Idiopathic PD is the second most common neurodegenerative disorder, affecting roughly 1.5 million Americans and 6 million people worldwide. The diagnosis of PD remains entirely clinical and no objective diagnostic tests have been approved by the FDA or widely accepted. Several neurodegenerative disorders can clinically mimic PD, most notably progressive supranuclear palsy (PSP) and multisystem atrophy (MSA), and these conditions account for approximately 25-30% of all cases of parkinsonism. Subjects with REM behavior disorder (RBD) represent an at-risk population for developing PD, with its prevalence, age and gender distribution closely resembling those of PD. Metabolic imaging with FDG PET and multivariate spatial covariance analysis has provided excellent differential diagnostic accuracy in PD, MSA and PSP. This is based on identifying unique covariance patterns of abnormal brain metabolism and their forward applications in individual patients. With the introduction of low-cost, non-invasive fMRI techniques for functional-anatomical brain mapping in recent years, fMRI-based imaging modalities combined with spatial covariance pattern analysis may be a promising approach for accurate early diagnosis of PD vs. MSA or PSP. Moreover, longitudinal follow-up of RBD subjects with such parkinsonism-related patterns may indicate the prognosis of disease during prodromal phases of PD. In this longitudinal prospective study we plan to develop disease-related covariance patterns in patients with PD, MSA and PSP using both multispectral fMRI and FDG PET, and compare the progression of fMRI- and PET-derived covariance patterns in each disease category over two years. We will also develop disease- related covariance patterns in patients with RBD and evaluate the changes in the expression of all these disease-related patterns in each imaging modality with the progression of RBD. By working with our Chinese partner institution, we will be able to enhance our bilateral collaborations and evaluate this novel approach across different ethnic populations, movement disorder clinics and imaging centers. We will address the following Specific Aims: (1) To evaluate disease-related brain networks in parkinsonian patients using fMRI and FDG PET; (2) To investigate the progression of these disease-related brain networks in parkinsonian patients using fMRI and FDG/FPCIT PET; (3) To evaluate disease-related brain networks in RBD patients using fMRI and FDG PET; and (4) To investigate the progression of the disease-related brain networks in RBD using fMRI and FDG/FPCIT PET. If successful this project will produce disease-related brain networks using alternative imaging techniques and provide viable biomarkers from fMRI for early PD diagnosis.
Metabolic PET imaging with spatial covariance analysis has become a gold standard in early differential diagnosis of parkinsonism. In this international collaborative study with a Chinese medical institution, we seek to develop novel brain network biomarkers for parkinsonian disorders using newly available fMRI methods and to assess their progression in patients with prodromal PD (i.e. REM behavior disorder-RBD). The development of a technology for the early, objective, and accurate diagnosis of PD will help to improve clinica management and optimize the conduct of clinical research in PD.
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