during a 10-month period , 30 non - consecutive patients ( 6 males and 24 females [ age range ; 32 - 80 years , mean age ; 53.7 years ] ) with 30 rccs that were detected on ct scan were referred to us for performing us before the masses were histologically confirmed . all of the patients underwent a gray - scale us and an adi scan that were performed by one radiologist ( b.k.p . ) . all the patients gave us an informed written consent for the adi , and this study was approved by the institutional review board of the seoul national university hospital , korea . the rccs measured from 1.5 cm to 10 cm in size ( meanstandard deviation ; 4.92.7 cm ) and they consisted of 27 clear cell , two papillary and one chromophobe type masses . partial ( n=1 ) or total nephrectomies ( n=29 ) were performed on all the patients . on the pathologic exams , pseudocapsule and intratumoral cyst or necrosis were found in 93% ( 28/30 ) and 90% ( 27/30 ) of all the rccs . the us contrast agent used in this study was sh u 508a ( levovist ; schering ag , berlin , germany ) ; it consists of galactose microparticles ( 99.9% ) and palmitic acid ( 0.1% ) . four grams of sh u 508 a at a concentration of 300 mg / ml were intravenously administered by a manual bolus injection via an 18-gauge cannula inserted into an antecubital vein . the us exams were performed with a high - resolution us unit ( sequoia ; siemens medical solutions , mountainview , ca , usa ) that was equipped with adi software . the acoustic power of the adi was adjusted to the default maximal setting ( mechanical index , 1.9 ) . a 4c1 convex - array probe only was used for the adi scan . before the adi scan , the gray - scale exam was conducted ( a ) in order to determine the optimal imaging plane to display the renal masses because the shorter the distance between the probe and the renal masses , the stronger the signal , ( b ) to compare the diagnostic accuracy between the gray - scale us and the adi . real - time scanning commenced immediately after the intravenous injection of the contrast agent , and the scan time was measured when the contrast agent passed the intravenous cannula . when the first signal of contrast agent appeared in the kidney , we rapidly moved the probe to cover the region including the lesions . rapid sweeping was repeated every 10 - 15 seconds ( interval delay scan ) . for each sweep , we used clip store that can record the continuous images displayed on the monitor during a 6-second period , in a manner similar to video recording , and we also captured still images by employing cine loops . all of the scanned images were automatically stored in the picture archiving communication system ( marotech , seoul , korea ) . h.j.c ) working in consensus retrospectively analyzed all of the us images for the enhancement patterns and the presence or absence of intratumoral anechoic areas and pseudocapsule . the enhancement patterns of the tumor were classified as homogeneous , heterogeneous , stippled and peripheral irregular enhancement . homogeneous enhancement was defined as an even signal intensity over the whole tumor with no signal defects . peripheral irregular enhancement was defined as a discontinuous ring of contrast - enhanced peripheral nodules . intratumoral cysts or necrosis were noted depending on whether the contour of the signal defect was smooth or irregular . pseudocapsule was defined as a hypoechoic halo on the gray - scale us and as a peritumoral rim that showed no enhancement in the early phase and delay enhancement in the late phase of adi . we retrospectively compared the diagnostic accuracy for rcc between the gray - scale us and the adi . on the gray - scale us examination , when the lesion had more than two imaging features among intratumoral anechoic areas , pseudocapsule and hyperechogenicity relative to that of the normal renal parenchyma , then we made a diagnosis of rcc . on the adi exam , when the lesion had more than two imaging features among the most common enhancement patterns of rcc , intratumoral anechoic areas and pseudocapsule , then we made a diagnosis of rcc . we then compared the diagnostic accuracy for rcc between the gray - scale us and the adi exam . fisher 's exact test was used to compare the imaging features of rcc that were seen on gray - scale us and adi . the diagnostic accuracy , which included the sensitivity , specificity , positive predictive value , negative predictive value and overall accuracy for rcc on the adi exam , was calculated and then compared with those of the gray - scale us by using the mcnemar test . during a 10-month period , 30 non - consecutive patients ( 6 males and 24 females [ age range ; 32 - 80 years , mean age ; 53.7 years ] ) with 30 rccs that were detected on ct scan were referred to us for performing us before the masses were histologically confirmed . all of the patients underwent a gray - scale us and an adi scan that were performed by one radiologist ( b.k.p . ) . all the patients gave us an informed written consent for the adi , and this study was approved by the institutional review board of the seoul national university hospital , korea . the rccs measured from 1.5 cm to 10 cm in size ( meanstandard deviation ; 4.92.7 cm ) and they consisted of 27 clear cell , two papillary and one chromophobe type masses . partial ( n=1 ) or total nephrectomies ( n=29 ) were performed on all the patients . on the pathologic exams , pseudocapsule and intratumoral cyst or necrosis were found in 93% ( 28/30 ) and 90% ( 27/30 ) of all the rccs . the us contrast agent used in this study was sh u 508a ( levovist ; schering ag , berlin , germany ) ; it consists of galactose microparticles ( 99.9% ) and palmitic acid ( 0.1% ) . four grams of sh u 508 a at a concentration of 300 mg / ml were intravenously administered by a manual bolus injection via an 18-gauge cannula inserted into an antecubital vein . the us exams were performed with a high - resolution us unit ( sequoia ; siemens medical solutions , mountainview , ca , usa ) that was equipped with adi software . the acoustic power of the adi was adjusted to the default maximal setting ( mechanical index , 1.9 ) . a 4c1 convex - array probe only was used for the adi scan . before the adi scan , the gray - scale exam was conducted ( a ) in order to determine the optimal imaging plane to display the renal masses because the shorter the distance between the probe and the renal masses , the stronger the signal , ( b ) to compare the diagnostic accuracy between the gray - scale us and the adi . real - time scanning commenced immediately after the intravenous injection of the contrast agent , and the scan time was measured when the contrast agent passed the intravenous cannula . when the first signal of contrast agent appeared in the kidney , we rapidly moved the probe to cover the region including the lesions . rapid sweeping was repeated every 10 - 15 seconds ( interval delay scan ) . for each sweep , we used clip store that can record the continuous images displayed on the monitor during a 6-second period , in a manner similar to video recording , and we also captured still images by employing cine loops . all of the scanned images were automatically stored in the picture archiving communication system ( marotech , seoul , korea ) . h.j.c ) working in consensus retrospectively analyzed all of the us images for the enhancement patterns and the presence or absence of intratumoral anechoic areas and pseudocapsule . the enhancement patterns of the tumor were classified as homogeneous , heterogeneous , stippled and peripheral irregular enhancement . homogeneous enhancement was defined as an even signal intensity over the whole tumor with no signal defects . peripheral irregular enhancement was defined as a discontinuous ring of contrast - enhanced peripheral nodules . intratumoral cysts or necrosis were noted depending on whether the contour of the signal defect was smooth or irregular . pseudocapsule was defined as a hypoechoic halo on the gray - scale us and as a peritumoral rim that showed no enhancement in the early phase and delay enhancement in the late phase of adi . we retrospectively compared the diagnostic accuracy for rcc between the gray - scale us and the adi . on the gray - scale us examination , when the lesion had more than two imaging features among intratumoral anechoic areas , pseudocapsule and hyperechogenicity relative to that of the normal renal parenchyma , then we made a diagnosis of rcc . on the adi exam , when the lesion had more than two imaging features among the most common enhancement patterns of rcc , intratumoral anechoic areas and pseudocapsule , then we made a diagnosis of rcc . we then compared the diagnostic accuracy for rcc between the gray - scale us and the adi exam . fisher 's exact test was used to compare the imaging features of rcc that were seen on gray - scale us and adi . the diagnostic accuracy , which included the sensitivity , specificity , positive predictive value , negative predictive value and overall accuracy for rcc on the adi exam , was calculated and then compared with those of the gray - scale us by using the mcnemar test . on the adi exam , the rccs showed as being heterogeneous in 87% of the patients ( 26/30 ) , homogeneous in 7% of the patients ( 2/30 ) , and peripheral irregular enhancement in 7% of the patients ( 2/30 ) . heterogeneous enhancement was the most common enhancement pattern of the rccs , and thus , it was included into the diagnostic criteria for rcc on the adi exams ( figs . 1 , 2 ) . the rccs revealed intratumoral anechoic areas in 87% of the cases ( 26/30 ) , and intratumoral cysts ( n=25 ) , necrosis ( n=21 ) or both ( n=20 ) were also noted ( figs . 1 , 2 ) . on the gray - scale us , the intratumoral anechoic areas were seen in 53% of the cases ( 16/30 ) , of which ten of the rccs were not able to be classified into cysts or necrosis . the intratumoral anechoic areas were more commonly detected on the adi exam than on the gray - scale us ( p < 0.05 ) . pseudocapsule was seen in 77% of the cases ( 23/30 ) of rcc on the adi exam , whereas it was seen only in 17% of the cases ( 5/30 ) of rcc on the gray - scale us ( p < 0.05 ) ( figs . 1 , 2 ) . rccs appeared as hyperechoic in 90% of the cases ( 27/30 ) , and as iso or hypoechoic in 10% of the cases ( 3/30 ) , relative to the normal renal parenchyma ( figs . 1 , 2 ) . table summarizes the diagnostic accuracy of rcc with using adi and gray - scale us . when the presence of two or more adi features was noted out of heterogeneous enhancement , intratumoral anechoic areas and pseudocapsule , then this was regarded as positive findings for rcc , and the sensitivity , specificity , and accuracy for rcc were 97% , 93% , and 95% , respectively . however , those for the rcc on the gray - scale us were 70% , 86% , and 78% , respectively and its diagnostic accuracy were significantly different from that of the adi ( p < 0.05 ) . agent detection imaging is a microbubble - specific harmonic us modality that is designed for the optimal detection of signals from sh u 508a with using high mechanical index technique ( 8 , 9 ) . it can produce signals from stationary microbubbles as easily as from those that are moving in the vessels , and this unlike conventional us that relies on doppler shift signals . other techniques of the gray - scale contrast - enhanced harmonic imagings such as pulse inversion harmonic imaging ( pihi ) and coded harmonic imaging ( cha ) , have been developed by various us equipment manufacturers ( 7 , 10 , 11 ) . pulse inversion harmonic imaging uses a pair of pulses with opposite polarity , and the nonlinear echoes of the tissue harmonic and the contrast agent responses are detected , while the linear echoes of the fundamental tissue are canceled . coded harmonic imaging uses digital encoding and decoding of the transmitted pulses , and it can separate the contrast from the tissue and reduce the unwanted echoes from the fundamental frequency and the tissue harmonic signals . agent detection imaging uses two pulses with the same polarity and it subtracts the signals from the two pulses . the introduction of us has led to improving the detection of renal tumors in asymptomatic patients . renal cell carcinoma seen on gray - scale us has specific features including intratumoral cyst and pseudocapsule , and aml characteristically shows posterior shadowing ( 2 - 4 ) . these features are important findings that may help distinguish rcc from aml , but the presence of these features is not sufficient to differentiate rccs from the other solid renal masses that are incidentally detected on gray - scale us . on the power doppler us , the analysis of the vascular distribution has not increased the diagnostic accuracy for small solid renal tumors ( 4 ) . contrast - enhanced doppler us can increase the detection of intratumoral vascularity compared to color / power doppler us ( 5 , 6 ) . however , its signal intensity hasn't been found to be sufficiently intense for tumor characterization , and it contains artifacts or noises that prevent a correct diagnosis . recently , the development of contrast - enhanced harmonic us imaging has provided for a better assessment of the vascular morphology and the enhancing patterns ; thus , it has improved the detection and characterization of focal liver lesions ( 7 - 9 ) . to the best of our knowledge , there have been a few reports about the differentiation of rcc with employing contrast - enhanced harmonic us imaging using sh u 508a ( 10 - 12 ) . however , these studies did not completely evaluate the various enhancement patterns and the intratumoral or peritumoral features of rcc on the adi exam as compared with those features on the gray - scale us and pathologic exams . on the adi exam , heterogeneous enhancement was most commonly seen in the rcc because most of the lesions contain intratumoral signal defects that pathologically corresponded to cystic change , necrosis or both . homogeneous enhancement was shown for the small rccs , and cystic change or necrosis was not found in these tumors on the pathologic exam . intratumoral anechoic areas have been reported to be pathologically cystic change , degeneration or necrosis . on gray - scale us , these were specific for rcc , but their frequency was previously reported as being 12 - 31% ( 2 - 4 ) . the number of intratumoral cysts in the rccs was larger on the ad scan than on the gray - scale us because the signal of the contrast agent on the adi can be seen in almost all the tissue with vessels , except for the avascular areas such as cysts or necrosis . the pseudocapsule pathologically corresponds to fibrous tissue and renal parenchyma that is compressed by the rcc ( 13 , 14 ) . the preoperative identification of the pseudocapsule was one of the criteria that allow nephronsparing surgery ( 15 ) . ascenti et al . , reported that the pseudocapsule appeared as a nonenhancing peritumoral rim in the early phase and as a well - enhancing rim in the late phase on the contrast - enhanced harmonic us ( 12 ) . in their study , the contrast - enhanced second - harmonic us showed a higher sensitivity for the peritumoral pseudocapsule of rcc than did the gray - scale us ( 12 ) . similarly , the gray - scale us and adi detected the encapsulated rccs in 18% ( 5/28 ) and 82% ( 23/28 ) of all the cases , respectively . . a larger scale of study will be necessary to support our results for the adi exam . second , it was nearly impossible for us to detect the contrast signals of the rcc situated 10 cm or deeper from the us probe . body habitus , lung or bowel gas , ribs and the location of the lesions also affected the signal intensity of the renal tumors . third , color / power doppler us , which can provide more information on intratumoral vascular distribution , was not performed to evaluate the rcc in this study . it is necessary to compare the diagnostic accuracy between the adi scan and the combination of gray - scale us with power doppler us for the diagnostic accuracy of the solid renal masses . fourth , the diagnostic criteria for rcc with using gray - scale us and adi exams have not been established . we made a diagnosis of rcc when the tumor showed two out of the three most common imaging features on the gray - scale us and adi exams . in conclusion it can improve the diagnostic accuracy of rcc as compared with gray - scale us by allowing better visualization of the intratumoral anechoic areas and the pseudocapsule than can the gray - scale us .