Parkinsonism as Model to Detect Neurodegeneration using High Field MRI

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. Although the exact cause of PD is still unknown, there is increasing evidence that exposure to environmental toxins that can include nerve agents, pesticides, and herbicides as well as traumatic brain injury, can play a major role in the pathophysiology of PD. Military personnel deployed in times of war are at increased risk for exposure to environmental toxins and head trauma, resulting in an increased risk for the later development of PD. While there is currently no cure for the disease, new medications are being developed that may slow disease progression. As new drugs become available, it will be important to recognize and diagnose PD as early as possible when pharmacologic interventions are likely most effective. Currently, the accurate diagnosis of PD, especially early in the course of the disease, can be difficult. The main goal of this project is to accurately diagnose PD with the use of two novel MRI methods: 1) susceptibility weighted imaging (SWI), which can indirectly measure brain iron, a key player in the etiology of PD and 2) diffusion tensor imaging (DTI), which can detect subtle ultrastructural changes in brain tissue, such as disintegration of white matter fibers. Since the sensitivity of both SWI and DTI increases considerably with higher magnet field strength, the study will be conducted at 4 Tesla. The study is designed to test the following main hypotheses: 1) High field strength MRI can distinguish patients with PD from controls by increased phase evolution on SWI in the substantia nigra pars compacta and the striatum, reflecting increased iron deposition in these regions. 2) High field strength MRI can distinguish patients with PD from controls by decreased directionality of brain water diffusion on DTI in nigrostriatal and corticostriatal fibers, indicating disintegration of these fibers. The hypotheses will be tested initially on 40 patients with a diagnosis of idiopathic PD and 20 healthy subjects. It is expected that this study will help to identify new imaging markers, which will improve the diagnosis of PD, and potentially increase therapeutic options for the patient.

PI: Norbert Schuff, PhD.
Funding Source: Department of Defense