Study Rationale: Parkinson's disease (PD) is a neurodegenerative disease that affects the quality of life of more than one million people in the United States alone. Abnormal brain energy metabolism and mitochondrial dysfunction is associated with Parkinson’s disease, and better imaging methods that are sensitive to such abnormalities will provide effective tools for better understanding the disease and monitoring of treatment response in PD. This project aims to develop an advanced phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) technique to assess brain energetic changes in patients with early-stage PD compared with controls.
Hypothesis: The next-generation 31P MRSI-based molecular imaging tools with optimal sensitivity, adequate resolution, and whole-brain coverage can detect and quantify mitochondrial dysfunction and neuroenergetic impairment in both cortical and subcortical brain regions of Parkinson’s disease patients.
Study Design: First, we will build next-generation molecular imaging tools by integrating advanced hardware and software to achieve unprecedented imaging sensitivity and resolution for the proposed whole-brain 31P-MRSI measurements on an FDA-approved 7 Tesla clinical MRI scanner. Second, we will develop a novel quantification method to obtain metabolite contents and metabolic rates in interested brain regions from 31P MRSI data; the reproducibility of the measurement will then be assessed in the healthy human brain. Finally, we will apply these imaging tools to detect abnormalities in mitochondrial function and energy metabolism in the brain of early-stage PD patients and identify brain regions susceptible to pathophysiological changes.
Impact on Diagnosis/Treatment of Parkinson’s disease: Success of this project will offer new molecular imaging tools capable of visualizing and quantifying altered mitochondrial function and energy metabolism in the brains of PD patients. It has the potential to improve the detection of regional brain metabolic changes in PD and provide sensitive therapeutic biomarkers to monitor treatment effects and guide disease management.
Next Steps for Development: The pilot data obtained from this project will not only verify the utility and fidelity of the proposed molecular imaging tools, but will also provide valuable information for designing larger-scale human studies or clinical trials to test efficacy of new therapies. We will seek federal and/or private funding to support future research in this area.