Midbrain Microstructural Atrophy Associated with Parkinson’s Disease Motor and Cognitive Symptoms Using 7-Tesla MRI (S57.004)

OBJECTIVE: Using ultra-high field 7 Tesla (T) MRI, we investigated the relationship between midbrain microstructural atrophy and symptom severity in Parkinson9s disease (PD). BACKGROUND: Midbrain pathology is the hallmark of PD; however, midbrain nuclei are difficult to distinguish on conventional MRI, therefore correlation between microstructural volumes and motor symptoms can only be performed at autopsy. Further, the role of midbrain pathology in the development of PD cognitive symptoms remains unclear. DESIGN/METHODS: We used susceptibility-weighted 3D 7T MRI to identify midbrain nuclei in 15 PD patients (MDS-UPDRS-III 29.85±13.02), who completed motor and neuropsychological testing. The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) were segmented both manually and semi-automatically using ITK-SNAP software. We calculated volumetric measurements for each nuclei and performed correlation analysis between these volumes and measures of motor and cognitive performance. RESULTS: Twelve PD patients tolerated 7T MRI without significant movement-related artifact, including 6 tremor-dominant patients (MDS-UPDRS tremor range 0-16). PD-MCI diagnostic criteria (Litvan 2012, Level-II) were used to categorize 7 no-MCI and 5 MCI. We found higher (worse) MDS-UPDRS-III scores correlated with smaller SN volume (r=-0.56, p=0.04). Further, higher akinesia/rigidity subscores correlated with smaller SN volume (r=-0.65, p=0.01). When considering the more- versus less-affected side, we found higher motor subscores on the less-affected body-side trended toward correlation with smaller contralateral SN volume (r=-0.51, p=0.07). Poorer performance on the Hooper Visual Organization Test correlated with smaller SN volume (r=0.65, p=0.04). No correlations were found between motor or cognitive tests and STN or RN volumes. CONCLUSIONS: Ultra-high field 7T MRI with midbrain microstructural visualization and segmentation is feasible in PD patients, even with moderate to severe limb tremor. Correlations with the less-affected body-side suggest SN volume changes may be sensitive to early motor symptoms, particularly bradykinesia and rigidity. In addition, SN pathology could directly contribute to visuo-spatial cognitive deficits in PD. Study Supported by: NIH/NINDS, NIH/NIA, MJFF Disclosure: Dr. Poston has nothing to disclose. Dr. Santoso has nothing to disclose. Dr. Bernstein has nothing to disclose. Dr. Cruadhlaoich has nothing to disclose. Dr. Everling has nothing to disclose. Dr. YorkWilliams has nothing to disclose. Dr. Fenesy has nothing to disclose. Dr. Zeineh has nothing to disclose. Dr. Kerchner has received personal compensation for activities with Phloronol, Inc. as an advisory board member.