In vivo characterization of brain tumor biomechanics: magnetic resonance elastography in intracranial B16 melanoma and GL261 glioma mouse models

脑肿瘤生物力学的体内表征:颅内 B16 黑色素瘤和 GL261 胶质瘤小鼠模型中的磁共振弹性成像

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作者:Anastasia Janas #, Jakob Jordan #, Gergely Bertalan, Tom Meyer, Jan Bukatz, Ingolf Sack, Carolin Senger, Melina Nieminen-Kelhä, Susan Brandenburg, Irina Kremenskaia, Kiril Krantchev, Sanaria Al-Rubaiey, Susanne Mueller, Stefan Paul Koch, Philipp Boehm-Sturm, Rolf Reiter, Daniel Zips, Peter Vajkoczy,

Discussion

Our results indicate that while both, MBM and GBM, exhibited softer properties compared to healthy brain, imaging and histological analysis revealed different underlying microstructural causes: hemorrhages in MBM and increased vascularization and glycosaminoglycan content in GBM, further corroborated by DWI and T2/T2* contrast. These findings underscore the complementary nature of MRE and its potential to enhance our understanding of tumor characteristics when used alongside established techniques. This comprehensive approach could lead to improved clinical outcomes and a deeper understanding of brain tumor pathophysiology.

Methods

Intracranial B16 MBM (n = 6) and GL261 GBM (n = 7) mouse models were used. Magnetic Resonance Imaging (MRI) was performed at set intervals after tumor implantation: 5, 7, 12, 14 days for MBM and 13 and 22 days for GBM. The investigations were performed using a 7T preclinical MRI with 20 mm head coil. The protocol consisted of single-shot spin echo-planar multifrequency MRE with tomoelastography post processing, contrast-enhanced T1- and T2-weighted imaging and diffusion-weighted imaging (DWI) with quantification of apparent diffusion coefficient of water (ADC). Elastography quantified shear wave speed (SWS), magnitude of complex MR signal (T2/T2*) and loss angle (φ). Immunohistological investigations were performed to assess vascularization, blood-brain-barrier integrity and extent of glucosaminoglucan coverage.

Results

Volumetric analyses displayed rapid growth of both tumor entities and softer tissue properties than healthy brain (healthy: 5.17 ± 0.48, MBM: 3.83 ± 0.55, GBM: 3.7 ± 0.23, [m/s]). SWS of MBM remained unchanged throughout tumor progression with decreased T2/T2* intensity and increased ADC on days 12 and 14 (p<0.0001 for both). Conversely, GBM presented reduced φ values on day 22 (p=0.0237), with no significant alterations in ADC. Histological analysis revealed substantial vascularization and elevated glycosaminoglycan content in both tumor types compared to healthy contralateral brain.

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