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Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation

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Abstract

Yttrium-90 (Y-90) transarterial radioembolization uses radioactive microspheres injected into the hepatic artery to irradiate liver tumors internally. One of the major challenges is the lack of reliable dosimetry methods for dose prediction and dose verification. We present a patient-specific dosimetry approach for personalized treatment planning based on computational fluid dynamics (CFD) simulations of the microsphere transport combined with Y-90 physics modeling called CFDose. The ultimate goal is the development of a software to optimize the amount of activity and injection point for optimal tumor targeting. We present the proof-of-concept of a CFD dosimetry tool based on a patient’s angiogram performed in standard-of-care planning. The hepatic arterial tree of the patient was segmented from the cone-beam CT (CBCT) to predict the microsphere transport using multiscale CFD modeling. To calculate the dose distribution, the predicted microsphere distribution was convolved with a Y-90 dose point kernel. Vessels as small as 0.45 mm were segmented, the microsphere distribution between the liver segments using flow analysis was predicted, the volumetric microsphere and resulting dose distribution in the liver volume were computed. The patient was imaged with positron emission tomography (PET) 2 h after radioembolization to evaluate the Y-90 distribution. The dose distribution was found to be consistent with the Y-90 PET images. These results demonstrate the feasibility of developing a complete framework for personalized Y-90 microsphere simulation and dosimetry using patient-specific input parameters.

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References

  1. Aramburu, J., R. Antón, A. Rivas, J. C. Ramos, G. S. Larraona, B. Sangro, and J. I. Bilbao. A methodology for numerically analysing the hepatic artery haemodynamics during b-TACE: a proof of concept. Comput. Methods Biomech. Biomed. Eng. 22:518–532, 2019.

    Google Scholar 

  2. Aramburu, J., R. Antón, A. Rivas, J. C. Ramos, B. Sangro, and J. I. Bilbao. The role of angled-tip microcatheter and microsphere injection velocity in liver radioembolization: a computational particle-hemodynamics study. Int. J. Numer. Method Biomed. Eng. 33:e2895, 2017.

    Google Scholar 

  3. Aramburu, J., R. Antón, A. Rivas, J. C. Ramos, B. Sangro, and J. I. Bilbao. Liver radioembolization: an analysis of parameters that influence the catheter-based particle-delivery via CFD. Curr. Med. Chem. 25:1–15, 2018.

    Google Scholar 

  4. Basciano, C. A., C. Kleinstreuer, A. S. Kennedy, W. A. Dezarn, and E. Childress. Computer modeling of controlled microsphere release and targeting in a representative hepatic artery system. Ann. Biomed. Eng. 38:1862–1879, 2010.

    PubMed  Google Scholar 

  5. Braat, A. J. A. T., M. L. J. Smits, M. N. G. J. A. Braat, A. F. Van Den Hoven, J. F. Prince, H. W. A. M. De Jong, M. A. A. J. Van Den Bosch, and M. G. E. H. Lam. 90Y hepatic radioembolization: an update on current practice and recent developments. J. Nucl. Med. 56:1079–1087, 2015.

    PubMed  Google Scholar 

  6. BTG. http://www.therasphere.com/.

  7. Celik, I. B., U. Ghia, P. J. Roache, and C. J. Freitas. Procedure for estimation and reporting of uncertainty due to discretization in CFD applications. J. Fluids Eng. 130:078001, 2008.

    Google Scholar 

  8. Cheneler, D., and M. Ward. Power output and efficiency of beta-emitting microspheres. Radiat. Phys. Chem. 106:204–212, 2015.

    CAS  Google Scholar 

  9. Couinaud, C. Le foie: Études anatomiques et chirurgicales. Paris: Masson, 1957.

    Google Scholar 

  10. Crookston, N. R., G. S. K. Fung, and E. C. Frey. Development of a customizable hepatic arterial tree and particle transport model for use in treatment planning. IEEE Trans. Rad. Plasma Med. Sci. 3:31–37, 2019.

    Google Scholar 

  11. Dieudonné, A., R. F. Hobbs, R. Lebtahi, F. Maurel, S. Baechler, R. L. Wahl, A. Boubaker, D. Le Guludec, G. Sgouros, and I. Gardin. Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: Comparison between dose kernel convolution and direct Monte Carlo methods. J. Nucl. Med. 54:236–243, 2013.

    PubMed  Google Scholar 

  12. Elschot, M., J. F. W. Nijsen, A. J. Dam, and H. W. A. M. De Jong. Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization. PLoS ONE 6:e26174, 2011.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Elschot, M., B. J. Vermolen, M. G. Lam, B. De Keizer, M. A. Van Den Bosch, and H. W. De Jong. Quantitative comparison of PET and bremsstrahlung SPECT for imaging the in vivo yttrium-90 microsphere distribution after liver radioembolization. PLoS ONE 8:2, 2013.

    Google Scholar 

  14. Favelier, S., T. Germain, P. Y. Genson, J. P. Cercueil, A. Denys, D. Krause, and B. Guiu. Anatomy of liver arteries for interventional radiology. Diagn. Interv. Imaging 96:537–546, 2015.

    CAS  PubMed  Google Scholar 

  15. Fowler, K. J., N. M. Maughan, R. Laforest, N. E. Saad, A. Sharma, J. Olsen, C. K. Speirs, and P. J. Parikh. PET/MRI of hepatic 90Y microsphere deposition determines individual tumor response. Cardiovasc. Interv. Radiol. 39:855–864, 2016.

    Google Scholar 

  16. Gulec, S. A., G. Mesoloras, and M. Stabin. Dosimetric techniques in 90Y-microsphere therapy of liver cancer: the MIRD equations for dose calculations. J. Nucl. Med. 47:1209–1211, 2006.

    CAS  PubMed  Google Scholar 

  17. Ho, S., W. Y. Lau, W. T. Leung, M. Chan, K. W. Chan, P. J. Johnson, and A. K. C. Li. Arteriovenous shunts in patients with hepatic tumors. J. Nucl. Med. 38:1201–1205, 1997.

    CAS  PubMed  Google Scholar 

  18. Ho, S., W. Y. Lau, T. W. Leung, M. Chan, Y. K. Ngar, P. J. Johnson, and A. K. Li. Partition model for estimating radiation doses from yttrium-90 microspheres in treating hepatic tumours. EJNMMI 23:947–952, 1996.

    CAS  Google Scholar 

  19. Högberg, J., M. Rizell, R. Hultborn, J. Svensson, O. Henrikson, J. Mölne, P. Gjertsson, and P. Bernhardt. Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy. EJNMMI Res. 4:1–9, 2014.

    Google Scholar 

  20. Ilhan, H., A. Goritschan, P. Paprottka, T. F. Jakobs, W. P. Fendler, A. Todica, P. Bartenstein, M. Hacker, and A. R. Haug. Predictive value of 99mTc-MAA SPECT for 90Y-labeled resin microsphere distribution in radioembolization of primary and secondary hepatic tumors. J. Nucl. Med. 56:1654–1660, 2015.

    CAS  PubMed  Google Scholar 

  21. Kennedy, A. S., C. Kleinstreuer, C. A. Basciano, and W. A. Dezarn. Computer modeling of yttrium-90-microsphere transport in the hepatic arterial tree to improve clinical outcomes. Int. J. Radiat. Oncol. Biol. Phys. 76:631–637, 2010.

    CAS  PubMed  Google Scholar 

  22. Lam, M. G. E. H., J. D. Louie, M. H. K. Abdelmaksoud, G. A. Fisher, C. D. Cho-Phan, and D. Y. Sze. Limitations of body surface area–based activity calculation for radioembolization of hepatic metastases in colorectal cancer. J. Vasc. Interv. Radiol. 25:1085–1093, 2014.

    PubMed  Google Scholar 

  23. Lorensen, W. E., and H. E. Cline. Marching cubes: a high resolution 3D surface construction algorithm. SIGGRAPH Comput. Graph. 21:163–169, 1987.

    Google Scholar 

  24. Martini, F., J. L. Nath, and E. F. Bartholomew. Fundamentals of Anatomy & Physiology. San Francisco: Pearson Benjamin Cummings, 2015.

    Google Scholar 

  25. Moghadam, K. M., A. Kamali Asl, P. Geramifar, and H. Zaidi. Evaluating the application of tissue-specific dose kernels instead of water dose kernels in internal dosimetry: a Monte Carlo study. Cancer Biother. Radiopharm. 31(3):67–379, 2016.

    Google Scholar 

  26. Pewowaruk, R., and A. Roldan-Alzate. 4D flow MRI estimation of boundary conditions for patient specific cardiovascular simulation. Ann. Biomed. Eng. 47:1786–1798, 2019.

    PubMed  Google Scholar 

  27. Reneman, R. S., and A. P. Hoeks. Wall shear stress as measured in vivo: consequences for the design of the arterial system. Med. Biol. Eng. Comput. 46:499–507, 2008.

    PubMed  PubMed Central  Google Scholar 

  28. Rhee, S., S. Kim, J. Cho, J. Park, J. S. Eo, S. Park, E. Lee, Y. H. Kim, and J.-G. Choe. Semi-quantitative analysis of post-transarterial radioembolization 90Y microsphere positron emission tomography combined with computed tomography (PET/CT) images in advanced liver malignancy: comparison with 99mTc macroaggregated albumin (MAA) single photon emission computed tomography (SPECT). Nucl. Med. Mol. Imaging 50:63–69, 2016.

    CAS  PubMed  Google Scholar 

  29. Riaz, A., R. J. Lewandowski, L. M. Kulik, M. F. Mulcahy, K. T. Sato, R. K. Ryu, R. A. Omary, and R. Salem. Complications following radioembolization with yttrium-90 microspheres: a comprehensive literature review. J. Vasc. Interv. Radiol. 20:1121–1130, 2009.

    PubMed  Google Scholar 

  30. Ryde, H., P. Thieberger, and T. Alväger. Two-photon de-excitation of the 0 + level in Zr90. Phys. Rev. Lett. 6:475–478, 1961.

    CAS  Google Scholar 

  31. Salem, R., V. Mazzaferro, and B. Sangro. Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges and clinical perspectives. Hepatology 2013. https://doi.org/10.1002/hep.26382.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sarrut, D., M. Bardiès, N. Boussion, N. Freud, S. Jan, J.-M. Létang, G. Loudos, L. Maigne, S. Marcatili, T. Mauxion, P. Papadimitroulas, Y. Perrot, U. Pietrzyk, C. Robert, D. R. Schaart, D. Visvikis, and I. Buvat. A review of the use and potential of the GATE Monte Carlo simulation code for radiation therapy and dosimetry applications. Med. Phys. 41:064301, 2014.

    PubMed  Google Scholar 

  33. Silveira, L. A. D., F. B. C. Silveira, and V. P. S. Fazan. Arterial diameter of the celiac trunk and its branches: anatomical study. Acta Cir. Bras. 24:43–47, 2009.

    PubMed  Google Scholar 

  34. Simoncini, C., K. Jurczuk, D. Reska, S. Esneault, J. C. Nunes, J. J. Bellanger, H. Saint-Jalmes, Y. Rolland, P. A. Eliat, J. Bezy-Wendling, and M. Kretowski. Towards a patient-specific hepatic arterial modeling for microspheres distribution optimization in SIRT protocol. Med. Biol. Eng. Comput. 56:515–529, 2018.

    PubMed  Google Scholar 

  35. Stenvall, A., E. Larsson, S. E. Strand, and B. A. Jonsson. A small-scale anatomical dosimetry model of the liver. Phys. Med. Biol. 59:3353–3371, 2014.

    PubMed  Google Scholar 

  36. Tiwari, A., S. Graves, and J. Sunderland. Measurements of dose point kernels using GATE Monte Carlo toolkit for personalized convolution dosimetry. J. Nucl. Med. 60:274, 2019.

    Google Scholar 

  37. Updegrove, A., N. M. Wilson, J. Merkow, H. Lan, A. L. Marsden, and S. C. Shadden. Simvascular: an open source pipeline for cardiovascular simulation. Ann. Biomed. Eng. 45:525–541, 2017.

    PubMed  Google Scholar 

  38. Walrand, S., M. Hesse, C. Chiesa, R. Lhommel, and F. Jamar. The low hepatic toxicity per gray of 90Y glass microspheres is linked to their transport in the arterial tree favoring a nonuniform trapping as observed in posttherapy PET imaging. J. Nucl. Med. 55:135–140, 2014.

    CAS  PubMed  Google Scholar 

  39. Wang, T., F. Liang, Z. Zhou, and X. Qi. Global sensitivity analysis of hepatic venous pressure gradient (HVPG) measurement with a stochastic computational model of the hepatic circulation. Comput. Biol. Med. 97:124–136, 2018.

    PubMed  Google Scholar 

  40. Willowson, K., N. Forwood, B. W. Jakoby, A. M. Smith, and D. L. Bailey. Quantitative 90Y image reconstruction in PET. Med. Phys. 39:7153–7159, 2012.

    CAS  PubMed  Google Scholar 

  41. Willowson, K. P., A. R. Hayes, D. L. H. Chan, M. Tapner, E. J. Bernard, R. Maher, N. Pavlakis, S. J. Clarke, and D. L. Bailey. Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: A retrospective exploratory analysis. EJNMMI Res. 7:46, 2017.

    PubMed  PubMed Central  Google Scholar 

  42. Wondergem, M., M. L. J. Smits, M. Elschot, H. W. A. M. De Jong, H. M. Verkooijen, M. A. A. J. Van Den Bosch, J. F. W. Nijsen, and M. G. E. H. Lam. 99mTc-macroaggregated albumin poorly predicts the intrahepatic distribution of 90Y resin microspheres in hepatic radioembolization. J. Nucl. Med. 54:1294–1301, 2013.

    CAS  PubMed  Google Scholar 

  43. Yzet, T., R. Bouzerar, J. D. Allart, F. Demuynck, C. Legallais, B. Robert, H. Deramond, M. E. Meyer, and O. Baledent. Hepatic vascular flow measurements by phase contrast MRI and Doppler echography: a comparative and reproducibility study. J. Magn. Reson. Imaging 31:579–588, 2010.

    PubMed  Google Scholar 

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Acknowledgments

This work was funded by NIH R35 CA197608, CCSG P30 (NCI P30CA093373), UC Davis Academic Federation Innovation Development Award, and NIH R21 CA237686 (ITCR). The authors thank Dr Bahman S. Roudsari, Denise T. Caudle, Michael Rusnak, and Dr. Sara St. James for the angiogram interpretation, 90Y PET scans, and dose kernel computation.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Emilie Roncali & Amirtahà Taebi

  2. Department of Radiology, UC Davis Medical Center, Sacramento, CA, 95817, USA

    Cameron Foster & Catherine Tram Vu

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  1. Emilie Roncali
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Correspondence to Emilie Roncali.

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10439_2020_2469_MOESM1_ESM.eps

Figure S1. Hepatic artery segmentation pipeline. CBCT images with a resolution of 0.25 mm and slice thickness of 1 mm are segmented to extract blood vessels using a semi-automatic approach. Supplementary material 1 (EPS 634 kb).

10439_2020_2469_MOESM2_ESM.eps

Figure S2. 90Y dose kernel. (a) 90Y beta energy spectrum with a maximum energy of 2.28 MeV and peak at 860 keV. (b) Projection of the 1 mm dose point kernel computed with the 90Y spectrum shown in (a). (c) The energy deposited is highest close to the 90Y point source (located at 0 mm) and decreasing rapidly with increasing distance from the point source (note the log scale). Supplementary material 2 (EPS 140 kb).

10439_2020_2469_MOESM3_ESM.eps

Figure S3. Predicted dose distribution for the lobar and selective injections separately, which are shown combined in Fig. 7c. (a) Selective injection, coronal view, with a total dose of 58.3 Gy. (b) Lobar injection, coronal view, with a total of 67 Gy. Supplementary material 3 (EPS 59 kb).

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Roncali, E., Taebi, A., Foster, C. et al. Personalized Dosimetry for Liver Cancer Y-90 Radioembolization Using Computational Fluid Dynamics and Monte Carlo Simulation. Ann Biomed Eng 48, 1499–1510 (2020). https://doi.org/10.1007/s10439-020-02469-1

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