title: Simulation Model of Microsphere Distribution for Selective Internal Radiation Therapy Agrees With Observations.
abstract: To perform a detailed analysis of microsphere distribution in biopsy material from a patient treated with (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.
  
  
  
  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).
  
  
  
  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(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(3). The opposite trend was observed for 28 microspheres/mg: ACV = 0.49, HDV = 20 cm(3), and ADR = 8 μm.
  
  
  
  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.
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: jonas.hogberg@radfys.gu.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Högberg
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Rizell
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Svensson
authors.affiliation: Department of Radiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Henrikson
authors.affiliation: Department of Pathology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.affiliation: Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Gjertsson
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Medical Physics and Biomedical Engineering, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
mesh_terms: D001783:Blood Flow Velocity / Q000502:physiology; D003198:Computer Simulation; D006499:Hepatic Artery / Q000502:physiology*; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008863:Microspheres; D008955:Models, Cardiovascular; D010316:Particle Size; D011829:Radiation Dosage; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000097:blood*
chemical_list: D015021:Yttrium Radioisotopes