Morphological, functional, and molecular assessment of breast cancer bone metastases by experimental ultrasound techniques compared with magnetic resonance imaging and histological analysis.
Animal model
Bone metastases
Imaging
Magnetic resonance imaging
Microbubbles
Ultrasound
Journal
Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
24
04
2020
revised:
11
12
2020
accepted:
14
12
2020
pubmed:
22
12
2020
medline:
6
7
2021
entrez:
21
12
2020
Statut:
ppublish
Résumé
The imaging of bone metastases, which is regularly performed by cross-sectional modalities, is clinically vital when characterizing and staging osseous lesions. In this paper, we aimed to establish a novel methodology using experimental ultrasound (US) techniques to assess the morphological, functional, and molecular features of breast cancer bone metastases in an animal model, compared with magnetic resonance imaging (MRI) and histological analysis. Nude rats were implanted intra-arterially with MDA-MB-231 breast cancer cells to induce osteolytic metastasis in their right hind legs. Once tumors had developed, an experimental US technique using automatic 3D scanning and MRI were performed. For assessment of perfusion, functional imaging techniques included contrast-enhanced US (CEUS) and dynamic contrast-enhanced MRI (DCE-MRI). For molecular ultrasound, anti-VEGFR2 conjugated microbubbles were applied and correlated with immunostaining for VEGFR2 expression. 3D US enabled the automatic assessment of osteolytic lesions, including the largest tumor diameters along the x-, y- and z-axes as well as the segmented tumor volumes, without significant differences between US and MRI (p > 0.18). The CEUS and DCE-MRI of osseous lesions showed corresponding results for the parameters peak enhancement, wash-in area under the curve (both, r > 0.5) and wash-in perfusion index (r > 0.3) when differentiating between tumor, necrotic tissue and healthy muscle tissue (all, p < 0.01). Finally, molecular US allowed the non-invasive assessment of increased VEGFR2 expression in skeletal lesions compared with surrounding muscle tissue (p = 0.03), while a control antibody could not discriminate between these tissues (p = 0.44)-a factor which was confirmed by histological analysis. To the best of our knowledge, this is the first report on an imaging protocol for breast cancer bone metastasis using an experimental US scanner. Therefore, we present a novel methodology to characterize these osseous lesions on the morphological, functional, and molecular level in correlation with MRI and histological analysis.
Sections du résumé
BACKGROUND
The imaging of bone metastases, which is regularly performed by cross-sectional modalities, is clinically vital when characterizing and staging osseous lesions. In this paper, we aimed to establish a novel methodology using experimental ultrasound (US) techniques to assess the morphological, functional, and molecular features of breast cancer bone metastases in an animal model, compared with magnetic resonance imaging (MRI) and histological analysis.
MATERIALS AND METHODS
Nude rats were implanted intra-arterially with MDA-MB-231 breast cancer cells to induce osteolytic metastasis in their right hind legs. Once tumors had developed, an experimental US technique using automatic 3D scanning and MRI were performed. For assessment of perfusion, functional imaging techniques included contrast-enhanced US (CEUS) and dynamic contrast-enhanced MRI (DCE-MRI). For molecular ultrasound, anti-VEGFR2 conjugated microbubbles were applied and correlated with immunostaining for VEGFR2 expression.
RESULTS
3D US enabled the automatic assessment of osteolytic lesions, including the largest tumor diameters along the x-, y- and z-axes as well as the segmented tumor volumes, without significant differences between US and MRI (p > 0.18). The CEUS and DCE-MRI of osseous lesions showed corresponding results for the parameters peak enhancement, wash-in area under the curve (both, r > 0.5) and wash-in perfusion index (r > 0.3) when differentiating between tumor, necrotic tissue and healthy muscle tissue (all, p < 0.01). Finally, molecular US allowed the non-invasive assessment of increased VEGFR2 expression in skeletal lesions compared with surrounding muscle tissue (p = 0.03), while a control antibody could not discriminate between these tissues (p = 0.44)-a factor which was confirmed by histological analysis.
CONCLUSION
To the best of our knowledge, this is the first report on an imaging protocol for breast cancer bone metastasis using an experimental US scanner. Therefore, we present a novel methodology to characterize these osseous lesions on the morphological, functional, and molecular level in correlation with MRI and histological analysis.
Identifiants
pubmed: 33348127
pii: S8756-3282(20)30609-8
doi: 10.1016/j.bone.2020.115821
pii:
doi:
Substances chimiques
Contrast Media
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115821Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.