title: Correlative dynamic contrast MRI and microscopic assessments of tumor vascularity in RIP-Tag2 transgenic mice.
abstract: The purpose of this study was to define the feasibility of dynamic contrast-enhanced magnetic resonance imaging (MRI) to estimate the vascular density and leakiness of spontaneous islet cell tumors in RIP-Tag2 transgenic mice. Dynamic T(1)-weighted spoiled gradient echo (SPGR) imaging at 2.0 T was performed in 17 RIP-Tag2 mice using a prototype blood pool macromolecular contrast medium (MMCM), albumin-(Gd-DTPA)(35). Kinetic analysis of the dynamic enhancement responses based on a two-compartment model was used to estimate fractional plasma volume (fPV) and the coefficient of endothelial permeability (K(PS)) for each tumor. The MRI estimate of fPV was correlated on a tumor-by-tumor basis with corresponding microscopic measurements of vascular density. The fPV assays by MMCM-enhanced imaging ranged from 2.4%-14.1% of tissue volume. Individual tumor fPV values correlated significantly (r = 0.79, P < 0.001) with the corresponding microscopic estimates of vascularity consisting of the combined area densities of lectin-perfused microvessels plus erythrocyte-stained blood lakes. A biotinylated derivative of the albumin-based MMCM confirmed extravasation of the contrast agent from some tumor blood vessels and accumulation in 25% of blood lakes. The K(PS) values ranged from 0 (no detectable leak) to 0.356 mL/min/100 cm(3). Dynamic MMCM-enhanced MRI is feasible in RIP-Tag2 pancreatic tumors, yielding estimates of vascular permeability and microscopically validated measurements of vascular richness.
authors.affiliation: Department of Cardiovascular Research Institute, Comprehensive Cancer Center, University of California, San Francisco, California, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sennino
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Raatschen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Wendland
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Fu
authors.forename: Weon-Kyoo
authors.initials: WK
authors.lastname: You
authors.forename: David M
authors.initials: DM
authors.lastname: Shames
authors.forename: Donald M
authors.initials: DM
authors.lastname: McDonald
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brasch
mesh_terms: D000418:Albumins; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005240:Feasibility Studies; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000473:pathology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics; D013223:Statistics as Topic
chemical_list: D000418:Albumins; D003287:Contrast Media; C058946:albumin-(gadolinium-DTPA); D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D019786:Gadolinium DTPA