Magnetic Resonance Elastography reveals effects of anti-angiogenic glioblastoma treatment on tumor stiffness and captures progression in an orthotopic mouse model

Autor: Ralph Sinkus, Rachel Zane, Navid Nazari, Miklos Palotai, Sean E. Lawler, Samuel Patz, Katharina Schregel, Michał Nowicki
Přispěvatelé: Harvard Medical School [Boston] (HMS), Boston University [Boston] (BU), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2019
Předmět:
Vascular Endothelial Growth Factor A
Pathology
Necrosis
[SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging
Angiogenesis Inhibitors
030218 nuclear medicine & medical imaging
Myelin
Mice
0302 clinical medicine
Anti-angiogenic treatment
Edema
Radiological and Ultrasound Technology
medicine.diagnostic_test
Brain Neoplasms
Anti-VEGF antibody
[SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph]
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Magnetic Resonance Imaging
3. Good health
medicine.anatomical_structure
Oncology
Tumor stiffness
Elasticity Imaging Techniques
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Female
medicine.symptom
Research Article
lcsh:Medical physics. Medical radiology. Nuclear medicine
medicine.medical_specialty
lcsh:R895-920
Mice
Nude
[SDV.CAN]Life Sciences [q-bio]/Cancer
lcsh:RC254-282
Antibodies
03 medical and health sciences
medicine
Animals
Radiology
Nuclear Medicine and imaging
business.industry
Anti angiogenic
Magnetic resonance imaging
medicine.disease
Magnetic resonance elastography
Histopathology
business
Glioblastoma
030217 neurology & neurosurgery
Zdroj: Cancer Imaging
Cancer Imaging, Vol 20, Iss 1, Pp 1-16 (2020)
Cancer Imaging, BMC, 2020, 20, pp.35. ⟨10.1186/s40644-020-00314-1⟩
Cancer Imaging, BMC, 2020, 20 (1), ⟨10.1186/s40644-020-00314-1⟩
ISSN: 1470-7330
1740-5025
DOI: 10.1186/s40644-020-00314-1⟩
Popis: Background Anti-angiogenic treatment of glioblastoma (GBM) complicates radiologic monitoring. We evaluated magnetic resonance elastography (MRE) as an imaging tool for monitoring the efficacy of anti-VEGF treatment of GBM. Methods Longitudinal studies were performed in an orthotopic GBM xenograft mouse model. Animals treated with B20 anti-VEGF antibody were compared to untreated controls regarding survival (n = 13), classical MRI-contrasts and biomechanics as quantified via MRE (n = 15). Imaging was performed on a 7 T small animal horizontal bore MRI scanner. MRI and MRE parameters were compared to histopathology. Results Anti-VEGF-treated animals survived longer than untreated controls (p = 0.0011) with progressively increased tumor volume in controls (p = 0.0001). MRE parameters viscoelasticity |G*| and phase angle Y significantly decreased in controls (p = 0.02 for |G*| and p = 0.0071 for Y). This indicates that untreated tumors became softer and more elastic than viscous with progression. Tumor volume in treated animals increased more slowly than in controls, indicating efficacy of the therapy, reaching significance only at the last time point (p = 0.02). Viscoelasticity and phase angle Y tended to decrease throughout therapy, similar as for control animals. However, in treated animals, the decrease in phase angle Y was significantly attenuated and reached statistical significance at the last time point (p = 0.04). Histopathologically, control tumors were larger and more heterogeneous than treated tumors. Vasculature was normalized in treated tumors compared with controls, which showed abnormal vasculature and necrosis. In treated tumors, a higher amount of myelin was observed within the tumor area (p = 0.03), likely due to increased tumor invasion. Stiffness of the contralateral hemisphere was influenced by tumor mass effect and edema. Conclusions Anti-angiogenic GBM treatment prolonged animal survival, slowed tumor growth and softening, but did not prevent progression. MRE detected treatment effects on tumor stiffness; the decrease of viscoelasticity and phase angle in GBM was attenuated in treated animals, which might be explained by normalized vasculature and greater myelin preservation within treated tumors. Thus, further investigation of MRE is warranted to understand the potential for MRE in monitoring treatment in GBM patients by complementing existing MRI techniques.
Databáze: OpenAIRE
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