UCLA

Magnetic resonance imaging (MRI) is a valuable tool for the clinical management and scientific investigation of patients diagnosed with brain tumors. Continued efforts in brain tumor imaging research are critical because of the ever-evolving landscape of MRI technological advancements and new insights into brain tumor biology. For example, while historically, tumor tissue diagnoses relied on histopathological features, today, tumor molecular genetic features are the foundational component of tumor classification and patient management. Isocitrate dehydrogenase (IDH)-mutant gliomas are a specific brain tumor molecular subtype that particularly impact younger adults and remain incurable. Within IDH-mutant gliomas, there are also now molecularly defined IDH-mutant astrocytomas (1p/19q intact) and IDH-mutant oligodendrogliomas (1p/19q-codeleted). Although IDH-mutant gliomas often present as indolent, low-grade tumors, these tumors eventually become more aggressive in a process clinically described as “malignant transformation” into high-grade tumors, which are more resistant to therapy and have worse prognosis. This dissertation focuses on developing novel MRI tools to characterize molecular subtypes of IDH-mutant gliomas and malignant transformation. Specifically, this dissertation introduces four new tools for IDH-mutant glioma imaging research and clinical care: (1) optimal normal appearing white matter-normalization for diffusion and perfusion MRI analyses, (2) T2-FLAIR subtraction maps for quantitative T2-FLAIR mismatch analyses, (3) pseudo-resting-state functional MRI for functional connectivity analyses using DSC perfusion MRI (provisional patent filed), and (4) digital flipbooks of patient MRI scans to visually assess brain tumors. This dissertation utilized these tools to study IDH-mutant gliomas, particularly focusing on classifying glioma molecular subtypes, assessing cognitive impairment in patients, characterizing IDH inhibitor targeted therapy treatment response, and identifying IDH-mutant glioma tumor progression, including malignant transformation.