A simulation model of microsphere distribution for selective internal radiation therapy agrees with observations

Publication date: Available online 13 May 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Jonas Högberg, Magnus Rizell, Ragnar Hultborn, Johanna Svensson, Olof Henrikson, Johan Mölne, Peter Gjertsson, Peter Bernhardt
PurposeLarge clusters of resin microspheres are common in normal liver tissue arteries after selective internal radiation therapy, which might lead to pronounced heterogeneity in the absorbed dose distribution. To describe microsphere-clustering properties, we constructed a hepatic artery branching tree model and tested it against biopsy findings.MethodsOur virtual model consisted of arteries that successively branched into two new generations of arteries at 20 nodes. The artery diameter exponentially decreased from the lowest generation to the highest generation. Three variable parameters were optimised 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 one patient. In 16/84 biopsies, the microsphere distribution regarding cluster size and localisation in the artery tree was determined via light microscopy of 30-μm sections (mean concentration, 14 microspheres/mg; distributions divided into three groups with mean microsphere concentrations of 4.6, 14, and 28 microspheres/mg).ResultsSingle spheres and small clusters were observed in terminal arterioles while large clusters, up to 450 microspheres, were observed in larger arterioles. For 14 microspheres/mg, the optimised parameter values were ACV=0.35, HDV=50 cm³, and ADR=6 μm. For 4.6 microspheres/mg, ACV and ADR decreased to 0.26 and 0 μm, respectively, while HDV increased to 130 cm³. The opposite trend was observed for 28 microspheres/mg: ACV=0.49, HDV=20 cm³, and ADR=8 μm.ConclusionSimulations 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.

Teaser

Microsphere clusters are common in normal liver tissue arteries after radioembolisation. To describe microsphere-clustering properties, we analysed the microsphere distribution in patient biopsies and constructed a hepatic artery branching tree model that successively branched into two new generations of arteries at 20 nodes. In agreement with the clinical findings, simulations revealed that microsphere clusters are larger and more common in volumes with high microsphere concentrations than has been previously predicted.


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