MRI T 2 and T 2 relaxometry to visualize neuromelanin in the dorsal substantia nigra pars compacta

• Published in: NeuroImage (Orlando, Fla.) Vol. 211; p. 116625
• Main Authors: Lee, Hansol, Baek, Sun-Yong, Kim, Eun-Joo, Huh, Gi Yeong, Lee, Jae-Hyeok, Cho, HyungJoon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.05.2020
• Subjects: Aged; Aged, 80 and over; Basal ganglia; Biomarkers; Brain; Central nervous system diseases; Diagnosis; Disease; Disease Progression; Dopamine transporter; Feasibility Studies; Female; Humans; Iron; Localization; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mass spectroscopy; Melanins - metabolism; Movement disorders; Neostriatum; Neurodegenerative diseases; Neuroimaging; Neuroimaging - methods; Neurons; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pars Compacta - diagnostic imaging; Pars Compacta - metabolism; Pars Compacta - pathology; Pigments; Positron emission tomography; Substantia nigra; Transverse magnetic resonance relaxometries; Neuromelanin; Substantia nigra; Depigmentation; Parkinson’s disease
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2020.116625

Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T and T *) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T and T * mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T and T * mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T and T * mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T and T * mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T and T * mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson's disease patients. The length of the dorsal linear mismatch line based on the T *-T mask was significantly shorter in the Parkinson's disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [ F] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T and T * mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.