Cluster analysis of quantitative parametric maps from DCE-MRI: application in evaluating heterogeneity of tumor response to antiangiogenic treatment.

Abstract Purpose The objective of this study was to compare a clustering approach to conventional analysis methods for assessing changes in pharmacokinetic parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during antiangiogenic treatment in a breast cancer model. Materials and methods BALB/c mice bearing established transplantable her2+ tumors were treated with a DNA-based antiangiogenic vaccine or with an empty plasmid (untreated group). DCE-MRI was carried out by administering a dose of 0.05 mmol/kg of Gadocoletic acid trisodium salt, a Gd-based blood pool contrast agent (CA) at 1 T. Changes in pharmacokinetic estimates (K trans and v p ) in a nine-day interval were compared between treated and untreated groups on a voxel-by-voxel analysis. The tumor response to therapy was assessed by a clustering approach and compared with conventional summary statistics, with sub-regions analysis and with histogram analysis. Results Both the K trans and v p estimates, following blood-pool CA injection, showed marked and spatial heterogeneous changes with antiangiogenic treatment. Averaged values for the whole tumor region, as well as from the rim/core sub-regions analysis were unable to assess the antiangiogenic response. Histogram analysis resulted in significant changes only in the v p estimates (p  trans and v p estimates, with significant spatial heterogeneity in v p maps in response to treatment (p  Conclusions This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy.