title: Quantification of viable tumor microvascular characteristics by multispectral analysis.
abstract: Tumor heterogeneity complicates the quantification of tumor microvascular characteristics assessed by dynamic contrast-enhanced MRI (DCE-MRI). To address this issue a novel approach was developed that combines DCE-MRI with diffusion-based multispectral (MS) analysis to quantify the microvascular characteristics of specific tumor tissue populations. Diffusion-based MS segmentation (feature space: apparent diffusion coefficient, T(2) and proton density) was performed to identify tumor tissue populations and the DCE-MRI characteristics were determined for each tissue class. The ability of this MS DCE-MRI technique to detect microvascular changes due to treatment with an antibody (G6-31) to vascular endothelial growth factor-A (VEGF) was evaluated in a tumor xenograft mouse model. Anti-VEGF treatment resulted in a significant reduction in K(trans) for the MS viable tumor tissue class (-0.0034 +/- 0.0022 min(-1), P < 0.01) at 24 hr posttreatment that differ significantly from the change observed in the control group (0.0002 +/- 0.0025 min(-1)). Viable tumor K(trans) for the anti-VEGF group was also reduced 62% relative to the pretreatment values (P < 0.01). Necrotic tissue classes were found to add only noise to DCE-MRI estimates. This approach provides a means to measure physiological parameters within the viable tumor and address the issue of tumor heterogeneity that complicates DCE-MRI analysis.
authors.affiliation: Department of Translational Oncology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Leanne R
authors.initials: LR
authors.lastname: Berry
authors.forename: Kai H
authors.initials: KH
authors.lastname: Barck
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Go
authors.forename: Jed
authors.initials: J
authors.lastname: Ross
authors.forename: Xiumin
authors.initials: X
authors.lastname: Wu
authors.forename: Simon P
authors.initials: SP
authors.lastname: Williams
authors.forename: Alvin
authors.initials: A
authors.lastname: Gogineni
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Cole
authors.forename: Nicholas
authors.initials: N
authors.lastname: Van Bruggen
authors.forename: Germaine
authors.initials: G
authors.lastname: Fuh
authors.forename: Frank
authors.initials: F
authors.lastname: Peale
authors.forename: Napoleone
authors.initials: N
authors.lastname: Ferrara
authors.forename: Sarajane
authors.initials: S
authors.lastname: Ross
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Schwall
authors.forename: Richard A D
authors.initials: RA
authors.lastname: Carano
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D005260:Female; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation / Q000033:anatomy & histology; D009374:Neoplasms, Experimental / Q000098:blood supply*; D014022:Tissue Survival; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D000906:Antibodies; D042461:Vascular Endothelial Growth Factor A