Perfusion CT assessment of tissue hemodynamics following hepatic arterial infusion of increasing doses of angiotensin II in a rabbit liver tumor model.
Perfusion CT assessment of tissue hemodynamics following hepatic arterial infusion of increasing doses of angiotensin II in a rabbit liver tumor model.
复制标题
在兔肝肿瘤模型中肝动脉输注剂量增加的血管紧张素 II 后，灌注 CT 评估组织血流动力学。
DOI：
10.1148/radiol.11101868
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发表时间：
2011
期刊：
影响因子：
19.7
通讯作者：
Kundra,Vikas
中科院分区：
文献类型：
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作者：
Wright,KennethC;Ravoori,MuraliK;Dixon,KatherineA;Han,Lin;Singh,SheelaP;Liu,Ping;Gupta,Sanjay;Johnson,ValenE;Kan,Zuxing;Kundra,Vikas
目的应用动态对比剂增强灌注计算机断层扫描(CT)研究血管紧张素II对正常兔肝脏和肝脏VX2肿瘤模型肝脏血流动力学的影响。材料与方法本研究由机构动物护理与使用委员会批准。将肝脏VX2肿瘤单独移植于12只兔体内。分别在肝动脉注射不同剂量(0.1~5 0.0μg/m L)血管紧张素II前(基线)和肝动脉注射血管紧张素II后行肝脏CT灌注扫描，开始静脉注射造影剂后连续采集图像80s。计算肿瘤及邻近和远端正常肝组织的血流量(BF)、血容量(BV)、平均通过时间(MTT)和毛细血管通透性-表面积乘积。使用广义线性混合模型估计血管紧张素II剂量对预后指标的影响。结果血管紧张素II注射增加了肿瘤和肝远端血管的对比增强。2.5~2 5.0min g/mLAng/mLAng/mL2.5μg/mL2.5μg/mL2.5剂量组肿瘤血流量明显高于邻近(68.0mLvs2 6.3mLmin/100g，P<0.0 0 1)和远处(68.0vs28.3mLmin/100g，P=0.0 2)正常肝组织。肿瘤BV随血管紧张素II剂量的不同而不同，但仅在2.5μg/m L(4.8vs3.5m L/100g，4.8vs3.3m L/100g，P=0.006)和10.0μg/m L(4.9vs4.4m L/100g[P=0.007]，4.9vs4.3m L/100g[P=0.04])剂量时肿瘤的BV大于邻近和远端肝组织的BV。血管紧张素II剂量为2.5μg/mL时，肿瘤的MTT值明显短于癌旁肝组织(9.7vs15.8s，P=0.0 0 1)和10.0μg/mL时(5.1vs13.2s，P=0.0 0 7)，而仅在2.5μg/mL时，肿瘤组织的MTT值明显短于远端肝组织(9.7vs15.3s，P=.0 0 0 6)。在2.5min g/mLAng/mLAng-II剂量下，肿瘤的毛细血管通透性表面积乘积高于癌旁肝组织(11.5mLvs8.1mLmin/100g，P=0.01)。结论CT灌注成像可以从机制上了解血管紧张素II在肝脏内的灌注情况，并推导出最佳有效剂量。与邻近和远处的正常肝组织相比，2.5μg/mL的血管紧张素II剂量主要通过收缩正常的远端肝血管进而增加肿瘤的BF和BV来增加肝脏VX2肿瘤的血流灌注量。
PurposeTo investigate the effects of increasing doses of angiotensin II on hepatic hemodynamics in the normal rabbit liver and in hepatic VX2 tumors by using dynamic contrast material–enhanced perfusion computed tomography (CT).Materials and MethodsThis study was approved by the institutional animal care and use committee. Solitary hepatic VX2 tumors were implanted into 12 rabbits. In each animal, perfusion CT of the liver was performed before (at baseline) and after hepatic arterial infusion of varying doses (0.1–50.0 μg/mL) of angiotensin II. Images were acquired continuously for 80 seconds after the start of the intravenous contrast material administration. Blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability–surface area product were calculated for the tumor and the adjacent and distant normal liver tissue. Generalized linear mixed models were used to estimate the effects of angiotensin II dose on outcome measures.ResultsAngiotensin II infusion increased contrast enhancement of the tumor and distal liver vessels. Tumor BF increased in a dose-dependent manner after administration of 0.5–25.0 μg/mL angiotensin II, but only the 2.5 μg/mL dose induced a significant increase in tumor BF compared with BF in the adjacent (68.0 vs 26.3 mL/min/100 g,P< .0001) and distant (68.0 vs 28.3 mL/min/100 g,P= .02) normal liver tissue. Tumor BV varied with angiotensin II dose but was greater than the BV of the adjacent and distant liver tissue at only the 2.5 μg/mL (4.8 vs 3.5 mL/100 g for adjacent liver [P< .0001], 4.8 vs 3.3 mL/100 g for distant liver [P= .0006]) and 10.0 μg/mL (4.9 vs 4.4 mL/100 g for adjacent liver [P= .007], 4.9 vs 4.3 mL/100 g for distant liver [P= .04]) doses. Tumor MTT was significantly shorter than the adjacent liver tissue MTT at angiotensin II doses of 2.5 μg/mL (9.7 vs 15.8 sec,P= .001) and 10.0 μg/mL (5.1 vs 13.2 sec,P= .007) and significantly shorter than the distant liver tissue MTT at 2.5 μg/mL only (9.7 vs 15.3 sec,P= .0006). The capillary permeability–surface area product for the tumor was higher than that for the adjacent liver tissue at the 2.5 μg/mL angiotensin II dose only (11.5 vs 8.1 mL/min/100 g,P= .01).ConclusionPerfusion CT enables a mechanistic understanding of angiotensin II infusion in the liver and derivation of the optimal effective dose. The 2.5 μg/mL angiotensin II dose increases perfusion in hepatic VX2 tumors versus that in adjacent and distant normal liver tissue primarily by constricting normal distal liver vessels and in turn increasing tumor BF and BV.© RSNA, 2011