Abstract
BACKGROUND
Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion.
HYPOTHESIS
Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE).
STUDY TYPE
Experimental, animal model.
ANIMAL MODEL
Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 μL PBS (sham-injected mice).
FIELD STRENGTH/SEQUENCE
2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength).
ASSESSMENT
Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology.
STATISTICAL TESTS
Paired and unpaired t-tests, a P-value ≤0.05 was considered significant.
RESULTS
From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10 mm/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression.
DATA CONCLUSION
MRE is promising for the assessment of key glioma characteristics.
EVIDENCE LEVEL
NA TECHNICAL EFFICACY: Stage 2.