超声造影研究兔慢性肾衰肾血流灌注
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摘要
目的:以血肌酐、尿素氮、病理检查作为参照,应用实时超声造影技术结合时间-强度曲线定量评价兔慢性肾功能衰竭(CRF)不同阶段肾皮质血流灌注的变化。
方法:15只健康雄性家兔,通过连续注射阳离子化牛血清白蛋白(C-BSA)共8周,建立膜性肾病发展至CRF模型。分别于注射C-BSA前、注射后2 w、4 w、6 w、8 w抽血化验血肌酐、尿素氮;并于各时间点利用二维超声测量双侧肾脏大小、皮质厚度,之后在实时造影条件下(机械指数0.088)进行超声造影观察双侧肾脏血流灌注,并储存造影动态图像,然后应用仪器内置的Wash-in/Wash-out软件对肾脏皮质血流灌注进行定量分析,量化参数包括造影剂开始增强时间、达峰时间、峰值强度、曲线下面积以及峰值强度减半时间。每次造影结束后随机处死一只兔子,取出肾脏进行病理检查。以血生化及病理结果作为参照,比较不同阶段肾皮质的血流灌注及时间强度曲线量化参数的变化情况。
结果:血生化指标肌酐、尿素氮自6 w起升高,与注射C-BSA前比较有统计学意义。二维超声结果显示肾脏从2 w到6 w体积增大,皮质增厚,此时病理出现肾小囊腔扩大、肾小球细胞肿胀、炎性细胞浸润和囊腔内渗出物。8 w时肾脏出现减小的趋势,病理出现肾小球硬化、间质纤维化和肾小管萎缩。注射C-BSA后从4 w起肾皮质血流灌注减低,表现为时间-强度曲线参数中峰值强度减低。自4 w起皮质灌注速度和廓清速度均减低,表现为达峰时间和峰值强度减半时间延迟。曲线下面积在2 w、4 w、6 w时与注射前比较,差异无统计学意义,8 w时减小。
结论:超声造影结合时间-强度曲线可定量分析慢性肾功能衰竭不同阶段肾皮质血流灌注情况。肾血流灌注的下降早于常规实验室检查指标的异常。血流动力学的变化与病理变化密切相关。
Objective: To access the renal perfusion of chronic renal failure (CRF) at different stages in rabbits by contrast-enhanced ultrasound with time-intensity curve, compared with the pathological changes and serum creatinine (Scr), blood urea nitrogen (BUN).
Methods: Fifteen rabbit CRF models were established by intravenously injecting cationic bovine serum albumin (C-BSA) for 8 weeks. Scr and BUN were examined at pre-injection and 2w, 4w, 6w, 8w post-injection. Renal size was measured by 2D ultrasound at the same time points, and then contrast-enhanced ultrasound was performed on bilateral kidney. Renal perfusion was analyzed quantitatively with the time-intensity curve by Wash-in/Wash-out software. The parameters of the time intensity curve include time to enhancement (ET), time to peak intensity (PIT), peak signal intensity (PSI), area under the curve (AUC) and time to half of peak intensity (HPT). After that one rabbit was sacrificed randomly at each time point and its kidney was sampled for pathological examination. Investigate the changes of blood perfusion and time-intensity curve parameters in CRF rabbits at different stages with reference to the pathology and blood biochemistry.
Results: The level of Scr and BUN has increased since 6w after injection of C-BSA. 2D ultrasound showed the renal volume was enlarged and the cortex was thickened from 2w to 6w post-injection; the pathological examination exhibited glomerular cyst cavity expanding, glomerular cell swelling, and inflammatory cell infiltration and exudate. At 8w post-injection, the renal size had a decreasing trend and pathological studies showed glomerular sclerosis, renal interstitial fibrosis and tubular atrophy. Renal cortical perfusion reduced from 4w, manifested as the PSI of the time-intensity curve parameters decreased. The speed of infusion and clearance was slower, shown as PIT and HPT delayed. Compared with pre-injection, there was no difference in AUC at 2w, 4w and 6w post-injection, and then AUC decreased at 8w post-injection.
Conclusions: Contrast-enhanced ultrasound combined with time-intensity curve can analyze renal perfusion of CRF quantitatively at different stages. The reduction of renal perfusion was earlier than the changes of routine laboratory indexes in CRF. The change of haemodynamic was closely related with pathology.
方法:15只健康雄性家兔,通过连续注射阳离子化牛血清白蛋白(C-BSA)共8周,建立膜性肾病发展至CRF模型。分别于注射C-BSA前、注射后2 w、4 w、6 w、8 w抽血化验血肌酐、尿素氮;并于各时间点利用二维超声测量双侧肾脏大小、皮质厚度,之后在实时造影条件下(机械指数0.088)进行超声造影观察双侧肾脏血流灌注,并储存造影动态图像,然后应用仪器内置的Wash-in/Wash-out软件对肾脏皮质血流灌注进行定量分析,量化参数包括造影剂开始增强时间、达峰时间、峰值强度、曲线下面积以及峰值强度减半时间。每次造影结束后随机处死一只兔子,取出肾脏进行病理检查。以血生化及病理结果作为参照,比较不同阶段肾皮质的血流灌注及时间强度曲线量化参数的变化情况。
结果:血生化指标肌酐、尿素氮自6 w起升高,与注射C-BSA前比较有统计学意义。二维超声结果显示肾脏从2 w到6 w体积增大,皮质增厚,此时病理出现肾小囊腔扩大、肾小球细胞肿胀、炎性细胞浸润和囊腔内渗出物。8 w时肾脏出现减小的趋势,病理出现肾小球硬化、间质纤维化和肾小管萎缩。注射C-BSA后从4 w起肾皮质血流灌注减低,表现为时间-强度曲线参数中峰值强度减低。自4 w起皮质灌注速度和廓清速度均减低,表现为达峰时间和峰值强度减半时间延迟。曲线下面积在2 w、4 w、6 w时与注射前比较,差异无统计学意义,8 w时减小。
结论:超声造影结合时间-强度曲线可定量分析慢性肾功能衰竭不同阶段肾皮质血流灌注情况。肾血流灌注的下降早于常规实验室检查指标的异常。血流动力学的变化与病理变化密切相关。
Objective: To access the renal perfusion of chronic renal failure (CRF) at different stages in rabbits by contrast-enhanced ultrasound with time-intensity curve, compared with the pathological changes and serum creatinine (Scr), blood urea nitrogen (BUN).
Methods: Fifteen rabbit CRF models were established by intravenously injecting cationic bovine serum albumin (C-BSA) for 8 weeks. Scr and BUN were examined at pre-injection and 2w, 4w, 6w, 8w post-injection. Renal size was measured by 2D ultrasound at the same time points, and then contrast-enhanced ultrasound was performed on bilateral kidney. Renal perfusion was analyzed quantitatively with the time-intensity curve by Wash-in/Wash-out software. The parameters of the time intensity curve include time to enhancement (ET), time to peak intensity (PIT), peak signal intensity (PSI), area under the curve (AUC) and time to half of peak intensity (HPT). After that one rabbit was sacrificed randomly at each time point and its kidney was sampled for pathological examination. Investigate the changes of blood perfusion and time-intensity curve parameters in CRF rabbits at different stages with reference to the pathology and blood biochemistry.
Results: The level of Scr and BUN has increased since 6w after injection of C-BSA. 2D ultrasound showed the renal volume was enlarged and the cortex was thickened from 2w to 6w post-injection; the pathological examination exhibited glomerular cyst cavity expanding, glomerular cell swelling, and inflammatory cell infiltration and exudate. At 8w post-injection, the renal size had a decreasing trend and pathological studies showed glomerular sclerosis, renal interstitial fibrosis and tubular atrophy. Renal cortical perfusion reduced from 4w, manifested as the PSI of the time-intensity curve parameters decreased. The speed of infusion and clearance was slower, shown as PIT and HPT delayed. Compared with pre-injection, there was no difference in AUC at 2w, 4w and 6w post-injection, and then AUC decreased at 8w post-injection.
Conclusions: Contrast-enhanced ultrasound combined with time-intensity curve can analyze renal perfusion of CRF quantitatively at different stages. The reduction of renal perfusion was earlier than the changes of routine laboratory indexes in CRF. The change of haemodynamic was closely related with pathology.
引文
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[2]董怡,王文平.医学影像学技术定量评价肾功能研究进展.上海医学影像, 2007, 16(3): 255-257.
[3]张勉之,张敏英,沈伟梁,等.慢性肾功能衰竭原发病的流行病学研究.中国慢性病预防与控制, 2004,12(2): 70-72.
[4]刘国辉,叶任高.缬沙坦延缓慢性肾衰竭进展的临床研究.中国中西医结合肾病杂志, 2003, 4(8): 460-461.
[5]赵怡蕊,宋跃飞,王琴,等.疏血通注射液联合黄芪注射液治疗慢性肾衰竭的临床观察.中国中西医结合肾病杂志, 2004, 5(11): 669-670.
[6] Miles KA. Measurement of tissue perfusion by dynamic computed tomography. Br J Radiol, 1991, 64(5): 409-412.
[7] Lerman LO, Rodriguez-Porcel M. Functional assessment of the circulation of the single kidney. Hypertension, 2001, 38(3 Pt 2):625-629.
[8] Georage AT, Carol EB, Brent H, et al. Renal cortical ischemia in rabbits revealed by contrast enhanced power Doppler sonography. AJR, 1998, 170(2): 417-422.
[9]陆林忠.实时超声造影中MI和DP的意义和作用.声学技术, 2004, 23(3): 84-86.
[10] Wei K, Le E, Bin JP, et al. Quantification of renal blood flow with contrast-enhanced ultrasound. J Am Coll Cardiol, 2001, 37(4): 1135–1140.
[11]王健,康春松,徐琨,等.实时灰阶超声造影研究兔肾血流灌注.中华超声影像学杂志, 2008, 17(1): 170-172.
[12]王健,康春松,李嵘娟,等.实时灰阶超声造影评价肾动脉狭窄血流灌注的实验研究.中国医学影像技术,2007,23(10): 1449-1452.
[13]杨未晓,高云华,朱贤胜.声学造影与能量多普勒显像评价急性肾衰肾皮质血流灌注的实验研究.中国超声医学杂志, 2002, 18(6): 413-416.
[14] Border WA, Ward HJ, Kalim ES, et al. Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. Demonstration of pathogenic role for electrical charge. J Clin Invest, 1982, 69: 451-461.
[15]何立群,王怡,郑平东.阳离子化牛血清白蛋白制作慢性肾衰动物模型.安徽中医临床杂志,1998, 10(6): 356.
[16]李杰,梁萍.彩色多普勒超声和超声造影在肝脏占位性病变中的应用进展.消化外科, 2002, l(5): 377-380.
[17]金惠铭.病理生理学.第5版.北京:人民卫生出版社, 2001: 253.
[18] Ikee R, Kobayashi S, Hemmi N, et al. Correlation between the resistive index by Doppler ultrasound and kidney function and histology. Am J Kidney Dis, 2005, 46(4): 603-609.
[19] Galesic K, Sabljar-Matovinovic M, Tomic M, et al. Renal vascular resistance in glomerular diseases-correlation of resistance index with biopsy findings. Coll Antropol, 2004, 28(2): 667-674.
[20]姜玉新.超声造影的基础研究与临床应用.中国医学影像技术, 2004, 20(3): 325.
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