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...

Verfasser: 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 Alexandra
Schinner, Regina
Eisenblätter, Michel
Faber, Cornelius
Wildgruber, Moritz
FB/Einrichtung:FB 12: Chemie und Pharmazie
FB 05: Medizinische Fakultät
Dokumenttypen:Artikel
Medientypen:Text
Erscheinungsdatum:2022
Publikation in MIAMI:21.06.2023
Datum der letzten Änderung:21.06.2023
Angaben zur Ausgabe:[Electronic ed.]
Quelle:Frontiers in Oncology 12 (2022), 1000036, 1-17
Schlagwörter:oncologic imaging; tumor heterogeneity; tumor vasculature; MRI; LA-ICP-MS
Fachgebiet (DDC):610: Medizin und Gesundheit
Lizenz:CC BY 4.0
Sprache:English
Förderung:Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Förderer: Deutsche Forschungsgemeinschaft / Projektnummer: 446302350
Format:PDF-Dokument
URN:urn:nbn:de:hbz:6-89998685287
Weitere Identifikatoren:DOI: 10.17879/40009675254
Permalink:https://nbn-resolving.de/urn:nbn:de:hbz:6-89998685287
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Onlinezugriff:10.3389_fonc.2022.1000036.pdf

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 Ktrans 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 Ktrans 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 90th 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.