Glioblastoma multiforme (GBM) has a poor prognosis in spite of advanced MRI guided treatments today. Routine MRI using conventional T1 or advanced permeability based MRI of GBM often does not adequately represent changing tumor phases or overall survival. In this work, region of interest (ROI) based tissue MR standard deviation (SD) is demonstrated as an important MRI variable that could be a potential biomarker of GBM heterogeneity and radioresistance.
Materials and methods
MRI characterization is often qualitative and lacks reproducibility. Using standardized MRI phantoms we have normalized retrospective records of 12 radioresistant GBM patients that underwent radiation therapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy followed by serial MR imaging with gadolinium contrast.
Results and discussion
We have identified key variables like hardware, software and protocol variation and have standardized those using test phantoms at five MR systems. We suggest GBM growth during the treatment period can be linked to normalized MRI signal and its fluctuations from session to session and from magnet to magnet by using an ROI derived standard deviation that corresponds to heterogeneity of the tumor MRI signal and changes in magnetic susceptibility. The time period observed in our patient group for peak standard deviations is approximately halfway through the tumor course and may correspond to a growth of more aggressive MES subtype of cells. To model the GBM heterogeneity we performed in vitro T1 weighted inversion recovery MRI experiments at 3 T for porous media of silicate particles in 1% aq solution of Gadavist and linked SD with particle size and local gadolinium volume within porous media. Such in vitro models mimic the increased SD in radioresistant GBM and as a novel contribution suggest that finer texture with high surface area might arise approximately halfway through the overall survival duration in GBM.
Standard deviation as a measure of magnetic susceptibility may be collectively linked to the changes in texture, cell fractions (biological) and trapped contrast media (vascular as well as artifactual consequences) and should be evaluated as a potential biomarker of GBM aggressiveness than the overall MRI signal intensity from a GBM.