{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:38:39Z","timestamp":1761327519802,"version":"build-2065373602"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Noninvasive and objective biomarkers for disease-associated pathology are critical for clinical trials. For Fabry disease, one important pathological change due to the deficiency of the lysosomal enzyme \u03b1-galactosidase A (\u03b1-GAL) caused is accumulation of globotriaosylceramide (Gb3) in dorsal root ganglion (DRG) neurons, which manifests as the overall DRG hypertrophy. Magnetic resonance imaging (MRI) has been successfully used to noninvasively measure DRG enlargement in Fabry patients, and DRG volumetric MRI can be a potential noninvasive biomarker for Gb3 accumulations in DRG neurons in clinical trials. To evaluate disease progression and treatment response in preclinical proof-of-concept studies, we developed an\n                    <jats:italic>in vivo<\/jats:italic>\n                    MRI method to measure DRG size in the G3Stg\/GLA knockout mouse model of Fabry disease. Compared to the wild type mice, the DRG enlargement in the Fabry mice was observed as early as 8 weeks of age, and a single administration of the human \u03b1-GAL-encoding adeno-associated virus (AAV\n                    <jats:sub>GLA<\/jats:sub>\n                    ) normalized the enlarged DRG to the age-matched wild type mice. The DRG normalization was observed within 4 weeks of gene therapy (12 weeks of age) and was sustained up to 24 weeks of age. Furthermore, behavioral testing and histological\/immunohistochemistry analyses of the DRG tissues corroborated the MRI findings. Volumetric DRG MRI has the sensitivity to measure Gb3 pathology-induced DRG volume changes and treatment response in live mice and can be a translational imaging biomarker in clinical trials for Fabry disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0334840","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T17:33:18Z","timestamp":1761327198000},"page":"e0334840","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Volumetric MRI of dorsal root ganglia as a biomarker for disease progression and response to AAV treatment in a mouse model of Fabry 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Jabbarzadeh-Tabrizi","year":"2020","journal-title":"J Lipid Res"},{"issue":"4","key":"pone.0334840.ref003","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1136\/jmg.20.4.309","article-title":"Involvement of dorsal root ganglia in Fabry\u2019s disease","volume":"20","author":"N Gadoth","year":"1983","journal-title":"J Med Genet"},{"key":"pone.0334840.ref004","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.39300","article-title":"Characterization of small fiber pathology in a mouse model of Fabry disease","volume":"7","author":"L Hofmann","year":"2018","journal-title":"Elife"},{"key":"pone.0334840.ref005","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13023-014-0111-y","article-title":"Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4\u2009+\u2009919G>A)","volume":"9","author":"H-C Liu","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"pone.0334840.ref006","doi-asserted-by":"crossref","first-page":"232640981666135","DOI":"10.1177\/2326409816661351","article-title":"Small Fiber Neuropathy in Fabry Disease: a Review of Pathophysiology and Treatment","volume":"4","author":"JM Politei","year":"2016","journal-title":"J Inborn Errors Metabolism Screening"},{"issue":"12","key":"pone.0334840.ref007","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1212\/WNL.0000000000004396","article-title":"Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy","volume":"89","author":"T Godel","year":"2017","journal-title":"Neurology"},{"issue":"6","key":"pone.0334840.ref008","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1007\/s00415-019-09262-8","article-title":"Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y","volume":"266","author":"T Godel","year":"2019","journal-title":"J Neurol"},{"issue":"11","key":"pone.0334840.ref009","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1007\/s00415-018-9053-y","article-title":"Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease","volume":"265","author":"T Godel","year":"2018","journal-title":"J Neurol"},{"issue":"12","key":"pone.0334840.ref010","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.3390\/diagnostics10121027","article-title":"Assessment of Peripheral Nervous System Alterations in Patients with the Fabry Related GLA-Variant p.A143T","volume":"10","author":"T Godel","year":"2020","journal-title":"Diagnostics (Basel)"},{"key":"pone.0334840.ref011","doi-asserted-by":"crossref","first-page":"121189","DOI":"10.1016\/j.neuroimage.2025.121189","article-title":"Automated segmentation of the dorsal root ganglia in MRI","volume":"311","author":"AC 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Castillo","year":"1996","journal-title":"Neuroradiology"},{"issue":"6","key":"pone.0334840.ref018","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3390\/ani11061702","article-title":"Changes of dorsal root ganglion volume in dogs with clinical signs of degenerative myelopathy detected by water-excitation magnetic resonance imaging","volume":"11","author":"E Naito","year":"2021","journal-title":"Animals (Basel)"},{"key":"pone.0334840.ref019","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.omtm.2022.01.013","article-title":"Characterization of AAV-mediated dorsal root ganglionopathy","volume":"24","author":"N Buss","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"issue":"1","key":"pone.0334840.ref020","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.expneurol.2006.07.013","article-title":"Volumetric magnetic resonance imaging of dorsal root ganglia for the objective quantitative assessment of neuron death after peripheral nerve injury","volume":"203","author":"CA West","year":"2007","journal-title":"Exp Neurol"},{"issue":"3","key":"pone.0334840.ref021","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.ajpath.2014.11.004","article-title":"\u03b1-Galactosidase A knockout mice: progressive organ pathology resembles the type 2 later-onset phenotype of Fabry disease","volume":"185","author":"DS Bangari","year":"2015","journal-title":"Am J Pathol"},{"issue":"3","key":"pone.0334840.ref022","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/BJ20130825","article-title":"A symptomatic Fabry disease mouse model generated by inducing globotriaosylceramide synthesis","volume":"456","author":"A Taguchi","year":"2013","journal-title":"Biochem J"},{"issue":"11","key":"pone.0334840.ref023","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1194\/jlr.RA120000909","article-title":"Assessing the role of glycosphingolipids in the phenotype severity of Fabry disease mouse 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Taguchi","year":"2013","journal-title":"Biochem J"},{"key":"pone.0334840.ref027","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neuroimage.2012.11.048","article-title":"Vertebral landmarks for the identification of spinal cord segments in the mouse","volume":"68","author":"M Harrison","year":"2013","journal-title":"Neuroimage"},{"key":"pone.0334840.ref028","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1089\/hum.2023.222","article-title":"Developing gene therapy for mitigating multisystemic pathology in fabry disease: proof of concept in an aggravated mouse model","volume":"35","author":"N Boukharov","year":"2024","journal-title":"Hum Gene Ther"},{"issue":"1","key":"pone.0334840.ref029","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1037\/1082-989X.1.1.30","article-title":"Forming inferences about some intraclass correlation coefficients.","volume":"1","author":"KO McGraw","year":"1996","journal-title":"Psychological Methods"},{"unstructured":"Salarian A. Intraclass Correlation Coefficient (ICC). https:\/\/www.mathworks.com\/matlabcentral\/fileexchange\/22099-intraclass-correlation-coefficient-icc. Accessed 2023.","key":"pone.0334840.ref030"},{"issue":"8476","key":"pone.0334840.ref031","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"327","author":"J Martin Bland","year":"1986","journal-title":"The Lancet"},{"issue":"2","key":"pone.0334840.ref032","doi-asserted-by":"crossref","first-page":"141","DOI":"10.11613\/BM.2015.015","article-title":"Understanding Bland Altman analysis","volume":"25","author":"D Giavarina","year":"2015","journal-title":"Biochem Med (Zagreb)"},{"issue":"3","key":"pone.0334840.ref033","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3390\/biomedicines13030577","article-title":"Reversing pathology in an aggravated fabry mouse model using low-dose engineered human alpha-galactosidase A AAV gene therapy","volume":"13","author":"W Ruangsiriluk","year":"2025","journal-title":"Biomedicines"},{"issue":"7","key":"pone.0334840.ref034","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.3390\/diagnostics12071570","article-title":"Dorsal Root Ganglia Volume-Normative Values, Correlation with Demographic Determinants and Reliability of Three Different Methods of Volumetry","volume":"12","author":"M Kronlage","year":"2022","journal-title":"Diagnostics (Basel)"},{"issue":"4","key":"pone.0334840.ref035","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.neuroimage.2005.11.013","article-title":"Cortical layer-dependent BOLD and CBV responses measured by spin-echo and gradient-echo fMRI: insights into hemodynamic regulation","volume":"30","author":"F Zhao","year":"2006","journal-title":"Neuroimage"},{"issue":"2","key":"pone.0334840.ref036","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.neuroimage.2005.04.011","article-title":"Spatial specificity of cerebral blood volume-weighted fMRI responses at columnar resolution","volume":"27","author":"F Zhao","year":"2005","journal-title":"Neuroimage"},{"issue":"1","key":"pone.0334840.ref037","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41598-017-18801-0","article-title":"Skeletal Characterization of the Fgfr3 Mouse Model of Achondroplasia Using Micro-CT and MRI Volumetric Imaging","volume":"8","author":"MS Shazeeb","year":"2018","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0334840.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0183845","article-title":"Dorsal root ganglia hypertrophy as in vivo correlate of oxaliplatin-induced polyneuropathy","volume":"12","author":"L Apostolidis","year":"2017","journal-title":"PLoS One"},{"issue":"4","key":"pone.0334840.ref039","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1002\/ana.25191","article-title":"Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2","volume":"83","author":"T Godel","year":"2018","journal-title":"Ann Neurol"},{"issue":"4","key":"pone.0334840.ref040","doi-asserted-by":"crossref","first-page":"851","DOI":"10.3171\/2014.6.JNS132364","article-title":"Minimally invasive convection-enhanced delivery of biologics into dorsal root ganglia: validation in the pig model and prospective modeling in humans. Technical note","volume":"121","author":"J Pleticha","year":"2014","journal-title":"J Neurosurg"},{"key":"pone.0334840.ref041","doi-asserted-by":"crossref","first-page":"149872","DOI":"10.1016\/j.brainres.2025.149872","article-title":"In vivo imaging of dorsal root ganglia in the mouse: from ex vivo MR-microscopy towards quantitative in vivo MRI","volume":"1865","author":"F Hessenauer","year":"2025","journal-title":"Brain Res"},{"issue":"3","key":"pone.0334840.ref042","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00428-005-0089-x","article-title":"Pathological findings in a patient with Fabry disease who died after 2.5 years of enzyme replacement","volume":"448","author":"R Schiffmann","year":"2006","journal-title":"Virchows Arch"},{"issue":"3","key":"pone.0334840.ref043","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.ajpath.2014.11.004","article-title":"\u03b1-Galactosidase A knockout mice: progressive organ pathology resembles the type 2 later-onset phenotype of Fabry disease","volume":"185","author":"DS Bangari","year":"2015","journal-title":"Am J Pathol"},{"issue":"11","key":"pone.0334840.ref044","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0015033","article-title":"Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease","volume":"5","author":"J Marshall","year":"2010","journal-title":"PLoS One"},{"issue":"1","key":"pone.0334840.ref045","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2119\/molmed.2015.00088","article-title":"Efficacy of Enzyme and Substrate Reduction Therapy with a Novel Antagonist of Glucosylceramide Synthase for Fabry Disease","volume":"21","author":"KM Ashe","year":"2015","journal-title":"Mol Med"},{"issue":"1","key":"pone.0334840.ref046","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12979-023-00346-8","article-title":"Age-related neuroimmune signatures in dorsal root ganglia of a Fabry disease mouse 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Med"},{"issue":"10","key":"pone.0334840.ref050","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.3390\/jcm10102160","article-title":"High prevalence of late-onset fabry cardiomyopathy in a cohort of 499 non-selective patients with left ventricular hypertrophy: the asian fabry cardiomyopathy high-risk screening study (ASIAN-FAME)","volume":"10","author":"Y Fan","year":"2021","journal-title":"J Clin Med"},{"key":"pone.0334840.ref051","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12968-015-0217-y","article-title":"Mapping tissue inhomogeneity in acute myocarditis: a novel analytical approach to quantitative myocardial edema imaging by T2-mapping","volume":"17","author":"B Bae\u00dfler","year":"2015","journal-title":"J Cardiovasc Magn Reson"},{"issue":"3","key":"pone.0334840.ref052","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3390\/biomedicines13030592","article-title":"MRI T2 mapping of dorsal root ganglia reveals increased T2 relaxation time in 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