ASSESSMENT OF BRAIN IRON IN PATIENTS WITH PARKINSON?S DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Assessment of Brain Iron and Neuronal Integrity in Patients with Parkinson's Disease Using Novel MRI Contrasts Postmortem demonstration of increased iron in the substantia nigra (SN) is a well appreciated finding in Parkinson's disease (PD). Iron facilitates generation of free radicals which are thought to play a role in dopamine neuronal loss. To date, however, conventional MRI has failed to show significant in vivo differences in SN iron levels in subjects with PD versus control subjects. This may be due to the limitations in tissue contrasts achievable with conventional T1- and T2-weighted sequences that have been employed. With the recent development of novel rotating frame transverse (T2¿) and longitudinal (T1¿) relaxation MRI methods that appear to be sensitive to iron and neuronal loss, respectively, we embarked on a study of eight individuals with PD and eight age-matched control subjects. Employing these techniques using our 4T MRI magnet, we assessed iron deposits and neuronal integrity in the SN. Firstly, T2¿ MRI, which is reflective of iron-related dynamic dephasing mechanisms (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities), demonstrated a statistically significant difference between the PD and control group, while routine T2 MRI did not. Secondly, T1¿ measurements, which appear to reflect upon neuronal count, indicated neuronal loss in the SN in PD. We show here that sub-millimeter resolution T1¿ and T2¿ MRI relaxation methods can provide a non-invasive measure of iron content as well as evidence of neuronal loss in the midbrain of patients with PD