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Title: Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations

Abstract

Purpose: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with {sup 90}Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. Methods and Materials: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-μm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). Results: Singlemore » spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV=0.35, HDV = 50 cm{sup 3}, and ADR=6 μm. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 μm, respectively, whereas HDV increased to 130 cm{sup 3}. The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm{sup 3}, and ADR = 8 μm. Conclusion: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.« less

Authors:
 [1];  [2]; ;  [3];  [4];  [5];  [6];  [1];  [7]
  1. Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden)
  2. Department of Surgery, Sahlgrenska University Hospital, Gothenburg (Sweden)
  3. Department of Oncology, Sahlgrenska University Hospital, Gothenburg (Sweden)
  4. Department of Radiology, Sahlgrenska University Hospital, Gothenburg (Sweden)
  5. Department of Pathology, Sahlgrenska University Hospital, Gothenburg (Sweden)
  6. Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg (Sweden)
  7. (Sweden)
Publication Date:
OSTI Identifier:
22645659
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ARTERIES; BIOPSY; CONCENTRATION RATIO; ECOLOGICAL CONCENTRATION; LIVER; MICROSPHERES; RADIOTHERAPY; SIMULATION; SPATIAL DISTRIBUTION

Citation Formats

Högberg, Jonas, E-mail: jonas.hogberg@radfys.gu.se, Rizell, Magnus, Hultborn, Ragnar, Svensson, Johanna, Henrikson, Olof, Mölne, Johan, Gjertsson, Peter, Bernhardt, Peter, and Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg. Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.05.007.
Högberg, Jonas, E-mail: jonas.hogberg@radfys.gu.se, Rizell, Magnus, Hultborn, Ragnar, Svensson, Johanna, Henrikson, Olof, Mölne, Johan, Gjertsson, Peter, Bernhardt, Peter, & Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg. Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations. United States. doi:10.1016/J.IJROBP.2016.05.007.
Högberg, Jonas, E-mail: jonas.hogberg@radfys.gu.se, Rizell, Magnus, Hultborn, Ragnar, Svensson, Johanna, Henrikson, Olof, Mölne, Johan, Gjertsson, Peter, Bernhardt, Peter, and Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg. 2016. "Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations". United States. doi:10.1016/J.IJROBP.2016.05.007.
@article{osti_22645659,
title = {Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations},
author = {Högberg, Jonas, E-mail: jonas.hogberg@radfys.gu.se and Rizell, Magnus and Hultborn, Ragnar and Svensson, Johanna and Henrikson, Olof and Mölne, Johan and Gjertsson, Peter and Bernhardt, Peter and Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg},
abstractNote = {Purpose: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with {sup 90}Y-labeled resin spheres and characterize microsphere distribution in the hepatic artery tree, and to construct a novel dichotomous bifurcation model for microsphere deposits and evaluate its accuracy in simulating the observed microsphere deposits. Methods and Materials: Our virtual model consisted of arteries that successively branched into 2 new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimized to obtain concordance between simulations and measure microsphere distributions: an artery coefficient of variation (ACV) for the diameter of all artery generations and the microsphere flow distribution at the nodes; a hepatic tree distribution volume (HDV) for the artery tree; and an artery diameter reduction (ADR) parameter. The model was tested against previously measured activity concentrations in 84 biopsies from the liver of 1 patient. In 16 of 84 biopsies, the microsphere distribution regarding cluster size and localization in the artery tree was determined via light microscopy of 30-μm sections (mean concentration, 14 microspheres/mg; distributions divided into 3 groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg). Results: Single spheres and small clusters were observed in terminal arterioles, whereas large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimized parameter values were ACV=0.35, HDV = 50 cm{sup 3}, and ADR=6 μm. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 μm, respectively, whereas HDV increased to 130 cm{sup 3}. The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm{sup 3}, and ADR = 8 μm. Conclusion: Simulations and measurements reveal that microsphere clusters are larger and more common in volumes with high microsphere concentrations and indicate that the spatial distribution of the artery tree must be considered in estimates of microsphere distributions.},
doi = {10.1016/J.IJROBP.2016.05.007},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = 2016,
month =
}
  • Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy.more » Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y.« less
  • In selective internal radiation (SIR) therapy of hepatic metastases, tumor vasculature is preferentially embolized with high-energy beta-emitting yttrium-90-labeled microspheres. To enable accurate estimation of the resultant absorbed radiation doses to tissues, an intraoperative beta detection probe is used to scan the liver surface. The validity of the response of this probe to Y-90 and its clinical application were assessed with a phantom containing varying activities and with biopsy samples obtained from patients being treated with SIR therapy. A linear relationship was found between the probe counts taken from the biopsy samples and the calculated tissue radiation doses from the specificmore » activities of each sample. This relationship was repeated with probe counts determined against a water phantom containing various activities of Y-90. The probe was shown to respond minimally to bremsstrahlung. The use of the probe in measuring tissue radiation doses at laparotomy provides the opportunity to control dose administration during SIR therapy. In this way, subtherapeutic exposure of normal tissue can be assured while tumor tissue receives maximal radiation levels.« less
  • Ten patients with liver metastases from primary tumors in the colorectum were treated with selective internal radiation (SIR) therapy. This involved the embolisation of yttrium-90-containing microspheres into the hepatic artery at the time of laparotomy. The microspheres were concentrated in the microvasculature of the tumour nodules by the concurrent administration of angiotensin II. The radiation dose being delivered to liver parenchyma was measured at the time of operation by use of an intraoperative radiation detection probe. All nine patients in whom the preoperative carcinoembryonic antigen (CEA) level was elevated experienced a decrease in CEA levels posttreatment. Intraoperative dosimetry confirmed themore » poor correlation between total radioactivity used and radiation dose received by normal liver parenchyma.« less
  • Introduction: Selective internal radiation therapy (SIRT) is a relatively new commercially available microbrachytherapy technique for treatment of malignant hepatic lesions using {sup 9}Y embedded in resin microspheres, which are infused directly into the hepatic arterial circulation. It is FDA approved for liver metastases secondary to colorectal carcinoma and is under investigation for treatment of other liver malignancies, such as hepatocellular carcinoma and neuroendocrine malignancies. Materials/Methods: A modest number of clinical trials, preclinical animal studies, and dosimetric studies have been reported. Here we review several of the more important results. Results: High doses of beta radiation can be selectively delivered tomore » tumors, resulting in impressive local control and survival rates. Ex vivo analyses have shown that microspheres preferentially cluster around the periphery of tumor nodules with a high tumor:normal tissue ratio of up to 200:1. Toxicity is usually mild, featuring fatigue, anorexia, nausea, abdominal discomfort, and slight elevations of liver function tests. Conclusions: Selective internal radiation therapy represents an effective means of controlling liver metastases from colorectal adenocarcinoma. Clinical trials have demonstrated improved local control of disease and survival with relatively low toxicity. Investigations of SIRT for other hepatic malignancies and in combination with newer chemotherapy agents and targeted biologic therapies are under way or in planning. A well-integrated team involving interventional radiology, nuclear medicine, medical oncology, surgical oncology, medical physics, and radiation oncology is essential for a successful program. Careful selection of patients through the combined expertise of the team can maximize therapeutic efficacy and reduce the potential for adverse effects.« less
  • The imaging of Bremsstrahlung radiation is performed after hepatic radioembolization to assess the distribution of the injected radioactive material. This review assesses the role of Bremsstrahlung imaging and its relation to the angiographic procedure and technique in hepatic selective internal radiation therapy on 21 patients undergoing this procedure at a single center.