Radiosurgery inhibits tumor softening in glioma mouse model:first findings from in vivo elastography
PD-0819
Abstract
Radiosurgery inhibits tumor softening in glioma mouse model:first findings from in vivo elastography
Authors: Güliz Acker1,2,3, Anastasia Janas1, Gregor Bertalan4, Anne Kluge2,5, Ingolf Sack4, Daniel Zips2, Peter Vajkoczy1, Carolin Senger2,6
1Charité - Universitätsmedizin Berlin, Department of Neurosurgery, Berlin, Germany; 2Charité - Universitätsmedizin Berlin, Department of Radiation Oncology, Berlin, Germany; 3Berlin Institute of Health, Clinician Scientist Program, Berlin, Germany; 4Charité - Universitätsmedizin Berlin, Department of Radiology, Berlin, Germany; 5Charité - Universitätsmedizin Berlin, Cyberknife Center, Berlin, Germany; 6Charité - Universitätsmedizin Berlin, CyberKnife Center, Berlin, Germany
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Purpose or Objective
CyberKnife stereotactic radiosurgery (CK-SRS) precisely delivers high irradiation doses to intracranial tumors. The underlying radiobiology is however not fully understood. Furthermore, whilst it is known that malignant gliomas present with softer tissue properties than healthy brain tissue, the influence of irradiation on tumor biomechanical properties is still unknown. Therefore, our aim was to (1) validate the recently established tomoelastography modality known as magnetic resonance elastography (MRE) for deployment in tumor bearing mouse brain followed by (2) investigation of the alterations of glioma stiffness after CK-SRS.
Material and Methods
GL261 cells (20.000) were implanted into striatum of C57BL6/N mice (d0). Animals received either 20 (n=24) or 40 Gy (n=25) CK-SRS in a single dose on day 15, non-irradiated GL261 mice served as controls (n=13). MRI investigations were carried out prior (d13) and longitudinally after irradiation (timepoints: d22, d45, d105, d195 after tumor cell implantation) using a 7T MRI scanner. The protocol included T1-weighted imaging with contrast agent followed by multifrequency MRE with mechanical vibrations of 1000, 1200, 1400 Hz generated by a nonmagnetic piezoceramic actuator [1]. 3D wave fields in a coronal view of the mouse brain were acquired using a modified single shot spin echo echo-planar imaging sequence with a sinusoidal motion-encoding gradient and sample interval modulation acquisition strategy [2]. In total eight time points, equally spaced over an oscillation period, were measured to assess the dynamics of the wave field. Total acquisition time per measurement with 11 contiguous slices, three wave field components, 8 wave dynamics, 3 averages and 3 frequencies was 12 min. The calculated shear wave speed (SWS) of generated elastograms served as surrogate for tissue stiffness. For statistical analysis one way Anova with Bonferroni correction was used (significance: p≤0.05).
Results
Mean tumor volume significantly decreased by ≈ 60 to 65% after CK-SRS after 40 and 20 Gy SRS, respectively. Analysis of MRE data in the non-irradiated control group revealed a significant decrease of SWS on d22 compared to d13 indicating increasing softness of the growing tumors. In the irradiated group, the SWS of tumors remained comparable at all investigation timepoints after 20 Gy treatment without significant alterations. In the cohort treated with 40 Gy a significant softening process was observed up to d45 that was followed by tumor stiffening in the long term.
Conclusion
The increasing softness of the non-irradiated tumors is due to the well-known soft tissue properties of malignant gliomas [3-5]. We successfully validated the suitability of tomoelastography of the mouse brain for stiffness mapping within only 12 min per animal. The data obtained indicate that irradiation has an impact on the biomechanics of the tumor. The results are to be further elucidated with other MRI sequences, longer observation period and histological appraisal.
