Objective: To evaluate microstructural integrity of the dentato-rubro thalamo-cortical tract (DRTT) in tremor dominant Parkinson’s disease (TDPD) and ET plus (ETP) syndrome using a multimodal approach of diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and free-water (FW) based analysis.

Background: The DRTT plays a crucial role in tremor disorders as it is the main white matter (WM) conduit in the cerebello-thalamocortical (CTC) network, and part of the basal ganglia-thalamocortical (BGTC) network. TDPD and ETP are tremor dominant disorders, and it is imperative to evaluate WM integrity of the DRTT to understand the role and possible variability in site of involvement.

Method: Multi-shell DWI was acquired for 25 patients of TDPD, 25 of ETP (ET with rest tremor) and 22 healthy controls (HC). Disease severity was measured using the Fahn-Tolosa-Marin tremor rating scale (FTMRS). Following preprocessing, DTIFit from the FMRIB diffusion toolbox was used to fit the tensor model to generate fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues for radial and axial diffusivity (RD, AD). The Watson model for NODDI from the CUDA diffusion modelling toolbox[1] was used to generate neurite density index (NDI), orientation dispersion index (ODI), and CSF volume fraction (fiso). The bi-tensor FW model in DIPY[2] was used to generate FW corrected FA (fwFA) and MD (fwMD). TBSS was run with nonlinear transforms to the MNI152 space. Non-FA images (MD, AD, RD, NDI, fiso, fwFA, fwMD) were processed using tbss_non_FA.  A binary-probabilistic tractography-based DRTT template[3] was used as the mask image for voxel-wise statistics using TFCE with FWE correction, at 5000 permutations, and age and gender as covariates.

Results: There was no difference in total FTMRS scores. NDI of bilateral DRTT (TDPD<HC), and fwMD of the left DRTT (TDPD>HC) was significantly abnormal with significant clusters in the supra-thalamic section of the DRTT [Figure-1]. In the same region, NDI (ETP<HC) of the left DRTT neared significance. No difference was observed between TDPD and ETP.

Conclusion: In both disorders, WM damage was observed in the central pathway common to both BGTC and CTC. The absence of any difference between ETP and TDPD may suggests the possibility of similarities in tremor pathogenesis in these disorders.

References: 1. Hernandez-Fernandez M, Reguly I, Jbabdi S, Giles M, Smith S, Sotiropoulos SN. Using GPUs to accelerate computational diffusion MRI: From microstructure estimation to tractography and connectomes. Neuroimage. 2019 Mar 1;188:598-615.
2. Henriques, R.N., Rokem, A., Garyfallidis, E., St-Jean, S., Peterson E.T., Correia, M.M., 2017. [Re] Optimization of a free water elimination two-compartment model for diffusion tensor imaging. ReScience volume 3, issue 1, article number 2
3. Dembek TA, Petry-Schmelzer JN, Reker P, Wirths J, Hamacher S, Steffen J, Dafsari HS, Hövels M, Fink GR, Visser-Vandewalle V, Barbe MT. PSA and VIM DBS efficiency in essential tremor depends on distance to the dentatorubrothalamic tract. NeuroImage: Clinical. 2020 Jan 1;26:102235.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microstructural-abnormalities-of-the-dentato-rubro-thalamo-cortical-tract-in-tremor-dominant-pd-and-et-plus-syndrome-a-dti-noddi-and-free-water-based-analysis/