Contrast-enhanced Ultrasonography Quantitative Technique: Animal Experiments And Clinical Assessment

Part one:Feasibility Analysis of Contrast-enhanced Ultrasonography Quantitative Technique and Establishment of Kidney dysfunction Animal Models1.Quantitative evaluation of contrast-enhanced ultrasound in healthy rabbitsObjective:To evaluate the quantitative value of contrast-enhanced ultrasound in kidneys of rabbit.To compare different quantitative results with different sets of region of interests(ROI) Methods:The contrast-enhanced ultrasound examinations were performed for both kidneys in 28 healthy rabbits.The slope rate of ascending curve(A ),the slope rate of descending curve(α),area under curve(AUC),derived peak intensity(DPI ),and time to peak(TTP) were measured in renal of rabbits using QLAB software package(PHILIPS) and statistically analyzed.Quantitative results of different ROIs were compared.Results:changes in the slope rate of ascending curve (A ),the slope rate of descending curve(α),area under curve(AUC),derived peak intensity(DPI) were not statistically significant between different shape of ROIs, respectively(P＞0.05).Various changes of quantitative indexes were observed between ROI in cortex and medullar of rabbits' kidney.As to the different set of ROIs in renal cortex,significant changes in DPI and TTP were found.Conclusions: Contrast-enhanced ultrasound can accurately and conveniently display the hemodynamic blood perfusion statu of kidney in rabbits.The shape,position and size of ROI will play an important role in the quantitative results.2.Establishment and evaluation of acute tubular necrosis in a rabbit modelObjective:To establish a rabbit model of acute tubular necrosis(ATN) and to evaluate its application value in quantitatively evaluating the perfusion changes of renal cortex in acute renal failure.Methods:The model of ATN was established in 20 healthy rabbits by intramuscular injection of 50%glycerin(12ml/kg).The blood serum urea nitrogen(BUN) and serum creatinine(SCr) level were tested before,6 hours and 24hours after injection.Histopathological examination was performed to testify the existence of ATN.Results:Changes in BUN and SCr were observed 6 hours and 24 hours after injection.No significant change was observed in histopathologic analysis 6 hours after the injection of glycerin.However 24 hours later,typical changes can be observed.Conclusions:ATN rabbit model can be established successfully by injection of glycerin,which can reveal the hemodynamic changes of ARF.It's suitable for our further quantitative research.3.Establishment and evaluation of chronic ischemic renal disease in a dog modelObjective:To establish a dog model of chronic ischemic renal disease(CIRD) and to evaluate its application value in quantitatively evaluating the perfusion changes of renal cortex in chronic renal dysfunction.Methods:The dog's model of CIRD was established by placing the Ameroid ring on the distal portion of right renal artery through operation.After 4-16 weeks continuous observation,histopathologhic examinations were performed to testify the existence of CIRD.Results:After our experiment,Ameroid rings showed constricted changes.Both renal arteries and right kidneys showed typical ischemic changes with the progress of CIRD.Conclusions: CIRD dog model can be established successfully with Ameroid ring.It's suitable for our further quantitative research of CIRD.Part Two:Quantitative Evaluation of Renal Cortex Perfusion Changes with Contrast-enhanced Ultrasound in Kidney dysfunction Animal Models1.Quantitative Evaluation of Contrast-enhanced Ultrasound in the Early Diagnosis of Acute Renal Failure of RabbitsObjective:To evaluate the early diagnostic value of contrast-enhanced ultrasound (CEUS) in acute renal failure(ARF) of rabbit.Methods:The rabbit model of ARF was established by intramuscular injection of 50%glycerin(12ml/kg) into the hind legs of New Zealand rabbits.CEUS were performed for both kidneys before injection and 6 hours after the injection.The slope rate of ascending curve(A),the slope rate of descending curve(α),area under curve(AUC),derived peak intensity(DPI),and time to peak(TTP)were measured in renal cortex of rabbits using QLAB software package (PHILIPS) and statistically analyzed.Blood serum urea nitrogen(BUN) and serum creatinine(SCr) of rabbits were also tested.Results:A,αbefore injected glycerin were(3.07±1.83)dB/sec,(0.19±0.15) sec^-1,which were significantly high than values after injecting glycerin,(2.76±1.31) dB/sec,(0.09±0.02) sec^-1(P＜0.05). AUC,TTP before injected glycerin were(137.4±68.4) dB sec,(6.33±3.71)sec, which were significantly low than values after injecting glycerin,(309.5±88.9) dB sec,(8.61±3.97)sec(P＜0.05).No significant change in DP1,BUN or SCr was found.Conclusions:CEUS can precisely display the hemodynamic change of ARF model of rabbit in the early stage.It's more sensitive than the BUN and SCr,which may be a promising imaging method for early diagnosis of ARF.2.Quantitative evaluation of contrast-enhanced ultrasound in the diagnosis of chronic ischemic renal disease of dogsObjective:To evaluate the diagnostic value of contrast-enhanced ultrasound(CEUS) in chronic ischemic renal disease(CIRD) of dogs.Methods:The dog's model of CIRD was established by placing the Ameroid ring on the distal portion of right renal artery through operation.CEUS were performed every one week after the operation. The slope rate of ascending curve(A),the slope rate of descending curve(α),area under curve(AUC),derived peak intensity(DPI),and time to peak(TTP) were measured in renal cortex of dogs using QLAB software package(PHILIPS) and statistically analyzed.Blood serum urea nitrogen(BUN) and serum creatinine(SCr) of dogs were also tested.Results:With the progress of CIRD,dogs showed decreased enhancement and delayed perfusion in the renal perfusion curve.AUC,TTP,DPI and A were gradually increased,however,αwas decreased.Earliest significant changes happened 4 weeks after operation on DPI and TTP,the most late significant change happened 7 weeks after operation on A and 11 weeks on BUN and SCr(P＜0.05)。Conclusions:CEUS can accurately display the perfusion changes of CIRD model of dogs.It's more sensitive than the BUN and SCr.DPI and TTP are the most sensitive indexes of CEUS.Part Three:Clinical Application of Quantitative Analysis Method with Contrast-enhanced Ultrasound in Evaluation of Kidney dysfunction 1.Quantitative evaluation of real time contrast-enhanced ultrasonography in normal renal cortex perfusionObjective:To evaluate the feasibility of real time contrast-enhanced ultrasonography (CEUS) in quantitative analysis of normal renal cortex perfusion.Methods: Forty-five healthy volunteers were included in our research,real time contrast-enhanced harmonic imaging of renal blood perfusion were collected successively,and a time-intensity curve(TIC) were created with system's QLAB software.SonoVue was used in CEUS,1 ml for each kidney.All quantitative data were compared between two kidneys and different regions of interest(ROIs).Results: CEUS enjoyed clear imaging of kidney cortex perfusion.Compared between two kidneys,there was no statistical difference between quantitative data.Differences in area under curve(AUC),derived peak intensity(DPI) and slope rate of ascending curve(A) between different ROIs were statistically significant(P＜0.005).However the slope rate of descending curve(α),time to peak(TTP) have no statistical difference.Conclusions:CEUS can precisely display the quantitative perfusion of renal cortex.Perfusion data of different ROI setting have concordance to some extent. Key words:renal cortex;contrast-enhanced ultrasonography;quantitative analysis2.Correlative analysis between contrast-enhanced ultrasonography and ^99mTc-DTPA renography in evaluation of kidney dysfunctionObjective:To evaluate the value of contrast-enhanced ultrasonography(CEUS) in quantitative diagnosis of chronic kidney dysfunction by comparing ultrasonographic indexes with glomerular filtration rate(GFR).Methods:33 cases(15 males and 18 females) of clinical confirmed chronic renal dysfunction patients were included in our research,average age(43.33±6.78岁) years.After intravenous bolus injection of 1ml SonoVue,real time CEUS of renal cortex blood perfusion were collected successively,and a time-intensity curve(TIC) were created with PHILIPS iU22 system's QLAB software.A 4.0-6.0mCi dose of ^99mTc-DTPA was injected as a bolus in an antecubital vein.Renal scintigraphic images were collected immediately and GFR were obtained.Correlative analysis between GFR and ultrasonographic indexes were performed.Results:The significant correlation coefficients between GFR and ultrasonographic indexes were as follows:rAUC=0.886(P＜0.05),rA=0.804(P＜0.05 ).Conclusions:CEUS can precisely display the hemodynamic change of chronic kidney dysfunction.It will enjoy a promising future in clinical application for its sensitive,no-radiation,accurate and convenient.3.Quantitative evaluation of contrast-enhanced ultrasound in chronic renal dysfunctionObjective:To evaluate the value of contrast-enhanced ultrasonography(CEUS) in quantitative diagnosis of chronic renal dysfunction.Methods:33 cases(15 males and 18 females) of clinical confirmed chronic renal dysfunction patients were included in our research,average age(43.33±6.78)years.45 healthy volunteers were performed as control group.After intravenous bolus injection of 1 ml SonoVue,real time CEUS of renal cortex blood perfusion were collected successively,and a time-intensity curve (TIC) were created with PHILIPS iU22 system's QLAB software.Results:Compared with normal kidney,CKD patients had delayed perfusion and decreased intensity. Changes of area under curve(AUC),derived peak intensity(DPI),slope rate of ascending curve(A) and time to peak(TTP) were statistically significant(P＜0.05).Conclusions:CEUS can precisely display the hemodynamic change in chronic renal dysfunction.It will enjoy a promising future in clinical application for its sensitive, no-radiation,accurate and convenient.4.Quantitative evaluation of contrast-enhanced ultrasound in early period of diabetic nephropathiesObjective:To evaluate the value of contrast-enhanced ultrasonography(CEUS) in quantitative diagnosis of diabetic nephropathies in its early period.Methods:16 cases (11 males and 5 females) of clinical confirmed early diabetic nephropathies patients were included in our research,average age(55.6±4.14) years.45 healthy volunteers were performed as control group.After intravenous bolus injection of 1ml SonoVue, real time CEUS of renal cortex blood perfusion were collected successively,and a time-intensity curve(TIC) were created with PHILIPS iU22 system's QLAB software.Results:Changes of area under curve(AUC),derived peak intensity(DPI) were statistically significant(P＜0.05) in early period of diabetic nephropathies.Conclusions:CEUS can precisely display the hemodynamic change of diabetic nephropathies in early period.It will enjoy a promising future in clinical application for its sensitive,no-radiation,accurate and convenient.5.Quantitative evaluation of contrast-enhanced ultrasound in the early diagnosis of renal dysfunctionObjective:To evaluate the clinical value of contrast-enhanced ultrasonography (CEUS) in quantitative diagnosis of early renal dysfunction.Methods:41 cases(26 males and 15 females) of clinical early renal dysfunction patients were included in our research,average age 35.2 years.Each patient had normal results in blood serum urea nitrogen(BUN) and serum creatinine(Scr) tests.After intravenous bolus injection of lml SonoVue,real time CEUS of renal cortex blood perfusion were collected successively,and a time-intensity curve(TIC) were created with PHILIPS iU-22 system's QLAB software.All of quantitative indexes were compared with 45 healthy volunteers,and results of renal scintigraphy were regarded as golden standard. Results:Real time CEUS enjoyed clear imaging of kidney perfusion.Compared with normal kidney,The area under curve(AUC),time to peak(TTP),derived peak intensity(DPI),slope rate of ascending curve(A),slope rate of descending curve (α) of patients with early renal dysfunction were(1178.99±468.28) vs(1308.76±503.65) and(1156.22±352.59) vs(1261.22±430.44) dB sec,(16.01±0.45) vs (14.61±1.84) and(15.64±0.45) vs(14.69±0.63) dB,(16.01±0.45) vs(14.61±1.84) and(15.64±0.45) vs(14.69±0.63)sec,(2.24±0.69) vs(2.46±0.67) and (2.17±0.96) vs(2.63±0.89) dB/sec,(0.01±0.01)vs(0.01±0.02) sec^-1 in left kidney, and(992.89±257.71) vs(1261.22±430.44) dB sec,(16.39±3.23) vs(14.96±2.63) dB, (20.74±7.37) vs(21.15±4.71) sec,(2.01±0.75) vs(2.63±0.89) dB/sec,(0.01±0.01)vs (0.01±0.02) and(0.01±0.00) vs(0.02±0.00) sec^-1 in right kidney respectively.The changes of AUC,DPI,A were statistically significant(P＜0.05).Conclusions:CEUS can precisely display the hemodynamic change of renal dysfunction in the early stage. It will enjoy a promising future in clinical application for its sensitive,no-radiation, accuracy and convenient.