UCSF

Advances in targeted therapies for patients with glioblastoma require simultaneous advances in noninvasive imaging in order to clinically manage these new treatments. Patients diagnosed with glioblastoma, a highly malignant form of brain cancer, have limited survival. Significant improvements in outcome for these patients will likely rest on both advances in targeted therapies and individualization of treatment regimens.

Standard clinical magnetic resonance imaging (MRI) provides insight into tissue structure and is used as a noninvasive surrogate marker of tumor presence. Physiologic MRI offers insight into tumor tissue physiology including surrogate markers of vascularization, cell density, and metabolic activity. The integration of physiologic imaging into the clinical exam has the opportunity to significantly improve decision making in the care of patients with brain cancer.

This dissertation project investigated dynamic susceptibility contrast (DSC) MRI and diffusion weighted (DWI) MRI as complementary methods for characterizing tumor burden prior to therapy and for assessing response during therapy. Specialized methods for acquiring and post-processing DSC data were developed to be feasible in the clinical setting. Noninvasive surrogate markers of vascular morphology and histopathologic features were identified in de novo GBM. Initial vascularization and changes in permeability within the tumor measured with DSC MRI were found to relate to patient response to antiangiogenic therapy. DWI was used to detect treatment-specific changes in tumor burden in order to further develop biomarkers of response.

The results of this dissertation support integrating physiologic MRI into the clinical exam of patients with glioblastoma. DSC and DWI can provide valuable insight into tumor physiology, which will allow clinicians to better tailor treatments to individual patients and assess response to antiangiogenic therapy.