Small Liver Nodule Detection With a High-Frequency Transducer in Patients With Chronic Liver Disease

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1 SE SERIES Small Liver Nodule Detection With a High-Frequency Transducer in Patients With hronic Liver Disease Report of 3 cases nnemarie uadu, MD, Monique. Meyer, MD We report 3 cases in which small liver lesions were revealed on sonography with the supplemental use of a high-frequency transducer. In all 3 cases, the patients had cirrhosis or chronic liver disease. The lesions were not seen on computed tomography or magnetic resonance imaging. Sonography plays a pivotal role in surveillance for hepatocellular carcinoma and, with modern transducer technology, may be the first imaging modality to show an early small tumor. more thorough search for focal liver lesions with adjunctive use of high-frequency transducers may prolong the examination time but can improve surveillance for hepatocellular carcinoma. Key Words cirrhosis; hepatocellular carcinoma; high-frequency transducer; sonography Received February 7, 2012, from the Department of Radiology, University of rizona Health Science enter, Tucson, rizona US. Revision requested March 27, Revised manuscript accepted for publication July 12, We thank Tracy Sheldon, RT, RDMS, and Eva Lehrman, RT, for help with acquiring images. ddress correspondence to nnemarie uadu, MD, Department of Radiology, University of rizona Health Science enter, 1501 N ampbell ve, Tucson, Z US. a_buadu@yahoo.com bbreviations T, computed tomography; MRI, magnetic resonance imaging I n hepatic sonography, there has been a growing interest in the supplemental use of high-frequency transducers to better evaluate the liver surface for cirrhosis. 1 5 There has been resulting delineation of small focal lesions near the liver surface, which are not seen with low-frequency transducers. 1 In patients with cirrhosis or chronic liver disease, some of these liver lesions are benign, but some are hepatocellular carcinomas. 6 The use of highfrequency transducers plays an important role in delineating focal liver lesions. Jung at al 7 described 9 cases in which small liver lesions (4 15 mm), including tumors, were detected during intraoperative sonography with high-frequency transducers and contrast-enhanced sonography. Some of these liver lesions had not been detected on computed tomography (T) or magnetic resonance imaging (MRI). There is little information in the literature describing detection of liver lesions measuring less than 8 mm with sonography even without contrast-enhanced sonography. We describe 3 cases in which small focal liver lesions, measuring 8 mm or less, were revealed with the use of a high-frequency transducer. These lesions, being small, were not proved by pathologic examination to be hepatocellular carcinomas; however, these cases underscore the benefit of high-frequency transducer use in delineating very small liver lesions, some of which could represent early malignant disease by the merican Institute of Ultrasound in Medicine J Ultrasound Med 2013; 32:

Materials and Methods Three patients with a known history of cirrhosis or other chronic liver disease underwent abdominal sonography.

curved low-frequency 1- to 5-MHz transducer (1-5 D) was used for the examination.

olor Doppler imaging was performed to further characterize identified focal lesions.

2 Materials and Methods Three patients with a known history of cirrhosis or other chronic liver disease underwent abdominal sonography. In all 3 cases, a LOGIQ E9 ultrasound machine (GE Healthcare, Milwaukee, WI) equipped with harmonics, speckle reduction imaging, and spatial compounding was used. curved low-frequency 1- to 5-MHz transducer (1-5 D) was used for the examination. In addition, a matrix linear array high-frequency 6- to 15-MHz transducer (ML 6-15 D) was used to evaluate the liver surface. olor Doppler imaging was performed to further characterize identified focal lesions. ase Descriptions ase 1 56-year-old woman with hepatic failure and a history of idiopathic cirrhosis underwent abdominal sonography. The examination revealed cirrhosis of the liver with 4 focal hypoechoic liver lesions in the left lobe. The largest liver lesion, measuring cm was seen with the lowfrequency transducer at 4 MHz (Figure 1) as well as with the high-frequency transducer at 8 MHz (Figure 1). The lesion showed no central flow (Figure 1) and was hypoechoic in appearance with the high- and low-frequency transducers. The other 3 liver lesions measured 5, 5, and 8 mm, respectively and were seen only with the highfrequency transducer (Figure 1). Differential diagnostic considerations for these lesions were regenerating nodules, hepatocellular carcinoma, and dysplastic nodules. Magnetic resonance imaging was recommended but was not performed. On noncontrast T of the liver, the lesions were not delineated. random biopsy of the liver was performed. Pathologic findings described chronic fibrosis. ase 2 67-year-old man with a known history of hepatitis infection had been treated previously with interferon therapy and had a relapse. He had been unable to enroll in a retreatment plan (protease study) because of his age. bdominal sonography was performed to evaluate the liver. Results of liver function tests performed 1 month before abdominal sonography were normal. His serum α-fetoprotein level was normal. Sonography of the abdomen showed a liver Figure 1. ase 1: 4 focal liver lesions in a 56-year-old woman with idiopathic cirrhosis., Transverse grayscale sonogram obtained with a curved low-frequency transducer at 4 MHz showing a 1.6-cm hypo echoic lesion (calipers) in the left lobe, the largest of the 4 lesions., Transverse grayscale sonogram obtained with a matrix linear array high- frequency transducer at 8 MHz showing all 4 hypoechoic lesions. The largest liver lesion (blue arrow) was seen with the low-frequency transducer as well and was hypoechoic with the low- and high-frequency transducers. The smaller lesions (white arrows) were seen only with the highfrequency transducer and measured 8, 5, and 5 mm, respectively., olor Doppler sonogram showing the largest of 4 liver lesions with no central vascularity. 356 J Ultrasound Med 2013; 32:

Threephase T of the liver with 3-mm axial sections performed 1 month later did not reveal liver lesions. Magnetic resonance imaging was not performed.

3 with a coarse echo texture. Three echogenic liver lesions were seen only with use of the high-frequency transducer at 9 MHz (Figure 2). The largest of these lesions measured 4 mm and showed no internal flow (Figure 2, and ). Short-term follow-up abdominal sonography or MRI of the liver was recommended for further evaluation. Threephase T of the liver with 3-mm axial sections performed 1 month later did not reveal liver lesions. Magnetic resonance imaging was not performed. ase 3 38-year-old man with a history of hepatitis, hepatitis δ, and pancreatitis presented with abdominal pain. On abdominal sonography, the liver was normal in size but had a coarse echo texture. With the use of the low-frequency transducer at 3.5 MHz, no focal liver lesions were seen. With the use of the high-frequency transducer at 8 and 15 MHz, 4 small echogenic liver lesions were revealed. The largest lesion measured approximately 4 mm (Figure 3). Magnetic resonance imaging of the liver was recommended for further characterization of the lesions. The lesions were not shown on MRI. Discussion In 80% of cases worldwide, hepatocellular carcinoma develops in cirrhotic livers, and cirrhosis is the strongest predisposing factor. 8 ccording to the merican ssociation for the Study of Liver Diseases practice guidelines for management of hepatocellular carcinoma, surveillance has to be based on sonography. 6 Surveillance using α-fetoprotein evaluation has been determined to be inadequate in sensitivity and specificity. 6,8,9 Diagnosis of hepatocellular carcinoma should be based on imaging techniques, biopsy, or both. 6 Sonography of the liver is typically performed with a low-frequency 2- to 5-MHz transducer for adult patients. 10 djunctive use of higher-frequency 7- to 9-MHz transducers is primarily used to improve detection of liver surface nodularity. The added benefit of detecting focal liver lesions is invaluable. Some of these focal liver lesions have Figure 2. ase 2: 3 small liver lesions seen only with a high-frequency transducer in a 67-year-old man with hepatitis infection., Grayscale sonogram obtained with a matrix linear array high-frequency transducer at 9 MHz showing 2 of 3 echogenic liver lesions. The largest of the lesions (calipers) measured 4 mm. smaller lesion (arrow) is seen in this transducer field., olor Doppler sonogram obtained with the high-frequency transducer showing a liver lesion measuring 4 mm (arrow) with no central vascularity., Grayscale sonogram obtained with the high-frequency transducer at 9 MHz showing a third small liver lesion, which measured 2 mm J Ultrasound Med 2013; 32:

been confirmed to be benign lesions such as regenerating nodules, dysplastic nodules, or hemangiomas.

11 Needless to say, early detection of small liver lesions is of potential benefit in early diagnosis of small hepatocellular carcinomas.

These small lesions may not be seen on MRI or T, as in the cases presented here. In cases 1 and 2, the lesions were not shown on T, which may have been related to the T protocol used.

4 been confirmed to be benign lesions such as regenerating nodules, dysplastic nodules, or hemangiomas. However, up to 50% of lesions with a hemangioma-like appearance have been determined by histologic examination to be hepatocellular carcinomas. 11 Needless to say, early detection of small liver lesions is of potential benefit in early diagnosis of small hepatocellular carcinomas. Small liver lesions, measuring less than 1 cm, are relatively more difficult to diagnose by biopsy because of their small size. These small lesions may not be seen on MRI or T, as in the cases presented here. In cases 1 and 2, the lesions were not shown on T, which may have been related to the T protocol used. In case 3, the lesions were not shown on MRI and may have been lost to slice selection. In some cases, as in those presented here, small liver lesions are not revealed without use of a high-frequency transducer. High-frequency transducers, unlike low-frequency transducers, are useful for visualizing superficial structures, which explains their superior utility in detecting superficial liver lesions but also explains their limitations in evaluating deeper structures. There are other limitations to the adjunctive use of high-frequency transducers in hepatic sonography. First, the examination time is, at least, slightly increased. Schacherer et al 12 described an additional examination time range of 0.5 to 2 minutes (mean, 2.2 minutes). Other workers have described an average 4-minute increase in the examination time with the supplemental use of high-frequency trans- Figure 3. ase 3: 4 small liver lesions seen only with a high-frequency transducer in a 38-year-old man with abdominal pain and a history of hepatitis and hepatitis δ. Lesions were not seen with a 3.5-MHz transducer., Grayscale sonogram obtained with a matrix linear array high-frequency transducer at 15 MHz showing an echogenic liver lesion measuring 4 mm., Sagittal color Doppler sonogram obtained with the high-frequency transducer showing a second echogenic liver lesion (arrow) with no central vascularity, which measured 4 mm., Transverse grayscale sonogram obtained with the high-frequency transducer at 8 MHz showing a third echogenic liver lesion (arrow), which measured 2 mm. D, Transverse grayscale sonogram obtained with the high-frequency transducer at 8 MHz showing a fourth echogenic liver lesion (arrow), which measured 2 mm. D 358 J Ultrasound Med 2013; 32:

5 ducers to examine the liver. 13 Second, as with all conventional sonographic examinations, diagnosis of focal liver lesions using a high-frequency transducer is limited in specificity. 14 ontrast-enhanced sonography has been reported to improve specificity, accuracy, and confidence in diagnosis of focal liver lesions However, contrastenhanced sonography may offer a false-positive diagnosis of hepatocellular carcinoma in patients with cholangiocarcinoma and thus has been excluded from the techniques recommended by the merican ssociation for the Study of Liver Diseases in the algorithm for surveillance and diagnosis. Small hypovascular hepatocellular carcinomas have been described as especially less likely to be diagnosed by any sonographic technique. 19 In the merican ssociation for the Study of Liver Diseases diagnostic algorithm for suspected hepatocellular carcinoma, the recommendation for liver lesions smaller than 1 cm is to repeat sonographic examination at 3-month intervals for stable lesions and to further investigate growing lesions according to size. The recommendation for liver lesions larger than 1 cm is to perform dynamic multidetector T (4 phase) or dynamic contrast enhanced MRI. If a definite diagnosis is not derived by T or MRI, biopsy or another contrast-enhanced study (T or MRI) may be performed. 6 Sonography is operator dependent, and the sensitivity of lesion detection is largely influenced by the technique. onsidering the critical role of sonography in liver cancer surveillance, the importance of an improved technique in conventional sonography cannot be overstated. The additional time used in examining the liver surface with modern high-frequency transducers is likely to improve lesion detection during surveillance for hepatocellular carcinoma. Further studies in which such small liver lesions are followed in the long term will help determine how many of such small focal lesions in chronic liver disease become hepatocellular carcinomas. References 1. Di Leilo, estari, Lomazzi, eretta L. irrhosis: diagnosis with sonographic study of the liver surface. Radiology 1989; 172: Ferral H, Male R, ardiel M, Munoz L, Quiroz y Ferrari F. irrhosis: diagnosis by liver surface analysis with high-frequency ultrasound. Gastrointest Radiol 1992; 17: Simonovský V. The diagnosis of cirrhosis by high resolution ultrasound of the liver surface. r J Radiol 1999; 72: Ladenheim J, Luba DG, Yao F, Gregory P, Jeffrey R, Garcia G. Limitations of liver surface US in the diagnosis of cirrhosis. Radiology 1992; 185: olli, Fraquelli M, ndreoletti M, Marino, Zuccoli E, onte D. Severe liver fibrosis or cirrhosis: accuracy of US for detection analysis of 300 cases. Radiology 2003; 227: ruix J, Sherman M; merican ssociation for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: Jung EM, Ross J, Rennert J, et al. haracterization of microvascularization of liver tumor lesions with high resolution linear ultrasound and contrast enhanced ultrasound (EUS) during surgery: first results. lin Hemorheol Microcirc 2010; 46: Llovet JM, urroughs, ruix J. Hepatocellular carcinoma. Lancet 2003; 362: Lok S, Sterling RK, Everehart JE, et al; HLT- Trial Group. Desgamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology 2010; 138: merican Institute of Ultrasound in Medicine. IUM practice guideline for the performance of an ultrasound examination of the abdomen and/or retroperitoneum. J Ultrasound Med 2012; 31: aturelli E, Pompili M, artolucci F, et al. Hemangioma-like lesions in chronic liver disease: diagnostic evaluation in patients. Radiology 2001; 220: Schacherer D, Schuh, Strauch U, et al. Improvement in the routine diagnostic assessment of the liver by high-resolution sonography: an analysis of 999 cases. Scand J Gastroenterol 2007; 42: Poff J, oakley FV, Qayyum, et al. Frequency and histopathologic basis of hepatic surface nodularity in fulminant hepatic failure. Radiology 2008; 249: Outwater EK. Imaging of the liver for hepatocellular carcinoma. ancer ontrol 2010; 17: Georgio, alisti G, di Sarno, et al. haracterization of dysplastic nodules, early hepatocellular carcinoma and progressed hepatocellular carcinoma in cirrhosis with contrast-enhanced ultrasound. nticancer Res 2011; 31: Martie, Sporea I, Popescu, et al. ontrast enhanced ultrasound for the characterization of hepatocellular carcinoma. Med Ultrason 2011; 13: Wilson, SR, Jang HJ, Kim TK, urns PN. Diagnosis of focal liver masses on ultrasonography: comparison of unenhanced and contrast-enhanced scans. J Ultrasound Med 2007; 26: Quaia E. The real capabilities of contrast-enhanced ultrasound in the characterization of solid focal liver lesions. Eur Radiol 2011; 21: olondi L, Gaiani S, elli N, et al. haracterization of small nodules in cirrhosis by assessment of vascularity: the problem of hypovascular hepatocellular carcinoma. Hepatology 2005; 42: J Ultrasound Med 2013; 32:

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