Skip to main content
SpringerLink
Log in

Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

  • Technical Note
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

Radiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).

Methods

Patients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluable liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.

Results

Fourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.

Conclusions

Absence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.

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

References

  1. Boda-Heggemann J, Dinter D, Weiss C, Frauenfeld A, Siebenlist K, Attenberger U, Ottstadt M, Schneider F, Hofheinz RD, Wenz F, Lohr F (2012) Hypofractionated image-guided breath-hold SABR (stereotactic ablative body radiotherapy) of liver metastases–clinical results. Radiat Oncol 7:92

    Article  PubMed Central  PubMed  Google Scholar 

  2. Campbell AM, Bailey IH, Burton MA (2001) Tumour dosimetry in human liver following hepatic yttrium-90 microsphere therapy. Phys Med Biol 46(2):487–498

    Article  CAS  PubMed  Google Scholar 

  3. Cosimelli M, Golfieri R, Cagol PP, Carpanese L, Sciuto R, Maini CL, Mancini R, Sperduti I, Pizzi G, Diodoro MG, Perrone M, Giampalma E, Angelelli B, Fiore F, Lastoria S, Bacchetti S, Gasperini D, Geatti O, Izzo F (2010) Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. Br J Cancer 103(3):324–331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Dawson LA, Normolle D, Balter JM, McGinn CJ, Lawrence TS, Ten Haken RK (2002) Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 53(4):810–821

    Article  PubMed  Google Scholar 

  5. de Haen C, Gozzini L (1993) Soluble-type hepatobiliary contrast agents for MR imaging. J Magn Reson Imaging 3(1):179–186

    Article  PubMed  Google Scholar 

  6. de Haen C, Lorusso V, Tirone P (1996) Hepatic transport of gadobenate dimeglumine in TR-rats. Acad Radiol 3(Suppl 2):S452–S454

    Article  PubMed  Google Scholar 

  7. Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21(1):109–122

    Article  CAS  PubMed  Google Scholar 

  8. Fajardo LF, Colby TV (1980) Pathogenesis of veno-occlusive liver disease after radiation. Arch Pathol Lab Med 104(11):584–588

    CAS  PubMed  Google Scholar 

  9. Farthing MJ, Clark ML, Sloane JP, Powles RL, McElwain TJ (1982) Liver disease after bone marrow transplantation. Gut 23(6):465–474

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Fox RA, Klemp PF, Egan G, Mina LL, Burton MA, Gray BN (1991) Dose distribution following selective internal radiation therapy. Int J Radiat Oncol Biol Phys 21(2):463–467

    Article  CAS  PubMed  Google Scholar 

  11. Geraci JP, Mariano MS (1993) Radiation hepatology of the rat: parenchymal and nonparenchymal cell injury. Radiat Res 136(2):205–213

    Article  CAS  PubMed  Google Scholar 

  12. Gil-Alzugaray B, Chopitea A, Inarrairaegui M, Bilbao JI, Rodriguez-Fraile M, Rodriguez J, Benito A, Dominguez I, D’Avola D, Herrero JI, Quiroga J, Prieto J, Sangro B (2013) Prognostic factors and prevention of radioembolization-induced liver disease. Hepatology 57(3):1078–1087

    Article  CAS  PubMed  Google Scholar 

  13. Grosser OS, Conrad S, Steffen IG, Seidensticker M, Ulrich G, Nultsch M, Furth C, Ricke J, Amthauer H (2012) Therapievalidierung der yttrium-90-radioembolisation durch Bestimmung der Dosisverteilung in einem softwareassistierten workflow. Nuklearmedizin 51:A84

    Article  Google Scholar 

  14. Herfarth KK, Debus J, Lohr F, Bahner ML, Rhein B, Fritz P, Hoss A, Schlegel W, Wannenmacher MF (2001) Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial. J Clin Oncol 19(1):164–170

    CAS  PubMed  Google Scholar 

  15. Herfarth KK, Hof H, Bahner ML, Lohr F, Hoss A, van Kaick G, Wannenmacher M, Debus J (2003) Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors. Int J Radiat Oncol Biol Phys 57(2):444–451

    Article  PubMed  Google Scholar 

  16. Jacobs P, Miller JL, Uys CJ, Dietrich BE (1979) Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukaemia. S Afr Med J 55(1):5–10

    CAS  PubMed  Google Scholar 

  17. Kennedy AS, McNeillie P, Dezarn WA, Nutting C, Sangro B, Wertman D, Garafalo M, Liu D, Coldwell D, Savin M, Jakobs T, Rose S, Warner R, Carter D, Sapareto S, Nag S, Gulec S, Calkins A, Gates VL, Salem R (2009) Treatment parameters and outcome in 680 treatments of internal radiation with resin 90Y-microspheres for unresectable hepatic tumors. Int J Radiat Oncol Biol Phys 74(5):1494–1500

    Article  CAS  PubMed  Google Scholar 

  18. Kennedy AS, Nutting C, Coldwell D, Gaiser J, Drachenberg C (2004) Pathologic response and microdosimetry of (90)Y microspheres in man: review of four explanted whole livers. Int J Radiat Oncol Biol Phys 60(5):1552–1563

    Article  CAS  PubMed  Google Scholar 

  19. Kirchin MA, Pirovano GP, Spinazzi A (1998) Gadobenate dimeglumine (Gd-BOPTA). An overview. Invest Radiol 33(11):798–809

    Article  CAS  PubMed  Google Scholar 

  20. Lam MG, Abdelmaksoud MH, Chang DT, Eclov NC, Chung MP, Koong AC, Louie JD, Sze DY (2013) Safety of 90Y radioembolization in patients who have undergone previous external beam radiation therapy. Int J Radiat Oncol Biol Phys 87(2):323–329

    Article  PubMed  Google Scholar 

  21. Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174

    Article  CAS  PubMed  Google Scholar 

  22. Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF (1995) Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 31(5):1237–1248

    Article  CAS  PubMed  Google Scholar 

  23. Marzola P, Maggioni F, Vicinanza E, Dapra M, Cavagna FM (1997) Evaluation of the hepatocyte-specific contrast agent gadobenate dimeglumine for MR imaging of acute hepatitis in a rat model. J Magn Reson Imaging 7(1):147–152

    Article  CAS  PubMed  Google Scholar 

  24. Mohnike K, Wieners G, Schwartz F, Seidensticker M, Pech M, Ruehl R, Wust P, Lopez-Hanninen E, Gademann G, Peters N, Berg T, Malfertheiner P, Ricke J (2010) Computed tomography-guided high-dose-rate brachytherapy in hepatocellular carcinoma: safety, efficacy, and effect on survival. Int J Radiat Oncol Biol Phys 78(1):172–179

    Article  PubMed  Google Scholar 

  25. Pascolo L, Cupelli F, Anelli PL, Lorusso V, Visigalli M, Uggeri F, Tiribelli C (1999) Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents. Biochem Biophys Res Commun 257(3):746–752

    Article  CAS  PubMed  Google Scholar 

  26. Pastor CM, Planchamp C, Pochon S, Lorusso V, Montet X, Mayer J, Terrier F, Vallee JP (2003) Kinetics of gadobenate dimeglumine in isolated perfused rat liver: MR imaging evaluation. Radiology 229(1):119–125

    Article  PubMed  Google Scholar 

  27. Reed GB Jr, Cox AJ Jr (1966) The human liver after radiation injury A form of veno-occlusive disease. Am J Pathol 48(4):597–611

    PubMed Central  PubMed  Google Scholar 

  28. Ricke J, Mohnike K, Pech M, Seidensticker M, Ruhl R, Wieners G, Gaffke G, Kropf S, Felix R, Wust P (2010) Local response and impact on survival after local ablation of liver metastases from colorectal carcinoma by computed tomography-guided high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 78(2):479–485

    Article  PubMed  Google Scholar 

  29. Ricke J, Seidensticker M, Ludemann L, Pech M, Wieners G, Hengst S, Mohnike K, Cho CH, Lopez Hanninen E, Al-Abadi H, Felix R, Wust P (2005) In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation. Int J Radiat Oncol Biol Phys 62(3):776–784

    Article  PubMed  Google Scholar 

  30. Rohlfing T, West JB, Beier J, Liebig T, Taschner CA, Thomale UW (2000) Registration of functional and anatomical MRI: accuracy assessment and application in navigated neurosurgery. Comput Aided Surg 5(6):414–425

    Article  CAS  PubMed  Google Scholar 

  31. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, Dousset B, Morel P, Soubrane O, Chaussade S, Mentha G, Terris B (2004) Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 15(3):460–466

    Article  CAS  PubMed  Google Scholar 

  32. Sangro B, Gil-Alzugaray B, Rodriguez J, Sola I, Martinez-Cuesta A, Viudez A, Chopitea A, Inarrairaegui M, Arbizu J, Bilbao JI (2008) Liver disease induced by radioembolization of liver tumors: description and possible risk factors. Cancer 112(7):1538–1546

    Article  PubMed  Google Scholar 

  33. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, Nagtegaal ID, Beets-Tan RG, Arnold D, Ciardiello F, Hoff P, Kerr D, Kohne CH, Labianca R, Price T, Scheithauer W, Sobrero A, Tabernero J, Aderka D, Barroso S, Bodoky G, Douillard JY, El Ghazaly H, Gallardo J, Garin A, Glynne-Jones R, Jordan K, Meshcheryakov A, Papamichail D, Pfeiffer P, Souglakos I, Turhal S, Cervantes A (2012) ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23(10):2479–2516

    Article  CAS  PubMed  Google Scholar 

  34. Schuhmann-Giampieri G, Schmitt-Willich H, Frenzel T, Schitt-Willich H (1993) Biliary excretion and pharmacokinetics of a gadolinium chelate used as a liver-specific contrast agent for magnetic resonance imaging in the rat. J Pharm Sci 82(8):799–803

    Article  CAS  PubMed  Google Scholar 

  35. Schuhmann-Giampieri G, Schmitt-Willich H, Press WR, Negishi C, Weinmann HJ, Speck U (1992) Preclinical evaluation of Gd-EOB-DTPA as a contrast agent in MR imaging of the hepatobiliary system. Radiology 183(1):59–64

    Article  CAS  PubMed  Google Scholar 

  36. Seidensticker M, Seidensticker R, Mohnike K, Wybranski C, Kalinski T, Luess S, Pech M, Wust P, Ricke J (2011) Quantitative in vivo assessment of radiation injury of the liver using Gd-EOB-DTPA enhanced MRI: tolerance dose of small liver volumes. Radiat Oncol 6:40

    Article  PubMed Central  PubMed  Google Scholar 

  37. Seidensticker R, Denecke T, Kraus P, Seidensticker M, Mohnike K, Fahlke J, Kettner E, Hildebrandt B, Dudeck O, Pech M, Amthauer H, Ricke J (2012) Matched-pair comparison of radioembolization plus best supportive care versus best supportive care alone for chemotherapy refractory liver-dominant colorectal metastases. Cardiovasc Intervent Radiol 35(5):1066–1073

    Article  PubMed  Google Scholar 

  38. Sempoux C, Horsmans Y, Geubel A, Fraikin J, Van Beers BE, Gigot JF, Lerut J, Rahier J (1997) Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event. Hepatology 26(1):128–134

    Article  CAS  PubMed  Google Scholar 

  39. Shin NY, Kim MJ, Lim JS, Park MS, Chung YE, Choi JY, Kim KW, Park YN (2012) Accuracy of gadoxetic acid-enhanced magnetic resonance imaging for the diagnosis of sinusoidal obstruction syndrome in patients with chemotherapy-treated colorectal liver metastases. Eur Radiol 22(4):864–871

    Article  PubMed  Google Scholar 

  40. Shulman HM, McDonald GB, Matthews D, Doney KC, Kopecky KJ, Gauvreau JM, Thomas ED (1980) An analysis of hepatic veno occlusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology 79(6):1178–1191

    CAS  PubMed  Google Scholar 

  41. Spinazzi A, Lorusso V, Pirovano G, Kirchin M (1999) Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers. Acad Radiol 6(5):282–291

    Article  CAS  PubMed  Google Scholar 

  42. Watanabe H, Kanematsu M, Goshima S, Kondo H, Onozuka M, Moriyama N, Bae KT (2011) Staging hepatic fibrosis: comparison of gadoxetate disodium-enhanced and diffusion-weighted MR imaging–preliminary observations. Radiology 259(1):142–150

    Article  PubMed  Google Scholar 

  43. Wybranski C, Seidensticker M, Mohnike K, Kropf S, Wust P, Ricke J, Ludemann L (2009) In vivo assessment of dose volume and dose gradient effects on the tolerance dose of small liver volumes after single-fraction high-dose-rate 192Ir irradiation. Radiat Res 172(5):598–606

    Article  CAS  PubMed  Google Scholar 

  44. Yuan Y, Andronesi OC, Bortfeld TR, Richter C, Wolf R, Guimaraes AR, Hong TS, Seco J (2013) Feasibility study of in vivo MRI based dosimetric verification of proton end-of-range for liver cancer patients. Radiother Oncol 106(3):378–382

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None in context of the presented study for all authors. Possible Coi outside study matter: Max Seidensticker: reports to receive research grants by SIRTEX medical and Bayer Healthcare and honoraria by Bayer Healthcare. Miroslaw Burak: no conflict of interest. Thomas Kalinski: no conflict of interest. Benjamin Garlipp: reports to receive lecture fees by SIRTEX medical. Konrad Koelble: no conflict of interest. Peter Wust: no conflict of interest. Kai Antweiler: no conflict of interest. Ricarda Seidensticker: reports to receive research grants by SIRTEX medical and Bayer Healthcare and honoraria by Bayer Healthcare. Konrad Mohnike: no conflict of interest. Maciej Pech: no conflict of interest. Jens Ricke: reports to receive research grants by SIRTEX medical, Bayer Healthcare and Siemens.

Author information

Authors and Affiliations

  1. Klinik für Radiologie und Nuklearmedizin, Universitätsklinik Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Max Seidensticker, Ricarda Seidensticker, Konrad Mohnike, Maciej Pech & Jens Ricke

  2. Department of Diagnostic Imaging and Interventional Radiology, Pomeranian Medical University, 1, Unii Lubelskiej St, 71-252, Szczecin, Poland

    Miroslaw Burak

  3. Institut für Pathologie, Universitätsklinik Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Thomas Kalinski

  4. Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinik Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Benjamin Garlipp

  5. Fachbereich Medizin der, Abteilung für Neuropathologie, Philipps Universität Marburg, Baldingerstrasse, 35043, Marburg, Germany

    Konrad Koelble

  6. Klinik für Radioonkologie und Strahlentherapie, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Peter Wust

  7. Institut für Biometrie und Medizinische Informatik, Universitätsklinik Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Kai Antweiler

Authors
  1. Max Seidensticker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miroslaw Burak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Kalinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Benjamin Garlipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Konrad Koelble
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter Wust
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kai Antweiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ricarda Seidensticker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Konrad Mohnike
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Maciej Pech
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jens Ricke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Max Seidensticker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seidensticker, M., Burak, M., Kalinski, T. et al. Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study. Cardiovasc Intervent Radiol 38, 213–221 (2015). https://doi.org/10.1007/s00270-014-0872-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-014-0872-7

Keywords

Search

Navigation