Synopsis

Keywords: White Matter, Brain

A pilot study to examine the structural MRI features of patients with dysthyroid optic neuropathy (DON) as compared to normal controls, and correlate pathologic MRI changes to clinical symptoms of the disease. DON patients show reduced cortical volume in precuneus and occipital pole, decrease area in precuneus and precentral gyrus, and widespread decreased FA value, mainly in genu of corpus callosuma and body of corpus callosum. Meanwhile, the FA of was associated with visual acuity. Our study provides a new insight of pathological mechanism of DON.

Introduction

Dysthyroid optic neuropathy (DON) is a serious complication of Graves orbitopathy (GO) that may result in permanent loss of vision. DON shows ischemia and axonal loss of the optic nerve that could be identified by measuring the diffusion tensor imaging[1]and T2 mapping[2]. However, the degree to which dysthyroid optic neuropathy has effects in the brain beyond the eye and the visual pathways is unclear. This study aimed to explore the morphological and microstructural changes of grey and white matter in DON patients.

Methods

We acquired magnetic resonance imaging (MRI) scans from 42 DON patients and 42 well-matched healthy controls (HCs). GO diagnosis was based on the diagnostic criteria postulated by Bartley GB et al. [3]. DON diagnosis was based on at least two of the following signs: the deterioration of VA (< 1.0), loss of color vision, optic disc swelling, and relative afferent pupillary defect [4]. Exclusion criteria were: 1) no history of neurological, psychiatric, major-medical conditions, or substance abuse; 2) no intracranial or other intra-orbital lesions on routine MR images. Scanning was performed on a 3T MRI system (MAGNETOM Prisma, Siemens Healthcare, Erlangen, Germany) using a 64-channel head coil. The protocol included high-resolution T1-weighted MR images and q-space acquisition mode diffusion weight image (DWI) data. T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence scans were acquired at a resolution of 0.8 mm3, 224 slices, TR/TE = 2300 ms/2.43 ms, scan time = 6 min. DWI data was acquired using a 7 min spin-echo echo-planar imaging sequence with a half coverage Cartesian q-space grid scheme. the DWI parameters: TR/TE = 3700 ms/72 ms, FOV = 220 × 220 mm2, voxel size = 2 × 2 × 2 mm3, in-plane acceleration factor=2, slice acceleration factor=2. Multiple b-values with the maximum 3000 s/mm2 along 99 diffusion gradient directions were sampled on the grid points in the 3D q-space. DTI parameters were calculated using NeuDiLab software developed in-house with Python, which is based on an open-resource tool DIPY (Diffusion Imaging in Python). Cortical thickness, cortical volume and area were measured using the surface-based morphometry (SBM) approach. We also evaluated DTI-metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)) derived from DWI data using tract-based spatial statistics (TBSS). For those brain regions exhibiting altered structure, correlations between alterations and visual acuity were analyzed in all patients

Results:

Brain region of significant change in grey matter and white matter between DON patients and healthy controls revealed by SBM and TBSS were summarized in Table 2. Compared with controls, DON patients exhibited decrease cortical volume in precuneus and occipital pole (Fig1A-B). DON patients exhibited decrease cortical area in precuneusand precentral gyrus (Fig1C-D). However, cortical thickness showed no significance between DON patents and HC. DON exhibited widespread decreased FA value (Genu of corpus callosum, body of corpus callosum, anterior corona radiata superior corona radiata, posterior corona radiata and superior longitudinal fasciculus) (Fig2). MD, AD and RD showed no significant difference between DON patents and HC. In patient group, Pearson partial correlation showed no significant correlation between the change of cortical volume in precuneus and visual acuity (r = 0.143, P = 0.387), the change of cortical volume in occipital pole showed no significant correlation with visual acuity (r = 0.252, P = 0.121). the FA value in the body of corpus callosum was positively correlated with visual acuity (r = 0.446, P = 0.015). (Fig. 3)

Discussion

To the best of our knowledge, this is the first study to investigate brain morphometric alterations in DON patients using multimodal neuroimaging measures including cortical thickness, cortical volume and area, as well as white matter integrity. The use of multimodal in brain imaging analysis allows us to conduct a more comprehensive understanding in the neuropathology of DON. Additionally, we analyzed correlation between visual acuity and altered brain structure. The main findings of our study are that DON patients have significantly reduced cortical volume and area structural alteration of precuneus, and cortical volume change in occipital pole. And lower FA in brain white matter compared with HC. Especially, the FA value in the body of corpus callosum was positively correlated with visual acuity.

Conclusions

DON patients demonstrated reduced cortical volume and area structural alteration of precuneus, and cortical volume change in occipital pole. Microstructural alterations in brain white matter. Combined multimodal neuroimaging methods may provide a more comprehensive perspective to clarify the neuropathology of DON patient.

Acknowledgements

No acknowledgements

References

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