Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS) measured continuously from the arterial phase to the late phase (3 minutes). Material and Methods. We present a retrospective analysis of 20 patients with malignant ( ) or benign ( ) liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5？T MRI (liver specific contrast medium) or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5？MHz) and a bolus injection of 2.4？mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak), RBV (regional blood volume), RBF (regional blood flow), and Peak. Results. Statistics revealed a significant difference ( ) between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP ( ). Receiver operating curves (ROC) were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors. 1. Introduction The radiomorphological differentiation between benign and malignant liver tumors with contrast-enhanced ultrasound is based on a continuous, dynamic evaluation of microvascularization of the tumor [1] and has been shown to be extremely reliable [2, 3]. Malignant liver tumors (HCC, CCC, and metastasis) often have an irregular, sometimes chaotic, early-arterial and arterial (15–45？secs) microvascularization showing a hyperenhancement or rim enhancement [4] in the arterial phase and a hypoechogenic pattern in the portal-venous and the late (2–5？mins) venous phases [4–6]. Metastasis can be hypovascular (e.g., adenocarcinoma) with necrotic, nonenhanced areas or hypervascular (e.g., neuroendocrine tumors) with complete or partial hyperenhancement in the arterial phase. A common feature of almost all metastases is hypo- or nonenhancement in the portal and late phases [7–9]. Most benign hepatic lesions (haemangioma, focal nodular hyperplasia, and adenoma) show a rapid enhancement in the arterial phase with a prolonged enhancement in the late venous phase. They display mainly not only hyperechogenic but also isoechogenic patterns in the late phase [4–6]. Classical patterns include nodular, wheel-spike, or mixed accumulations as seen in haemangioma, focal nodular hyperplasia (FNH), and adenoma,
References
[1]
D. A. Clevert, M. D'Anastasi , and E. M. Jung, “Contrast-enhanced ultrasound and microcirculation: efficiency through dynamics—current developments,” Clinical Hemorheology and Microcirculation, vol. 53, no. 1-2, pp. 171–186, 2013.
[2]
K. Seitz, T. Bernatik, D. Strobel et al., “Contrast-enhanced ultrasound (CEUS) for the characterization of focal liver lesions in clinical practice (DEGUM Multicenter Trial): CEUS vs. MRI—a prospective comparison in 269 patients,” Ultraschall in der Medizin, vol. 31, no. 5, pp. 492–499, 2010.
[3]
F. Moriyasu and K. Itoh, “Efficacy of perflubutane microbubble-enhanced ultrasound in the characterization and detection of focal liver lesions: phase 3 multicenter clinical trial,” American Journal of Roentgenology, vol. 193, no. 1, pp. 86–95, 2009.
[4]
H.-J. Jang, H. Yu, and T. K. Kim, “Contrast-enhanced ultrasound in the detection and characterization of liver tumors,” Cancer Imaging, vol. 9, no. 1, pp. 96–103, 2009.
[5]
J. Y. Jang, M. Y. Kim, S. W. Jeong, et al., “Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions,” Clinical and Molecular Hepatology, vol. 19, no. 1, pp. 1–16, 2013.
[6]
E. Quaia, F. Calliada, M. Bertolotto et al., “Characterization of focal liver lesions with contrast-specific US modes and a sulfur hexafluoride-filled microbubble contrast agent: diagnostic performance and confidence,” Radiology, vol. 232, no. 2, pp. 420–430, 2004.
[7]
E. Quaia, M. D'Onofrio, A. Palumbo, S. Rossi, S. Bruni, and M. Cova, “Comparison of contrast-enhanced ultrasonography versus baseline ultrasound and contrast-enhanced computed tomography in metastatic disease of the liver: diagnostic performance and confidence,” European Radiology, vol. 16, no. 7, pp. 1599–1609, 2006.
[8]
F. Piscaglia, F. Corradi, M. Mancini et al., “Real time contrast enhanced ultrasonography in detection of liver metastases from gastrointestinal cancer,” BMC Cancer, vol. 7, article 171, 2007.
[9]
J. R. Janica, U. Lebkowska, A. Ustymowicz et al., “Contrast-enhanced ultrasonography in diagnosing liver metastases,” Medical Science Monitor, vol. 13, supplement 1, pp. 111–115, 2007.
[10]
C. Greis, “Ultrasound contrast agents as markers of vascularity and microcirculation,” Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 1–9, 2009.
[11]
M. Claudon, C. F. Dietrich, B. I. Choi, et al., “Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver—update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS,” Ultraschall in der Medizin, vol. 34, no. 1, pp. 11–29, 2013.
[12]
J. Bruix and M. Sherman, “Management of hepatocellular carcinoma: an update,” Hepatology, vol. 53, no. 3, pp. 1020–1022, 2011.
[13]
E. R. DeLong, D. M. DeLong, and D. L. Clarke-Pearson, “Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach,” Biometrics, vol. 44, no. 3, pp. 837–845, 1988.
[14]
X. Robin, N. Turck, A. Hainard et al., “pROC: an open-source package for R and S+ to analyze and compare ROC curves,” BMC Bioinformatics, vol. 12, no. 1, article 77, 2011.
[15]
N. Lassau, M. Chebil, L. Chami, S. Bidault, E. Girard, and A. Roche, “Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment,” Targeted Oncology, vol. 5, no. 1, pp. 53–58, 2010.
[16]
D. Strobel, K. Seitz, W. Blank et al., “Tumor-Specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1349 liver lesions in contrast-enhanced ultrasound (CEUS),” Ultraschall in der Medizin, vol. 30, no. 4, pp. 376–382, 2009.
[17]
H. Ngan and W. C. Peh, “Arteriovenous shunting in hepatocellular carcinoma: its prevalence and clinical significance,” Clinical Radiology, vol. 52, no. 1, pp. 36–40, 1997.
[18]
P. Reimer, E. J. Rummeny, H. E. Daldrup, et al., “Enhancement characteristics of liver metastases, hepatocellular carcinomas, and hemangiomas with Gd-EOB-DTPA: preliminary results with dynamic MR imaging,” European Radiology, vol. 7, no. 2, pp. 275–280, 1997.
[19]
F. Ridolfi, T. Abbattista, P. Busilacchi, and E. Brunelli, “Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases,” World Journal of Gastroenterology, vol. 18, no. 37, pp. 5225–5230, 2012.
[20]
X. Q. Pei, L. Z. Liu, Y. H. Xiong, et al., “Quantitative analysis of contrast-enhanced ultrasonography: differentiating focal nodular hyperplasia from hepatocellular carcinoma,” The British Journal of Radiology, vol. 86, no. 1023, Article ID 20120536, 2013.
[21]
M. Palmowski, W. Lederle, J. Gaetjens et al., “Comparison of conventional time-intensity curves vs. maximum intensity over time for post-processing of dynamic contrast-enhanced ultrasound,” European Journal of Radiology, vol. 75, no. 1, pp. e149–e153, 2010.
[22]
C. F. Dietrich, M. E. Maddalena, X. W. Cui, D. Schreiber-Dietrich, and A. Ignee, “Liver tumor characterization—review of the literature,” Ultraschall in der Medizin, vol. 33, supplement 1, pp. S3–S10, 2012.
