Diagnostic Value Of Contrast-enhanced Ultrasonography In Evaluating Renal Artery Stenosis

Objective: The characteristics of contrast-enhanced ultrasonography(CEUS)parameters in the rabbit model of renal artery stenosis,the diagnostic value of CEUS in grading renal artery stenosis,the characteristics of CEUS parameters and its correlation with the rate of renal artery stenosis were studied in order to investigate the value of CEUS in evaluating renal artery stenosis.Methods: A total of 64 healthy New Zealand rabbits were selected and randomly divided into control group,sham group,renal artery stenosis rate <50%group,renal artery stenosis rate ≥50% group,with 16 rabbits in each group.8rabbits were randomly selected from each group.The rabbit model of renal artery stenosis was established。All of them underwent the following three tests:CEUS examination of renal cortex,renal function test,renal histopathological examination.The main parameters of CEUS examination included peak intensity(PI),time to peak(TTP),wash in slope(WIS)and area under the curve(AUC).Renal function indexes included blood urea nitrogen(BUN)and serum creatinine(SCr).The histopathological score of renal tubular was quantified by Jablonski method.The relationship between CEUS parameters or renal function indexes and the histopathological score of renal tubular was analyzed by Pearson correlation analysis.122 renal arteries with suspicious stenosis from 63 patients were included in the study.All patients with suspected renal artery stenosis underwent CEUS,doppler ultrasonography and digital subtraction angiography DSA examination.The rate of renal artery stenosis was calculated using the imaging methods described above.The severity of renal artery stenosis was determined according the rate of renal artery stenosis.The results of DSA were used as the gold standard to analyze the diagnostic value of CEUS in different grades of renal artery stenosis.130 renal arteries of 69 patients with suspected renal artery stenosis were included in the study group.32 renal arteries of 16 healthy subjects were included in the control group.The correlation between CEUS parameters and the rate of renal artery stenosis was investigated.The value of CEUS parameters and conventional ultrasonography parameters in predicting the rate of renal artery stenosis was analyzed.Results: On the 7th day after modeling,Pearson correlation analysis showed that both BUN and Scr were positively correlated with the histopathological score of renal tubular(r=0.613,0.677,all P<0.05).There was a positive correlation between TTP and renal tubule pathology score(r=0.733,P<0.05).The parameters WIS,PI,AUC were negatively correlated with the renal tubule pathology score(r=-0.537,-0.593,-0.513,all P<0.05).The consistency between doppler ultrasonography and DSA was moderate(Kappa=0.486),and the consistency between CEUS and DSA was good(Kappa=0.749).The sensitivity,specificity and accuracy of CEUS in the diagnosis of renal artery stenosis were 88.9%,87.8%,88.5%,93.5% and 80.0%,respectively.Pearson correlation analysis showed that there was a positive correlation between TTP and renal artery stenosis rate(r=0.638,P<0.05),WIS,PI and AUC were negatively correlated with renal artery stenosis rate(r=-0.624,-0.660,-0.425,P<0.05).Receiver operating characteristic(ROC)curve showed that both CEUS parameters could predict the renal artery stenosis rate,area under the curve of PI was the largest.In the single index prediction model,PI had a higher diagnostic efficiency,when the cut-off value was 17.8 d B,the sensitivity and specificity are87.2% and 80.7%,respectively.Conclusions: CEUS can be used to evaluate the features of renal cortical perfusion changes in the rabbit model of renal artery stenosis and it can reflect the histopathological score of renal tubular.CEUS is a reliable diagnostic method for grading renal artery stenosis and it can be used to evaluate the characteristics of renal cortical blood perfusion in patients renal artery stenosis.Part Ⅰ:The Value of Contrast-enhanced Ultrasonography in Evaluating Renal Histopathological Changes in the Rabbit Model of Renal Artery StenosisObjective: The characteristics and correlation of contrast-enhanced ultrasonography(CEUS)parameters,renal function indexes and the histopathological score of renal tubular in the rabbit model of renal artery stenosis were studied in order to investigate the value of CEUS in evaluating renal histopathological changes caused by renal artery stenosis.Methods: From March to September 2020,64 healthy New Zealand rabbits were selected and randomly divided into control group,sham group,renal artery stenosis rate <50% group,renal artery stenosis rate ≥50% group,with 16 rabbits in each group.The rabbit model of renal artery stenosis was established by pressing the renal artery wall inside a tube.On day 2 and day 7 after modeling,8 rabbits were randomly selected from each group.All of them underwent the following three tests: CEUS examination of renal cortex,renal function test,renal histopathological examination.The main parameters of CEUS examination included peak intensity(PI),time to peak(TTP),wash in slope(WIS)and area under the curve(AUC).Renal function indexes included blood urea nitrogen(BUN)and serum creatinine(SCr).BUN and SCr were detected by colorimetric and enzymatic methods.The histopathological examination was performed using hematoxylin-eosin(HE)staining,and the histopathological score of renal tubular was quantified by Jablonski method.The differences of CEUS parameters,renal function indexes and the histopathological score of renal tubular among the four groups were compared using one-way analysis of variance,and LSD-t test was used for pairwise comparison.Two independent sample t-tests were used to compare the indexes between the 2nd and 7th day after modeling.The relationship between CEUS parameters or renal function indexes and the histopathological score of renal tubular was analyzed by Pearson correlation analysis.Results: Contrast-enhanced ultrasonography showed that on the 2nd day after the establishment of renal artery stenosis model,PI decreased in the renal artery stenosis rate <50% group comparing with the control group and the sham group(all P<0.05);Comparing with the control group,sham group and the renal artery stenosis rate <50% group,the renal artery stenosis rate≥50% group could lead to the increase of time to peak(TTP)and the decrease of WIS,PI and AUC(all P < 0.05).On the 7th day after the establishment of renal artery stenosis model,comparing with the control group and sham group,TTP increased,WIS and PI decreased in the group with renal artery stenosis rate <50%(all P<0.05).Comparing with the control group,sham group and the renal artery stenosis rate <50% group,the renal artery stenosis rate ≥50% group could lead to the increase of TTP and the decrease of WIS,PI and AUC(all P<0.05).On the 7th day after modeling,BUN and SCr in the ≥50% renal artery stenosis group were higher than those on the 2nd day,respectively.(all P<0.05).On the 2nd day after the establishment of renal artery stenosis model.The renal tubular pathological score of the renal artery stenosis rate ≥50% group was significantly higher than that of the control group,the sham group and the renal artery stenosis rate < 50% group(all P < 0.05).On the 7th day after the establishment of renal artery stenosis model,the renal tubular pathological score of the renal artery stenosis rate ≥50% group was significantly higher than that of the control group,the sham group and the renal artery stenosis rate <50% group(all P<0.05).On the 7th day after the establishment of renal artery stenosis model,comparing with the 2nd day,the renal tubular pathological score was significantly increased in the renal artery stenosis rate <50% group and the renal artery stenosis rate ≥50% group(all P < 0.05).On the 7th day after modeling,Pearson correlation analysis showed that both BUN and Scr were positively correlated with the histopathological score of renal tubular(r=0.613,0.677,all P<0.05).There was a positive correlation between TTP and renal tubule pathology score(r=0.733,P<0.05).The parameters WIS,PI,AUC were negatively correlated with the renal tubule pathology score(r=-0.537,-0.593,-0.513,all P<0.05).Conclusions: CEUS can be used to evaluate the features of renal cortical perfusion changes in the rabbit model of renal artery stenosis.The changes of CEUS parameters in renal cortical blood perfusion are earlier than BUN and Scr.CEUS can reflect the histopathological score of renal tubular.CEUS is an effective adjunctive diagnostic method for noninvasive evaluation of renal histopathological changes.Part Ⅱ:Diagnostic Value of CEUS in Grading Renal Artery StenosisObjective: The degree of renal artery stenosis was graded by CEUS and doppler ultrasound,and then compared with the results of digital subtraction angiography(DSA),to explore the diagnostic value of CEUS in grading renal artery stenosis.Methods: 102 patients with suspected renal artery stenosis admitted to the department of Cardiology and Nephrology of our hospital from February 2019 to July 2021 were enrolled in the study.39 patients were excluded,and 122 renal arteries with suspicious stenosis from 63 patients were included in the study.All patients with suspected renal artery stenosis underwent CEUS,doppler ultrasonography and DSA examination.The rate of renal artery stenosis was calculated using the imaging methods described above.The severity of renal artery stenosis was determined according the rate of renal artery stenosis.The stenosed renal arteries were divided into grade I-IV: grade I(stenosis rate 30%-49%),grade II(stenosis rate 50%-69%),grade III(stenosis rate 70%-99%)and grade IV(stenosis rate 100%),respectively.The results of DSA were used as the gold standard to analyze the diagnostic value of CEUS and doppler ultrasonography in different grades of renal artery stenosis.To evaluate the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of CEUS and doppler ultrasonography in the diagnosis of renal artery stenosis.Kappa consistency analysis was performed between CEUS or doppler ultrasonography with DSA.The receiver operating characteristic(ROC)curve was analyzed,and the area under the curve(AUC)was used to evaluate the diagnostic efficacy of doppler ultrasonography and CEUS in diagnosing renal artery stenosis.Results: Among the 122 renal arteries included in the study,DSA showed that 41 of them had no obvious stenosis,and the lumen of renal arteries was well filled with contrast agent.There were 81 renal arteries with the stenosis rate ≥30%,grade I to IV: 25,36,16 and 4,respectively.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of doppler ultrasonography were 74.1%,78.0%,75.4%,87.0% and 60.4%,respectively.Doppler ultrasonography and DSA were consistent in the classification of 51 renal arteries,grade I to IV: 12,26,10,3,respectively.There was statistically significant difference between doppler ultrasonography and DSA in the classification of renal artery stenosis(Z=2.090,P=0.037),and the consistency between them was moderate(Kappa=0.486).The sensitivity,specificity and accuracy of CEUS in the diagnosis of renal artery stenosis were 88.9%,87.8%,88.5%,93.5% and 80.0%,respectively.77 renal arteries with the stenosis rate ≥30% were diagnosed by CEUS,grade I to IV: 21,34,19,3,respectively.CEUS and DSA were consistent in the classification of 66 renal arteries,grade I to IV: 17,30,16,3,respectively.There was no significant difference in the classification of renal artery stenosis between CEUS and DSA(Z=0.512,P=0.609),and the consistency was good(Kappa=0.749).Conclusions: CEUS can enhance the display of renal artery blood flow and has high diagnostic efficiency in the diagnosis of renal artery stenosis.CEUS is a reliable diagnostic method for grading renal artery stenosis.Part Ⅲ:Clinical Study of CEUS in Evaluating Renal Cortical Perfusion Characteristics in Patients with Renal Artery StenosisObjective: To investigate the clinical value of CEUS in evaluating renal cortical blood perfusion in patients with different grades of renal artery stenosis by analyzing the characteristics of CEUS parameters and its correlation with the rate of renal artery stenosis.Methods: From September 2018 to October 2021,106 patients with suspected renal artery stenosis admitted to the department of Cardiology and Nephrology of our hospital who had undergone renal artery DSA examination were selected,of which 37 patients were excluded,and 130 renal arteries of 69 patients were included in the study group.In addition,32 renal arteries of 16 healthy subjects from the physical examination center were included in the control group.According to the renal artery stenosis rate diagnosed by DSA,the 130 renal arteries in the study group were divided into 4 groups,including the non-stenosis group(stenosis rate 0-29%,n=49),grade I stenosis group(30%-49%,n=34),grade II stenosis group(50%-69%,n=28),grade III stenosis group(stenosis rate 70%-99%,n=19).Conventional ultrasonography and CEUS were performed in both the study group and the control group.Conventional ultrasonography parameters included renal length diameter,cortical thickness,and peak systolic flow velocity of interlobular artery.The CEUS parameters included TTP,PI,WIS,and AUC of renal cortex perfusion.The differences between conventional ultrasonography parameters and CEUS parameters were evaluated.Pearson correlation analysis was used to investigate the correlation between conventional ultrasonography or CEUS parameters and the rate of renal artery stenosis.The ROC curve was used to analyze the value of CEUS parameters and conventional ultrasonography parameters in predicting the rate of renal artery stenosis.Results: Conventional ultrasonography examination results showed that in terms of renal length and cortical thickness,there were statistically significant differences between grade III stenosis group and control group,non-stenosis group,grade I stenosis group and grade II stenosis group(P<0.05).Comparing with the control group,the non-stenosis group and the grade I stenosis group,the peak systolic blood velocity of the interlobular artery decreased in the grade II stenosis group and the grade III stenosis group,and the difference was statistically significant(P<0.05).There was no significant difference in peak systolic velocity of interlobar artery between grade II stenosis group and grade III stenosis group(P>0.05).CEUS results of renal cortical blood perfusion showed that comparing with the control group,WIS decreased and TTP increased in grade I stenosis group,the differences were statistically significant(all P < 0.05);WIS,PI and AUC decreased and TTP increased in grade II stenosis group and grade III stenosis group,the differences were statistically significant(all P < 0.05).Comparing with the non-stenosis group,WIS decreased and TTP increased in grade I stenosis group,the differences were statistically significant(P < 0.05);WIS,PI and AUC decreased and TTP increased in grade II stenosis group and grade III stenosis group,the differences were statistically significant(P<0.05).Comparing with grade I stenosis group,WIS,PI and AUC decreased in grade II stenosis group and grade III stenosis group,while TTP increased,and the differences were statistically significant(P<0.05).Comparing with grade II stenosis group,PI and AUC in grade III stenosis group decreased,while TTP increased,with statistical significance(P<0.05).Pearson correlation analysis showed that the length of the kidney was negatively correlated with renal artery stenosis rate(r=-0.267,P<0.05).There was a negative correlation between cortical thickness and renal artery stenosis rate(r=-0.199,P < 0.05).Peak interlobular artery velocity was negatively correlated with renal artery stenosis rate(r=-0.344,P < 0.05).There was a positive correlation between TTP and renal artery stenosis rate(r=0.638,P<0.05),WIS,PI and AUC were negatively correlated with renal artery stenosis rate(r=-0.624,-0.660,-0.425,P<0.05).ROC curve showed that both CEUS parameters and conventional ultrasonography parameters in renal cortex could predict the renal artery stenosis rate,the area under ROC curve of PI was the largest(AUC=0.872,P<0.05).In the single index prediction model,PI had a higher diagnostic efficiency,when the cut-off value was 17.8 d B,the sensitivity and specificity are 87.2% and 80.7%,respectively.Conclusions: CEUS can be used to evaluate the characteristics of renal cortical blood perfusion in different degrees of renal artery stenosis,and it can reflect the changes of renal cortical blood perfusion time,velocity and blood flow volume at an early stage,and it can be used as an auxiliary examination method for clinical evaluation of the severity of renal artery stenosis.