郭婷婷,劉松,周楠,周正揚(yáng)
體素內(nèi)不相干運(yùn)動(dòng)磁共振成像評(píng)估鼻咽癌同步放化療療效
郭婷婷,劉松,周楠,周正揚(yáng)*
作者單位:
南京中醫(yī)藥大學(xué)中西醫(yī)結(jié)合鼓樓臨床醫(yī)學(xué)院醫(yī)學(xué)影像科, 南京 210008
目的探討體素內(nèi)不相干運(yùn)動(dòng)磁共振成像(intravoxel incoherent motion magnetic resonance imaging,IVIM-MRI)評(píng)估鼻咽癌放化療療效的價(jià)值。材料與方法27例經(jīng)活檢證實(shí)為鼻咽癌的患者,于治療前、放療開始后1個(gè)月及結(jié)束后1個(gè)月行MRI掃描,掃描序列包括T1WI、T2WI、IVIM (9個(gè)b值,范圍0~800 s/mm2)及T1WI增強(qiáng)。放療過程中接受3個(gè)周期的同步化療。使用單指數(shù)模型獲得表觀擴(kuò)散系數(shù)(apparent diffusion coefficient,ADC)值,雙指數(shù)模型測得體素內(nèi)的純擴(kuò)散系數(shù)(true molecular diffusion coefficient,D)、灌注分?jǐn)?shù)(perfusion fraction,f)、偽擴(kuò)散系數(shù)(pseudodiffusion coefficient,D*)。測量各掃描時(shí)間點(diǎn)腫瘤最大面積及IVIM參數(shù),并分析其動(dòng)態(tài)變化及相關(guān)性。結(jié)果排除圖像偽影病例,最終23例患者被納入。鼻咽癌病灶A(yù)DC及D值在整個(gè)治療過程中逐步升高,治療前與結(jié)束后1個(gè)月ADC均值為0.80×10-3mm2/s和1.57×10-3mm2/s (P1/3<0.001), D均值為0.68×10-3mm2/s和1.31×10-3mm2/s (P1/3<0.001)。f值先上升后下降,治療前與放療開始后1個(gè)月f值分別為11%、19%(P1/2<0.001)。D*值在1組與2組、1組與3組及2組與3組間差異均無統(tǒng)計(jì)學(xué)意義。結(jié)論IVIM-MRI可監(jiān)測鼻咽癌在放化療過程中的動(dòng)態(tài)變化。組織內(nèi)微循環(huán)灌注對(duì)單指數(shù)ADC值有影響,體素內(nèi)水分子的擴(kuò)散被高估了。而D值的計(jì)算是選取高b值(>200 s/mm2),微循環(huán)灌注對(duì)MR信號(hào)的影響微乎其微,反映的是純擴(kuò)散信息。因而,D值更能有效監(jiān)測放化療療效,f值可作為潛在觀察指標(biāo)。
體素內(nèi)不相干運(yùn)動(dòng);鼻咽腫瘤;放化療;磁共振成像
鼻咽癌是中國南方發(fā)病率較高的惡性腫瘤[1]。由于鼻咽的特殊解剖位置及臨床癥狀的非特異性,大部分患者在初診時(shí)已為晚期。同步放化療是當(dāng)前鼻咽癌的標(biāo)準(zhǔn)治療方法。早期監(jiān)測、評(píng)估放化療療效是目前關(guān)注的問題。
目前主要依據(jù)腫瘤大小評(píng)估療效,但腫瘤的形態(tài)學(xué)改變通常晚于其內(nèi)部結(jié)構(gòu)及功能的變化。磁共振成像(magnetic resonance imaging,MRI)能觀察腫瘤在放化療過程中內(nèi)部微觀環(huán)境的變化,體素內(nèi)不相干運(yùn)動(dòng)磁共振成像(intravoxel incoherent motion magnetic resonance imaging,IVIM-MRI)可無創(chuàng)定量分析活體組織水分子擴(kuò)散及微血管灌注信息。IVIM在其他腫瘤的放化療評(píng)估中取得較好效果,如宮頸癌[2]、直腸癌[3]等。本研究旨在通過IVIM-MRI評(píng)估鼻咽癌組織水分子擴(kuò)散及灌注特征,并觀察相關(guān)參數(shù)動(dòng)態(tài)變化,探索IVIM-MRI評(píng)估及監(jiān)測鼻咽癌放化療療效的價(jià)值。
本研究得到醫(yī)院倫理委員會(huì)許可,并簽署患者知情同意書。前瞻性納入2015年4月至2016年10月在南京鼓樓醫(yī)院接受診治的鼻咽癌患者。納入標(biāo)準(zhǔn):(1)經(jīng)病理活檢證實(shí)為鼻咽鱗形細(xì)胞癌;(2)未接受任何治療;(3)擬在本院行放化療聯(lián)合治療。放療采用調(diào)強(qiáng)放療法,總劑量為70 Gy,2 Gy/d,5次/周。放療過程中接受3個(gè)周期以奈達(dá)鉑為主的同步化療,1 w為1個(gè)周期,間隔1 w,靜脈滴注,劑量60 mg/m2;(4)能接受MR隨訪復(fù)查(治療前、放療開始后1個(gè)月及放療完成后1個(gè)月)。共納入27例(男20例,女7例)患者,年齡32~70歲,中位年齡54歲。其臨床分期為:Ⅱ期6例,Ⅲ期20例,Ⅳa期1例。4例患者圖像有吞咽偽影影響數(shù)據(jù)測量,最終23例患者被納入。某一位患者的3組圖像見圖1~3。
患者3次掃描的序列和參數(shù)一致。MR檢查采用全數(shù)字3.0 T掃描儀(Ingenia,Philips Medical Systems,Best,the Netherlands),使用16通道頭頸聯(lián)合線圈。仰臥位,頭先進(jìn),自由呼吸。行鼻咽部及頸部常規(guī)MRI、IVIM-MRI及增強(qiáng)MRI掃描。掃描序列:軸位及冠狀位T2壓脂(short time inversion recovery,T2-STIR),軸位T2加權(quán)成像(T2 weighted image,T2WI),IVIM-MRI以及橫冠矢三方位增強(qiáng)T1WI。在常規(guī)序列及IVIM-MRI掃描完成后,靜脈推注釓雙胺(0.2 ml/kg,GE Healthcare Ireland,Shanghai,China)對(duì)比劑,速率3.0 ml/s,劑量0.2 mmol/kg。常規(guī)掃描參數(shù):(1)軸位T2WI,TR 2500~3500 ms,TE 90 ms,矩陣276×215,F(xiàn)OV 22 cm×22 cm,層厚5 mm,層距default,NSA 3;(2)軸位T2-STIR,TR 3000 ms,TE 80 ms,矩陣276×212,F(xiàn)OV 22 cm×22 cm,層厚5 mm,層距default,NSA 2;(3)冠狀位T2-STIR,TR 1500~2500 ms,TE 60 ms,矩陣200× 309,F(xiàn)OV 20 cm×25.2 cm,層厚4 mm,層距default,NSA 1。增強(qiáng)掃描參數(shù):TR 400~675 ms,TE 18 ms,F(xiàn)OV 22 cm×22 cm,層距default,NSA 2,橫斷位、冠狀位、矢狀位的矩陣分別為276×221、316×258、317×258,層厚分別為5 mm、4 mm、4 mm。IVIM參數(shù):TR/TE=6000 ms/shortest,矩陣88×104,F(xiàn)OV 22 cm×22 cm,層厚4 mm,層距0.4 mm,NSA 2。b值取9個(gè)(0 s/mm2、25 s/mm2、50 s/mm2、75 s/mm2、100 s/mm2、150 s/mm2、200 s/mm2、500 s/mm2和800 s/mm2)。
將患者的IVIM數(shù)據(jù)輸入IDL 6.3 后處理軟件(ITT Visual Information Solutions,Boulder,CO),2名年資分別為3年和5年的擅長鼻咽部MR診斷的影像醫(yī)師,在不知曉患者資料的情況下分析圖像。采用Le[4]提出的雙指數(shù)模型,公式:Sb/S0=(1-f)×exp(-b×D)+f×exp[-b×(D*+D)],其中Sb和S0分別代表b為任意值和b=0 s/mm2時(shí)體素內(nèi)平均信號(hào),生成D圖、f圖及D*圖。D為純擴(kuò)散系數(shù)(true molecular diffusion coefficient),反映真實(shí)水分子擴(kuò)散信號(hào);f代表灌注分?jǐn)?shù)(perfusion fraction),反映血管容積占整個(gè)組織容積比例,組織內(nèi)的血管密度;D*是偽擴(kuò)散系數(shù)(pseudodiffusion coefficient),反映組織內(nèi)灌注信號(hào)。用單指數(shù)模型獲得表觀擴(kuò)散系數(shù)(apparent diffusion coefficient,ADC)圖,ADC反映組織中水分子的總體擴(kuò)散信號(hào)。
將放療前、放療開始后1個(gè)月及放療完成后1個(gè)月的圖像分成1、2、3組。具體測量步驟如下:2位閱片者獨(dú)立參考3組圖像的軸位T2-STIR和T1WI增強(qiáng)圖像,選腫瘤最大橫斷面,勾畫整個(gè)腫瘤范圍作為感興趣區(qū)(region of interest,ROI),盡量避開壞死區(qū),獲得不同參數(shù)值(D、f、D*及ADC值),并記錄腫瘤最大面積。若放化療后病灶消失,最大面積記0 mm2,在治療前病灶位置畫約5 mm2的ROI。每位閱片者測量3次取平均值,取2位閱片者測量值的平均值作為參數(shù)值。
腫瘤消退率(regression rate,RSO)=(治療前腫瘤面積-治療后腫瘤面積)/治療前腫瘤面積×100%。依據(jù)RECIST 1.1標(biāo)準(zhǔn)[5],將療效分為4組:(1)完全緩解(complete response, CR)組:病灶消失,RSO=100%;(2)部分緩解(partial response,PR)組:RSO≥30%;(3)疾病穩(wěn)定(stable disease,SD)組:介于PR與PD 之間;(4)疾病進(jìn)展(progress disease,PD)組:病灶面積增大超過25%。
數(shù)據(jù)采用SPSS 18.0軟件分析,計(jì)量資料中正態(tài)分布以均數(shù)±標(biāo)準(zhǔn)差表示。配對(duì)t檢驗(yàn)分析不同時(shí)間點(diǎn)IVIM參數(shù)的差異,Pearson相關(guān)性分析腫瘤面積與IVIM各參數(shù)間的相關(guān)性,獨(dú)立t檢驗(yàn)分析不同療效組治療前IVIM參數(shù)的差異,使用非參數(shù)檢驗(yàn)(Wilcoxon秩和檢驗(yàn))比較各參數(shù)不同時(shí)間點(diǎn)間的差異。P<0.05認(rèn)為差異有統(tǒng)計(jì)學(xué)意義。
表1 鼻咽癌患者完全緩解組與部分緩解組治療前各參數(shù)平均值及相關(guān)性Tab.1 IVIM parameters and correlation of group CR and PR before treatment in nasopharyngeal carcinoma patients
表2 鼻咽癌患者在放化療過程中不同時(shí)間點(diǎn)的腫瘤面積及IVIM參數(shù)平均值Tab.2 Changes of IVIM parameters and tumor size during the concurrent chemo-radiotherapy course in nasopharyngeal carcinoma patients
表3 鼻咽癌患者在放化療過程中腫瘤面積及各參數(shù)不同時(shí)間點(diǎn)間的相關(guān)性Tab.3 Correlations of IVIM parameters between different time points in nasopharyngeal carcinoma patients under concurrent chemo-radiotherapy
放療完成后1個(gè)月,完全緩解組10例,部分緩解組13例。如表1所示,完全緩解組與部分緩解組治療前的D值差異有統(tǒng)計(jì)學(xué)意義(P=0.04),其他參數(shù)差異無統(tǒng)計(jì)學(xué)意義。ADC及D值在治療中逐漸升高,f值先上升后下降。治療后腫瘤面積逐漸縮小,D*先下降后升高。見表2。1組與3組、1組與2組及2組與3組的腫瘤面積均有較好相關(guān)性。而治療前的腫瘤最大面積與f、ADC、D*及D值差異均無統(tǒng)計(jì)學(xué)意義(P值分別為0.986、0.189、0.190、0.234)。見表3。如表3所示,ADC值:1組與3組及1組與2組有較好相關(guān)性(P<0.001),D值亦如此。f值:1組與2組也有較好相關(guān)性。D*值:1組與2組、1組與3組及2組與3組差異均無統(tǒng)計(jì)學(xué)意義。每組ADC與D值均有較好相關(guān)性。1組ADC與D值的相關(guān)系數(shù)為0.869,P<0.001,2組ADC與D值的相關(guān)系數(shù)為0.775,P<0.001,3組ADC與D值的相關(guān)系數(shù)為0.766,P<0.001。見表4。
本研究中治療前鼻咽癌組織的ADC值和D值均較低,這與Jia等[6]的研究結(jié)果類似。這是因?yàn)锳DC值和D值反映活體組織中水分子擴(kuò)散程度,而鼻咽癌組織中腫瘤細(xì)胞多,密度高,細(xì)胞核漿比大,排列紊亂,細(xì)胞外間隙變小,水分子擴(kuò)散受限。而治療后,ADC及D值逐漸升高,這可能是由于治療后腫瘤細(xì)胞減少,密度減低,細(xì)胞外間隙增加,水分子自由擴(kuò)散增加。
雖然放療后ADC與D值均增加,且每組的ADC與D值間相關(guān)性均較好,但D值均低于ADC值。因?yàn)榻M織內(nèi)微循環(huán)灌注對(duì)單指數(shù)ADC值亦有影響,體素內(nèi)水分子的擴(kuò)散被高估了。雙指數(shù)模型在低b值(<200 s/mm2)時(shí),微循環(huán)灌注對(duì)MR信號(hào)衰減影響大。而D值的計(jì)算是選取高b值(>200 s/mm2),此時(shí),微循環(huán)灌注對(duì)MR信號(hào)的影響微乎其微,反映的是純擴(kuò)散信息[3,7],因而ADC值大于D值。這說明治療過程中ADC和D值的變化可觀測同步放化療療效。D值可更準(zhǔn)確地反映腫瘤內(nèi)水分子擴(kuò)散信息。
表4 鼻咽癌患者在放化療過程中每個(gè)時(shí)間點(diǎn)各參數(shù)間的相關(guān)性Tab.4 Correlations of IVIM parameters at each time point in nasopharyngeal carcinoma patients under concurrent chemoradiotherapy
完全緩解組患者治療前的D值高于部分緩解組,治療前D值高,療效好,差異有統(tǒng)計(jì)學(xué)意義。而之前的研究認(rèn)為,治療前低D值預(yù)示頭頸部腫瘤的放化療療效好[7]。這可能是由于本研究的樣本量較少,且23例患者病灶局部均得到有效控制,沒有患者被認(rèn)定為疾病進(jìn)展或疾病穩(wěn)定,需擴(kuò)大樣本研究。
f值可反映腫瘤的血管容積比例,主要與局部的血流灌注有關(guān)。本研究治療前的f值與Xiao等[8]研究中治療前鼻咽癌的f值[(0.18±0.03)%]接近。在放化療后1個(gè)月,f值增高。可能由于治療后腫瘤局部組織充血,亦伴有炎性細(xì)胞及成纖維細(xì)胞等組織增生,可促進(jìn)瘤內(nèi)新生毛細(xì)血管增多,導(dǎo)致局部灌注增加。同時(shí),腫瘤組織灌注及血管容積與含氧狀態(tài)密切相關(guān)。放療后局部組織灌注增加,提高了腫瘤細(xì)胞的血供和含氧狀態(tài),從而達(dá)到更好的治療效果[9]。f值可作為觀測放化療療效的潛在指標(biāo)。在放化療結(jié)束后1個(gè)月,f值降低。這可能因?yàn)殡S著照射劑量的累積,腫瘤細(xì)胞減少,部分血管堵塞、減少或消失,以及病灶纖維化,使得組織灌注減低[10]。
本研究顯示,治療前f值低,療效好,這與之前研究結(jié)果一致[10]。與本結(jié)果不同的是,Hou等[11]在研究動(dòng)態(tài)對(duì)比增強(qiáng)(dynamic contrastenhanced,DCE) MRI預(yù)測鼻咽癌放化療療效中發(fā)現(xiàn),治療前腫瘤高灌注,放化療效果較好??赡苁莊值不僅受血管容積的影響,還受腫瘤的血流以及自旋弛緩時(shí)間的影響[12]。此外,不同的磁共振掃描技術(shù)有差別。因此,不能直接把f值與DCEMRI的參數(shù)進(jìn)行比較。但本研究中完全緩解組與部分緩解組治療前f值的差異無統(tǒng)計(jì)學(xué)意義,需增加樣本量。
D*值反映組織內(nèi)灌注信號(hào)。本研究中,D*值先下降后上升。然而,D*值在1組與2組、1組與3組及2組與3組間差異均無統(tǒng)計(jì)學(xué)意義,其穩(wěn)定性較差。Federau等[13]認(rèn)為D*值受心跳周期的影響,心臟收縮時(shí)的D*值比舒張時(shí)大。而本研究未使用心電觸發(fā),因此D*值會(huì)有波動(dòng)。Kakite等[14]對(duì)肝細(xì)胞癌IVIM成像的研究表明,D*值的穩(wěn)定性差。D*值在很多臨床應(yīng)用中受限。
本研究也存在局限性。首先,樣本量相對(duì)較少,本研究只納入23例患者,有待增加。其次,觀察期較短,只隨訪到放療完成后1個(gè)月。第三,沒有組織病理學(xué)證實(shí)。磁共振無法確診殘留腫瘤和放療后纖維化。
總之,IVIM-MRI可監(jiān)測鼻咽癌在放化療過程中的動(dòng)態(tài)變化。其中,D值更能有效監(jiān)測放化療療效,f值可作為潛在觀察指標(biāo)。IVIM-MRI將成為鼻咽癌臨床研究的有效方法之一。
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Intravoxel incoherent motion magnetic resonance imaging for evaluating the efficacy of concurrent chemoradiotherapy in nasopharyngeal carcinoma
GUO Ting-ting, LIU Song, ZHOU Nan, ZHOU Zheng-yang*
Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine,Nanjing 210008, China
*Correspondence to: Zhou ZY, E-mail: zyzhou@nju.edu.cn
Objective:To explore the value of intravoxel incoherent motion magnetic resonance imaging in evaluating the efficacy of chemoradiotherapy in nasopharyngeal carcinoma (NPC).Materials and Methods:Twenty-seven patients with nasopharyngeal carcinoma proved by biopsy pathology were enrolled. Those patients underwent MRI at the time points of pretreatment (group 1), one month after the start of radiotherapy (group 2) and one month after the end of radiotherapy (group 3). T1WI, T2WI, IVIM (9 b-factors,0~800 s/mm2) and contrast-enhanced T1WI were included. They
concurrent chemotherapy for 3 cycles during radiotherapy. The apparent diffusion coefficient (ADC)was derived from the mono-exponential model, while the diffusion coefficient (D),perfusion fraction (f) and pseudodiffusion coefficient (D*) were calculated via the biexponential model. The values of IVIM parameters and maximum area for NPC lesions were measured at each time point, and their dynamic changes and correlation were analyzed.Results:Patients whose images had artifact were excluded, and 23 patientswere included in this study finally. The ADC and D values increased throughout the whole course. ADC value of group 1 and 3 was 0.80×10-3mm2/s and 1.57×10-3mm2/s, respectively (P1/3<0.001); D value of group 1 and 3 was 0.68×10-3mm2/s and 1.31×10-3mm2/s,respectively (P1/3<0.001). f value was increased originally then decreased. f value of group 1 and 2 was 11% and 19% (P1/2<0.001).There were no correlations between group 1 and group 2, group 1 and group 3, group 2 and group 3 for D*value.Conclusion:IVIMMRI could monitor dynamic changes of NPC during treatment. ADC value was influenced by microcirculation perfusion, therefore the diffusion of water molecules were overrated. D value was calculated from high b values (>200 s/mm2), so microcirculation perfusion had little effect on MR signal, it reflected pure diffusion information. D value was better at monitoring the efficacy of chemoradiotherapy. f value might be a potential biomarker.
Intravoxel incoherent motion; Nasopharyngeal neoplasms; Chemoradiotherapy; Magnetic resonance imaging
10 Jan 2017, Accepted 22 Mar 2017
國家自然科學(xué)基金項(xiàng)目(編號(hào):81371516);國家衛(wèi)生和計(jì)劃生育委員會(huì)基金項(xiàng)目(編號(hào):W201306)
周正揚(yáng),E-mail:zyzhou@nju.edu.cn
2017-01-10
接受日期:2017-03-22
R445.2;R739.62;R739.63
A
10.12015/issn.1674-8034.2017.04.004
郭婷婷, 劉松, 周楠, 等. 體素內(nèi)不相干運(yùn)動(dòng)磁共振成像評(píng)估鼻咽癌同步放化療療效. 磁共振成像, 2017, 8(4):254-259.
ACKNOWLEDGMENTS This work was part of National Natural Science Foundation of China (No.81371516); Foundation of National Health and Family Planning Commission (No.W201306).