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

2015; Elsevier BV; Volume: 33; Issue: 6 Linguagem: Inglês

10.1016/j.mri.2015.03.005

1873-5894

Dario Livio Longo, Walter Dastrù, Lorena Consolino, Miklos Espak, Maddalena Arigoni, Federica Cavallo, Silvio Aime,

Advanced MRI Techniques and Applications

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. 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 (Ktrans and vp) 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. Both the Ktrans and vp 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 vp estimates (p < 0.05). The proposed clustering approach depicted marked changes in both the Ktrans and vp estimates, with significant spatial heterogeneity in vp maps in response to treatment (p < 0.05), provided that DCE-MRI data are properly clustered in three or four sub-regions. This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy.