Skip to main content
SpringerLink
Log in

Inherently Radiopaque Narrow-Size-Calibrated Microspheres: Proof of Principle in a Pig Embolization Model

  • Laboratory Investigation
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

To investigate radiopacity, size and size calibration, morphology, and vascular distribution of inherently radiopaque microspheres in vitro and in a pig embolization model.

Materials and Methods

We compared three types of microspheres: DCBead™ (size 100–300 µm) and Embozene™ (250 µm) as clinically established microspheres, and the prototype Visible (250 µm) that contains additional radiopaque material. Size and size calibration of microspheres were examined by laser diffraction. Pulmonary artery embolization was performed in 12 pigs, and radiopacity was examined by in vitro micro-computed tomography (CT), in vivo cone-beam CT, and ex vivo micro-CT after killing. Morphology and vascular distribution of microspheres were microscopically examined.

Results

In in vitro and ex vivo micro-CT, radiopacity of Visible was higher than that of Embozene™, whereas DCBead™ showed no radiopacity. In in vivo cone-beam CT, radiopacity was observed with Visible but not with Embozene™ and DCBead™. Laser diffraction revealed that 7.0% (Visible), 6.5% (Embozene™), and 22.5% (DCBead™) of microspheres were smaller than 223.5 μm. Visible and Embozene™ microspheres were very often located in bronchiolus-associated arteries, but rarely in subsegmental and capillary arteries, whereas DCBead™ were very often and often detected in bronchiolus-associated arteries and capillary arteries, respectively (and rarely in subsegmental arteries).

Conclusion

After pulmonary artery embolization, Visible but not Embozene™ or DCBead™ provide in vivo radiopacity in cone-beam CT. In contrast to non-narrow-size-calibrated DCBead™, pulmonary artery embolization with narrow-size-calibrated Visible and Embozene™ result in a predictable arterial distribution without embolization-related hemorrhagic lung infarction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Sharma KV, Bascal Z, Kilpatrick H, Ashrafi K, Willis SL, Dreher MR, et al. Long-term biocompatibility, imaging appearance and tissue effects associated with delivery of a novel radiopaque embolization bead for image-guided therapy. Biomaterials. 2016;103:293–304. https://doi.org/10.1016/j.biomaterials.2016.06.064.

    Article  PubMed  CAS  Google Scholar 

  2. Ashrafi K, Tang Y, Britton H, Domenge O, Blino D, Bushby AJ, et al. Characterization of a novel intrinsically radiopaque Drug-eluting Bead for image-guided therapy: DC Bead LUMI. J Control Release. 2017;250:36–47. https://doi.org/10.1016/j.jconrel.2017.02.001.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Duran R, Sharma K, Dreher MR, Ashrafi K, Mirpour S, Lin M, et al. A novel inherently radiopaque bead for transarterial embolization to treat liver cancer—A pre-clinical study. Theranostics. 2016;6(1):28–39. https://doi.org/10.7150/thno.13137.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Golowa YS, Cynamon J, Reinus JF, Kinkhabwala M, Abrams M, Jagust M, et al. Value of noncontrast CT immediately after transarterial chemoembolization of hepatocellular carcinoma with drug-eluting beads. J Vasc Interv Radiol. 2012;23(8):1031–5. https://doi.org/10.1016/j.jvir.2012.04.020.

    Article  PubMed  Google Scholar 

  5. Loffroy R, Lin M, Yenokyan G, Rao PP, Bhagat N, Noordhoek N, et al. Intraprocedural C-arm dual-phase cone-beam CT: can it be used to predict short-term response to TACE with drug-eluting beads in patients with hepatocellular carcinoma? Radiology. 2013;266(2):636–48. https://doi.org/10.1148/radiol.12112316.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tacher V, Duran R, Lin M, Sohn JH, Sharma KV, Wang Z, et al. Multimodality imaging of ethiodized oil-loaded radiopaque microspheres during transarterial embolization of rabbits with VX2 liver tumors. Radiology. 2016;279(3):741–53. https://doi.org/10.1148/radiol.2015141624.

    Article  PubMed  Google Scholar 

  7. Takayasu K, Muramatsu Y, Maeda T, Iwata R, Furukawa H, Muramatsu Y, et al. Targeted transarterial oily chemoembolization for small foci of hepatocellular carcinoma using a unified helical CT and angiography system: analysis of factors affecting local recurrence and survival rates. AJR Am J Roentgenol. 2001;176(3):681–8. https://doi.org/10.2214/ajr.176.3.1760681.

    Article  PubMed  CAS  Google Scholar 

  8. Sommer CM, Stampfl U, Bellemann N, Holzschuh M, Kueller A, Bluemmel J, et al. Multimodal visibility (radiography, computed tomography, and magnetic resonance imaging) of microspheres for transarterial embolization tested in porcine kidneys. Invest Radiol. 2013;48(4):213–22. https://doi.org/10.1097/RLI.0b013e31827f6598.

    Article  PubMed  Google Scholar 

  9. Stampfl U, Sommer CM, Bellemann N, Holzschuh M, Kueller A, Bluemmel J, et al. Multimodal visibility of a modified polyzene-F-coated spherical embolic agent for liver embolization: feasibility study in a porcine model. J Vasc Interv Radiol. 2012;23(9):1225–31. https://doi.org/10.1016/j.jvir.2012.06.008.

    Article  PubMed  Google Scholar 

  10. Carnevale FC, Iscaife A, Yoshinaga EM, Moreira AM, Antunes AA, Srougi M. Transurethral resection of the prostate (TURP) versus original and PErFecTED prostate artery embolization (PAE) due to benign prostatic hyperplasia (BPH): Preliminary results of a single center, prospective, urodynamic-controlled analysis. Cardiovasc Intervent Radiol. 2016;39(1):44–52. https://doi.org/10.1007/s00270-015-1202-4.

    Article  PubMed  Google Scholar 

  11. Uflacker A, Haskal ZJ, Bilhim T, Patrie J, Huber T, Pisco JM. Meta-analysis of prostatic artery embolization for benign prostatic hyperplasia. J Vasc Interv Radiol. 2016;27(11):1686–97. https://doi.org/10.1016/j.jvir.2016.08.004.

    Article  PubMed  Google Scholar 

  12. Gadaleta CD, Solbiati L, Mattioli V, Rubini G, Fazio V, Goffredo V, et al. Unresectable lung malignancy: combination therapy with segmental pulmonary arterial chemoembolization with drug-eluting microspheres and radiofrequency ablation in 17 patients. Radiology. 2013;267(2):627–37. https://doi.org/10.1148/radiol.12120198.

    Article  PubMed  Google Scholar 

  13. Sommer CM, Do TD, Schlett CL, Flechsig P, Gockner TL, Kuthning A, et al. In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization. J Biomater Appl. 2018;32(7):932–44. https://doi.org/10.1177/0885328217746674.

    Article  PubMed  CAS  Google Scholar 

  14. Heffernan BM, Heinson YW, Maughan JB, Chakrabarti A, Sorensen CM. Backscattering measurements of micron-sized spherical particles. Appl Opt. 2016;55(12):3214–8. https://doi.org/10.1364/AO.55.003214.

    Article  PubMed  CAS  Google Scholar 

  15. Aliberti C, Carandina R, Sarti D, Pizzirani E, Ramondo G, Cillo U, et al. Transarterial chemoembolization with DC Bead LUMI radiopaque beads for primary liver cancer treatment: preliminary experience. Future Oncol. 2017;13(25):2243–52. https://doi.org/10.2217/fon-2017-0364.

    Article  PubMed  CAS  Google Scholar 

  16. Stampfl S, Bellemann N, Stampfl U, Sommer CM, Thierjung H, Lopez-Benitez R, et al. Arterial distribution characteristics of Embozene particles and comparison with other spherical embolic agents in the porcine acute embolization model. J Vasc Interv Radiol. 2009;20(12):1597–607. https://doi.org/10.1016/j.jvir.2009.08.018.

    Article  PubMed  Google Scholar 

  17. Gnutzmann DM, Mechel J, Schmitz A, Kohler K, Krone D, Bellemann N, et al. Evaluation of the plasmatic and parenchymal elution kinetics of two different irinotecan-loaded drug-eluting embolics in a pig model. J Vasc Interv Radiol. 2015;26(5):746–54. https://doi.org/10.1016/j.jvir.2014.12.016.

    Article  PubMed  Google Scholar 

  18. Pereira PL, Plotkin S, Yu R, Sutter A, Wu Y, Sommer CM, et al. An in vitro evaluation of three types of drug-eluting microspheres loaded with irinotecan. Anticancer Drugs. 2016;27(9):873–8. https://doi.org/10.1097/CAD.0000000000000408.

    Article  PubMed  CAS  Google Scholar 

  19. Derdeyn CP, Graves VB, Salamat MS, Rappe A. Collagen-coated acrylic microspheres for embolotherapy: in vivo and in vitro characteristics. AJNR Am J Neuroradiol. 1997;18(4):647–53.

    PubMed  CAS  Google Scholar 

  20. Dreher MR, Sharma KV, Woods DL, Reddy G, Tang Y, Pritchard WF, et al. Radiopaque drug-eluting beads for transcatheter embolotherapy: experimental study of drug penetration and coverage in swine. J Vasc Interv Radiol. 2012;23(2):257–64. https://doi.org/10.1016/j.jvir.2011.10.019.

    Article  PubMed  Google Scholar 

  21. Stampfl S, Stampfl U, Rehnitz C, Schnabel P, Satzl S, Christoph P, et al. Experimental evaluation of early and long-term effects of microparticle embolization in two different mini-pig models. Part II: liver. Cardiovasc Intervent Radiol. 2007;30(3):462–8. https://doi.org/10.1007/s00270-005-0350-3.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

CeloNova BioSciences, San Antonio, USA supported technically this trial.

Author information

Author notes

  1. Christof M. Sommer and A. Harms contributed equally to this work.

Authors and Affiliations

  1. Clinic for Diagnostic and Interventional Radiology, University Hospital Heidelberg, INF 110, 69120, Heidelberg, Germany

    Christof M. Sommer, T. D. Do, C. L. Schlett, D. Vollherbst, H. U. Kauczor & P. Flechsig

  2. Clinic for Diagnostic and Interventional Radiology, Klinikum Stuttgart, Stuttgart, Germany

    Christof M. Sommer

  3. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany

    A. Harms, M. Kriegsmann, K. Holzer & A. Warth

  4. Clinic for Diagnostic and Interventional Radiology, University Hospital Mainz, Mainz, Germany

    T. L. Gockner

  5. Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany

    D. Vollherbst

  6. Clinic for Radiology, Minimally-Invasive Therapies and Nuclear Medicine, SLK Kliniken Heilbronn GmbH, Heilbronn, Germany

    P. L. Pereira

  7. Core Facility Small Animal Imaging, German Cancer Research Center (dkfz), Heidelberg, Germany

    V. Eichwald & M. Jugold

  8. Clinic for Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany

    P. Flechsig

Authors
  1. Christof M. Sommer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Harms
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. D. Do
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T. L. Gockner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Kriegsmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. L. Schlett
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Holzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Vollherbst
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Warth
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. L. Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V. Eichwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M. Jugold
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. H. U. Kauczor
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P. Flechsig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christof M. Sommer.

Ethics declarations

Conflict of interest

All authors declared that they have conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sommer, C.M., Harms, A., Do, T.D. et al. Inherently Radiopaque Narrow-Size-Calibrated Microspheres: Proof of Principle in a Pig Embolization Model. Cardiovasc Intervent Radiol 41, 1404–1411 (2018). https://doi.org/10.1007/s00270-018-1986-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-018-1986-0

Keywords

Search

Navigation