In Vivo Assessment of Brainstem Depigmentation in Parkinson Disease: Potential as a Severity Marker for Multicenter Studies.
Purpose To investigate the pattern of neuromelanin signal intensity loss within the substantia nigra pars compacta (SNpc), locus coeruleus, and ventral tegmental area in Parkinson disease (PD); the specific aims were (a) to study regional magnetic resonance (MR) quantifiable depigmentation in association with PD severity and (b) to investigate whether imaging- and platform-dependent signal intensity variations can be normalized. Materials and Methods This prospective case-control study was approved by the local ethics committee and the research department of Nottingham University Hospitals. Written informed consent was obtained from all participants before enrollment in the study. Sixty-nine participants (39 patients with PD and 30 control subjects) were investigated with neuromelanin-sensitive MR imaging by using two different 3-T platforms and three differing protocols. Neuromelanin-related volumes of the anterior and posterior SNpc, locus coeruleus, and ventral tegmental area were determined, and normalized neuromelanin volumes were assessed for protocol-dependent effects. Diagnostic test performance of normalized neuromelanin volume was investigated by using receiver operating characteristic analyses, and correlations with the Unified Parkinson's Disease Rating Scale scores were tested. Results Reduction of normalized neuromelanin volume in PD was most pronounced in the posterior SNpc (median, -83%; P < .001), followed by the anterior SNpc (-49%; P < .001) and the locus coeruleus (-37%; P < .05). Normalized neuromelanin volume loss of the posterior and whole SNpc allowed the best differentiation of patients with PD and control subjects (area under the receiver operating characteristic curve, 0.92 and 0.88, respectively). Normalized neuromelanin volume of the anterior, posterior, and whole SNpc correlated with Unified Parkinson's Disease Rating Scale scores (r2= 0.25, 0.22, and 0.28, respectively; all P < .05). Conclusion PD-induced neuromelanin loss can be quantified across imaging protocols and platforms by using appropriate adjustment. Depigmentation in PD follows a distinct spatial pattern, affords high diagnostic accuracy, and is associated with disease severity.©RSNA, 2016 Online supplemental material is available for this article.
From the Department of Radiological Sciences, Division of Clinical Neuroscience, School of Medicine (S.T.S., Y.X., P.T., D.P.A.), and The Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy (S.T.S., Y.X., D.P.A.), University of Nottingham, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, England; Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, England (N.B.); and Department of Radiology, Cardiff and Vale University Health Board, Cardiff, Wales (S.T.S.).
Stefan T
ST
Schwarz
From the Department of Radiological Sciences, Division of Clinical Neuroscience, School of Medicine (S.T.S., Y.X., P.T., D.P.A.), and The Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy (S.T.S., Y.X., D.P.A.), University of Nottingham, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, England; Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, England (N.B.); and Department of Radiology, Cardiff and Vale University Health Board, Cardiff, Wales (S.T.S.).
Yue
Y
Xing
From the Department of Radiological Sciences, Division of Clinical Neuroscience, School of Medicine (S.T.S., Y.X., P.T., D.P.A.), and The Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy (S.T.S., Y.X., D.P.A.), University of Nottingham, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, England; Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, England (N.B.); and Department of Radiology, Cardiff and Vale University Health Board, Cardiff, Wales (S.T.S.).
Pragya
P
Tomar
From the Department of Radiological Sciences, Division of Clinical Neuroscience, School of Medicine (S.T.S., Y.X., P.T., D.P.A.), and The Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy (S.T.S., Y.X., D.P.A.), University of Nottingham, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, England; Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, England (N.B.); and Department of Radiology, Cardiff and Vale University Health Board, Cardiff, Wales (S.T.S.).
Nin
N
Bajaj
From the Department of Radiological Sciences, Division of Clinical Neuroscience, School of Medicine (S.T.S., Y.X., P.T., D.P.A.), and The Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy (S.T.S., Y.X., D.P.A.), University of Nottingham, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, England; Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, England (N.B.); and Department of Radiology, Cardiff and Vale University Health Board, Cardiff, Wales (S.T.S.).
Dorothee P
DP
Auer
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001933:Brain Stem / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008543:Melanins / Q000032:analysis; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010300:Parkinson Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D011446:Prospective Studies; D012720:Severity of Illness Index
D015415:Biomarkers; D008543:Melanins; C014121:neuromelanin