Abstract Details

Title Microstructural and connectivity brainstem changes in REM Sleep Behavior Disorder by 7 Tesla MRI

Topic Sleep

Presentation(s) S3 - Sleep Medicine: Highlights 2020 (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Objective

To investigate the presence of microstructural and connectivity brainstem changes in REM-sleep-behavior-disorder (RBD) by the use of high-resolution 7 Tesla MRI, and our recently developed stereotaxic probabilistic structural atlas of brainstem-nuclei in living humans.

Background RBD is characterized by the absence of muscle-atonia during REM-sleep, and represents a prodromal clinical manifestation of evolving synucleinopathy. Interestingly, changes in brainstem-nuclei microstructure/connectivity are expected in RBD/premanifest-synucleinopathy based on ex-vivo human staging models of synucleinopathy progression, and in-vivo lesion/connectivity animal and human studies of non-idiopathic-RBD. Yet, brainstem changes underlying idiopatic-RBD/premanifest-synucleinopathy remain understudied in living humans.

Design/Methods Data acquisition: At 7 Tesla, under IRB-approval, we acquired on 10 idiopathic-RBD patients (9m/1f, age 70±2years) and 10 elder controls (9m/1f, 67±2years) 0.75mm-isotropic T₁-weighted M2PRAGE andT₂*-weighted GRE, as well as 1.7mm-isotropic spin-echo diffusion-weighted MRI. Data analysis: To evaluate brainstem microstructural changes, from the MP2RAGE-derived T₁-map we automatically detected regions-of-interest displaying T₁-hyperintensity (T₁>2500ms) within a brainstem mask, and precisely co-registered them to the brainstem-nuclei atlas space. For connectivity analysis, we used as seeds 33 brainstem-nuclei atlas-labels, and as targets 88 cortical/subcortical regions (i.e. 55 MP2RAGE-based Freesurfer parcellations and the seeds). On the diffusion-weighted MRI, we run probabilistic-tractography (iFOD2-MRtrix3) propagating 100,000 streamlines from each seed, then computed the structural-connectivity-index as the fraction of streamlines reaching each target mask, and averaged it across subjects.

Results In 80% of RBD patients we detected regions-of-interest with microstructural changes (i.e. T₁-hyperintensity, colocalized to T₂*-weighted-hyperintensity) in the ventro-caudal part of the substantia-nigra subregion1 (compatible with pars-reticulata) and in a paranigral region. The group structural-connectome of brainstem-nuclei (including substantia-nigra subregion1, reticular formation and raphe nuclei) demonstrated overall decreased connectivity within the brainstem and with the striatum in RBD compared to controls (two-sample t-test, p < 0.05).

Conclusions These results provide compelling empirical evidence for the hypothesized role of specific brainstem-nuclei in the pathogenesis of idiopatic-RBD/premanifest-synucleinopathy.

Authors/Disclosures
PRESENTER	No disclosure on file
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	No disclosure on file
Bruce R. Rosen, MD (Massachusetts General Hosp.)	No disclosure on file
Aleksandar Videnovic, MD, MSc, FAAN (MGH Neurological Clinical Research Institute)	Dr. Videnovic has nothing to disclose.

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