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Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging
Author(s) -
Consolino Lorena,
Longo Dario Livio,
Dastrù Walter,
Cutrin Juan Carlos,
Dettori Daniela,
Lanzardo Stefania,
Oliviero Salvatore,
Cavallo Federica,
Aime Silvio
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30073
Subject(s) - magnetic resonance imaging , hyperplasia , pathology , breast cancer , dynamic contrast enhanced mri , medicine , neovascularization , cancer , microvessel , angiogenesis , cancer research , immunohistochemistry , radiology
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 ( v p , 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; v p = 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.