Predicting the microscopic spread of glioma using a random walk model based on diffusion tensor imaging

Current methods of determining the treatment margin for Stereotactic Radiotherapy (SRT) 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 tumor cells migrate preferentially along white matter tracts, determined non-invasively using Magnetic Resonance Diffusion Tensor Imaging (MR-DTI). By performing tractography through the primary tumor using MR-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 fiber architecture determined using DTI data sets obtained as a part of both prospective and retrospective clinical studies. The areas of higher flux of tumor cells determined by the model were coincident with the direction/location of recurrences and/or secondary tumors. If my hypothesis is true then future SRT treatment margins would be modified to increase the margin along areas of higher flux of tumor cells determined by the model and decrease the margin in low-risk directions to improve patient outcomes.