Multimodality Neuroimaging Evaluation of Cognitive Functioning in Lower Grade Astrocytoma

PROJECT SUMMARY Survival outcomes for patients with lower grade gliomas continue to improve as diagnosis and treatment evolve. However, damage caused by tumor growth and by the consequences of treatment often leads to significantly impaired cognitive function. Our previous work has demonstrated that radiation therapy reduced ratios of N-acetyl-aspartate (a neuronal biomarker) levels to creatine derive from proton-1 MR spectroscopic imaging within the normal-appearing white matter. This steady state metabolic imaging also provides other metabolic parameters to differentiate tumor cells from normal brain, detect the presentence of IDH mutation and predict survival in lower grade glioma. In addition, stable and treatment-free lower grade glioma had impaired cognition and quality of life, with the severity associated with the history of treatment and the volume of T2 lesions. These results suggest that the use of multiparametric MRI could improve tumor delineation, identify patients at risk for specific deficits and provide an opportunity for intervention. The objective of this translational proposal is to utilize a novel multimodality MR protocol, which integrates dynamic and steady state MR metabolic imaging with diffusion, perfusion, and resting-state functional MRI to provide quantitative metrics on dynamic and steady-state metabolism, white matter integrity, blood volume, and functional networks, to evaluate cognitive functioning and quality of life in patients with lower grade astrocytoma. We will take advantage of our unique experience in proton-1 MR spectroscopic imaging, which has been implemented into routine clinical examinations, and hyperpolarized carbon-13 pyruvate imaging, where we performed the first-in-human [2-13C]pyruvate study to image real-time glycolysis and oxidative metabolism simultaneously, to assess tumor burden, cognitive functioning, and quality of life. Once the multimodality MR protocol has been established in Aim 1, we will evaluate the normal and abnormal brain changes during radiation therapy and then correlate these changes to impairments in cognitive functioning and quality of life in Aim 2. Aim 3 will examine signatures associated with recurrent tumors and evaluate the impact of tumor burden on cognition and quality of life. The results of the proposed study will be critical for assessing response to treatment, developing effective treatment strategies, and improving quality of life. Ultimately, it will provide effective clinical management of patients and aid neuro-oncologists in making timely decisions.