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by the American Institute of Ultrasound in Medicine J Ultrasound Med 21:821-824 • 0278-4297
Relationship Between Flash Echo Gray Scale Imaging Features and Pathologic Findings in Hepatic AdenomaDivision of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China. Address correspondence and reprint requests to Jing-Houng Wang, MD, Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Rd, Kaohsiung, Taiwan, Republic of China.
Abbreviations: FEI, flash echo imaging • MI, mechanical index
Hepatic adenoma is a rare solid liver lesion consisting of normal hepatocytes in cords or sheets without portal tracts and bile ducts. Because the potential for malignant transformation and risk of hemorrhage is substantial, it is important to differentiate this lesion from other hepatic tumors such as hepatocellular carcinoma, focal nodular hyperplasia, and hemangioma.1 A number of imaging modalities are used for the diagnosis of hepatic adenoma.2–4 To the best our knowledge, however, no report has characterized the pathologic features of hepatic adenoma with the use of flash echo imaging (FEI)1 of the newly developed interval delay, contrast-enhanced, secondary-harmonic sonographic types.
A 36-year-old woman was referred to our hospital because of epigastric fullness for 3 months. Prior use of oral contraceptive pills was denied. Laboratory studies revealed elevated alanine aminotransferase and aspartate aminotransferase values of 113 and 273 U/L, respectively. The alkaline phosphatase level was 273 U/L. Hepatitis B surface antigen and anti–hepatitis C virus antibody test results were negative. The  -fetoprotein value was 4.44 µg/L.
Conventional sonography showed marked fatty metamorphosis of the liver and a 9-cm hypoechoic lobulated mass over the left hepatic lobe. This mass consisted of 2 distinct portions, with a homogeneous hypoechoic pattern (Fig. 1A
The patient underwent left hepatic lobectomy. Gross tissue (Fig. 2D  ) revealed a single 9.0-cm lobulated tumor, with the lower right portion of this mass having some intratumoral hemorrhage in comparison with the intact upper left portion. Histologic study confirmed the diagnosis of hepatic adenoma, with marked intratumoral hemorrhage of the lower right portion. Before the operation, subtraction mode FEI (PowerVision 6000; Toshiba Medical Systems, Co, Ltd, Tokyo, Japan) was performed. Levovist (SH U 508A; Schering AG, Berlin, Germany), an intravenously injectable water suspension of galactose microparticles stabilized with 0.1% palmitic acid, was administered at a concentration of 350 mg/mL (2.5 g in 7 mL of distilled water) by manual bolus injection over 7 seconds. The FEI system was set according to the manufacturer's instructions. The ultrasonic scanner transmitted at 2.1 MHz and received at double that frequency. With the FEI system in the subtraction mode, the scanner was set to generate 2 shots in rapid succession, at a mechanical index (MI) of 1.2. Intermittent imaging, with a 2-second interval between exposures, was obtained at 20 seconds and 1 and 5 minutes after the Levovist injection. The subtraction image was derived from merging the second image with the first. Real-time monitoring with a low–acoustic power image (MI, 0.2) was performed during the intervals between FEI. The images were stored using the cine loop of the sonography system and a video system.
Heterogeneous enhancement was shown in the upper left portion of the tumor at 20 seconds after the contrast agent injection. More homogeneous enhancement was noted in the upper left portion at 1 minute after the contrast agent injection; however, some perfusion defects, corresponding to the hemorrhagic segment in the lower right portion of this mass, were still shown (Fig. 3B
In terms of their appearance on conventional sonography, hepatic adenomas were thought to be nonspecific.3,5 In our previous report of 12 surgically proved cases, however, a good association between sonographic features and pathologic findings was shown.4 Hypoechoic, hyperechoic, and mixed echoic patterns represented simple adenoma, adenoma with fatty metamorphosis, and hemorrhagic necrosis, respectively. The conventional sonographic features of this case confirm our previous observations. The introduction of microbubble contrast agents for diagnostic sonography has afforded the opportunity for assessment of hepatic lesion vascularity and perfusion states.6 Furthermore, the use of these contrast agents in color or power Doppler sonographic detection has improved delineation of lesion vascularity in hepatic tumors. There are several limitations to microbubble Doppler studies, however, including blooming artifacts and pericardial tissue motion artifacts. Subtraction mode FEI is an interval delay imaging technique with a gray scale display, which may reduce the severity of these drawbacks. Furthermore, in the interval delay variant, the imaging process is interrupted for several seconds. This allows the entire vascular volume, including the microvessels, to fill with contrast medium. Imaging is then commenced at a high MI. This destroys the accumulated microbubbles, causing the release of highintensity, nonlinear ultrasonic echoes that are optimally detected using harmonic imaging.7–11 At a low MI, monitoring performed during the FEI intervals allows real-time evaluation of blood vessels without destruction of the microbubbles. Interval delay harmonic sonography has improved characterization of various common hepatic focal lesions.8–11 Likewise, we have also confirmed the potential of this technique for evaluation of the therapeutic effect of percutaneous ethanol injection for the treatment of small hepatocellular carcinomas.10 In this hepatic adenoma perfusion study, the characteristics of sequential heterogeneous and homogeneous enhancement of the nonhemorrhagic area in the early phase and the persistent nonenhancement of the hemorrhagic area may prove helpful for differentiating a hepatic adenoma from other forms of hepatic tumor. A number of technique-associated factors determine the echoic intensity obtained with FEI. The longer the interval delay, the greater the enhancement intensity attributable to the increased number of microbubbles entering the vessels of the lesion and subsequently destroyed during high-MI shots. The optimal delay interval is not known as yet, however, and it may depend on the velocity of the vascular flow in the examined tissue. The last-frame image in the short, single-trigger sequence is subtracted from the first, with the resultant image displaying only the vascular space containing the contrast agent.9,11 The fourth frame in a rapid sequence gives the most adequate baseline harmonic image.11 For the case presented here, the interval delay for the subtraction FEI was set at 2 seconds, with 2 rapid shots generated from 1 trigger. Increasing the interval delay and the number of frame images for 1 trigger may increase the sensitivity of microbubble detection. Hence, the results of our FEI may have somewhat underestimated the true vascularity of this large hepatic adenoma. The newly developed pulse inversion imaging technique,6,12 which takes advantage of the high signal-noise ratio of the second-harmonic frequency and the elimination of signal artifacts without filtering, is a very sensitive variant of contrast-enhanced imaging. Given the superior spatial and contrast resolution, it may prove more useful for characterization of liver tumors in the future. In summary, subtraction mode FEI after contrast agent injection provides useful information on perfusion. Specifically, the imaged features appear to reflect pathologic findings, with good perfusion representing an intact adenoma and poor perfusion indicating hemorrhage.
Received March 1, 2002, from the Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.
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