title: Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging.
abstract: Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non-invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB-neuT mice). Histological examination showed that BALB-neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE-MRI results highlighted marked functional changes in terms of vessel permeability (K(trans) , volume transfer constant) and vascularisation (vp , vascular volume fraction) in BALB-neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE-MRI biomarkers was observed in BALB-neuT in comparison to BALB/c mice (K(trans)  = 5.3 ± 0.7E-4 and 3.1 ± 0.5E-4; vp  = 7.4 ± 0.8E-2 and 4.7 ± 0.6E-2 for BALB-neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE-MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE-MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Consolino
authors.affiliation: (CNR) c/o Molecular Biotechnologies Center, Istituto di Biostrutture e Bioimmagini, via Nizza 52, Torino, 10126, Italy.|Molecular Imaging Center, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Dario Livio
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.|Molecular Imaging Center, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Dastrù
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Cutrin
authors.affiliation: Human Genetics Foundation (HuGeF), via Nizza 52, Torino, 10126, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Dettori
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.affiliation: Human Genetics Foundation (HuGeF), via Nizza 52, Torino, 10126, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oliviero
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino, 10126, Italy.|Molecular Imaging Center, University of Torino, via Nizza 52, Torino, 10126, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*
chemical_list: D003287:Contrast Media
keywords: DCE-MRI; angiogenesis; angiogenic switch; breast cancer; gadolinium-based contrast agents