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 1T. Changes in pharmacokinetic estimates (K(trans) 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. RESULTS: Both the K(trans) 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 K(trans) 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. CONCLUSIONS: This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy.

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

LONGO, DARIO LIVIO;DASTRU', Walter;CONSOLINO, LORENA;ARIGONI, MADDALENA;CAVALLO, Federica;AIME, Silvio
2015

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 1T. Changes in pharmacokinetic estimates (K(trans) 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. RESULTS: Both the K(trans) 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 K(trans) 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. CONCLUSIONS: This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy.
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www.elsevier.com/locate/mri
Antiangiogenic; Clustering; DCE-MRI; Gd-complexes; Pharmacokinetic modeling; Tumor heterogeneity; Biophysics; Radiology, Nuclear Medicine and Imaging; Biomedical Engineering
Longo, Dario Livio; Dastrù, Walter; Consolino, Lorena; Espak, Miklos; Arigoni, Maddalena; Cavallo, Federica; Aime, Silvio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1548094
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