Journal
ANNALS OF NEUROLOGY
Volume 85, Issue 1, Pages 96-104Publisher
WILEY
DOI: 10.1002/ana.25376
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Funding
- NIH National Institute of Neurological Disorders and Stroke [NS060722]
- Parkinson's Disease Biomarker Program [NS082151]
- Hershey Medical Center General Clinical Research Center (National Center for Advancing Translational Sciences) [UL1 TR000127]
- Pennsylvania Department of Health Tobacco CURE Funds
- Michael J. Fox Foundation for Parkinson's Research
- Alzheimer's Association
- Alzheimer's Research UK
- Weston Brain Institute
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Objective Newer magnetic resonance imaging (MRI) techniques have shown promise in capturing early Parkinson disease (PD)-related changes in the substantia nigra pars compacta (SNc), the key pathological loci. Their translational value, however, is hindered by technical complexity and inconsistent results. Methods A novel yet simple MRI contrast, the T1w/T2w ratio, was used to study 76 PD patients and 70 controls. The T1w/T2w ratio maps were analyzed using both voxel-based and region-of-interest approaches in normalized space. The sensitivity and specificity of the SNc T1w/T2w ratio in discriminating between PD and controls also were assessed. In addition, its diagnostic performance was tested in a subgroup of PD patients with disease duration <= 2 years (PDE). A second independent cohort of 73 PD patients and 49 controls was used for validation. Results Compared to controls, PD patients showed a higher T1w/T2w ratio in both the right (cluster size = 164mm(3), p < 0.0001) and left (cluster size = 213mm(3), p < 0.0001) midbrain that was located ventrolateral to the red nucleus and corresponded to the SNc. The region-of-interest approach confirmed the group difference in the SNc T1w/T2w ratio between PD and controls (p < 0.0001). The SNc T1w/T2w ratio had high sensitivity (0.908) and specificity (0.80) to separate PD and controls (area under the curve [AUC] = 0.926), even for PDE patients (AUC = 0.901, sensitivity = 0.857, specificity = 0.857). These results were validated in the second cohort. Interpretation The T1w/T2w ratio can detect PD-related changes in the SNc and may be used as a novel, parsimonious in vivo biomarker for the disease, particularly for early stage patients, with high translational value for clinical practice and research. ANN NEUROL 2019;85:96-104.
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