Reproducible in vivo detection of locus coeruleus pathology in Parkinson's disease

Patients with Parkinsons disease undergo a loss of melanized neurons in substantia nigra pars compacta and locus coeruleus. Very few studies have assessed substantia nigra pars compacta and locus coeruleus pathology in Parkinsons disease simultaneously with magnetic resonance imaging (MRI). Neuromelanin-sensitive MRI measures of substantia nigra pars compacta and locus coeruleus volume based on explicit magnetization transfer contrast have been shown to have high scan-rescan reproducibility in controls, but no study has replicated detection of Parkinsons disease-associated volume loss in substantia nigra pars compacta and locus coeruleus in multiple cohorts with the same methodology. Two separate cohorts of Parkinsons disease patients and controls were recruited from the Emory Movement Disorders Clinic and scanned on two different MRI scanners. In cohort 1, imaging data from 19 controls and 22 Parkinsons disease patients were acquired with a Siemens Trio 3 Tesla scanner using a 2D gradient echo sequence with magnetization transfer preparation pulse. Cohort 2 consisted of 33 controls and 39 Parkinsons disease patients who were scanned on a Siemens Prisma 3 Tesla scanner with a similar imaging protocol. Locus coeruleus and substantia nigra pars compacta volumes were segmented in both cohorts. Substantia nigra pars compacta volume (Cohort 1: p=0.0148; Cohort 2: p=0.0011) and locus coeruleus volume (Cohort 1: p=0.0412; Cohort 2: p=0.0056) were significantly reduced in the Parkinsons disease group as compared to controls in both cohorts. This imaging approach robustly detects Parkinsons disease effects on these structures, indicating that it is a promising marker for neurodegenerative neuromelanin loss.