{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:37:37Z","timestamp":1780393057904,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>We aim to explore the microstructural and metabolic changes in visual pathways in patients with thyroid eye disease (TED) using 3T multi-parametric MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty-four TED patients (inactive group = 20; active group = 14; acute group = 18; chronic group = 16) and 12 healthy controls (HC) were recruited from November 2020 to July 2021. Proton magnetic resonance spectroscopy (<jats:sup>1<\/jats:sup>H-MRS), glutamate chemical exchange saturation transfer (GluCEST) and diffusion kurtosis imaging (DKI) were performed on 3.0T MR scanner. Data analysis and group comparisons were performed after MR data processing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As compare to HC group, the levels of total choline (tCh) in optic radiation (OR) in active group ([1.404 \u00b1 0.560] vs. [1.022 \u00b1 0.260]; <jats:italic>p<\/jats:italic> &amp;lt; 0.05), together with tCh ([1.415 \u00b1 0.507] vs. [1.022 \u00b1 0.260]; <jats:italic>p<\/jats:italic> &amp;lt; 0.05) in OR in acute group were significantly increased. Glutamine (Gln) levels were higher in OR in the chronic group than those in HCs and were positively correlated with the levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3) and FT4 in chronic group. Glutamate (Glu) levels by <jats:sup>1<\/jats:sup>H-MRS did not show significant differences between any two groups. Interestingly, MTRasym (3.0 ppm) was higher in OL in inactive group, active group, acute group and chronic group than those in HCs, and was positively correlated with Glu levels in OL in <jats:sup>1<\/jats:sup>H-MRS. Fractional anisotropy (FA) values from DKI in OR in acute group were significantly lower than those in HCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our initial study demonstrate that GluCEST performs better than <jats:sup>1<\/jats:sup>H-MRS to monitor Glu alterations in visual pathway in TED patients. Changes of brain glutamine levels in TED patients are closely related to their associated hormones alterations, indicating that disease injury status could be reflected through non-invasive metabolites detection by brain <jats:sup>1<\/jats:sup>H-MRS. FA is the most sensitive DKI index to reveal the visual pathway impairment in TED patients. Altogether, our study revealed that 3T multiparametric MR techniques are useful to demonstrate metabolic and microstructural alterations in visual pathways in TED patients. We found that damage to visual pathways occurs in mild TED cases, which not only offers a new approach to the diagnosis of dysthyroid optic neuropathy, but also demonstrates neuropathy in TED is a gradual and continuous spatio-emporal progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2023.1306364","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:13:42Z","timestamp":1704773622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["3.0\u2009T multi-parametric MRI reveals metabolic and microstructural abnormalities in the posterior visual pathways in patients with thyroid eye disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Lan","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaidong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitian","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3348\/kjr.2019.0053","article-title":"Thyroid-associated orbitopathy: evaluating microstructural changes of extraocular muscles and optic nerves using readout-segmented Echo-planar imaging-based diffusion tensor imaging","volume":"21","author":"Chen","year":"2020","journal-title":"Korean J. Radiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1210\/jc.2007-2161","article-title":"Reduced parietooccipital white matter glutamine measured by proton magnetic resonance spectroscopy in treated graves' disease patients","volume":"93","author":"Danielsen","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/neuonc\/not068","article-title":"Fractional anisotropy of the optic radiations is associated with visual acuity loss in optic pathway gliomas of neurofibromatosis type 1","volume":"15","author":"de Blank","year":"2013","journal-title":"Neuro-Oncology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1212\/01.WNL.0000038911.07643.BF","article-title":"Reduced myo-inositol and total choline measured with cerebral MRS in acute thyrotoxic Graves' disease","volume":"60","author":"Elberling","year":"2003","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.acra.2011.12.005","article-title":"A new approach to assess intracranial white matter abnormalities in glaucoma patients: changes of fractional anisotropy detected by 3T diffusion tensor imaging","volume":"19","author":"Engelhorn","year":"2012","journal-title":"Acad. Radiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"100767","DOI":"10.1016\/j.preteyeres.2019.06.003","article-title":"Cholinergic nervous system and glaucoma: from basic science to clinical applications","volume":"72","author":"Faiq","year":"2019","journal-title":"Prog. Retin. Eye Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.mri.2013.02.008","article-title":"Non-gaussian diffusion MRI assessment of brain microstructure in mild cognitive impairment and Alzheimer's disease","volume":"31","author":"Falangola","year":"2013","journal-title":"Magn. Reson. Imaging"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1136\/bjophthalmol-2020-316433","article-title":"Subclinical dysthyroid optic neuropathy: tritan deficiency as an early sign of dysthyroid optic neuropathy","volume":"105","author":"Garip-Kuebler","year":"2021","journal-title":"Br. J. Ophthalmol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.mri.2012.10.027","article-title":"Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study","volume":"31","author":"Gong","year":"2013","journal-title":"Magn. Reson. Imaging"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.3389\/fneur.2019.01285","article-title":"Diffusion kurtosis imaging for detection of early brain changes in Parkinson's disease","volume":"10","author":"Guan","year":"2019","journal-title":"Front. Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1002\/jmri.26249","article-title":"Diffusion kurtosis at 3.0T as an in vivo imaging marker for breast cancer characterization: correlation with prognostic factors","volume":"49","author":"Huang","year":"2019","journal-title":"J magnetic resonance imaging: JMRI"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/s41433-020-0904-2","article-title":"Ultrasonographic measurement of the optic nerve sheath diameter in dysthyroid optic neuropathy","volume":"35","author":"Ji","year":"2021","journal-title":"Eye (Lond.)"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"750","DOI":"10.3389\/fnins.2020.00750","article-title":"Glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging in pre-clinical and clinical applications for encephalitis","volume":"14","author":"Jia","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1093\/brain\/aww285","article-title":"Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome","volume":"140","author":"Kanaan","year":"2017","journal-title":"Brain J. Neurol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1097\/RCT.0000000000000680","article-title":"Characterizing Intraorbital optic nerve changes on diffusion tensor imaging in thyroid eye disease before dysthyroid optic neuropathy","volume":"42","author":"Lee","year":"2018","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"146874","DOI":"10.1016\/j.brainres.2020.146874","article-title":"Altered information flow and microstructure abnormalities of visual cortex in normal-tension glaucoma: evidence from resting-state fMRI and DKI","volume":"1741","author":"Li","year":"2020","journal-title":"Brain Res."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/jmri.28352","article-title":"Preliminary diffusion-tensor imaging evidence for trans-synaptic axonal degeneration in dysthyroid optic neuropathy due to thyroid-associated ophthalmopathy","volume":"57","author":"Liu","year":"2023","journal-title":"J mag resonance imaging: JMRI"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1097\/RCT.0000000000000974","article-title":"Role of diffusional kurtosis imaging in differentiating neuromyelitis Optica-related and multiple sclerosis-related acute optic neuritis: comparison with diffusion-weighted imaging","volume":"44","author":"Lu","year":"2020","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.neuron.2010.06.020","article-title":"NMDA receptor contributions to visual contrast coding","volume":"67","author":"Manookin","year":"2010","journal-title":"Neuron"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.21037\/qims.2019.09.08","article-title":"Imaging of glutamate in acute traumatic brain injury using chemical exchange saturation transfer","volume":"9","author":"Mao","year":"2019","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3667","DOI":"10.1158\/1078-0432.CCR-16-2265","article-title":"Differentiation between radiation necrosis and tumor progression using chemical exchange saturation transfer","volume":"23","author":"Mehrabian","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"31464","DOI":"10.1038\/srep31464","article-title":"Retinal structures and visual cortex activity are impaired prior to clinical vision loss in glaucoma","volume":"6","author":"Murphy","year":"2016","journal-title":"Sci. Rep."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1002\/mrm.1910300604","article-title":"Estimation of metabolite concentrations from localized in vivo proton NMR spectra","volume":"30","author":"Provencher","year":"1993","journal-title":"Magn. Reson. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s12020-018-1733-y","article-title":"The relationship between quality of life, cognition, and thyroid status in Graves' disease","volume":"63","author":"Riguetto","year":"2019","journal-title":"Endocrine"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1159\/000486828","article-title":"Prevalence of radiological signs of dysthyroid optic neuropathy in magnetic resonance imaging in patients with active, moderate-to-severe, and very severe graves orbitopathy","volume":"7","author":"Rutkowska-Hinc","year":"2018","journal-title":"European thyroid journal"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4404","DOI":"10.1007\/s00330-016-4279-5","article-title":"In vivo proton magnetic resonance spectroscopy (1H-MRS) evaluation of the metabolite concentration of optic radiation in primary open angle glaucoma","volume":"26","author":"Sidek","year":"2016","journal-title":"Eur. Radiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Graves' disease","volume":"375","author":"Smith","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1002\/jmri.21098","article-title":"Reconstruction of the human visual system based on DTI fiber tracking","volume":"26","author":"Staempfli","year":"2007","journal-title":"Journal of magnetic resonance imaging: JMRI"},{"key":"ref29","first-page":"1746","article-title":"Diffusion kurtosis imaging reveals optic tract damage that correlates with clinical severity in glaucoma","author":"Sun","year":"2020"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1038\/s41380-020-00986-y","article-title":"Diminished reward responsiveness is associated with lower reward network Glu CEST: an ultra-high field glutamate imaging study","volume":"26","author":"Sydnor","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"578985","DOI":"10.3389\/fonc.2020.578985","article-title":"Noninvasive detection of extracellular pH in human benign and malignant liver Tumors using CEST MRI","volume":"10","author":"Tang","year":"2020","journal-title":"Front. Oncol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"833680","DOI":"10.3389\/fonc.2022.833680","article-title":"XGboost prediction model based on 3.0T diffusion kurtosis imaging improves the diagnostic accuracy of MRI BiRADS 4 masses","volume":"12","author":"Tang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41574-019-0305-4","article-title":"New insights into the pathogenesis and nonsurgical management of graves orbitopathy","volume":"16","author":"Taylor","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1093\/brain\/awv396","article-title":"Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis","volume":"139","author":"Tur","year":"2016","journal-title":"Brain J. Neurol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e9","DOI":"10.1016\/j.crad.2018.01.010","article-title":"Microstructural visual pathway abnormalities in patients with primary glaucoma: 3 T diffusion kurtosis imaging study","volume":"73","author":"Xu","year":"2018","journal-title":"Clin. Radiol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"4447","DOI":"10.1007\/s00330-018-5461-8","article-title":"Optic radiations are thinner and show signs of iron deposition in patients with long-standing remitting-relapsing multiple sclerosis: an enhanced T (2)(*)-weighted angiography imaging study","volume":"28","author":"Zeng","year":"2018","journal-title":"Eur. Radiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1080\/02713683.2020.1849729","article-title":"Bulbar conjunctival microvascular alterations in thyroid-associated ophthalmopathy patients with different activities","volume":"46","author":"Zhang","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1167\/iovs.18-25941","article-title":"Peripapillary and macular vessel density in dysthyroid optic neuropathy: an optical coherence tomography angiography study","volume":"60","author":"Zhang","year":"2019","journal-title":"Invest. Ophthalmol. Vis. 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