Objective: An unmet need exists to develop a methodology to diagnose Parkinson’s disease (PD) in the premotor stage, so that patients can be enrolled in neuroprotection trials at a timepoint when they’re likely to be more effective.

Background: Nigrosome 1 (N1) is the subregion of the substantia nigra pars compacta that degenerates earliest and to the greatest degree in PD. 7 Tesla magnetic resonance imaging (7T MRI) allows high enough resolution to distinctly image N1 in healthy controls (HCs), and quantify N1 signal loss in PD. We report qualitative and quantitative signal loss in N1 in new onset PD (motor symptoms <1 year), and in subjects with idiopathic REM sleep behavior disorder (RBD) without PD.

Methods: 16 subjects have thus far been recruited, 6 with idiopathic PD, 5 with RBD, and 5 age-matched HCs. All subjects underwent clinical histories and exams, completed the Scales for Outcomes in PD-Autonomic (SCOPA-AUT) questionnaire of autonomic dysfunction, and the 40-item University of Pennsylvania Smell Identification Test (UPSIT). All subjects underwent 7T MRI with a specific protocol including T2* gradient echo sequences (voxel resolution = 0.28 x 0.28 x 0.8mm). Qualitative analysis of N1 signal was performed by two trained neuroradiologists blinded to subject status. Quantitative analysis of N1 signal was performed in 6 serial axial slices.

Results: Qualitative analysis of a predefined N1 region of interest was able to separate out PD subjects from HCs with 100% accuracy. Intraclass correlation between the blinded readers was perfect. When compared to healthy controls, quantitative analyses of N1 image signal strength in PD and RBD subjects showed significant degradation in the most rostral (PD: p=0.011, RBD: p=0.0097) and two most caudal slices (slice 5 – PD: p=0.048; RBD: p=0.094; slice 6 – PD: p=0.0039, RBD: p<0.001). Additionally, RBD subjects had significantly lower mean scores for both SCOPA-AUT (p=0.010) and UPSIT (p=0.0028).

Conclusions: Preliminary data suggests that 7T MRI structural imaging of N1 is a reliable diagnostic biomarker of new onset and premotor PD. N1 signal loss is greatest at the rostral and caudal tails. Olfactory and autonomic symptom testing further distinguish individuals with RBD as a risk for developing motor PD. Prospective changes in N1 signal are being tracked and may serve as a useful independent biomarker of disease progression.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ultra-high-field-magnetic-resonance-imaging-of-nigrosome-1-is-a-biomarker-of-new-onset-and-premotor-parkinsons-disease/