BME PhD Defense: Anitha Priya Krishnan

Predicting the Microscopic Spread of Glioma Using a Random Walk Model Based on Diffusion Tensor Imaging

Supervised by Professor Walter O'Dell

Abstract

Current methods of determining the treatment margin for Stereotactic Radiotherapy (SRT) and Stereotactic Radiosurgery (SRS) of glioma patients are inadequate as recurrences/secondary tumors often occur at or near the boundary of the treatment margin. To account for the microscopic spread of disease, radiation oncologists usually include a 2-3 cm isotropic margin for SRT of gliomas. This margin is unnecessarily large in certain directions where no microscopic spread is present, causing significant damage to normal brain tissue and loss of cognitive function. The margin is often too small in some directions where microscopic cancer spread is present leading to recurrences.

My hypothesis is that paths of elevated water diffusion, particularly along white matter tracts, provide a preferred and expedited route for migration of tumor cells. By performing tractography through the primary tumor using Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) data sets obtained retrospectively in glioma patients, we have shown that there exists a high qualitative correlation between the location of the secondary tumor and the fibers passing through the primary tumor. We developed a random walk model of tumor cell migration, seeded from the surface of the primary tumor and constrained by the local diffusion environment where the DTI data sets were obtained as a part of both prospective and retrospective clinical studies.

The areas of higher cell concentration predicted by our model foretold the possible areas of recurrence and were confirmed using follow-up magnetic resonance images. If my hypothesis is true then future SRT treatment margins would be modified to increase the margin along areas of high cell concentration predicted by the model and decrease the margin in low-risk directions to improve patient outcomes.