3.0TMR经导管动脉内灌注成像评价不同栓塞方法治疗兔VX2肝肿瘤的栓塞效果.pdf

9963.0TMR经导管动脉内灌注成像评价不同栓塞方法治疗兔VX2肝肿瘤的栓塞效果Modern Practical Medicine,August 2023,Vol.35,No.8吴安乐，滕飞，林佳，咸玉涛，韩瑞【摘要】目的通过4D-经导管动脉内灌注成像（4D-TRIP)测定肿瘤灌注值，旨在术中定量评价经动脉化疗栓塞序贯载药微球栓塞治疗肝肿瘤的栓塞效果。方法建立兔VX2移植瘤模型30 只，3周后免VX2肝肿瘤模型随机分成A、B、C 组3组各10 只，A组为碘油栓塞组（C-TACE组),B组为载药微球组（D-TACE组),C组为碘油栓塞序贯载药微球栓塞组（S-TACE组）。先行肝肿瘤微导管超选择性肿瘤供血动脉插管，栓塞治疗前（DayO）行3.0 TMRI常规序列和4D-TRIP扫描，扫描完成后根据分组行经导管栓塞治疗，治疗后即刻(Day1)再次行3.0 TMRI常规序列和4D-TRIP扫描。测定栓塞Day0、D a y 1肿瘤灌注值Fp，栓塞术后14d处死全部实验兔，取肝肿瘤组织行HE染色。结果所有实验免均完成超选择性肿瘤供血动脉插管，DayO时4D-TRIP提示肿瘤动脉期活性部分显著强化，中间囊变坏死区无强化;Day1时肿瘤强化明显减弱，或无明显活性强化。3组栓塞前后灌注值Fp差异均有统计学意义（均P0.05),3组栓塞术后即刻灌注值Fp差异有统计学意义(P0.05)。术后14d病理所见：A组肿瘤内可见成活肿瘤组织；B组肿瘤内可见散在分布血管巢，其内可见残留微球影，并可见灶性残存肿瘤细胞；C组内可见绝大多数肿瘤接近完全坏死，活性肿瘤细胞位于周边组织。结论4D-TRIP成像技术能在体状态下反映肿瘤栓塞前后肿瘤血供情况，较客观反映序贯栓塞术较常规碘油栓塞和载药微球栓塞具有更好的栓塞效果。【关键词】VX2肝肿瘤；经导管动脉灌注成像；载药微球；序贯栓塞doi:10.3969/j.issn.1671-0800.2023.08.005【中图分类号】R816.5【文献标志码】AEvaluation of the embolization effect of different embolization methods on rabbit VX2 liver tumors using 3.0TMR transcatheter arterial perfusion imagingWU Anle,TENG Fei,LIN Jia,XIAN Yutao,HAN Rui(The First Affiliated Hospital of Ningbo University,Ningbo315010,Zhejiang,China)AbstractObjective To quantitatively evaluate the embolization effect of sequential drug loaded microsphere em-bolization in the treatment of liver tumors during surgery with tumor perfusion value measured by 4D Transcatheter In-traarterial Perfusion Imaging(4D-TRIP).Methods Thirty rabbit VX2 transplanted tumor models were established.After three weeks,the rabbit VX2 liver tumor model was randomly divided into three groups:A,B,and C,with ten micein each group.Group A was treated with lipiodol embolization(C-TACE group),Group B was treated with drug loadedmicrospheres(D-TACE group),and Group C was treated with lipiodol embolization sequential drug loaded micro-spheres embolization(S-TACE group).First,liver tumor microcatheter superselective tumor supply artery catheteriza-tion was performed.Before embolization treatment(DayO),3.0T MRI routine sequence and 4D-TRIP scanning wereperformed.After scanning,transcatheter embolization treatment was performed according to the grouping.Immediatelyafter treatment(Day 1),3.0T MRI routine sequence and 4D-TRIP scanning were performed again.Tumor perfusion valueF was measured during embolization on Day0 and Day1.All experimental rabbits were killed 14 days after emboliza-tion,and liver tumor tissues were taken for HE staining.Results All experimental rabbits completed superselectivetumor supply artery catheterization.At Dayo,4D-TRIP showed significant enhancement of tumor arterial phase activity,with no enhancement in the middle cystic necrotic area.On Day l,tumor enhancement significantly weakened or showedno significant activity enhancement.The differences of three sets of perfusion values Fp before and afer embolizationwere statistically significant(all P 0.05),and the immediate perfusion value after embolization in the three groups【文章编号】16 7 1-0 8 0 0(2 0 2 3)0 8-0 9 9 6-0 5基金项目：宁波市科技计划项目(2 0 0 9 A610165)作者单位：315010宁波，宁波大学附属第一医院通信作者：吴安乐，Email：f y w u a n l e n b u.e d u.c n现代实用医学2 0 2 3年8 月第35卷第8 期were statistically different(all P/max(Ca(t),max(Gt(t)代表对比剂最大摄取浓度梯度；max(Ga(t)代表肿瘤供血动脉对比剂最大浓度，即max(Ga(t)G d 注射。将微导管头端附近供血动脉作为入流动脉，感兴趣区（ROD选定为肿瘤组织，包括活性强化部分和坏死囊性部分，测定灌注值Fp。1.4病理分析栓塞术后14d空气栓塞处死所有实验兔，取出肿瘤组织，用10%中性甲醛溶液固定，石蜡包埋肿瘤组织,HE染色病理观察。1.5统计方法采用SPSS20.0统计软件进行分析，Modern Practical Medicine,August 2023,Vol.35,No.8表1常规TIW、T W I 和TRIPMRI扫描参数T,W(TSE)TIW(FLASH)冠状位轴位1 769 4 341/39200/2.3918018018018019219222422417172/0.62/0.615070T,W(TSE)轴位22474384/39180180192192172/0.6150计量资料以均数土标准差表示，多组比较采用方差分析，栓塞前后比较采用t检验。P0.05表示差异有统计学意义。2结果2.1常规MR及TRIP灌注成像表现MRI能清楚显示肝内肿瘤，所有实验兔均接受栓塞前(DayO)和栓塞后即刻(Day1)经导管动脉内灌注成像检查，无术中栓塞死亡。常规MRI图像显示肿瘤形态不同，呈圆形、卵圆形、不规则型等多种形态，边界相对清楚，中间有大小不等囊变坏死区，所有肿瘤均无脉管侵犯和淋巴结转移，无腹水等表现。术前MRI可见肿瘤呈TWI低信号，TWI高信号，DWI高信号，ADC图显著低信号，见图14。术前4D-TRIP提示肿瘤动脉期活性部分显著强化，中间囊变坏死区无强化，栓塞术后当天肿瘤强化明显减弱或无明显活性强化，见图56。3组栓塞前后灌注值Fp差DWI(EPI)+ADCTRIP轴位6300/9321021025619217MRI(GRE)轴位2.6/1.2128112128112202/0.68图1T,WI图像提示肝左叶肿瘤呈低信号，边界清晰（箭头）图2 TSE序列T2WI图像提示肝左叶肿瘤内混杂高信号（箭头）图3DWI图像（b500）栓塞术前DWI图像提示肿瘤扩散受限、肿瘤高信号（箭头）图4ADC图(b500)栓塞术前ADC图肿瘤显著低信号（箭头）图5C组，栓塞术前TRIP可见肿瘤周围显著强化而内部轻中度强化（箭头）图6 C组，栓塞术后即刻TRIP图像提示肿瘤栓塞术后无强化（箭头）现代实用医学2 0 2 3年8 月第35卷第8 期异均有统计学意义（均P0.05)，3组栓塞术后即刻灌注值Fp差异有统计学意义(P0.05流出，减少了MRI信号饱和；4D采集时间更快，对病灶血供的判断更加准确；同时MRI提供了更优越的周围软组织对比度和周围正常肝组织解部特征，有效解决了时间分辨率不足的弊端，更准确反映肿瘤栓塞前后的灌注值差异。本研究采用4D-TRIP研究肿瘤栓塞前后灌注值，经肝动脉插管成功后，3组实验兔栓塞术前测定的Fp均较高,与肿瘤血管生成机制活跃、肿瘤细胞和活化内皮细胞大量释放VEGF和HIF-因子相关17-8。而栓塞术后即刻(Day1)三种治疗方法栓塞后灌注值下降，表明三种不同栓塞方法均能起到栓塞效果,栓塞后即刻C组较A组和B组灌注值下降(P 0.05),这提示S-TACE较C-TACE和D-TACE肿瘤微血管床更彻底被栓塞。病理组织中A组可见周围成活肿瘤组织，其内可见坏死区，坏死组织表现为无定型样物质。B组可见散在分布微球影，在被微球栓塞的血管周边可见大量坏死区，镜下仍可见少许灶性残存肿瘤细胞。C组内可见绝大多数肿瘤接近完全坏死，少许活性肿瘤细胞主要位于周边组织。这表明 S-TACE治疗肝VX2瘤可以有效阻断肝VX2瘤血供，并持续缓慢释放高浓度局部化疗药物，短时间内杀灭肿瘤细胞，疗效较C-TACE和D-TACE更确切。利益冲突所有作者声明无利益冲突作者贡献声明吴安乐：实验操作、论文撰写、修改；滕飞、林佳、咸玉涛、韩瑞：数据整理、统计学分析1 PAPACONSTANTINOU D,TSILIMIGRAS D I,PAWLIK T M.Recurrent hepatocellular carcinoma:Patterns,detection,stagingand treatmentJ.J Hepatocell Carcinoma,2022,9:947-957.2ZHU X D,SUN H C.Emerging agents and regimens for hepatoc-ellular carcinomaJ.J Hematol Oncol,2019,12(1):110-119.3HOLZWANGER D J,MADOFF D C.Role of interventional radi-ology in the management of hepatocellular 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rabbit VX2 tumor model.J Magn Reson Imaging,2010,31(5):1137-1143.15 SATO K T,WANG D X,LEWANDOWSKI R J,et al.Four-dimen-sional transcatheter intraarterial perfusion MRI monitoring of radi-ofrequency ablation of rabbit VX2 liver tumorsJ.J Magn ResonImaging,2011,34(3):563-569.16 PAN L,SUN C,ZHOU K,et al.Transcatheter intraarterial perf-usion MRI approaches to differentiate reversibly electroporatedpenumbra from irreversibly electroporated zones in rabbit liverJ.Acad Radiol,2020,27(12):1727-1733.17 CHEN H,CHEN J,YUAN HX,et al.Hypoxia-inducible factor-1:A critical target for inhibiting the metastasis of hepatocellular car-cinomaJ.Oncol Lett,2022,24(2):284-290.18 HATZIDAKIS A,MuLLER A L,KROKIDIS M,et al.Local andregional therapies for hepatocellular carcinoma and future com-binationsJ.Cancers(Basel),2022,14(10):2469-2493.收稿日期：2 0 2 3-0 4-11(本文编辑：陈志翔）编读往来作者书写统计学符号须知论文中统计学符号应按GB3358-82统计学名词及符号的有关规定书写如下：（1)样本的算术平均数用英文小写x（中位数仍用M)；（2)标准差用英文小写s；（3)标准误用英文Sx（4)t 检验用英文小写t；（5)F检验用英文大写F；（6)卡方检验用希文x：（7)相关系数用英文小写r；（8)自由度用希文小写v；（9)概率用英文大写P(P值前应给出具体检验值，如t值、x值、q值等）。以上符号均用斜体。(本刊编辑部）