Mechelle M Lewis1,2, Guangwei Du1, Jennifer Baccon3,4, Amanda M Snyder5, Ben Murie3, Felicia Cooper1, Christy Stetter6, Lan Kong6, Christopher Sica6, Richard B Mailman1,2, James R Connor5, Xuemei Huang1,2,5,7,8. 1. Departments of Neurology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 2. Pharmacology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 3. Pathology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 4. Department of Pathology and Laboratory Medicine, Akron Children's Hospital, Akron, Ohio, USA. 5. Neurosurgery, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 6. Public Health Sciences, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 7. Radiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 8. Kinesiology, Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.
Abstract
BACKGROUND: Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonian patients, although the exact underlying pathology of these alterations is unknown. OBJECTIVE: The current study investigated the pathological correlates of these susceptibility MRI measures. METHODS: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. RESULTS: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). CONCLUSIONS: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.
BACKGROUND:Parkinsonisms are neurodegenerative disorders characterized pathologically by α-synuclein-positive (e.g., PD, diffuse Lewy body disease, and MSA) and/or tau-positive (e.g., PSP, cortical basal degeneration) pathology. Using R2* and quantitative susceptibility mapping, susceptibility changes have been reported in the midbrain of living parkinsonianpatients, although the exact underlying pathology of these alterations is unknown. OBJECTIVE: The current study investigated the pathological correlates of these susceptibility MRI measures. METHODS: In vivo MRIs (T1- and T2-weighted, and T2*) and pathology were obtained from 14 subjects enrolled in an NINDS PD Biomarker Program (PDBP). We assessed R2* and quantitative susceptibility mapping values in the SN, semiquantitative α-synuclein, tau, and iron values, as well as neuronal and glial counts. Data were analyzed using age-adjusted Spearman correlations. RESULTS: R2* was associated significantly with nigral α-synuclein (r = 0.746; P = 0.003). Quantitative susceptibility mapping correlated significantly with Perls' (r = 0.758; P = 0.003), but not with other pathological measurements. Neither measurement correlated with tau or glial cell counts (r ≤ 0.11; P ≥ 0.129). CONCLUSIONS: Susceptibility MRI measurements capture nigral pathologies associated with parkinsonian syndromes. Whereas quantitative susceptibility mapping is more sensitive to iron, R2* may reflect pathological aspects of the disorders beyond iron such as α-synuclein. They may be invaluable tools in diagnosing differential parkinsonian syndromes, and tracking in living patients the dynamic changes associated with the pathological progression of these disorders.
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