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Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer
OBJECTIVE: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) ap...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667047/ https://www.ncbi.nlm.nih.gov/pubmed/36408159 http://dx.doi.org/10.3389/fonc.2022.1000036 |
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author | Gerwing, Mirjam Hoffmann, Emily Kronenberg, Katharina Hansen, Uwe Masthoff, Max Helfen, Anne Geyer, Christiane Wachsmuth, Lydia Höltke, Carsten Maus, Bastian Hoerr, Verena Krähling, Tobias Hiddeßen, Lena Heindel, Walter Karst, Uwe Kimm, Melanie A. Schinner, Regina Eisenblätter, Michel Faber, Cornelius Wildgruber, Moritz |
author_facet | Gerwing, Mirjam Hoffmann, Emily Kronenberg, Katharina Hansen, Uwe Masthoff, Max Helfen, Anne Geyer, Christiane Wachsmuth, Lydia Höltke, Carsten Maus, Bastian Hoerr, Verena Krähling, Tobias Hiddeßen, Lena Heindel, Walter Karst, Uwe Kimm, Melanie A. Schinner, Regina Eisenblätter, Michel Faber, Cornelius Wildgruber, Moritz |
author_sort | Gerwing, Mirjam |
collection | PubMed |
description | OBJECTIVE: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach. METHODS: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy. RESULTS: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher K(trans) values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower K(trans) values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90(th) percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models. CONCLUSIONS: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time. |
format | Online Article Text |
id | pubmed-9667047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96670472022-11-17 Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer Gerwing, Mirjam Hoffmann, Emily Kronenberg, Katharina Hansen, Uwe Masthoff, Max Helfen, Anne Geyer, Christiane Wachsmuth, Lydia Höltke, Carsten Maus, Bastian Hoerr, Verena Krähling, Tobias Hiddeßen, Lena Heindel, Walter Karst, Uwe Kimm, Melanie A. Schinner, Regina Eisenblätter, Michel Faber, Cornelius Wildgruber, Moritz Front Oncol Oncology OBJECTIVE: The objective of this study was to non-invasively differentiate the degree of malignancy in two murine breast cancer models based on identification of distinct tissue characteristics in a metastatic and non-metastatic tumor model using a multiparametric Magnetic Resonance Imaging (MRI) approach. METHODS: The highly metastatic 4T1 breast cancer model was compared to the non-metastatic 67NR model. Imaging was conducted on a 9.4 T small animal MRI. The protocol was used to characterize tumors regarding their structural composition, including heterogeneity, intratumoral edema and hemorrhage, as well as endothelial permeability using apparent diffusion coefficient (ADC), T1/T2 mapping and dynamic contrast-enhanced (DCE) imaging. Mice were assessed on either day three, six or nine, with an i.v. injection of the albumin-binding contrast agent gadofosveset. Ex vivo validation of the results was performed with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), histology, immunhistochemistry and electron microscopy. RESULTS: Significant differences in tumor composition were observed over time and between 4T1 and 67NR tumors. 4T1 tumors showed distorted blood vessels with a thin endothelial layer, resulting in a slower increase in signal intensity after injection of the contrast agent. Higher permeability was further reflected in higher K(trans) values, with consecutive retention of gadolinium in the tumor interstitium visible in MRI. 67NR tumors exhibited blood vessels with a thicker and more intact endothelial layer, resulting in higher peak enhancement, as well as higher maximum slope and area under the curve, but also a visible wash-out of the contrast agent and thus lower K(trans) values. A decreasing accumulation of gadolinium during tumor progression was also visible in both models in LA-ICP-MS. Tissue composition of 4T1 tumors was more heterogeneous, with intratumoral hemorrhage and necrosis and corresponding higher T1 and T2 relaxation times, while 67NR tumors mainly consisted of densely packed tumor cells. Histogram analysis of ADC showed higher values of mean ADC, histogram kurtosis, range and the 90(th) percentile (p90), as markers for the heterogenous structural composition of 4T1 tumors. Principal component analysis (PCA) discriminated well between the two tumor models. CONCLUSIONS: Multiparametric MRI as presented in this study enables for the estimation of malignant potential in the two studied tumor models via the assessment of certain tumor features over time. Frontiers Media S.A. 2022-11-02 /pmc/articles/PMC9667047/ /pubmed/36408159 http://dx.doi.org/10.3389/fonc.2022.1000036 Text en Copyright © 2022 Gerwing, Hoffmann, Kronenberg, Hansen, Masthoff, Helfen, Geyer, Wachsmuth, Höltke, Maus, Hoerr, Krähling, Hiddeßen, Heindel, Karst, Kimm, Schinner, Eisenblätter, Faber and Wildgruber https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Gerwing, Mirjam Hoffmann, Emily Kronenberg, Katharina Hansen, Uwe Masthoff, Max Helfen, Anne Geyer, Christiane Wachsmuth, Lydia Höltke, Carsten Maus, Bastian Hoerr, Verena Krähling, Tobias Hiddeßen, Lena Heindel, Walter Karst, Uwe Kimm, Melanie A. Schinner, Regina Eisenblätter, Michel Faber, Cornelius Wildgruber, Moritz Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title | Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title_full | Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title_fullStr | Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title_full_unstemmed | Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title_short | Multiparametric MRI enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
title_sort | multiparametric mri enables for differentiation of different degrees of malignancy in two murine models of breast cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9667047/ https://www.ncbi.nlm.nih.gov/pubmed/36408159 http://dx.doi.org/10.3389/fonc.2022.1000036 |
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