PI: Norbert Schuff, PhD, Radiology UCSF
1. Aims/Project Summary
The primary goal of the proposal is to identify MRI based markers that 1) accurately distinguish idiopathic PD from healthy aging and 2) objectively measure disease progression and response to treatment. In addition to the initial imaging study, the PI was successful in securing additional researching funding for PD studies. Specifically, the PI received funding to include resting-state fMRI in the MRI marker study and furthermore, recruit a new cohort of subjects. In addition, the PI is participating in the Parkinson’s Disease Progression Marker Initiative (PPMI), an international biomarker study of PD, by performing processing and analysis of a DTI substudy.
2. Scientific Progress:
Structural brain changes: We measured the volumes of about 80 major brain structures, including volumes of the basal ganglia and regional cortical thickness, using Freesurfer software (http://surfer.nmr.mgh.harvard.edu/). We reported previously PD is associated with reduced cortical thickness in absence of apparent cognitive deficits, suggesting that cortical alterations reflecting PD pathology. In an extension of the initial report, we studied longitudinal variations in brain volumes and cortical thinning. We found significant cortical thinning (p <0.01) in PD patients in the left orbito-frontal cortex and left precuneus as well as in premotor areas. Importantly, this pattern of cortical thinning was different from that of advancing age, which showed cortical thinning primarily in mesial temporal and posterior brain regions, including the posterior cingulate. Given that the PD patients in our study had no apparent cognitive deficits, the findings suggest that PD is associated with increased rates of cortical thinning in specific brain regions.
Diffusion Tensor imaging (DTI) findings: We continued studying white matter changes in PD using DTI. Because of our involvement in the PPMI study, we had the opportunity to study a larger and potentially more diverse group of patients. Moreover, since subjects in the PPMI also received a dopamine transporter imaging scan (DAT), we were able for the first time to correlate DTI changes with abnormalities on DAT. Preliminary DTI results in PD patients show that increased severity of motor symptoms is associated with abnormal FA values in the substantia nigra and inferior frontal gyrus. Both regions are known for presence of dopaminergic neurons. In contrast, increased abnormality on DAT scans was associated with abnormal FA levels in supplementary motor regions and frontal lobe regions. The findings imply effects of PD are distributed throughout the brain following a characteristic distribution along the known movement control network. Moreover, the findings of DTI correlations between motor deficits and abnormalities of dopamine transporters imply that DTI could be useful for disease staging.
3. Benefit from the R&D activities of the P41
This clinical collaborative project benefits greatly from the P41 project in multiple ways. First, this project made use of a processing pipeline of DTI data, including coregistration of DTI with structural MRI and spatial distortion correction. Furthermore, this collaborative project benefitted from novel approaches of forming population based brain atlases and applications of multivariate statistics, developed by the image processing Core.
4. PROJECT-GENERATED RESOURCES
All MRI scans and data in the database are available to this P41 center. Moreover, DTI data from the PPMI that were processed using resources of the Center, are publicly available to a large international science community via the databank maintained by the Laboratory for Neuroimaging (LONI) at the University of California Los Angeles.
