Imaging Biomarkers in Parkinson's Disease

• Using MRI, we will measure signal intensities of iron-rich structures using T2 sequences and calculate phase shift values in these structures with susceptibility weighted sequences. We will also measure clinical symptom severity with the UPDR sc...
  

• We will measure nigral echogenicity using transcranial ultrasound, dopaminergic function using Dat SPECT, structural changes using MRI, functional connectivity analysis using fMRI and magnetoencephagraphy and brain metabolism using MR spectoscop...
  

Objectives:

The purpose of this protocol is to evaluate possible biomarkers for diagnosis and assessment of disease progression in Parkinson disease (PD) through multi-modal neuroimaging studies. The study will have two parts:

1. Part 1: Compare brain images of PD subjects and healthy volunteers (HVs) using various imaging techniques in a case-control analysis.
2. Part 2: Compare findings on serial brain images with clinical assessments of PD subjects, subjects with early parkinsonism and healthy volunteers over the following 9 years. The findings from this exploratory study will help develop additional hypothesis-driven studies investigating PD pathology. PD patients will yield information about how biomarkers change over time; the patients with early parkinsonism will give information as to which biomarkers might predict the development of PD.

Study Population:

Part 1 (Case-control study): We will study 30 patients with well-defined PD, as defined by the UK Parkinson's Society Brain Bank diagnostic criteria [1-3]. We will also study 15 age-matched healthy volunteers (HVs) as controls.

Part 2 (Longitudinal study): We will continue to study all of the subjects from Part 1 periodically over the following 9 years. We will also study 30 subjects with early parkinsonism (EP). EP subjects are defined as individuals who have experienced at least one but fewer than 3 of the cardinal symptoms of PD at the time of enrollment.

Design:

Part 1: (Case-control study). Eligible participants will come for a 2-3 day visit. They will have a clinical assessment, brain ultrasound (transcranial sonography or TCS), dopamine transporter single photon emission computed tomography (DAT SPECT) scan, a magnetic resonance (MR) scan, and magnetoencephalography (MEG). Subjects on Parkinson medications may have 2-3 additional MR scans in the off medications condition as tolerated.

Part 2: (Longitudinal study). PD and EP subjects will be asked to follow-up annually for a total of 10 visits. After a screening visit, HV subjects will be asked to follow up annually for the first 3 years, and then every 3 years for the following 6 years, for a total of 6 visits. Each follow-up will involve a 2-3 day visit and will consist of repeat clinical evaluations and imaging studies (TCS, SPECT, MEG, MR scans).

Outcome Measures:

1. MRI: To measure the difference in susceptibility in iron-rich structures (using susceptibility weighted imaging); the difference in fractional anisotropy between seed and target regions of interest (using DTI); the difference in gray and white mattervolume of brain regions (using VBM); fluctuations of the blood oxygen level dependent (BOLD) signal during resting state (using fMRI); and the signal amplitude of phosphorus-containing compounds and neurotransmitters in brain regions of interest (ROIs) (using MRS).
2. TCS: To measure parameters such as the difference in the area of increased signal (hyperechogenicity) seen in brain structures such as the substantia nigra (SN).
3. SPECT: To measure the amount of dopamine reuptake in the striatal part of the brain.
4. MEG: To quantify measures such as task-related potentials, relative spectral power, and synchronization.