title: Cluster analysis of DCE-MRI data identifies regional tracer-kinetic changes after tumor treatment with high intensity focused ultrasound.
abstract: Evaluation of high intensity focused ultrasound (HIFU) treatment with MRI is generally based on assessment of the non-perfused volume from contrast-enhanced T1-weighted images. However, the vascular status of tissue surrounding the non-perfused volume has not been extensively investigated with MRI. In this study, cluster analysis of the transfer constant K(trans) and extravascular extracellular volume fraction ve , derived from dynamic contrast-enhanced MRI (DCE-MRI) data, was performed in tumor tissue surrounding the non-perfused volume to identify tumor subregions with distinct contrast agent uptake kinetics. DCE-MRI was performed in CT26.WT colon carcinoma-bearing BALB/c mice before (n = 12), directly after (n = 12) and 3 days after (n = 6) partial tumor treatment with HIFU. In addition, a non-treated control group (n = 6) was included. The non-perfused volume was identified based on the level of contrast enhancement. Quantitative comparison between non-perfused tumor fractions and non-viable tumor fractions derived from NADH-diaphorase histology showed a stronger agreement between these fractions 3 days after treatment (R(2) to line of identity = 0.91) compared with directly after treatment (R(2) = 0.74). Next, k-means clustering with four clusters was applied to K(trans) and ve parameter values of all significantly enhanced pixels. The fraction of pixels within two clusters, characterized by a low K(trans) and either a low or high ve , significantly increased after HIFU. Changes in composition of these clusters were considered to be HIFU induced. Qualitative H&E histology showed that HIFU-induced alterations in these clusters may be associated with hemorrhage and structural tissue disruption. Combined microvasculature and hypoxia staining suggested that these tissue changes may affect blood vessel functionality and thereby tumor oxygenation. In conclusion, it was demonstrated that, in addition to assessment of the non-perfused tumor volume, the presented methodology gives further insight into HIFU-induced effects on tumor vascular status. This method may aid in assessment of the consequences of vascular alterations for the fate of the tissue.
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Igor
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.|Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Stefanie J C G
authors.initials: SJ
authors.lastname: Hectors
authors.affiliation: Imaging Research Center, Oregon Health and Science University, Portland, OR, USA.|Utah Center for Advanced Imaging Research, University of Utah, Salt Lake City, UT, USA.
authors.forename: Matthias C
authors.initials: MC
authors.lastname: Schabel
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.|Oncology solutions, Philips Research, Eindhoven, The Netherlands.
authors.forename: Holger
authors.initials: H
authors.lastname: Grüll
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.|Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.affiliation: Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007700:Kinetics; D008536:Meglumine / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; C072417:gadoterate meglumine
keywords: cancer treatment response; cluster analysis; dynamic contrast-enhanced MRI; high intensity focused ultrasound