Abstract
Background
To show the effectiveness of plane wave HighFrame-Rate CEUS (HiFR-CEUS) compared with “conventional” (plane wave) CEUS (C-CEUS) in the characterization of small (< 2 cm) focal liver lesions (FLLs) not easily detected by CT in cirrhotic patients. HiFR-CEUS exploit an ultra-wideband nonlinear process to combine fundamental, second and higher-order harmonic signals generated by ultrasound contrast agents to increase the frame rate. C-CEUS is limited by the transmission principle, and its frame-rate is around 10 FPS. With HiFR-CEUS (Shenzhen Mindray Bio-Medical Electronics Co., China), the frame-rate reached 60 FPS.
Material and methods
Ultrasound detected small FLLs (< 2 cm) in 63 cirrhotic patients during follow-up (June 2019–February 2020); (7 nodules < 1 cm and were not evaluable by spiral CT). Final diagnosis was obtained with MRI (47) or fine needle aspiration (16 cases) C-CEUS was performed and HiFR-CEUS was repeated after 5 min; 0.8–1.2 ml of contrast media (SonoVue, Bracco, Italy) was used. 57 nodules were better evaluable with HiFR-CEUS; 6 nodules were equally evaluable by both techniques; final diagnosis was: 44 benign lesions (29 hemangiomas, 1 amartoma, 2 hepatic cysts; 2 focal nodular hyperplasias, 3 regenerative macronodules, 3 AV-shunts, 3 hepatic sparing areas and 1 focal steatosis) and 19 malignant one (17 HCCs, 1 cholangioca, 1 metastasis); statistical evaluation for better diagnosis with X2 test (SPSS vers. 26); we used LI-RADS classification for evaluating sensitivity, specificity PPV, NPV and diagnostic accuracy of C- and HFR-CEUS. Corrispective AU-ROC were calculated.
Results
C-CEUS and HiFR-CEUS reached the same diagnosis in 29 nodules (13 nodules > 1 < 1.5 cm; 16 nodules > 1.5 < 2 cm); HiFR-CEUS reached a correct diagnosis in 32 nodules where C-CEUS was not diagnostic (6 nodules < 1 cm; 17 nodules > 1 < 1.5 cm; 9 nodules > 1.5 < 2 cm); C-CEUS was better in 2 nodules (1 < 1 cm and 1 > 1 < 1.5 cm). Some patient’s (sex, BMI, age) and nodule’s characteristics (liver segment, type of diagnosis, nodule’s dimensions (p = 0.65)) were not correlated with better diagnosis (p ns); only better visualization (p 0.004) was correlated; C-CEUS obtained the following LI-RADS: type-1: 18 Nodules, type-2: 21; type-3: 7, type-4: 7; type-5: 8; type-M: 2; HiFR-CEUS: type-1: 38 Nodules, type-2: 2; type-3:4, type-4: 2; type-5: 15; type-M: 2; In comparison with final diagnosis: C-CEUS: TP: 17; TN: 39; FP: 5; FN:2; HIFR-CEUS: TP: 18; TN: 41; FP: 3; FN:1; C-CEUS: sens: 89.5%; Spec: 88.6%, PPV: 77.3%; NPV: 95.1%; Diagn Acc: 88.6% (AU-ROC: 0.994 ± SEAUC: 0.127; CI: 0.969–1.019); HiHFR CEUS: sens: 94.7%; Spec: 93.2%, PPV: 85.7%; NPV: 97.6%; Diagn Acc: 93.2% (AU-ROC: 0.9958 ± SEAUC: 0.106; CI: 0.975–1.017) FLL vascularization in the arterial phase was more visible with HiFR-CEUS than with C-CEUS, capturing the perfusion details in the arterial phase due to a better temporal resolution. With a better temporal resolution, the late phase could be evaluated longer with HiFR-CEUS (4 min C-CEUS vs. 5 min HiFR-CEUS).
Conclusion
Both C-CEUS and HIFR-CEUS are good non invasive imaging system for the characterization of small lesions detected during follow up of cirrhotic patients. HiFR-CEUS allowed better FLL characterization in cirrhotic patients with better temporal and spatial resolution capturing the perfusion details that cannot be easily observed with C-CEUS.
Similar content being viewed by others
References
Bruix J, Sherman M (2011) American association for the study of liver D. Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022
El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365(12):1118–1127
Singal AG, Lampertico P, Nahon P (2020) Epidemiology and surveillance for hepatocellular carcinoma: new trends. J Hepatol 72(2):250–261
Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67(1):358–380
Liver (2018) EAftSot. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236
Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H et al (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4(2):439–474
Shiina S, Gani RA, Yokosuka O, Maruyama H, Nagamatsu H, Payawal DA et al (2020) APASL practical recommendations for the management of hepatocellular carcinoma in the era of COVID-19. Hepatol Int 14:920–929
Kim TH, Kim SY, Tang A, Lee JM (2019) Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update. Clin Mol Hepatol 25(3):245–263
Korean Liver Cancer A, National Cancer C (2019) 2018 Korean Liver Cancer Association-National Cancer Center Korea practice guidelines for the management of hepatocellular carcinoma. Gut Liver 13(3):227–299
Foerster F, Galle PR (2019) Comparison of the current international guidelines on the management of HCC. JHEP Rep 1(2):114–119
Niu Y, Huang T, Lian F, Li F (2013) Contrast-enhanced ultrasonography for the diagnosis of small hepatocellular carcinoma: a meta-analysis and meta-regression analysis. Tumour Biol 34(6):3667–3674
Westwood M, Joore M, Grutters J, Redekop K, Armstrong N, Lee K et al (2013) Contrast-enhanced ultrasound using SonoVue (R) (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and cost-effectiveness analysis. Health Technol Assess 17(16):1–243
Hanna RF, Miloushev VZ, Tang A, Finklestone LA, Brejt SZ, Sandhu RS et al (2016) Comparative 13-year meta-analysis of the sensitivity and positive predictive value of ultrasound, CT, and MRI for detecting hepatocellular carcinoma. Abdom Radiol 41(1):71–90
Vilana R, Forner A, Bianchi L, Garcia-Criado A, Rimola J, de Lope CR et al (2010) Intrahepatic peripheral cholangiocarcinoma in cirrhosis patients may display a vascular pattern similar to hepatocellular carcinoma on contrast-enhanced ultrasound. Hepatology 51(6):2020–2029
Galassi M, Iavarone M, Rossi S, Bota S, Vavassori S, Rosa L et al (2013) Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound. Liver Int 33(5):771–779
de Sio I, Iadevaia MD, Vitale LM, Niosi M, Del Prete A, de Sio C et al (2014) Optimized contrast-enhanced ultrasonography for characterization of focal liver lesions in cirrhosis: a single-center retrospective study. United Eur Gastroenterol J 2(4):279–287
Liu GJ, Wang W, Lu MD, Xie XY, Xu HX, Xu ZF et al (2015) Contrast-enhanced ultrasound for the characterization of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Liver cancer 4(4):241–252
Wildner D, Bernatik T, Greis C, Seitz K, Neurath MF, Strobel D (2015) CEUS in hepatocellular carcinoma and intrahepatic cholangiocellular carcinoma in 320 patients—early or late washout matters: a subanalysis of the DEGUM multicenter trial. Ultraschall Med 36(2):132–139
Wildner D, Pfeifer L, Goertz RS, Bernatik T, Sturm J, Neurath MF et al (2014) Dynamic Contrast-Enhanced Ultrasound (DCE-US) for the characterization of hepatocellular carcinoma and cholangiocellular carcinoma. Ultraschall Med. https://doi.org/10.1055/s-0033-1354813
Piscaglia F, Kudo M, Han KH, Sirlin C (2017) Diagnosis of hepatocellular carcinoma with non-invasive imaging: a plea for worldwide adoption of standard and precise terminology for describing enhancement criteria. Ultraschall Med 38(1):9–11
Piscaglia F, Wilson SR, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ et al (2017) American College of Radiology contrast enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) for the diagnosis of hepatocellular carcinoma: a pictorial essay. Ultraschall Med 38(3):320–324
Aube C, Oberti F, Lonjon J, Pageaux G, Seror O, N’Kontchou G et al (2017) EASL and AASLD recommendations for the diagnosis of HCC to the test of daily practice. Liver Int 37(10):1515–1525
Kim TH, Yoon JH, Lee JM (2019) Emerging role of hepatobiliary magnetic resonance contrast media and contrast-enhanced ultrasound for noninvasive diagnosis of hepatocellular carcinoma: emphasis on recent updates in major guidelines. Korean J Radiol 20(6):863–879
Kim JJ, Kim JY, Kang HJ, Shin JK, Kang T, Lee SW et al (2017) Computer-aided diagnosis-generated kinetic features of breast cancer at preoperative MR imaging: association with disease-free survival of patients with primary operable invasive breast cancer. Radiology 284:162079
Claudon M, Dietrich CF, Choi BI, Cosgrove DO, Kudo M, Nolsoe CP et al (2013) 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. Ultrasound Med Biol 39(2):187–210
Xu HX, Lu MD, Liu LN, Zhang YF, Guo LH, Xu JM et al (2012) Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound. Br J Radiol 85(1018):1376–1384
Cokkinos DD, Blomley MJ, Harvey CJ, Lim A, Cunningham C, Cosgrove DO (2007) Can contrast-enhanced ultrasonography characterize focal liver lesions and differentiate between benign and malignant, thus providing a one-stop imaging service for patients? (). J Ultrasound 10(4):186–193
Lu JY, Zou H, Greenleaf JF (1994) Biomedical ultrasound beam forming. Ultrasound Med Biol 20(5):403–428
Tanter M, Fink M (2014) Ultrafast imaging in biomedical ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 61(1):102–119
Camacho J, Parrilla M, Fritsch C (2009) Phase coherence imaging. IEEE Trans Ultrason Ferroelectr Freq Control 56(5):958–974
Fritsch C, Camacho J, Parrilla M (2010) New ultrasound imaging techniques with phase coherence processing. Ultrasonics 50(2):122–126
Montaldo G, Tanter M, Bercoff J, Benech N, Fink M (2009) Coherent plane-wave compounding for very high frame rate ultrasonography and transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control 56(3):489–506
Couture O, Fink M, Tanter M (2012) Ultrasound contrast plane wave imaging. IEEE Trans Ultrason Ferroelectr Freq Control 59(12):2676–2683
Viti J, Vos HJ, De Jong N, Guidi F, Tortoli P. Contrast detection efficacy for plane vs. focused wave transmission. In: IEEE International ultrasonics symposium proceedings. 2014:1750–3.
Viti J, Vos HJ, Jong N, Guidi F, Tortoli P (2016) Detection of contrast agents: plane wave versus focused transmission. IEEE Trans Ultrason Ferroelectr Freq Control 63(2):203–211
Schiefler NT Jr, Maia JM, Schneider FK, Zimbico AJ, Assef AA, Costa ET (2018) Generation and analysis of ultrasound images using plane wave and sparse arrays techniques. Sensors (Basel). 18(11):3660
Tanter M, Bercoff J, Sandrin L, Fink M (2002) Ultrafast compound imaging for 2-D motion vector estimation: application to transient elastography. IEEE Trans Ultrason Ferroelectr Freq Control 49(10):1363–1374
Bercoff J, Montaldo G, Loupas T, Savery D, Meziere F, Fink M et al (2011) Ultrafast compound Doppler imaging: providing full blood flow characterization. IEEE Trans Ultrason Ferroelectr Freq Control 58(1):134–147
Hasegawa H, Kanai H (2011) High-frame-rate echocardiography using diverging transmit beams and parallel receive beamforming. J Med Ultrason (2001) 38(3):129–140
Kusunose J, Caskey CF (2018) Fast, low-frequency plane-wave imaging for ultrasound contrast imaging. Ultrasound Med Biol 44(10):2131–2142
Jedrzejewicz T, Napolitano D, DeBusschere D, Chou CH, McLaughlin G. Two-way continuous transmit and receive focusing in ultrasound imaging. In: 2013 IEEE International Ultrasonics Symposium. IEEE International Ultrasonics Symposium. New York: Ieee; 2013.
Napolitano D, McLaughlin GW, DeBusschere D, Mo LYL. Zone-based B-mode imaging. Proc IEEE Ultrasonics Symp. 2003;23–8.
Holfort IK, Gran F, Jensen JA, editors. Plane wave medical ultrasound imaging using adaptive beamforming. In: 2008 5th IEEE Sensor Array and Multichannel Signal Processing Workshop; 2008 21–23 July 2008.
Yang Z, Tuthill TA, Raunig DL, Fox MD, Analoui M (2007) Pixel compounding: resolution-enhanced ultrasound imaging for quantitative analysis. Ultrasound Med Biol 33(8):1309–1319
Kono Y, Lyshchik A, Cosgrove D, Dietrich CF, Jang HJ, Kim TK et al (2017) Contrast Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS (R)): the official version by the American College of Radiology (ACR). Ultraschall Med 38(1):85–86
Huang JY, Li JW, Lu Q, Luo Y, Lin L, Shi YJ et al (2020) Diagnostic Accuracy of CEUS LI-RADS for the characterization of liver nodules 20 mm or smaller in patients at risk for hepatocellular carcinoma. Radiology 294(2):329–339
Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240(4857):1285–1293
Parikh ND, Singal AG, Hutton DW, Tapper EB (2020) Cost-effectiveness of hepatocellular carcinoma surveillance: an assessment of benefits and harms. Am J Gastroenterol 115(10):1642–1649
Nadarevic T, Giljaca V, Colli A, Fraquelli M, Casazza G, Miletic D et al (2021) Computed tomography for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 10:CD013362
Wang JH, Lu SN, Hung CH, Chen TY, Chen CH, Changchien CS et al (2006) Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography. Liver Int 26(8):928–934
Kim TK, Lee KH, Khalili K, Jang HJ (2011) Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound. Abdom Imaging 36(3):244–263
Forner A, Vilana R, Bianchi L, Rodriguez-Lope C, Reig M, Garcia-Criado MA et al (2015) Lack of arterial hypervascularity at contrast-enhanced ultrasound should not define the priority for diagnostic work-up of nodules <2 cm. J Hepatol 62(1):150–155
Bota S, Piscaglia F, Marinelli S, Pecorelli A, Terzi E, Bolondi L (2012) Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver Cancer 1(3–4):190–200
Huang J, Chen W, Yao S (2017) Assessing diagnostic value of contrast-enhanced ultrasound and contrast-enhanced computed tomography in detecting small hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore) 96(30):e7555
Wu M, Li L, Wang J, Zhang Y, Guo Q, Li X et al (2018) Contrast-enhanced US for characterization of focal liver lesions: a comprehensive meta-analysis. Eur Radiol 28(5):2077–2088
Barr RG (2018) Contrast enhanced ultrasound for focal liver lesions: how accurate is it? Abdom Radiol (NY) 43(5):1128–1133
Fei X, Han P, Jiang B, Zhu L, Tian W, Sang M et al (2022) High frame rate contrast-enhanced ultrasound helps differentiate malignant and benign focal liver lesions. J Clin Transl Hepatol 10(1):26–33
Funding
The authors have no relevant financial or non-financial interests to disclose.
Author information
Authors and Affiliations
Contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by FG. The first draft of the manuscript was written by FG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
No authors have Any conflict of interest (any financial or personal relationship with a third party whose interest could be positively or negatively influenced by the article’s content).
Ethical approval
This is an observational study. The Codogno Hospital Research Ethics Committee has confirmed that no ethical approval is required.
Informed consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Giangregorio, F., Garolfi, M., Mosconi, E. et al. High frame-rate contrast enhanced ultrasound (HIFR-CEUS) in the characterization of small hepatic lesions in cirrhotic patients. J Ultrasound 26, 71–79 (2023). https://doi.org/10.1007/s40477-022-00724-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40477-022-00724-w