British Journal of Radiology (2005) 78, 704-707
© 2005 British Institute of Radiology
doi: 10.1259/bjr/88181612
Differentiation of focal nodular hyperplasia and hepatocellular adenoma by contrast-enhanced ultrasound
C F Dietrich, MD1,
G Schuessler, MD1,
J Trojan, MD2,
C Fellbaum, MD3 and
A Ignee, MD1
1 1st Department of Internal Medicine, Caritas Hospital Bad Mergentheim, Uhlandstr. 7, 97980 Bad Mergentheim, 2 2nd Department of Internal Medicine and 3 Senckenberg Center of Pathology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt am Main, Germany
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Abstract
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Non-invasive differentiation of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) is difficult. The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between histologically proven FNH and HCA, analysing the arterial and (early) portal venous phase. 32 patients with histological proven FNH (n=24) or HCA (n=8) have been included in this prospective study. Examination technique: Siemens Elegra, phase inversion harmonic imaging (PIHI) with low mechanical index (MI)<0.2–0.3 using SonoVue® (BR 1). The contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8–22 s) and early portal venous phase (starting 12–30 s). The image analysis was performed by three examiners. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and (early) portal venous enhancement. Homogeneous enhancement was detected during the hepatic arterial phase in all eight patients with HCA. In contrast to patients with FNH, no enhancement was seen during the portal venous phase. In conclusion, contrast-enhanced phase inversion ultrasound demonstrated pronounced arterial and portal venous enhancement in patients with focal nodular hyperplasia. In contrast, after homogeneous enhancement during hepatic arterial phase, no enhancement during hepatic portal venous phase was detected in patients with hepatocellular adenoma. Therefore, this technique might improve the functional characterization of benign hypervascular focal liver lesions.
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Introduction
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Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are two benign, mostly incidentally discovered, hepatic neoplasms which occur predominantly in young and middle-aged women. Differentiation is essential because of different therapeutic approaches: HCA is an indication for surgery due to the risk of haemorrhage and a potential for malignant transformation; by contrast, FNH may be managed conservatively. However, until recently the non-invasive differentiation of FNH from HCA and other benign or malignant neoplasm has remained challenging with no satisfactory tests apart from histological examination of a liver biopsy sample [1].
Ultrasound features of FNH are often non-specific, whereas helical CT and MRI are able to provide some information for the diagnosis of FNH, especially when the lesion depicts typical features, such as a central scar and uniform hypervascularity. Typical histological features are controversial in the literature [2–7] and only reported in about 50–70% of patients. In a series of 305 FNH, a central scar could be found only in about 50% [8].
To improve the ultrasound detection and characterization of liver tumours micro-bubble echo-enhancers have been developed, which can be optimally utilized with the phase-inversion mode [9].
The aim of this study was to assess the accuracy of contrast-enhanced phase inversion ultrasound to differentiate between FNH and HCA analysing the arterial and portal venous phase.
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Subjects and methods
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Between 2000 and 2002, 32 patients with histologically proven FNH (n=24) or HCA (n=8) were included in this prospective study evaluating the tumour characteristics using SonoVue® (Bracco, Milan, Italy) contrast enhanced ultrasound before biopsy. Tumours suspected to be FNH or adenoma before biopsy, but which proved to be of different origin have been excluded from study analysis. All patients underwent B-mode ultrasound (Sonoline Elegra; Siemens, Erlangen, Germany) with a 3.5 MHz and a 7 MHz multifrequency transducer. The pattern of tumours was described as hypoechoic, isoechoic, or hyperechoic compared with the surrounding liver tissue; tumour vascularity was classified as hypervascular, isovascular, or hypovascular by power Doppler ultrasound. The internal vascular architecture was also documented. All examinations were carried out by the same examiner (CFD), but image analysis was performed by two additional examiners. Contrast sequences were regarded sufficiently evaluable, if all three examiners agreed on the adequate visualization; in three patients a second injection was necessary to ensure full agreement between examiners.
In a pre-study phase of 10 consecutive patients we could observe the onset of hepatic arterial enhancement between 8 s and 22 s, and the early onset of portal venous enhancement between 12 s and 30 s. Therefore, intravenous application of 4.8 ml SonoVue® was used with phase inversion ultrasound before biopsy using the following imaging parameters: mechanical index 0.2–0.3, power 3%, gain 52–60 dB and frame rate 10–14 s–1. The liver was scanned continuously for up to 5 min. Using this approach, contrast enhancing tumour characteristics were evaluated during the hepatic arterial (starting 8–22 s) and early portal venous phase (starting 12–30 s), as described previously, comparing the contrast enhancement in comparison with the enhancing hepatic artery and portal vein branches (Figure 1
) [11].
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Figure 1. Contrast-enhanced phase inversion ultrasound imaging of a patient with focal nodular hyperplasia. (a) Contrast-enhanced phase inversion ultrasound scanning 8–22 s (onset of arterial phase) after administration of SonoVue® revealed an hyperechoic hypervascular liver tumour with radial vascular architecture. (b) During the portal venous phase (onset 12–30 s after administration of SonoVue®) a pronounced enhancement could be detected by contrast-enhanced phase inversion ultrasound scanning. Hepatic artery (HA) and portal vein (PV) are indicated.
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Reference imaging examinations (e.g. CT, MRI and scintigraphy) were performed as part of the clinical work-up of the patients, in several cases outside our institution, and not for the purpose of this study. The standard practice used in our department included two different image procedures (US/CT/MRI) with inconclusive findings before liver biopsy. Institutional Board approval and oral informed consent, from all patients according to the ethical guidelines from Helsinki, were obtained. Patient's characteristics are summarized in (Table 1).
In a post-study phase we used Acuson Sequoia (contrast pulse sequencing (CPS); Siemens, Erlangen, Germany) techniques in an additional 12 patients with FNH and 2 patients with hepatocellular adenoma. Intravenous application of 1.2 ml/2.4 ml SonoVue® was applied using the following imaging parameters: mechanical index 0.21, gain 80 dB.
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Results
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In all 32 patients, enhancement of the hepatic artery and portal vein was observed. In 23 of 24 patients with FNH the contrast pattern revealed pronounced arterial and portal venous enhancement after SonoVue®. Only one patient with FNH lacked early portal venous enhancement, which might be explained by extensive histologically documented fibrosis. Using SonoVue® homogeneous tumour enhancement was detected during the hepatic arterial phase in all eight patients with HCA, preceding enhancement of normal liver parenchyma (Figure 2a). In contrast to patients with FNH, no portal venous enhancement was seen in HCA during the hepatic portal venous phase (Figure 2b) with isoechoic or, more often, slight hypoechoic appearance in the parenchymal later phases. Ultrasound findings of this study are summarized in Table 1
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Figure 2. Contrast-enhanced phase inversion ultrasound of a patient with hepatocellular adenoma (arrows). (a) Contrast-enhanced phase inversion ultrasound scanning revealed only arterial phase enhancement for 10 s (10–20 s) after administration of SonoVue®. (b) At the end of the arterial phase (22 s after administration of SonoVue®) a slightly hypoechoic liver tumour was detected by contrast-enhanced phase inversion ultrasound and no portal venous sinusoidal enhancement was observed.
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In the post-study phase using Acuson Sequoia CPS-technology, contrast-enhancing tumour characteristics were visible during the arterial and early portal venous phase in all 12 examined patients with FNH and only arterial enhancement in the two patients, with adenoma with slight hypoechoic appearance in the parenchymal later phases.
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Discussion
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The combination of phase inversion ultrasound and micro-bubble echo-enhancers has been demonstrated to significantly improve the detection of liver metastases [9]. Moreover, late-phase contrast-enhanced ultrasound can also differentiate between benign and malignant focal hepatic lesions [10, 11]. However, no systematic studies using contrast-enhanced phase inversion ultrasound for the further characterization of liver lesions with acoustic properties similar to those of surrounding normal liver parenchyma, especially FNH and HCA, have been reported. Here, we demonstrate that examination of the hepatic arterial and early portal venous phase by contrast-enhanced phase inversion ultrasound could consistently differentiate between FNH and HCA. This important finding could be explained by the lack of portal veins of HCA in contrast to FNH which presents (atypical) portal veins in many but not all patients. It is of importance that the described typical features can be observed in tumours <50 mm without regressive changes. The contrast behaviour in larger FNH and adenoma might be different due to regressive changes such as intratumoural haemorrhage, necrosis, fibrous tissue and calcifications.
The dose of SonoVue® was 4.8 ml, and the mechanical index 0.2–0.3 in the presented study lead to some bubble destruction and, therefore, improved visualization of vascularity but less homogeneous enhancement in the later phases. It has also to be taken into account that the dosage of 4.8 ml is too large to evaluate the wash-out kinetics using more recent technology since arterioportal overlap is too long. Therefore, using newer technology, 2.4 ml and even 1.2 ml may be superior for tumour perfusion analysis.
The even more important differential diagnosis between FNH and adenoma and malignant tumours was recently addressed [10, 11]. Analysis of the late portal venous (sinusoidal) phase shows that differentiation of benign and malignant lesions is possible in most patients without parenchymal (diffuse) liver disease. In our experience, results in patients with pronounced fatty liver disease and liver cirrhosis are less impressive, leading to false negative findings in some patients. In summary, contrast-enhanced phase inversion ultrasound with SonoVue®, can show more functional and morphological features of focal nodular hyperplasia and hepatocellular adenoma.
Received for publication July 1, 2004.
Revision received January 13, 2005.
Accepted for publication February 11, 2005.
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References
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Abstract
Introduction
