This document describes a study that used coded harmonic angio ultrasound with microbubble contrast agents to evaluate renal perfusion abnormalities. The study found that CHA ultrasound can effectively depict the enhancement patterns of various renal lesions and abnormalities compared to dynamic CT. For renal cell carcinomas, the most common enhancement pattern seen on CHA ultrasound was heterogeneous enhancement. Transitional cell carcinomas predominantly showed peripheral enhancement. Patients with acute pyelonephritis or renal trauma demonstrated focal perfusion defects not visible on pre-contrast images. The study concludes that CHA ultrasound with microbubble contrast is effective for evaluating tumor vascularity and other renal perfusion abnormalities.

1. Acta Radiologica 44 (2003) 166±171 Copyright # Acta Radiologica 2003
Printed in Denmark Á All rights reserved
ACTA RADIOLOGICA
ISSN 0284-1851
RENAL PERFUSION ABNORMALITY
Coded harmonic angio US with contrast agent
J. H. KIM1, H. W. EUN2, H. K. LEE3, S. J. PARK3, J. H. SHIN1, J. H. HWANG1, D. E. GOO1 and D. L. CHOI1
1
Department of Radiology, Soonchunhyang University Hospital, Seoul, 2Health Care Center, Samsung Medical Center, Sunkyunkwan
University, Seoul, 3Department of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon, Kyonggi-Do, Korea.
Abstract
Purpose: Coded harmonic angio (CHA) US is a recently developed technique Key words: Kidney, neoplasm;
that can depict the effects of contrast agents. The purpose of this study was to trauma; infection; CT; harmonic
determine the role of this technique in depicting the enhancement patterns of sonography; contrast medium.
various renal perfusion abnormalities compared with dynamic CT.
Material and Methods: During a 6-month period, various renal lesions Correspondence: Jung Hoon Kim,
including renal cell carcinoma (nˆ12), transitional cell carcinoma (nˆ5), acute Department of Radiology,
pyelonephritis (nˆ5), and renal trauma (nˆ2) were evaluated with CHA US Soonchunhyang University Hospital,
using a microbubble contrast agent. US images were obtained before contrast 657 Hannam-Dong, Youngsan-Ku,
administration and with a bolus injection of 4 g of microbubble contrast agent Seoul 140±743, Korea.
(300 mg/ml) every 10 s for 1 min and every minute for 5 min. The contrast FAX ‡82 2 795 3928.
enhancement patterns of various renal masses were compared with dynamic CT. E-mail: junghkim@hosp.sch.ac.kr
Results: Of 12 renal cell carcinomas, 9 (75%) showed heterogeneous enhance-
ment and the remaining 3 (25%) showed homogeneous enhancement. Enhance- Accepted for publication 7 November
ment of more than adjacent renal parenchyma was seen 16±252 s after injection. 2002.
The duration of enhancement was 13±208 s (mean, 80 s). All transitional cell
carcinomas showed peripheral enhancement. Enhancement was seen 22±270 s
after injection. The duration of enhancement was 191±238 s (mean, 291 s). Five
patients with acute pyelonephritis and 2 with renal trauma showed focal perfu-
sion defects not shown on the pre-contrast examinations.
Conclusion: CHA US with microbubble contrast agent is an effective US
technique for the evaluation of both tumor vascularity and renal perfusion
abnormality.
In radiographic studies, contrast agents are widely studies describing how the use of microbubble
used to evaluate renal perfusion abnormalities. agents on color and power Doppler US can
Dynamic enhancement patterns on contrast- improve the detection and characterization of vari-
enhanced CT or MR imaging can help in lesion ous renal perfusion abnormalities, including masses
characterization especially in cases of suspected (1, 2, 5, 6, 15, 20±22); however, there are hardly any
renal masses (11, 13, 23). human studies (9, 10, 16).
Since microbubble US contrast agents have The coded harmonic angio (CHA) US technique
become available, their efficacy for characterization is a new imaging technology using contrast agents
of focal renal lesions has been the subject of clinical based on digitally encoded US technology. This
investigations (12). There are many experimental imaging mode is particularly useful when imaging
166

2. RENAL PERFUSION ABNORMALITY BY CODED HARMONIC ANGIO US
the arterial or venous phases of tumor vascularity or 2±4 MHz curved linear array transducers. The
for imaging the stimulated acoustic emission signal acoustic power of CHA US was set at the default
of agents deposited in the tissue (7, 14). setting (maximum mechanical index X, MI).
We expected that CHA US with microbubble Before injection of the contrast agent, we deter-
contrast agents could effectively depict renal perfu- mined a scanning plane including the renal mass
sion abnormalities. The purpose of this study was and obtained a CHA US image. If the patient did
to determine the role of this technique in various not have an identified renal mass, we determined a
renal perfusion abnormalities compared with scanning plane that included the entire kidney. US
dynamic CT. images were obtained before contrast administra-
tion as well as with a bolus injection of microbubble
contrast agent every 10 s for 1 min and every minute
Material and Methods
for 5 min. All images were taken as static cine loops.
During a 6-month period, 24 patients who were We performed interval delay scanning: i.e. we froze
referred for renal US because of clinically or histo- the display between each scanning time and unfroze
pathologically diagnosed renal abnormality were it for a very short period (including 2 or 5 frames)
examined with CHA US (LogiQ 700 Expert Series; during each scanning time. Throughout the exam-
GE Medical Systems) with a microbubble contrast ination, we held the transducer still and unfroze it
agent. during the same status of the patient's respiration in
Twelve patients with renal cell carcinoma, 5 order to maintain the same scanning plane. The
patients with transitional cell carcinoma, 5 patients time delay from injection and the time at which
with acute pyelonephritis, and 2 patients with renal the image was obtained were recorded. All images
trauma were examined. The patients were 21±67 were stored digitally on the hard disk in the US unit
years old (mean 45 years). Of the 22 patients, 18 and transferred to a personal computer. The con-
were men. All patients gave their full informed trast enhancement patterns of the various renal
consent for the study and institutional review perfusion abnormalities were assessed.
board approval was obtained. Two-phase dynamic CT examinations were per-
Ten patients with renal cell carcinoma were diag- formed with a CT-W 2000 (Hitachi) unit. Each patient
nosed at surgery and 2 were diagnosed at percuta- received 120 ml of nonionic (iopromide, Ultravist 370;
neous needle biopsy. All patients with transitional Schering) contrast material intravenously at a rate of
cell carcinoma were diagnosed at surgery. Five 3 ml/s. Early phase and delay phase scans were
patients with acute pyelonephritis were diagnosed obtained 30 and 150 s after the initiation of injection
as follows: 4 by urine culture and 1 by clinical of the contrast material, respectively. All patents had a
laboratory data (pyuria and bacteriuria and typical CT examination within 1±3 days of CHA US examin-
symptoms including fever, chills, and flank pain) ation. CT examination was performed with a 5-mm
along with typical dynamic CT findings. Two thickness and 1.5 pitch.
patients with renal contusion were diagnosed by Analysis: US images were displayed on a compu-
means of their clinical history (1 victim of a motor ter screen and were evaluated by two radiologists
vehicle accident and the other victim of violent (H.W.E., S.J.P.) who were blinded to the diagnoses;
trauma) along with typical CT findings. decisions were made by consensus. CT images were
The microbubble contrast agent (Levovist; evaluated by one reader (D.E.G.) who was blinded
Schering), is a suspension of galactose micropar- to the diagnoses and US findings.
ticles in sterile water. The microbubbles (2±8 mm in The reviewers determined the diameters and echo-
diameter with a mean diameter of 3 mm), which are genicity of the unenhanced US images. The
stabilized in the microparticle suspension, can echogenicity of the tumors was classified as solid,
traverse the pulmonary capillary bed. Before the cystic, or mixed (mixed solid and cystic lesion). All
US examination, this agent was prepared for injec- observations of the enhancement patterns were
tion by shaking it for 5±10 s with 11 ml of water. totally subjective and no quantitative substantiation
A milky suspension of galactose microparticles and was performed. The contrast enhancement pattern was
microbubbles was created by disaggregation of the determined by evaluating the images obtained during
granules. After allowing it to stand for 2 min for the early enhancement phase, typically 20±60 s after
equilibration, the contrast agent was injected contrast injection. The enhancement patterns of the
intravenously as a bolus in a dose of 4 g at a lesions were classified as homogeneous, hetero-
concentration of 300 mg/ml flush using a 0.7- or geneous, peripheral, and perfusion defect.
0.9-mm peripheral i.v. cannula. The reviewers also determined the patterns of renal
CHA US was performed by one examiner mass on dynamic CT, classified as solid, cystic, or
(J.H.K.) with a LogiQ 700 apparatus and mixed (mixed solid and cystic lesion). They also
167

3. J. H. KIM ET AL.
evaluated the pattern of contrast enhancement of the compared with adjacent renal parenchyma was per-
renal mass. The enhancement patterns of the tumors ipheral in 5 patients (100%) (Fig. 2). Enhancement
were classified as homogeneous, heterogeneous, of more than adjacent renal parenchyma was seen
peripheral enhancement, and perfusion defect. 22±32 s (mean, 80 s) after injection. The intensity of
the tumor diminished progressively from 220 to
270 s (mean, 247 s) after injection. The duration of
Results
enhancement was 191±238 s (mean, 219 s).
The findings in the various renal masses on CHA Two-phase dynamic CT showed mixed pattern in
US and dynamic CT are summarized in Table 1. 3 patients and solid pattern in 2. All patients showed
Renal cell carcinoma: The tumor diameters as peripheral enhancement on the delayed phase.
measured on US were 17±87 mm (mean, 37 mm). Acute pyelonephritis: US findings in the 5 patients
Six patients had renal cell carcinomas equal to or with acute pyelonephritis included swelling, diffuse
less than 30 mm and the remaining 6 tumors were decreased parenchymal echogenicity, and loss of
larger than 30 mm. The echogenicity was solid in 3 corticomedullary differentiation. However, a definite
lesions and mixed in 9. focal parenchymal lesion was not detected on US
The most common enhancement pattern seen on imaging. After microbubble contrast injection, all 5
CHA US with microbubble contrast agent compared patients showed multifocal or segmental parenchy-
with adjacent renal parenchyma was heterogeneous mal perfusion defects (Fig. 3). Two-phase dynamic
in 9 lesions (75%) (Fig. 1). Homogeneous enhance- CT showed diffuse renal swelling and delayed
ment was seen in 3 lesions (25%). Enhancement nephrogram in 5 patients, and focal perfusion defects
more than that of adjacent renal parenchyma was in 4 patients.
seen 16±57 s (mean, 30 s) after injection. The intensity Renal trauma: The 2 patients with renal contu-
of the tumor diminished progressively from 51 to sion showed swelling and decreased parenchymal
252 s (mean, 82 s) after injection. Although the inten- echogenicity on US before contrast administration.
sity of enhanced portions of the tumor diminished, After microbubble contrast injection, both patients
the duration of enhancement was 13±208 s (mean, showed focal parenchymal perfusion defects
80 s) (Table 2). (Fig. 4). Two-phase dynamic CT also showed focal
Two-phase dynamic CT showed solid pattern in 3 perfusion defects.
lesions and mixed pattern in 9. The most common
enhancement pattern was heterogenous in 9 lesions
Discussion
(75%) and homogeneous in 3 lesions (25%). The
intratumoral enhancement of more than adjacent CHA US is based on digitally encoded US technol-
renal parenchyma in the early phase was seen in ogy combining the benefits of B-flow and coded har-
11 of 12 patients. monic imaging technology. CHA US uses the receive
Transitional cell carcinoma: The tumor diameters decoder, rather than a frequency filter, to suppress
as measured on US were 19±80 mm (mean, 40 mm). unwanted fundamental frequency components. The
The echogenicity was mixed in 3 patients and solid result is a harmonic image with wide band resolu-
in 2. The most common enhancement pattern tion, improved sensitivity, and reduced acoustic
at CHA US with microbubble contrast agent noise. B-flow is a flow imaging technique that
Table 1
Comparison of contrast enhancement patterns at CHA US and dynamic CT
Enhancement patterns at CHA US Enhancement patterns at CT
Patterns Enhancement patterns Patterns Enhancement patterns
Lesion S M C Ho He PE PD S M C Ho He PE PD
RCC, 3 9 3 9 3 9 3 9
nˆ12
TCC, 2 3 5 2 3 5
nˆ5
APN, 5 4
nˆ5
Trauma, 2 2
nˆ2
Sˆsolid, MˆMixed, Cˆcystic, Hoˆhomogeneous, Heˆheterogeneous, PEˆperipheral enhancement, PDˆperfusion defect, RCCˆrenal cell
carcinoma, TCCˆtransitional cell carcinoma, APNˆacute pyelonephritis.
168

4. RENAL PERFUSION ABNORMALITY BY CODED HARMONIC ANGIO US
a b c
Fig. 1. Renal cell carcinoma with heterogeneous enhancement. a) Delayed CT shows mass with heterogeneous enhancement in the right kidney.
b) US before injection of the contrast agent shows a solid and cystic mass (") in the right kidney. c) Contrast-enhanced CHA US image obtained
41 s after injection shows intratumoral heterogeneous enhancement. A thick septum is seen with intense enhancement (ˆ A).
extends B-mode imaging capabilities to blood flow. aliasing. In addition, their clinical usefulness has
B-flow provides direct visualization of blood echoes not yet been firmly established. Two experimental
without imitations of Doppler US (7, 14). studies (6, 22) showed that contrast-enhanced
The microbubble contrast agent is a blood pool harmonic US is an effective method for evaluating
agent, so that imaging of the microvascular system renal blood flow changes during acute urinary
can be performed by provoking the collapse of the obstruction and focal perfusion defects in embo-
microbubbles with diagnostically used US waves lized kidneys. In another experimental study (5),
with high mechanical index (19). In previous reports the use of contrast agent enhanced the depiction
(15, 16), only a short-lasting and weak effect could of an area of acute renal hemorrhage.
be visualized after microbubble contrast agent injec- From the results of this study, we believe that the
tion. In contrast to liver tissue, no late-phase con- pattern of enhancement on CHA US using a micro-
trast effect could be observed in kidney tissue. bubble contrast agent has potentially high sensitiv-
Microvascular imaging of the kidney is possible ity and specificity for the diagnosis of various renal
only during the blood pool phase. There are many perfusion abnormalities including masses compared
experimental studies of the use of microbubble with dynamic CT. In renal cell carcinoma, the most
agents having improved the detection and charac- common enhancement pattern on CHA US with
terization of vascularity in various renal lesions microbubble contrast agent was heterogeneous
(1, 2, 5, 6, 15, 20±22); however, there are only enhancement. Homogeneous enhancement was
a few applications of microbubble contrast in seen in 3 lesions (25%). While this enhancement
human kidney described (9, 10, 16). pattern was seen in patients with renal cell carcin-
Previous studies (8, 17, 18) have indicated that oma, this pattern did not occur in any nonmalig-
both spectral Doppler and color Doppler US can nant lesions. These enhancement patterns are
provide clinically useful information related to similar to dynamic CT.
tumor vascularity; however, these imaging modal- In transitional cell carcinoma, peripheral enhance-
ities have inherent limitations, such as a lack of ment was observed on interval delay scanning using
sensitivity to slow flow, angle dependency, and CHA US with a microbubble contrast agent.
Table 2
Enhancement duration in various renal masses on CHA US with microbubble contrast agent
Contrast enhancement time on CHA US with microbubble contrast in S
Lesion 10 20 30 40 50 60 120 180 240 300
RCC, 2 6 7 12 12 7 3 1 0 0
nˆ12
TCC, 0 2 3 3 5 5 5 5 2 0
nˆ5
Abbreviations as in Table 1.
169

5. J. H. KIM ET AL.
a b c
Fig. 2. Transitional cell carcinoma with peripheral enhancement. a) Delayed CT shows mass with peripheral enhancement in the right kidney.
b) US before injection of the contrast agent shows a solid mass in the right kidney ("). c) Contrast-enhanced CHA US image obtained 53 s after
injection shows a mass with peripheral enhancement (ˆ A).
In acute pyelonephritis, focally decreased par- signal on the next transmit firing (3). Each trans-
enchymal echogenicity cannot be detected on US. mitted US pulse in interval delay imaging will pro-
After microbubble contrast injection, all our duce the best possible harmonic signals because it
patients showed focal or segmental parenchymal can be arranged to allow areas of slow flow to fill
perfusion defects. While conventional US has a with intact microbubbles during the imaging pause.
very low sensitivity for acute pyelonephritis, CHA The optimal interval delay between each US pulse is
US with microbubble contrast agent is a sensitive not known and may depend on the flow velocity of
technique. Dynamic CT showed focal or segmental the vasculature of the examined tissue (4). Further
parenchymal perfusion defects in 4 patients (80%). studies will be necessary to compare various interval
KIM et al. (10) recently performed contrast- delays in imaging for various renal lesions.
enhanced pulse inversion harmonic imaging as a There are a few limitations of this study: there is a
sensitive technique for depicting renal parenchymal small number of cases, dynamic US scanning is only
lesions and abscess formation in patients with acute possible in one scanning plane, there is greater focal
pyelonephritis. Both patients with renal contusion zone dependency so that large or multiple masses
showed focal parenchymal perfusion defects after cannot be fully evaluated on CHA US, and interval
contrast injection, similar to dynamic CT. For accur- delay scanning in the same area is not easy for
ate differentiation, it is important to look for renal unskilled examiners to perform. On the other
perfusion in the vascular phase (typically 20±60 s hand, CHA US has the advantages of having higher
after bolus contrast injection). Thereafter, one spatial and temporal resolution compared with
should observe enhancement patterns on successive other imaging techniques, and yields simple and
scans in order to diagnose various renal perfusion immediate characterization of a newly detected
abnormalities including masses. renal lesion on US examination.
When imaging in a high MI mode, it is necessary In conclusion, CHA US with microbubble contrast
to wait for the area of interest to be reperfused by agent is an effective US technique for evaluating both
the agent before imaging again to ensure a sufficient tumor vascularity and renal perfusion abnormalities.
a b c
Fig. 3. Acute pyelonephritis with a multifocal perfusion defect. a) Delayed CT shows swelling and multifocal low density in right kidney. b) US
before injection of the contrast agent shows diffuse swelling (") but no focal lesions in the right kidney. c) Contrast-enhanced CHA US image
obtained 42 s after injection shows multifocal parenchymal perfusion defects (ˆ A).
170

6. RENAL PERFUSION ABNORMALITY BY CODED HARMONIC ANGIO US
a b c
Fig. 4. Renal contusion with a focal perfusion defect. a) Delayed CT shows focal perfusion defect in the posterior segment of the left kidney.
b) US before injection of the contrast agent shows a swelling and decreased parenchymal echogenicity in the posterior segment of left kidney.
c) Contrast-enhanced CHA US image obtained 33 s after injection shows focal parenchymal perfusion defects in posterior segment of the left
kidney (ˆA).
ACKNOWLEDGMENT sonographic contrast agent: correlation with computed
tomography. J. Ultrasound Med. 2001; 20: 5.
We thank Bonnie Hami, University Hospitals of Cleveland, for 11. Lang EK. Comparison of dynamic and conventional
her editorial assistance in the preparation of this manuscript. computed tomography, angiography and ultrasonography
in the staging of renal cell carcinoma. Cancer 1984; 54:
2205.
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