European Radiology

, Volume 23, Issue 3, pp 805–815 | Cite as

Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation

  • Aymeric Guibal
  • Thibaud Lefort
  • Laurence Chardon
  • Noura Benslama
  • Sébastien Mulé
  • Franck Pilleul
  • Catherine Lombard-Bohas
  • Lori Bridal
  • Jean Alain Chayvialle
  • Olivier Lucidarme
  • Alban Denys
  • Thomas Walter



To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE).


In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour’s major diameter and the viable tumour’s major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher’s test were used to compare treatment groups.


At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up.


One parameter, TVI, could evaluate the morphological and functional response to treatments.

Key Points

Contrast-enhanced ultrasound provides morphological and functional information about neuroendocrine hepatic metastases

CEUS can evaluate changes after transarterial chemoembolisation, transarterial-embolisation and transarterial radioembolisation

Functional (but not morphological) imaging reveals differences between TAE and DEB-TACE therapy

To combine morphological and functional parameters, a tumour vitality index is proposed

TVI can be used to monitor treatments acting on tumour vascularisation


Transarterial chemoembolization Doxorubicin drug-eluting beads (DEB) Contrast-enhanced ultrasound Perfusion imaging Tumour vitality index 



aspartate aminotransferase


alanine aminotransferase


blood flow


blood volume


contrast-enhanced ultrasound


contrast harmonic imaging


complete response


C-reactive protein


drug-eluting beads


lactate dehydrogenase


mechanical index


neuroendocrine tumour


relative blood flow


relative blood volume


progressive disease


partial response


response evaluation criteria in solid tumours


region of interest


stable disease


trans-arterial chemoembolisation


trans-arterial embolisation


tumour vitality index


tumour’s major diameter


viable tumour’s major diameter


well-differentiated endocrine carcinoma


  1. 1.
    Vogl TJ, Naguib NN, Zangos S, Eichler K, Hedayati A, Nour-Eldin NE (2009) Liver metastases of neuroendocrine carcinomas: interventional treatment via transarterial embolization, chemoembolization and thermal ablation. Eur J Radiol 72:517–528PubMedCrossRefGoogle Scholar
  2. 2.
    Walter T, Brixi-Benmansour H, Lombard-Bohas C, Cadiot G (2012) New treatment strategies in advanced neuroendocrine tumours. Dig Liver Dis 44:95–105PubMedCrossRefGoogle Scholar
  3. 3.
    Dominguez S, Denys A, Madeira I et al (2000) Hepatic arterial chemoembolization with streptozotocin in patients with metastatic digestive endocrine tumours. Eur J Gastroenterol Hepatol 12:151–157PubMedCrossRefGoogle Scholar
  4. 4.
    Jordan O, Denys A, De Baere T, Boulens N, Doelker E (2010) Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan. J Vasc Interv Radiol 21:1084–1090PubMedCrossRefGoogle Scholar
  5. 5.
    Lee KH, Liapi EA, Cornell C et al (2010) Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer. Cardiovasc Intervent Radiol 33:576–582PubMedCrossRefGoogle Scholar
  6. 6.
    Ohta S, Nitta N, Sonoda A et al (2009) Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits. Eur J Radiol 72:534–540PubMedCrossRefGoogle Scholar
  7. 7.
    Kettenbach J, Stadler A, Katzler IV et al (2008) Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent Radiol 31:468–476PubMedCrossRefGoogle Scholar
  8. 8.
    Namur J, Wassef M, Millot JM, Lewis AL, Manfait M, Laurent A (2011) Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model. J Vasc Interv Radiol 21:259–267CrossRefGoogle Scholar
  9. 9.
    Malagari K, Alexopoulou E, Chatzimichail K et al (2008) Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead. Abdom Imaging 33:512–519PubMedCrossRefGoogle Scholar
  10. 10.
    Lewis AL, Gonzalez MV, Leppard SW et al (2007) Doxorubicin eluting beads—1: effects of drug loading on bead characteristics and drug distribution. J Mater Sci Mater Med 18:1691–1699PubMedCrossRefGoogle Scholar
  11. 11.
    Nicolini A, Martinetti L, Crespi S, Maggioni M, Sangiovanni A (2010) Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma. J Vasc Interv Radiol 21:327–332PubMedCrossRefGoogle Scholar
  12. 12.
    Dhanasekaran R, Kooby DA, Staley CA, Kauh JS, Khanna V, Kim HS (2010) Comparison of conventional transarterial chemoembolization (TACE) and chemoembolization with doxorubicin drug eluting beads (DEB) for unresectable hepatocelluar carcinoma (HCC). J Surg Oncol 101:476–480PubMedGoogle Scholar
  13. 13.
    de Baere T, Deschamps F, Teriitheau C et al (2008) Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol 19:855–861PubMedCrossRefGoogle Scholar
  14. 14.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  15. 15.
    Forner A, Ayuso C, Varela M et al (2009) Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer 115:616–623PubMedCrossRefGoogle Scholar
  16. 16.
    Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481PubMedCrossRefGoogle Scholar
  17. 17.
    Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. European Association for the Study of the Liver. J Hepatol 35:421–430PubMedCrossRefGoogle Scholar
  18. 18.
    Memon K, Kulik L, Lewandowski RJ et al (2011) Radiographic response to locoregional therapy in hepatocellular carcinoma predicts patient survival times. Gastroenterology 141:526–535, 535 e521-522PubMedCrossRefGoogle Scholar
  19. 19.
    Rosen MA, Schnall MD (2007) Dynamic contrast-enhanced magnetic resonance imaging for assessing tumor vascularity and vascular effects of targeted therapies in renal cell carcinoma. Clin Cancer Res 13:770s–776sPubMedCrossRefGoogle Scholar
  20. 20.
    Miles KA (2003) Perfusion CT for the assessment of tumour vascularity: which protocol? Br J Radiol 76:S36–S42PubMedCrossRefGoogle Scholar
  21. 21.
    Padhani A (2006) PET imaging of tumour hypoxia. Cancer Imaging 6:S117–S121PubMedCrossRefGoogle Scholar
  22. 22.
    Rindi G, Kloppel G, Couvelard A et al (2007) TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 451:757–762PubMedCrossRefGoogle Scholar
  23. 23.
    Bouvier A, Ozenne V, Aube C et al (2011) Transarterial chemoembolisation: effect of selectivity on tolerance, tumour response and survival. Eur Radiol 21:1719–1726PubMedCrossRefGoogle Scholar
  24. 24.
    Malagari K, Pomoni M, Kelekis A et al (2009) Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 33:541–551PubMedCrossRefGoogle Scholar
  25. 25.
    Zachary JF, Blue JP, Miller RJ, O’Brien WD Jr (2006) Vascular lesions and s-thrombomodulin concentrations from auricular arteries of rabbits infused with microbubble contrast agent and exposed to pulsed ultrasound. Ultrasound Med Biol 32:1781–1791PubMedCrossRefGoogle Scholar
  26. 26.
    Guibal A, Taillade L, Mule S et al (2011) Noninvasive contrast-enhanced US quantitative assessment of tumor microcirculation in a murine model: effect of discontinuing anti-VEGF therapy. Radiology 254:420–429CrossRefGoogle Scholar
  27. 27.
    Lefort T, Pilleul F, Mule S et al (2012) Correlation and agreement between contrast-enhanced ultrasonography and perfusion computed tomography for assessment of liver metastases from endocrine tumors: normalization enhances correlation. Ultrasound Med Biol 38:953–961PubMedCrossRefGoogle Scholar
  28. 28.
    Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S (1998) Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 97:473–483PubMedCrossRefGoogle Scholar
  29. 29.
    Krix M, Plathow C, Essig M et al (2005) Monitoring of liver metastases after stereotactic radiotherapy using low-MI contrast-enhanced ultrasound–initial results. Eur Radiol 15:677–684PubMedCrossRefGoogle Scholar
  30. 30.
    Riaz A, Miller FH, Kulik LM et al (2010) Imaging response in the primary index lesion and clinical outcomes following transarterial locoregional therapy for hepatocellular carcinoma. JAMA 303:1062–1069PubMedCrossRefGoogle Scholar
  31. 31.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247PubMedCrossRefGoogle Scholar
  32. 32.
    Guiu B, Deschamps F, Aho S et al (2012) Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 56:609–617PubMedCrossRefGoogle Scholar
  33. 33.
    Moschouris H, Malagari K, Kornezos I, Papadaki MG, Gkoutzios P, Matsaidonis D (2010) Unenhanced and contrast-enhanced ultrasonography during hepatic transarterial embolization and chemoembolization with drug-eluting beads. Cardiovasc Intervent Radiol 33:1215–1222PubMedCrossRefGoogle Scholar
  34. 34.
    Riaz A, Memon K, Miller FH et al (2011) Role of the EASL, RECIST, and WHO response guidelines alone or in combination for hepatocellular carcinoma: radiologic-pathologic correlation. J Hepatol 54:695–704PubMedCrossRefGoogle Scholar
  35. 35.
    Krix M, Plathow C, Kiessling F et al (2004) Quantification of perfusion of liver tissue and metastases using a multivessel model for replenishment kinetics of ultrasound contrast agents. Ultrasound Med Biol 30:1355–1363PubMedCrossRefGoogle Scholar
  36. 36.
    Browder T, Butterfield CE, Kraling BM et al (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60:1878–1886PubMedGoogle Scholar
  37. 37.
    Gupta S, Kobayashi S, Phongkitkarun S, Broemeling LD, Kan Z (2006) Effect of transcatheter hepatic arterial embolization on angiogenesis in an animal model. Invest Radiol 41:516–521PubMedCrossRefGoogle Scholar
  38. 38.
    Liao XF, Yi JL, Li XR, Deng W, Yang ZF, Tian G (2004) Angiogenesis in rabbit hepatic tumor after transcatheter arterial embolization. World J Gastroenterol 10:1885–1889PubMedGoogle Scholar
  39. 39.
    Feingold S, Gessner R, Guracar IM, Dayton PA (2010) Quantitative volumetric perfusion mapping of the microvasculature using contrast ultrasound. Invest Radiol 45:669–674PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2012

Authors and Affiliations

  • Aymeric Guibal
    • 1
    • 6
    • 9
  • Thibaud Lefort
    • 1
  • Laurence Chardon
    • 2
  • Noura Benslama
    • 3
  • Sébastien Mulé
    • 4
  • Franck Pilleul
    • 1
  • Catherine Lombard-Bohas
    • 5
  • Lori Bridal
    • 6
  • Jean Alain Chayvialle
    • 5
  • Olivier Lucidarme
    • 6
    • 7
  • Alban Denys
    • 8
  • Thomas Walter
    • 5
  1. 1.Hospices Civils de Lyon, Hôpital Edouard Herriot, Service d’Imagerie DigestiveLyon cedex 03France
  2. 2.Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération de BiochimieLyon cedex 03France
  3. 3.Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités DigestivesLyon cedex 03France
  4. 4.Laboratoire d’imagerie fonctionnelle, UMR-S 678, Université Paris 6ParisFrance
  5. 5.Hospices Civils de Lyon, Hôpital Edouard Herriot, Fédération des Spécialités DigestivesLyon cedex 03France
  6. 6.Laboratoire d’imagerie paramétrique, UMR 7623, Université Paris 6ParisFrance
  7. 7.Hopital Pitié Salpétrière, Service de radiologie polyvalente diagnostique et interventionnelleParisFrance
  8. 8.Service de radiodiagnostic et radiologie interventionnelle, CHUVLausanneSwitzerland
  9. 9.Pavillon H, Hôpital Edouard HerriotLyon Cedex 03France

Personalised recommendations