫向弛豫率即R2*值對(duì)順磁性物質(zhì)濃度的變化極為敏感,是評(píng)價(jià)局部組織氧含量改變的定量指標(biāo)[7]。本研究擬探討R2*值預(yù)估EA病理分級(jí)的價(jià)值。
1.1 研究對(duì)象 回顧性分析2013年1月-2016年3月于大連醫(yī)科大學(xué)附屬第一醫(yī)院行MR檢查,并經(jīng)病理證實(shí)為EA的患者82例。年齡32~86歲,平均(58±11)歲。絕經(jīng)前28例,主要臨床表現(xiàn)為經(jīng)期不規(guī)律、月經(jīng)量增多等;絕經(jīng)后54例,主要臨床表現(xiàn)為不規(guī)則陰道流血。MRI表現(xiàn)為內(nèi)膜彌漫性增厚75例,厚度1.0~3.7 cm,其中16例形成腫塊填滿宮腔;7例表現(xiàn)為息肉狀局限性腫塊,最大徑1.5~5.5 cm。經(jīng)病理證實(shí)并按病理級(jí)別將EA患者分為高、中、低分化組,分別為37例、28例、17例。所有患者均無(wú)MR檢查禁忌證,術(shù)前均未接受放、化療或其他治療,在MR檢查后2周內(nèi)完成手術(shù)。
1.2 儀器與方法 采用 GE Signa HDxt 1.5T MR超導(dǎo)型掃描儀,體部8通道相控陣線圈。檢查前禁食4~6 h減輕腸道蠕動(dòng),并于檢查前1 h飲水約500 ml。掃描參數(shù):①軸位T1WI序列采用快速擾相梯度回波序列,TR 500 ms,TE 10.0 ms,激勵(lì)次數(shù)2,矩陣320×192,視野(FOV) 40 cm×40 cm,層厚5.0 mm,間隔l.0 mm,掃描時(shí)間1 min 40 s。②軸位T2WI序列采用快速自旋回波序列,TR 4000 ms,TE 125 ms,激勵(lì)次數(shù)4.0,矩陣320×192,F(xiàn)OV 40 cm×40 cm,層厚5.0 mm,間隔l.0 mm,掃描時(shí)間2 min 23 s。③增強(qiáng)T2*加權(quán)血管成像(enhanced T2 star weighted angiography,ESWAN)序列,軸位三維成像,TR 16.5 ms,8個(gè)回波,TE 2.1 ms,反轉(zhuǎn)角12°激勵(lì)次數(shù)0.71,矩陣 256×192,F(xiàn)OV 40 cm×40 cm,層厚2 mm,流動(dòng)補(bǔ)償,屏氣21 s。④肝臟快速容積成像動(dòng)態(tài)增強(qiáng)掃描,TR 3.7 ms,TE 1.8 ms, IT 7.0 ms,反轉(zhuǎn)角20°,激勵(lì)次數(shù)0.7,矩陣 272×180,F(xiàn)OV 40 cm×40 cm,層厚4.0 mm,層間隔2.0 mm,采集時(shí)間3 min 29 s,采用雙筒高壓注射器經(jīng)肘靜脈注射馬根維顯(拜耳醫(yī)藥,中國(guó)廣州),注射劑量0.1 ml/kg,速度2 ml/s。
1.3 圖像分析與數(shù)據(jù)測(cè)量 將ESWAN序列圖像傳至ADW4.6工作站,經(jīng)Functool軟件處理,選取閾值對(duì)相位圖進(jìn)行低通濾波過(guò)濾,采用多回波幅度平均、相位掩模等對(duì)保留回波的相位圖及幅度圖進(jìn)行處理,并獲得新的相位圖、幅度圖、R2*圖及T2*圖。由1名住院醫(yī)師及1名主治醫(yī)師采用盲法分析。應(yīng)用Viewer完成病灶R2*值的測(cè)量。方法為選擇R2*圖病灶橫軸位最大截面,在腫瘤實(shí)質(zhì)區(qū)放置圓形感興趣區(qū)(ROI),避開壞死、出血、含氣及偽影區(qū),取3個(gè)平均值(圖1)。所得各組R2*值結(jié)果的一致性用組內(nèi)相關(guān)系數(shù)(intraclass correlation coefficients,ICC)檢驗(yàn),ICC 取值為0~1,<0.4為一致性差,>0.75 為一致性良好。取2位觀察者測(cè)量結(jié)果平均值進(jìn)行分析。
圖1 女,55歲,低分化EA。R2*示在病灶最大截面不同區(qū)域放置3個(gè)ROI,每個(gè)ROI面積約1.0 cm2
1.4 統(tǒng)計(jì)學(xué)方法 采用SPSS 17.0軟件。R2*值與EA病理級(jí)別采用Spearman相關(guān)性分析,不同病理級(jí)別組EA的R2*值比較采用單因素方差分析,組間兩兩比較采用LSD法,P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。采用受試者工作特性(ROC)曲線評(píng)估R2*值對(duì)不同病理級(jí)別組EA的評(píng)判效能,計(jì)算曲線下面積(AUC),并根據(jù)最大約登指數(shù)確定相應(yīng)界值及其敏感度、特異度。
2.1 結(jié)果的一致性檢驗(yàn) 2位觀察者對(duì)不同病理級(jí)別組EA的R2*值測(cè)量結(jié)果的一致性均良好,高、中、低分化組測(cè)量的ICC值分別為0.894、0.930、0.923,各組測(cè)量結(jié)果見(jiàn)圖2。
2.2 R2*值與EA病理級(jí)別的相關(guān)性及病理級(jí)別組間比較 R2*值與EA病理級(jí)別呈弱相關(guān)性(r=0.464,P<0.001)。高、中和低分化組EA的R2*值分別為(12.54±2.75)Hz、(13.08±2.92)Hz和(18.71±3.80)Hz(圖3~5),高、低分化組EA的R2*值間差異有統(tǒng)計(jì)學(xué)意義(P<0.001),中、低分化組EA的R2*值間差異有統(tǒng)計(jì)學(xué)意義(P<0.001),高、中分化組EA的R2*值組間差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。
2.3 R2*值預(yù)估低分化EA的效能 R2*值預(yù)估低分化EA的AUC為0.893(圖6),R2*值≥16.17 Hz為其界值,靈敏度82.4%,特異度87.7%。
圖2 不同病理級(jí)別組EA的R2*值
圖3 女,56歲,高分化EA(箭)。R2*值為12.17 Hz
圖4 女,38歲,中分化EA(箭)。R2*值為14.48 Hz
圖5 女,67歲,低分化EA(箭)。R2*值為21.40 Hz
圖6 R2*值預(yù)估低分化EA的ROC曲線
ESWAN序列掃描可獲得多個(gè)回波的幅度圖及相位圖,具有高分辨率、薄層采集、同時(shí)獲得相位及幅度信息,并獲得多個(gè)定量參數(shù)[8],在定量評(píng)估方面頗具優(yōu)勢(shì)。R2*值可定量評(píng)估局部組織氧含量改變,與組織乏氧、出血等因素密切相關(guān)[9],在去氧血紅蛋白等順磁性物質(zhì)濃度增加等情況下R2*值升高。本研究結(jié)果顯示,低分化EA的R2*值較高、中分化EA高(P<0.001),可能是EA在腫瘤細(xì)胞增殖時(shí),由于血管內(nèi)皮生長(zhǎng)因子等物質(zhì)的誘導(dǎo)而產(chǎn)生病理性新生血管[10],并在低分化EA中的表達(dá)比高、中分化EA強(qiáng)烈,因此低分化EA可生成更多的新生血管[11]。雖然EA新生血管數(shù)量增多,但常有形態(tài)改變、走行紆曲、管壁基底膜缺陷等異常[12],可導(dǎo)致EA瘤體內(nèi)微出血、血液循環(huán)障礙等,使去氧血紅蛋白等順磁性物質(zhì)濃度增加,因低分化EA異常血管較多,導(dǎo)致微出血及血液動(dòng)力學(xué)變化更為顯著,因此R2*值較高、中分化EA增高。另外,低分化EA較高、中分化EA更高地表達(dá)Ki-67抗原,使腫瘤細(xì)胞增殖更加活躍,因此耗氧量更高,引起乏氧的程度更為嚴(yán)重,這也會(huì)導(dǎo)致R2*值增高[13-14]。Gheytanchi等[15]報(bào)道提出血管內(nèi)皮生長(zhǎng)因子與Ki-67可交互促進(jìn)腫瘤細(xì)胞增殖及新生血管生成,使低分化EA的R2*值增高更為顯著。此外,低分化EA的腫瘤細(xì)胞密度較高、中分化EA大,也會(huì)進(jìn)一步加重缺氧[16]。本研究同時(shí)發(fā)現(xiàn)R2*值在高、中分化EA間差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),其原因可能為兩者在異常血供、耗氧等方面無(wú)顯著差異。本研究中R2*值預(yù)估低分化EA的AUC為0.893,效能較高,以R2*值≥16.17 Hz作為判定低分化EA的界值,其敏感度與特異度均較高。本研究的局限性在于放置ROI的腫瘤實(shí)質(zhì)區(qū)缺乏病理對(duì)照。
總之,R2*值可作為預(yù)估低分化EA的定量指標(biāo),為MR無(wú)創(chuàng)、非強(qiáng)化方式預(yù)估EA病理分級(jí)提供了一種新的方法,有較好的臨床應(yīng)用前景。
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(本文編輯 周立波)
R2*Value in Predicting the Pathologic Grade of Endometrial Adenocarcinoma
Department of Radiology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
Address Correspondence to:LIU AilianE-mail: cjr.liuailian@vip.163.com
PurposeTo investigate the feasibility of R2*value generated from enhanced T2 star-weighted angiography (ESWAN) sequence in evaluating the pathological grade of endometrial adenocarcinoma (EA), in order to grade the EA accurately and to guide clinical treatment.Materials and MethodsImaging data of 82 EA cases confirmed by pathology were retrospectively analyzed. MRI scan including ESWAN sequence was performed on a 1.5T scanner. The patients were classified into three groups as follows according to the pathological grade: 37 in well differentiated group, 28 in moderately differentiated group, and 17 in poorly differentiated group. The R2*values of EA tumors were measured by two observers, and the consistency of the two observers was tested. The correlation between R2*value and pathological grade was analyzed. The R2*values of different pathological grades were compared. The efficacy of R2*value in predicting the different pathological grade was evaluated to find out the corresponding threshold.ResultsThe consistency of two observers was good (ICC>0.75). The R2*value was weak correlated with the pathological grade of EA (r=0.464,P<0.001). The R2*values of well, moderately, and poorly differentiated groups were (12.54±2.75)Hz, (13.08±2.92)Hz, and (18.71±3.80)Hz, respectively. There was statistic difference of R2*values between well and poorly group as well as moderately and poorly group (P<0.001), while there was no statistic difference of R2*values between well and moderately group (P>0.05). The Area Under Curve of R2*value for diagnosis of poorly differentiated EA was 0.893, and the cut off value was ≥16.17 Hz with sensitivity of 82.4% and the specificity of 87.7%.ConclusionR2*value can be used as a non-enhancement quantitative index for determining the poorly differentiated EA, which has a good application prospect.
Endometrial neoplasms; Adenocarcinoma; Magnetic resonance imaging; Susceptibility-weighted imaging; Pathology, surgical; Female
10.3969/j.issn.1005-5185.2016.11.016
大連醫(yī)科大學(xué)附屬第一醫(yī)院放射科 遼寧大連 116011
劉愛(ài)連
2016-05-27
2016-07-14
R445.2;R711.7