Development of Biomarkers Based on Brainstem Nuclei for Prodromal Parkinson's Disease

Study Rationale: Early diagnosis of Parkinson’s disease (PD) requires development of biomarkers that can be used to detect the first signs of neurodegeneration. Animal models suggest that tiny regions of gray matter, called brainstem nuclei, are involved in the prodromal stage of PD, before motor symptoms appear. However, brainstem nuclei are difficult to visualize using techniques such as magnetic resonance imaging (MRI). Our aim is to develop biomarkers of prodromal PD using our atlas of brainstem nuclei atlas. The ability to assess the early stages of neurodegeneration could facilitate treatment when it can most effectively delay the development of full-blown disease.

Hypothesis: We hypothesize that the microstructure and connectivity of brainstem nuclei are impaired in prodromal PD, and that this impairment worsens with disease progression.

Study Design: To test our hypothesis, we will map our atlas of brainstem nuclei to MRIs of prodromal PD, recently diagnosed PD and healthy subjects from the Parkinson’s-Progression-Markers-Initiative (PPMI). For each brainstem nucleus, we will calculate a measure of connectivity and assess whether these values differ in people with PD compared to healthy subjects and whether they diminish with disease progression. We will package our brainstem nuclei atlas and routines needed for use of the atlas in a toolkit, the Brainstem Navigator, that we will publicly release on a web platform.

Impact on Diagnosis/Treatment of PD: If successful, the developed biomarkers can be used to characterize neurodegeneration in early PD, monitor disease progression and assess the effect of therapeutics. Our toolkit will be released to the research and clinical community to automatically identify the location of brainstem nuclei in MRI of health and disease, including PD.

Next Steps for Development: Further steps of development would include interfacing our toolkit with clinical MRI scanners and neurosurgical tools to allow clinicians in hospital settings to automatically assess the integrity of brainstem nuclei at prodromal stages, assign a risk-status to individuals and apply personalized treatments targeted to the subject or to brainstem nuclei.