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High frame-rate contrast enhanced ultrasound (HIFR-CEUS) in the characterization of small hepatic lesions in cirrhotic patients

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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.

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References

  1. Bruix J, Sherman M (2011) American association for the study of liver D. Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022

    Article  PubMed  Google Scholar 

  2. El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365(12):1118–1127

    Article  CAS  PubMed  Google Scholar 

  3. Singal AG, Lampertico P, Nahon P (2020) Epidemiology and surveillance for hepatocellular carcinoma: new trends. J Hepatol 72(2):250–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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

    Article  PubMed  Google Scholar 

  5. Liver (2018) EAftSot. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 69(1):182–236

    Article  Google Scholar 

  6. 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

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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

    Article  PubMed  Google Scholar 

  8. 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

    Article  PubMed  PubMed Central  Google Scholar 

  9. 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

    Article  Google Scholar 

  10. Foerster F, Galle PR (2019) Comparison of the current international guidelines on the management of HCC. JHEP Rep 1(2):114–119

    Article  PubMed  PubMed Central  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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

    Article  Google Scholar 

  14. 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

    Article  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  Google Scholar 

  17. 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

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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

    Article  CAS  PubMed  Google Scholar 

  19. 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

    Article  PubMed  Google Scholar 

  20. 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

    Article  PubMed  Google Scholar 

  21. 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

    Article  PubMed  Google Scholar 

  22. 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

    Article  PubMed  Google Scholar 

  23. 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

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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

    Article  Google Scholar 

  25. 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

    Article  PubMed  Google Scholar 

  26. 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

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lu JY, Zou H, Greenleaf JF (1994) Biomedical ultrasound beam forming. Ultrasound Med Biol 20(5):403–428

    Article  CAS  PubMed  Google Scholar 

  29. Tanter M, Fink M (2014) Ultrafast imaging in biomedical ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control 61(1):102–119

    Article  PubMed  Google Scholar 

  30. Camacho J, Parrilla M, Fritsch C (2009) Phase coherence imaging. IEEE Trans Ultrason Ferroelectr Freq Control 56(5):958–974

    Article  PubMed  Google Scholar 

  31. Fritsch C, Camacho J, Parrilla M (2010) New ultrasound imaging techniques with phase coherence processing. Ultrasonics 50(2):122–126

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  PubMed  Google Scholar 

  33. Couture O, Fink M, Tanter M (2012) Ultrasound contrast plane wave imaging. IEEE Trans Ultrason Ferroelectr Freq Control 59(12):2676–2683

    Article  PubMed  Google Scholar 

  34. 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.

  35. 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

    Article  PubMed  Google Scholar 

  36. 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

    Article  PubMed  Google Scholar 

  37. 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

    Article  PubMed  Google Scholar 

  38. 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

    Article  PubMed  Google Scholar 

  39. 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

    Article  CAS  PubMed  Google Scholar 

  40. Kusunose J, Caskey CF (2018) Fast, low-frequency plane-wave imaging for ultrasound contrast imaging. Ultrasound Med Biol 44(10):2131–2142

    Article  PubMed  PubMed Central  Google Scholar 

  41. 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.

  42. Napolitano D, McLaughlin GW, DeBusschere D, Mo LYL. Zone-based B-mode imaging. Proc IEEE Ultrasonics Symp. 2003;23–8.

  43. 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.

  44. 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

    Article  PubMed  Google Scholar 

  45. 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

    Article  PubMed  Google Scholar 

  46. 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

    Article  PubMed  Google Scholar 

  47. Swets JA (1988) Measuring the accuracy of diagnostic systems. Science 240(4857):1285–1293

    Article  CAS  PubMed  Google Scholar 

  48. 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

    Article  PubMed  PubMed Central  Google Scholar 

  49. 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

    PubMed  Google Scholar 

  50. 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

    Article  PubMed  Google Scholar 

  51. Kim TK, Lee KH, Khalili K, Jang HJ (2011) Hepatocellular nodules in liver cirrhosis: contrast-enhanced ultrasound. Abdom Imaging 36(3):244–263

    Article  PubMed  Google Scholar 

  52. 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

    Article  PubMed  Google Scholar 

  53. 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

    Article  PubMed  PubMed Central  Google Scholar 

  54. 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

    Article  PubMed  Google Scholar 

  55. 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

    Article  PubMed  Google Scholar 

  56. Barr RG (2018) Contrast enhanced ultrasound for focal liver lesions: how accurate is it? Abdom Radiol (NY) 43(5):1128–1133

    Article  PubMed  Google Scholar 

  57. 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

    Article  PubMed  Google Scholar 

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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.

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Correspondence to F. Giangregorio.

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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

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