Grants and Contracts Details
Description
The hallmark of Parkinson's disease (PD) is the loss of dopamine neurons in the substantia nigra. However,
clinical symptoms of PD do not manifest until the loss of dopamine neurons exceeds a critical threshold.
Thus, for the early detection of PD, there is particular interest in using an objective, noninvasive, sensitive
and cost-effective imaging method to supplement existing clincal measures and response to treatments. The
primary goal of this project is to determine whether BOLD-phMRI can meet these aforementioned criteria as
an imaging biomarker of PD. Recently, we have demonstrated that the blood oxygenation level dependent
(BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated with
specific histological and behavioral features of the parkinsonian state. For example, d-amphetamine-evoked
activations correlated with the number of surviving dopamine neurons, and stronger apomorphine-induced
activations were seen in more severely motor impaired parkinsonian rhesus macaques (see preliminary
studies). In addtion, apomorphine-induced activations in the dopamine denervated putamen were attenuated
by a neurorestorative therapy (chronic intraputamenal infusion of GDNF). Therefore, by using the imaging
proctocol developed by our group over several years, we are now proposing a large scale study in groups of
rhesus monkeys that are: 1) normal animals, 2) MPTP-Iesioned but asymptomatic, 3) MPTP-Iesioned but
mild, unilateral symptoms and 4) MPTP-Iesioned with severe unilateral symptoms in order to address the
following specific aims: 1) whether BOLD-phMRI can be used to monitor the progression of the disease,
namely to determine if the BOLD effects will correlate with severity of PD features assessed behaivorally and
also with pathological stages of the disease; and 2) whether BOLD-phMRI can be used to assess responses
to therapy, such as L-dopa treatment. If proven predictive of changes in dopamine functions, BOLD-phMRI
could be used in the future as an imaging biomarker to supplement existing clinical measures and to provide
valuable information about the disease process or intervention. In addition, because of the noninvasive,
highly sensitive, highly reproducible and cost-effective features of BOLD-phMRI, this technique may be used
to screen the general population to investigate pathogenesis of the disease.
Status | Finished |
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Effective start/end date | 2/16/07 → 1/31/13 |
Funding
- National Institute of Neurological Disorders & Stroke: $1,592,731.00
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