The neurochemical profile of the substantia nigra (SN) of patients with Parkinson’s disease (PD) as measured by high field magnetic resonance spectroscopy (MRS) will differ from that of healthy controls, in that glutathione will be lower due to oxidative stress, lactate will be higher due to mitochondrial dysfunction, the gliosis markers myo-inositol and glutamine will be higher due to inflammation (glial activation), and N-acetylaspartate and glutamate will be lower due to neuronal loss/damage.
To develop non-invasive, quantitative, and reliable methods to assay neuronal status along with the major biochemical events thought to be involved in PD pathogenesis, namely oxidative stress, mitochondrial dysfunction, and inflammation, directly in the substantia nigra, the primary site of involvement in this neurodegenerative disease. Specifically, we will implement and optimize methodology for measuring 1H MR spectra from the SN at the magnetic field of 7 tesla (T); and with this optimized methodology we will quantify the neurochemical profile of the SN of healthy volunteers and patients with PD and compare glutathione, lactate, glutamine, myo-inositol, NAA, and glutamate levels in patients vs. controls.
Goal 1a) We will optimize a pulse sequence developed in our center (localization by adiabatic selective refocusing, LASER) (Garwood and DelaBarre, 2001) for achieving the best sensitivity to quantify the highest number of neurochemicals in the SN. These studies will be carried out with phantoms and healthy volunteers.
Goal 1b) We will recruit patients with idiopathic PD with mild-moderate severity (Hoehn & Yahr Stage II – III) and age-matched control participants. Localized 1H MR spectra will be acquired from volumes-of-interest of ~1 ml centered on the unilateral SN using the LASER sequence with optimized parameters. Absolute concentrations of neurochemicals will be determined using an automated deconvolution program (LCModel).