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Ultrasonography |
1 From the Department of Radiology and the Institute of Radiation Medicine, Seoul National University Hospital, 28, Yongon-dong, Chongno-gu, Seoul 110-744, South Korea. Received February 4, 1999; revision requested April 2; revision received May 14; accepted June 2. Supported in part by a grant from the 1998 Highly Advanced National Projects on the Development of Biomedical Engineering and Technology in Korea. Address reprint requests to B.I.C.
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Abstract |
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MATERIALS AND METHODS: Twenty patients with nodular HCCs (2.6–13.2 cm in diameter; mean diameter, 4.8 cm) were prospectively examined with both conventional and harmonic power Doppler US. US was performed with a 2–4-MHz curved linear-array transducer according to a standard examination protocol (1,000-Hz pulse repetition frequency, medium wall filter, and power gain of 55%–84% for conventional power Doppler US; 700-Hz pulse repetition frequency, low wall filter, and power gain of 95%–98% for harmonic power Doppler US). Serial, dynamic scans were obtained before intravenous injection of the contrast agent (SH U 508A) and at 30, 60, 90, 120, 180, 240, and 300 seconds after injection with both techniques.
RESULTS: The number of intratumoral power Doppler US signals was similar with both techniques at 30–90 seconds after contrast agent injection; however, after 90 seconds, conventional power Doppler US depicted significantly more signals than did harmonic power Doppler US. Harmonic power Doppler US was superior to conventional power Doppler US in terms of power Doppler artifacts such as "blooming" or motion-related artifacts.
CONCLUSION: Although the effective enhancement duration is relatively short compared with that for conventional power Doppler US, contrast-enhanced harmonic power Doppler US can be effective in evaluating the vascularity of HCCs because of the advantage of fewer power Doppler artifacts.
Index terms: Liver neoplasms, blood supply, 761.323, 761.99, 95.32, 95.99 • Liver neoplasms, US, 761.12983, 761.12988 • Ultrasound (US), artifact, 761.93 • Ultrasound (US), comparative studies, 761.12983, 761.12988, 761.12989 • Ultrasound (US), contrast media, 761.12988 • Ultrasound (US), harmonic study, 761.12989 • Ultrasound (US), power Doppler studies, 761.12983
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Introduction |
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Harmonics are those components of sound waves whose frequencies are integral multiples of the transmitted frequency (fundamental or first-harmonic frequency). Second-harmonic US technique involves transmitting at frequency f and receiving at frequency 2f, the second harmonic. Findings of recent studies in the US field of harmonics suggest that harmonics might be useful for improving lateral resolution and increasing the signal-to-noise ratio in medical US (10,11). Also, in Doppler modes, image-degrading noise or flash artifacts are much weaker in second-harmonic power Doppler US than in conventional power Doppler US (12). In addition, because of the nonlinear motion of a microbubble contrast agent driven by the ultrasound field at sufficiently high acoustic pressures (13), strong contrast agent–enhanced echoes can be obtained at the second harmonic frequency when Doppler US is performed with use of a microbubble contrast agent (12,14). Therefore, harmonic power Doppler US used in concert with a microbubble contrast agent offers the potential of providing extremely high quality and detailed vascular information while decreasing the artifacts associated with the contrast agent.
We performed this prospective study to compare contrast-enhanced harmonic power Doppler US with conventional power Doppler US in the assessment of HCC vascularity.
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MATERIALS AND METHODS |
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1-fetoprotein level greater than 100 µg/L) and typical findings of hepatic angiography in 18 patients. The patient population included 17 men and three women (age range, 45–73 years; mean age, 53 years). All patients gave full informed consent for our study, and approval by our institutional review board was obtained. In patients with multiple HCCs, we selected only the largest lesion because serial, dynamic US was possible for only one lesion in each patient. The longest dimension of tumors as measured on US images was 2.6–13.2 cm (mean, 4.8 cm). Fifteen patients had lesions in the right lobe, and five had lesions in the left lobe.
US Examination
The US contrast agent used in the study was SH U 508A (Levovist; Schering, Berlin, Germany). Before the US examination, this agent was prepared by shaking it with 11 mL of water for 5–10 seconds. A milky suspension of galactose microparticles and microbubbles was created with disaggregation of the granules. After standing for 2 minutes for equilibration, 6.5 mL of the contrast agent suspension, with a concentration of 300 mg/mL, was injected manually through a 20–22-gauge cannula (Cath-S; Boin Medica, Seoul, South Korea) placed in an antecubital vein followed by an additional 10 mL of physiologic saline to flush the cannula at the same injection rate. The injection techniques used were bolus injection at approximately 0.6 mL/sec for harmonic power Doppler US and manual injection at a rate of 0.2 mL/sec for conventional power Doppler US.
US was performed by one radiologist (T.K.K.) by using an HDI 3000 unit (Advanced Technology Laboratories, Bothell, Wash) and a 2–4-MHz curved linear-array probe. US protocols were as follows: a pulse repetition frequency of 1,000 Hz and a medium wall filter (high-pass filter) for conventional power Doppler US and a pulse repetition frequency of 700 Hz and a low wall filter for harmonic power Doppler US.
The color-write priority was set at the maximum. The color gain was manipulated until color noise first became apparent at the region of interest in the image background on power Doppler US scans. The resultant power Doppler gains ranged from 55% to 84% for conventional power Doppler US and from 95% to 98% for harmonic power Doppler US. With these predetermined gain settings, US scans were obtained in each tumor during suspended respiration. Serial, dynamic, power Doppler US scans obtained with either technique were recorded on videotape and stored in the hardware of the imaging unit until the signal enhancement had completely diminished. Static images were obtained before and at 30, 60, 90, 120, 180, 240, and 300 seconds after injection of the contrast agent.
US Image Analysis
Static images from harmonic and conventional power Doppler US were compared by three radiologists (T.K.K., B.I.C., A.Y.K.) by consensus to determine which of the two methods was better in depicting intratumoral and intrahepatic vasculature and eliminating power Doppler artifacts. The readers were not blinded to whether the harmonic or conventional technique was used since one of the readers performed all the US scanning. Intratumoral power Doppler US signals on images obtained after injection of the contrast material were also compared with those on preinjection images to determine the duration of contrast agent enhancement.
The distribution of intratumoral power Doppler US signals was classified as central, meaning power Doppler US signals were visualized in the central portion of the tumor, and as peripheral, meaning power Doppler US signals were visualized in the peripheral portion of the lesion. The power Doppler US signals that were present in the area where vascular flow could not exist or that showed an appearance inconsistent with vascular structures were regarded as power Doppler artifacts.
Statistical comparison was performed by using the sign test, and a P value less than .05 indicated a statistically significant difference.
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RESULTS |
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With a case-by-case comparison of static images, there was no significant difference between the two techniques in the depiction of intratumoral signals at 30, 60, and 90 seconds after injection of the contrast agent. At 2, 3, 4, and 5 minutes after injection, conventional power Doppler US depicted significantly more intratumoral power Doppler US signals than did harmonic power Doppler US.
Similarly, there was no significant difference between the two techniques in the depiction of signals in intrahepatic vessels at 60 and 90 seconds after injection. At 0 and 30 seconds and 2, 3, 4, and 5 minutes after injection, conventional power Doppler US depicted significantly more power Doppler US signals in intrahepatic vessels than did harmonic power Doppler US (Figs 1, 2) (Table).
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Power Doppler artifacts were seen to a variable degree. These artifacts were seen as gray-scale pixels that changed to color display in regions where the indicated flow is not possible (eg, perihepatic or periaortic fat, diaphragm, and gallbladder) or as unreasonably enlarged vascular structures with contrast agent enhancement (Figs 1–3).
Harmonic power Doppler US was superior to conventional power Doppler US in terms of power Doppler artifacts at any imaging time (Table). Among five lesions in the left lobe, one lesion was located near the heart. In this case, we used very low power Doppler gain (55%) to reduce power Doppler artifacts from cardiac pulsation at conventional power Doppler US; however, more intratumoral power Doppler US signals could be depicted with harmonic power Doppler US during most of the examination (Fig 3). In harmonic power Doppler US, continuous scanning during the patient's quiet breathing was possible without producing considerable motion-related artifacts, whereas severe motion-related artifacts were produced during the patient's breathing in conventional power Doppler US.
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DISCUSSION |
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In color Doppler or power Doppler US studies in which an US contrast agent is used, the effect of the arrival of the agent in a region of interest is often to produce blooming of the color image, whereby signals from major vascular targets spread out to occupy the entire region (15). Because of the temporal display characteristics of power Doppler US (high frame-rate averaging and persistence), blooming artifacts in power Doppler US are more notable and more detrimental to image quality than they are in color Doppler US (16). Thus, although flow from smaller vessels might be detectable at power Doppler US, it can be obscured by adjacent artifactual power Doppler US signals, and the size or extent of the vasculature within the lesion can be overestimated (17).
As compared with color Doppler US, power Doppler US has an advantage in that artifacts with lower-amplitude Doppler shifts are displayed at a lower visual amplitude, which renders them less conspicuous, while flow signals are displayed at a higher visual amplitude (18). Therefore, with contrast agent enhancement of the Doppler US signals, tissue vascularity can be demonstrated better with power Doppler US than with color Doppler US (16). Nonetheless, because of a considerable blooming artifact in the early phase of contrast agent enhancement at power Doppler US, exact evaluation of the intratumoral vasculature is greatly disturbed (4). Furthermore, increased susceptibility to tissue motion at power Doppler US limits use of this technique in patients with poor breath-holding ability and patients with hepatic masses near the heart or great vessels (1,4).
At the small expense of some sensitivity to detect vascular flow, which is compensated by the enhancement of power Doppler US signals by the contrast agent, harmonic power Doppler US effectively overcomes the problem of power Doppler artifacts. The results of the present study clearly demonstrate that the use of the harmonic mode in contrast-enhanced power Doppler US can effectively reduce power Doppler artifacts, including blooming and motion-related artifacts. This technique was also applicable to lesions near the heart or great vessels, without reducing power Doppler gain too much (Fig 3); thus, the harmonic power Doppler mode was superior to the conventional power Doppler mode in demonstrating intratumoral vessels in that area. In addition, in the harmonic mode, continuous scanning during the patient's quiet breathing was possible without producing considerable motion-related artifacts; therefore, this technique could be used in patients with poor breath-holding ability more easily than could the conventional power Doppler technique.
In the majority of cases in our study, the intensity of contrast-enhanced power Doppler US signals in the tumor and hepatic parenchyma with use of the conventional mode was stronger than that with use of the harmonic mode. This is not surprising when considering the relatively low intensity of second-harmonic echoes compared with the intensity of fundamental echoes (12).
By performing preliminary scanning in a few patients prior to this study, we found that slow injection of contrast material and power Doppler settings with a low or medium sensitivity to flow could not produce sufficient enhancement of the liver at harmonic power Doppler US. This is why we used different protocols for power Doppler scanning and contrast agent injection in both imaging techniques (pulse repetition frequency of 700 Hz, low wall filter, and rapid bolus injection of the contrast agent for the harmonic mode; pulse repetition frequency of 1,000 Hz, medium wall filter, and slow injection during 30 seconds for conventional mode).
In conventional power Doppler US, lowering the pulse repetition frequency and wall filter is not helpful for detecting slow vascular flow, because power Doppler artifacts markedly increase and can obscure or mimic true vascular flow (19). In harmonic power Doppler US, use of a pulse repetition frequency of 700 Hz and a low wall filter produced only minimal power Doppler artifacts, and use of this protocol was justified. However, the optimal method of injection of the contrast agent and the optimal scanning protocols for harmonic power Doppler US are not known yet, because no data on comparing different injection rates and scanning protocols are available.
The results of our study also show that the effective enhancement duration is shorter in the harmonic mode than in the conventional mode. This is probably due to a need for a higher intravascular concentration of the contrast agent to provide effective enhancement of the tumor in harmonic power Doppler US. When using our contrast agent injection protocols in harmonic power Doppler US, the effective enhancement duration for evaluating tumor vascularity is about 2 minutes. Harmonic imaging demands exceptional performance from the transducer array and system beam former (12). More important, contrast agents are now being developed specifically with a nonlinear response as a design criterion (20). Although the harmonic power Doppler US technique and the contrast agent in the present study provide relatively low-intensity power Doppler US signals and a short duration of effective contrast agent enhancement, further improvement of US technology in the future will provide a more improved sensitivity for detecting blood flow (12).
As described earlier in the Discussion, overestimation of the size of the contrast-enhanced vessel is evident at conventional power Doppler US. After contrast agent enhancement, the inferior vena cava or abdominal aorta looks much larger than its actual size (Fig 2). Similarly, the sizes of intrahepatic and intratumoral vessels also are likely to be overestimated. Therefore, the finding of our study that conventional imaging is superior to harmonic imaging for the detection of vascularity in the tumor and normal liver might be due in part to overestimation of vascular signals at conventional imaging and reduction of the artifacts at harmonic imaging.
Furthermore, contrast-enhanced vessels adjacent to a liver tumor can be seen as if they are located within the tumor at conventional power Doppler US. This can be an important problem when we want to know whether any residual viable tumor is present after local treatment for a malignant tumor, such as transcatheter arterial chemoembolization or percutaneous ethanol injection therapy. In that case, we think that harmonic power Doppler US might be superior to conventional power Doppler US.
One of the limitations of this study is that the readers were not blinded to whether the harmonic or conventional technique was used, since one of the readers did all the scanning. However, we think that blinding was not practically possible because the power Doppler US signals in the liver on preinjection images were completely different between the two techniques. This study is also limited in that there was no independent standard for the presence of tumoral vascularity. However, the evidence of HCC in our study group may be adequate for the limited goal of this study, which was to compare two US techniques in the assessment of tumor vascularity.
In summary, as compared with contrast-enhanced conventional power Doppler US, contrast-enhanced second-harmonic power Doppler US has the advantage of fewer power Doppler artifacts. However, harmonic power Doppler US requires a higher concentration of contrast agent to depict intratumoral flow signals than does conventional power Doppler US. Contrast-enhanced harmonic power Doppler US can be an effective method for evaluating the vascularity of HCCs, especially in patients with poor breath-holding ability or with lesions near the heart or great vessels.
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Footnotes |
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Author contributions: Guarantor of integrity of entire study, B.I.C.; study concepts, T.K.K., B.I.C.; study design, T.K.K.; definition of intellectual content, T.K.K., B.I.C.; literature research, T.K.K., B.I.C., A.Y.K., C.K.S.; clinical studies, T.K.K., A.Y.K., S.J.P.; data acquisition, T.K.K.; data analysis, T.K.K., A.Y.K.; statistical analysis, T.K.K.; manuscript preparation, T.K.K., B.I.C.; manuscript editing, J.K.H.; manuscript review, B.I.C.
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References |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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