(Sunday, 7/14/2019)
Room: ePoster Forums
Purpose: To develop in vivo diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) assays in a DYT1 ΔGAG heterozygous knock-in (DYT1 KI) mouse model in order to gain insight into the pathophysiology and neuroimaging biomarkers of DYT1 dystonia.
Methods: In the current study, we used two methods of MR imaging: NODDI-DTI for structural neuroimaging and functional MRI including resting-state and sensory-evoked fMRI. We've performed advanced, high-field brain imaging at 11.1 Tesla. In NODDI-DTI, we examined neurite orientation and dispersion parameters from a three-component diffusion tensor. We compared different diffusion maps of fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (FICVF), isotropic volume fraction (FISO) and orientation dispersion index (ODI) between KI and WT groups using voxel-wise independent samples t-tests and ANOVA tests. Next, we performed in vivo resting-state fMRI in both DYT1 KI mice and WT controls to define abnormalities in functional connectivity in cortical, sub-cortical and cerebellar networks. In addition, we developed a periodic sensory-evoked fMRI using a Pain & Sensory Evaluation System (PATHWAY) to examine the brain blood oxygenation level dependent (BOLD) signals in responses to peripheral stimulation.
Results: (1)NODDI-DTI: We've observed decreased mean diffusivity and increased orientation dispersion in DYT1 KI group. (2)Resting-state and sensory-evoked fMRI: We assessed functional connectivity between drawn ROIs and other brain regions. The calculated beta-coefficients for BOLD signal suggested impairments in cortical, basal ganglia, and cerebellar regions.
Conclusion: The current study provides in vivo MRI-based evidence that the removal of a single glutamic acid residue in the carboxyl terminus of the Tor1a protein engenders impaired network level functional connectivity and microstructural abnormalities across cortical, subcortical and cerebellar brain regions. Future studies that use these techniques in other animal models of dystonia that show a robust phenotype will further improve our understanding of connectivity abnormalities and pathophysiology of DYT1 dystonia.
Funding Support, Disclosures, and Conflict of Interest: a. The current research is supported by NIH RO1 (2RO1NS75012-06). b. A portion of this work was performed in the McKnight Brain Institute at the National High Magnetic Field Laboratory AMRIS Facility, which is supported by National Science Foundation Cooperative Agreement No. DMR-1644779. and the State of Florida.
Keywords
Diffusion, MRI, Image Analysis
Taxonomy
IM/TH- Image Analysis (Single modality or Multi-modality): Imaging biomarkers and radiomics
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