Update and Direction of Ultrasonic Contrast Agents

  • Masatoshi Kudo


At present, Levovist is the only commercially available ultrasonic contrast agent in Japan. It is based on galactose and palmitic acid forming microbubbles which produces harmonic signals under ultrasonic pressure. In addition, Definity, Optison, and NC 100/100 are also now being investigated in Japan (Table 20–1). It has been reported that these contrast agents do not need intermittent transmission because they are propane fluoride agents, and clear images can be visualized in near-real time in combination with pulse inversion harmonics. Contrast technique using ordinary B-mode equipment has also been studied. Therefore, a contrast effect may be obtained to a certain extent by using existing old B-mode equipment. NC 100/100 has a high deposit affinity for Kupffer cells or the endothelial cells of sinusoids and a promising application of this agent is the postvascu-lar phase sweep scan 5 or 10 min after administration.


Contrast Agent Ultra Sonography Focal Nodular Hyperplasia Ultrasound Contrast Agent Left Atrial Appendage Thrombus 
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  1. 1.
    Schrope B, Newhouse VL, Uhlendorf V: Simulated capillary blood flow measurement using a nonlinear ultrasonic contrast agent. Ultrason Imaging 1992; 14:134–158PubMedCrossRefGoogle Scholar
  2. 2.
    Burns PN: Harmonic imaging with ultrasound contrast agents. Clin Radiol 1996; 51(Suppl l):50–55PubMedGoogle Scholar
  3. 3.
    Shanker PM, Keiahn PD, Newhouse VL: Advantage of subharmonic over second harmonic backscatter for contrast-to-tissue echo enhancement. Ultrasound Med Biol 1998; 24:395–399CrossRefGoogle Scholar
  4. 4.
    Shi WT, Forsberg F, Hall AL, et al: Subharmonic imaging with microbubble contrast agents: initial results. Ultrason Imaging 1999; 21:79–94PubMedGoogle Scholar
  5. 5.
    Forsberg F, Shi WT, Goldberg BB: Subharmonic imaging of contrast agents. Ultrasonics 2000; 38:93–98PubMedCrossRefGoogle Scholar
  6. 6.
    Burns PN, Wilson SR, Simpson DH: Pulse inversion imaging of liver blood flow: improved method for characterizing focal masses with microbubble contrast. Invest Radiol 2000; 35:58–71PubMedCrossRefGoogle Scholar
  7. 7.
    Apfel RE, Holland CK: Gauging the likelihood of cavitation from short-pulse, low-duty cycle diagnostic ultrasound. Ultrasound Med Biol 1991; 17:179–185PubMedCrossRefGoogle Scholar
  8. 8.
    Klibanov AL, Ferrara KW, Hughes MS, et al: Direct video-microscopic observation of the dynamic effects of medical ultrasound on ultrasound contrast microspheres. Invest Radiol 1998; 33:863–870PubMedCrossRefGoogle Scholar
  9. 9.
    Albrecht T, Hoffmann CW, Schettler S, et al: B-mode enhancement at phase-inversion US with air-based microbubble contrast agent: initial experience in humans. Radiology 2000; 216:273–278PubMedGoogle Scholar
  10. 10.
    Blomley MJ, Albrecht T, Cosgrove DO, et al: Improved imaging of liver metastases with stimulated acoustic emission in the late phase of enhancement with the US contrast agent SH U 508A: early experience. Radiology 1999; 210:409–416PubMedGoogle Scholar
  11. 11.
    Uchimoto R, Niwa K, Eguchi H, et al: In vivo kinetics of microbubbles of SH U 508A (Levovist): comparison with indocyanine green in rabbits. Ultrasound Med Biol 1999; 25:1365–1370PubMedCrossRefGoogle Scholar
  12. 12.
    Tanaka S, Kitamura T, Yoshioka F, et al: Effectiveness of galactose-based intravenous contrast medium on color Doppler sonography of deeply located hepatocellular carcinoma. Ultrasound Med Biol 1995; 12:157–160CrossRefGoogle Scholar
  13. 13.
    Tanaka S, Kitamura T, Fujita M, et al: Value of contrast-enhanced color Doppler sonography in diagnosing hepatocellular carcinoma with special attention to the “color-filled pattern.” J Clin Ultrasound 1998; 26:207–212PubMedCrossRefGoogle Scholar
  14. 14.
    Kim AY, Choi BI, Kim TK, et al: Hepatocellular carcinoma: power Doppler US with a contrast agent: preliminary results. Radiology 1998; 209:135–140PubMedGoogle Scholar
  15. 15.
    Hosten N, Puls R, Lemke AJ, et al: Contrast enhanced power Doppler sonography: improved detection of characteristic flow patterns in focal liver lesions. J Clin Ultrasound 1999; 27:107–115PubMedCrossRefGoogle Scholar
  16. 16.
    Bartolozzi C, Lencioni R, Ricci P, et al: Hepatocellular carcinoma treatment with percutaneous ethanol injection: evaluation with contrast enhanced color Doppler US. Radiology 1998; 209:135–140Google Scholar
  17. 17.
    Solbiati L, Goldberg SN, Lerace T, et al: Radio-frequency ablation of hepatic metastases: postprocedural assessment with a US microbubble contrast agent: early experience. Radiology 1999; 211:643–649PubMedGoogle Scholar
  18. 18.
    Uggowitxer M, Kugler C, Groll R, et al: Sonographic evaluation of focal nodular hyperplasias (FNH) of the liver with a trans-pulmonary galactose-based contrast agent (Levovist). Br J Radiol 1998; 71:1026–1032Google Scholar
  19. 19.
    Blomley MJ, Albrecht T, Cosgrove DO, et al: Liver vascular transit time analyzed with dynamic hepatic venography with bolus injections of an US contrast agent: early experience in seven patients with metastases. Radiology 1998; 209:862–866PubMedGoogle Scholar
  20. 20.
    Forsberg F, Liu JB, Burns PN, et al: Artifacts in ultrasonic contrast agent studies. J Ultrasound Med 1994; 13:357–365PubMedGoogle Scholar
  21. 21.
    Petrich J, Zomack M, Schilief R: An investigation of the relationship between ultrasound echo enhancement and Doppler frequency shift using a pulsatile arterial flow phantom. Invest Radiol 1997; 32:225–235CrossRefGoogle Scholar
  22. 22.
    Darge K, Troeger J, Duetting T, et al: Reflux in young patients: comparison of voiding US of the bladder and retrovesical space with echo enhancement versus voiding cystourethrography for diagnosis. Radiology 1999; 210:201–207PubMedGoogle Scholar
  23. 23.
    Hauff P, Fritzsch T, Reinhardt M, et al: Delineation of experimental liver tumors in rabbits by a new ultrasound contrast agent and stimulated acoustic emission. Invest Radiol 1997; 32:94–99PubMedCrossRefGoogle Scholar
  24. 24.
    Goldberg BB, Merton DA, Liu JB, et al: Evaluation of bleeding sites with a tissue-specific sonographic contrast agent: preliminary experiences in an animal model. J Ultrasound Med 1998; 17:609–616PubMedGoogle Scholar
  25. 25.
    Forsberg F, Goldberg BB, Liu JB, et al: Tissue-specific US contrast agent for evaluation of hepatic and splenic parenchyma. Radiology 1999; 210:125–132PubMedGoogle Scholar
  26. 26.
    Wu Y, Unger EC, McCreery TP, et al: Binding and lysing of blood clots using MRX-408. Invest Radiol 1998; 33:880–885PubMedCrossRefGoogle Scholar
  27. 27.
    Takeuchi M, Ogunyankin K, Pandian NG, et al: Enhanced visualization of intravascular and left atrial appendage thrombus with the use of a thrombus-targeting ultrasonographic contrast agent (MRX-408A1): in vivo experimental echocardiographic studies. J Am Soc Echocardiogr 1999; 12:1015–1021PubMedCrossRefGoogle Scholar
  28. 28.
    Unger E, Metzger P 3rd, Krupinski E, et al: The use of a thrombus-specific ultrasound contrast agent to detect thrombus in arteriovenous fistulae. Invest Radiol 2000; 35:86–89PubMedCrossRefGoogle Scholar
  29. 29.
    Kim TK, Choi BI, Han JK, et al: Hepatic tumors: contrast agent-enhancement patterns with pulse-inversion harmonic US. Radiology 2000; 216:411–417PubMedGoogle Scholar
  30. 30.
    Ding H, Kudo M, Onda H, et al: Contrast-enhanced subtraction harmonic sonography for evaluating treatment response in patients with hepatocellular carcinoma. AJR 2001; 176:661–666PubMedGoogle Scholar
  31. 31.
    Ding H, Kudo M, Onda H, et al: Hepatocellular carcinoma: detection of tumor parenchymal flow with intermittent harmonic power Doppler US during the early arterial phase in dual-display mode. Radiology 2001; 220:349–356PubMedGoogle Scholar
  32. 32.
    Ding H, Kudo M, Onda H, et al: Sonographic diagnosis of pancreatic islet cell tumor: value of intermittent harmonic imaging. J Clin Ultrasound 2001; 29:411–416PubMedCrossRefGoogle Scholar
  33. 33.
    Kudo M: Morphological diagnosis of hepatocellular carcinoma: special emphasis on intranodular hemodynamic imaging. Hepato-Gastroenterology 1998; 45:1226–1231PubMedGoogle Scholar
  34. 34.
    Kudo M: Imaging diagnosis of hepatocellular carcinoma and premalignant/borderline lesions. Semin Liver Dis 1999; 19:297–309PubMedCrossRefGoogle Scholar
  35. 35.
    Kudo M: Imaging blood flow characteristics of hepatocellular carcinoma. Oncology 2002; 62(Suppl l):48–56PubMedCrossRefGoogle Scholar
  36. 36.
    Ding H, Kudo M, Maekawa K, et al: Detection of tumor parenchymal blood flow in hepatic tumors: value of second harmonic imaging with a galactose-based contrast agent. Hepatol Res 2001; 21:242–251PubMedCrossRefGoogle Scholar
  37. 37.
    Ding H, Kudo M, Onda H, et al: Evaluation of posttreat-ment response for hepatocellular carcinoma with contrast-enhanced coded phase-inversion harmonic US: comparison with dynamic CT. Radiology 2001; 221:721–730PubMedCrossRefGoogle Scholar
  38. 38.
    Kudo M: Contrast harmonic ultrasound is a breakthrough technology in the diagnosis and treatment of hepatocellular carcinoma. J Med Ultrasonics 2001; 28:79–81CrossRefGoogle Scholar
  39. 39.
    Wen YL, Kudo M, Kawasaki T, et al: Hepatocellular carcinoma treated with radiofrequency ablation: Evaluation of therapeutic response by contrast-enhanced Coded Harmonic Angio. Chinese J Ultrasound in Med 2002; 18:452–455Google Scholar
  40. 40.
    Wen YL, Kudo M, Maekawa K, et al: Evaluation of image quality of personal ultrasound imager: comparison with conventional machine. J Med Ultrasonics 2002; 29:41–46CrossRefGoogle Scholar
  41. 41.
    Zheng RQ, Kudo M, Inui K, et al: Transient portal vein thrombosis caused by radiofrequency ablation for hepatocellular carcinoma. J Gastroenterol 2003; 38:101–103PubMedCrossRefGoogle Scholar
  42. 42.
    Wen YL, Kudo M, Minami Y, et al: Value of newly developed contrast harmonic technique in detection tumor vascularity in hepatocellular carcinoma—preliminary results. J Med Ultrasonics 2003 (in press)Google Scholar
  43. 43.
    Wen YL, Kudo M, Minami Y, et al: Assessment of image quality of contrast-enhanced power Doppler imaging in hepatocellular carcinoma with a personal ultrasound imager: comparison with conventional machine. J Med Ultrasonics 2003 (in press)Google Scholar
  44. 44.
    Wen YL, Kudo M, Minami Y, et al: Detection of tumor vascularity in hepatocellular carcinoma with contrast enhanced Dynamic Flow imaging: comparison with contrast enhanced power Doppler imaging. J Med Ultrasonics 2003 (in press)Google Scholar
  45. 45.
    Wen YL, Kudo M, Minami Y, et al: Contrast-enhanced Agent Detection Imaging: preliminary study in hepatocellular carcinoma. J Med Ultrasonics 2003 (in press)Google Scholar
  46. 46.
    Wen YL, Kudo M, Maekawa K, et al: Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging: preliminary results in hepatic tumors. J Med Ultrasonics 2003 (in press)Google Scholar
  47. 47.
    Minami Y, Kudo M, Kawasaki, et al: Trascatheter arterial chemoembolization of hepatocellular carcinoma: usefulness of coded phase-inversion harmonic sonography. AJR 2003; 180:703–708PubMedGoogle Scholar
  48. 48.
    Wen YL, Kudo M, Minami Y, et al: Radio-frequency ablation in hepatocellular carcinoma: evaluation of therapeutic response by contrast-enhanced coded phase inversion harmonic imaging. AJR 2003 (in press)Google Scholar
  49. 49.
    Wen YL, Kudo M, Maekawa K, et al: Contrast Advenced Dynamic Flow imaging and contrast Pulse Subtraction imaging: pre-liminary results in hepatic tumors. J Med Ultrasonics 2002; 27:195–204CrossRefGoogle Scholar

Copyright information

© Springer Japan 2003

Authors and Affiliations

  • Masatoshi Kudo
    • 1
  1. 1.Department of Gastroenterology and HepatologyKinki University School of MedicineOsakaJapan

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