Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Quantifying changes in glioma biology with treatment using modeling of edema formation and clinical imaging
Kristin R. Swanson

Last modified: 2014-06-09


Glioblastoma, the most aggressive form of primary brain tumor, is predominantly assessed
with gadolinium‐enhancedT1‐weighted (T1Gd) and T2‐weighted magnetic resonance
imaging (MRI). Pixel intensity enhancement on the T1Gd image corresponds to the contrast
agent leaking from the tumor‐induced neovasculature, while hyperintensity on theT2/FLAIR
images represents a mix of edema and infiltrated tumor cells. None of these modalities
directly show tumor cells; rather, they capture abnormalities in the microenvironment
caused by the presence of tumor cells. Thus, clinical assessment of disease response after
treatments impacting the microenvironment remains challenging through the obscuring lens
of MR imaging. Anti‐angiogenic therapies have been used in the treatment of gliomas with
spurious results ranging from no apparent response to significant imaging improvement with
the potential for extremely diffuse patterns of tumor recurrence on imaging and autopsy.
Anti‐angiogenic treatment normalizes the vasculature, effectively decreasing vessel
permeability and thus reducing tumor‐induced edema, drastically altering T2‐weighted MRI.
We extend a previously developed mathematical model of glioma growth to explicitly
incorporate edema formation allowing us to directly characterize and potentially predict the
effects of anti‐angiogenics on imageable tumor growth. A comparison of simulated glioma
growth and imaging enhancement with and without bevacizumab supports the current
understanding that anti‐angiogenic treatment can serve as a surrogate for steroids and the
clinically driven hypothesis that anti‐angiogenic treatment may not have any significant
effect on the growth dynamics of the overall tumor cell populations. However, the
simulations do illustrate a potentially large impact on the level of edematous extracellular
fluid, and thus on what would be imageable on T2/FLAIR MR. Additionally, by evaluating
virtual tumors with varying growth kinetics, we see tumors with lower proliferation rates will
have the most reduction in swelling from such treatments.