{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:38:55Z","timestamp":1792647535049,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1F1A1064070"],"award-info":[{"award-number":["NRF\u20102022R1F1A1064070"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024838","name":"Samsung Medical Center, Sungkyunkwan University","doi-asserted-by":"publisher","award":["SMX1250051"],"award-info":[{"award-number":["SMX1250051"]}],"id":[{"id":"10.13039\/501100024838","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>Progressive intramuscular fat infiltration is a hallmark of neuromuscular degeneration in Charcot\u2013Marie\u2013Tooth disease type 1A (CMT1A). Quantitative assessment of muscle fat fraction (FF) by Dixon magnetic resonance imaging (MRI) provides an objective biomarker of disease severity, but manual segmentation is laborious and variable. This study explored whether automated MRI\u2010based FF quantification reflects disease severity and functional decline in CMT1A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sixty\u2010nine genetically confirmed patients with CMT1A who underwent 3D multi\u2010echo Dixon lower\u2010leg MRI were retrospectively analyzed. A deep learning\u2013based segmentation model delineated four muscle compartments (anterior, lateral, deep posterior, superficial posterior) and mean FFs were computed volumetrically. Correlations were tested between MRI\u2010derived FFs and clinical outcomes, including the Charcot\u2013Marie\u2013Tooth Neuropathy Score (CMTNSv2), Functional Disability Scale (FDS), and time\u2010, strength\u2010, distance\u2010, and repetition\u2010based performance. Partial correlations were adjusted for age and body mass index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All compartmental and total FFs correlated positively with CMTNSv2 and FDS (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.39\u20130.49,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). FFs were positively associated with time\u2010based and negatively with strength\u2010, distance\u2010, and repetition\u2010based measures. FF Anterior showed moderate correlations with stair climb time (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.68,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and 6\u2010min walk distance (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.66,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), with similar magnitudes across compartments. Most associations remained significant after adjustment. The lateral compartment showed the highest FF (median 33.2%), consistent with the peroneal pattern of CMT1A.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Automated MRI\u2010based FF quantification provides a reproducible biomarker of disease burden in CMT1A, reflecting clinical severity and functional decline, and may serve as an imaging outcome measure in future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70430","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:06:02Z","timestamp":1792645562000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MRI<\/scp>\n                    \u2010Derived Muscle Fat Fraction Reflects Disease Severity and Functional Impairment in Charcot\u2013Marie\u2013Tooth Disease Type\n                    <scp>1A<\/scp>"],"prefix":"10.1002","author":[{"given":"Jae\u2010Hun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Radiology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-5436","authenticated-orcid":false,"given":"Ji Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Radiology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7822-5344","authenticated-orcid":false,"given":"Young Cheol","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Radiology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo Kyoung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Radiology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Artificial Intelligence Ulsan National Institute of Science and Technology  Ulsan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8400-1593","authenticated-orcid":false,"given":"Majid","family":"Chalian","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Musculoskeletal Imaging and Intervention University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung\u2010Ok","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Neurology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0179-9542","authenticated-orcid":false,"given":"Hyun Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiology, Division of Musculoskeletal Imaging and Intervention University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"issue":"4","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.1007\/s13311-021-01145-z","article-title":"Mechanisms and Treatments in Demyelinating CMT","volume":"18","author":"Fridman V.","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"4","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1007\/s13311-021-01099-2","article-title":"Axonal Charcot\u2013Marie\u2013Tooth Disease: From Common Pathogenic Mechanisms to Emerging Treatment Opportunities","volume":"18","author":"McCray B. A.","year":"2021","journal-title":"Neurotherapeutics"},{"issue":"12","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1111\/ene.12783","article-title":"Responsiveness of Clinical Outcome Measures in Charcot\u2013Marie\u2013Tooth Disease","volume":"22","author":"Piscosquito G.","year":"2015","journal-title":"European Journal of Neurology"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1474-4422(15)00242-2","article-title":"MRI Biomarker Assessment of Neuromuscular Disease Progression: A Prospective Observational Cohort Study","volume":"15","author":"Morrow J. M.","year":"2016","journal-title":"Lancet Neurology"},{"issue":"12","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210120","article-title":"Clinical Outcome Assessments and Biomarkers in Charcot\u2013Marie\u2013Tooth Disease","volume":"103","author":"McCray B. A.","year":"2024","journal-title":"Neurology"},{"issue":"12","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"e1125","DOI":"10.1212\/WNL.0000000000006214","article-title":"Validation of MRC Centre MRI Calf Muscle Fat Fraction Protocol as an Outcome Measure in CMT1A","volume":"91","author":"Morrow J. M.","year":"2018","journal-title":"Neurology"},{"issue":"14","key":"e_1_2_10_8_1","first-page":"e1480","article-title":"Fat Fraction Distribution in Lower Limb Muscles of Patients With CMT1A: A Quantitative MRI Study","volume":"94","author":"Bas J.","year":"2020","journal-title":"Neurology"},{"issue":"9","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000209277","article-title":"One\u2010Year Longitudinal Assessment of Patients With CMT1A Using Quantitative MRI","volume":"102","author":"Fortanier E.","year":"2024","journal-title":"Neurology"},{"issue":"9","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0310203","article-title":"Efficient Data Labeling Strategies for Automated Muscle Segmentation in Lower Leg MRIs of Charcot\u2013Marie\u2013Tooth Disease Patients","volume":"19","author":"Lee S. A.","year":"2024","journal-title":"PLoS One"},{"issue":"6","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1136\/jnnp-2023-332454","article-title":"Quantitative MRI Outcome Measures in CMT1A Using Automated Lower Limb Muscle Segmentation","volume":"95","author":"O'Donnell L. F.","year":"2024","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"issue":"10","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000210013","article-title":"Comparison of Manual vs. Artificial Intelligence\u2010Based Muscle MRI Segmentation for Evaluating Disease Progression in Patients With CMT1A","volume":"103","author":"Fortanier E.","year":"2024","journal-title":"Neurology"},{"issue":"2","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12021-020-09485-5","article-title":"Musclesense: A Trained, Artificial Neural Network for the Anatomical Segmentation of Lower Limb Magnetic Resonance Images in Neuromuscular Diseases","volume":"19","author":"Kanber B.","year":"2021","journal-title":"Neuroinformatics"},{"issue":"4","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/acn3.52314","article-title":"Twelve\u2010Month Change in Quantitative MRI Calf Muscle Fat Fraction in CMT1A Predicts Clinical Change Over 4\u2009Years","volume":"12","author":"Evans M. R. B.","year":"2025","journal-title":"Annals of Clinical Translational Neurology"},{"issue":"8","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s13258-022-01253-w","article-title":"Identification and Clinical Characterization of Charcot\u2013Marie\u2013Tooth Disease Type 1C Patients With LITAF p.G112S Mutation","volume":"44","author":"Park J.","year":"2022","journal-title":"Genes & Genomics"},{"issue":"6","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.3390\/life11060494","article-title":"Clinical and Neuroimaging Features in Charcot\u2013Marie\u2010Tooth Patients With GNB4 Mutations","volume":"11","author":"Kwon H. M.","year":"2021","journal-title":"Life"},{"issue":"1","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"16622","DOI":"10.1038\/s41598-022-21112-8","article-title":"Magnetic Resonance Imaging\u2010Based Lower Limb Muscle Evaluation in Charcot\u2013Marie\u2013Tooth Disease Type 1A Patients and Its Correlation With Clinical Data","volume":"12","author":"Kim Y. J.","year":"2022","journal-title":"Scientific Reports"},{"issue":"1","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"37993","DOI":"10.1038\/s41598-025-21901-x","article-title":"Evaluation of Normalized T1 Signal Intensity Obtained Using an Automated Segmentation Model in Lower Leg MRI as a Potential Imaging Biomarker in Charcot\u2013Marie\u2013Tooth Disease Type 1 A","volume":"15","author":"Kim J. H.","year":"2025","journal-title":"Scientific Reports"},{"issue":"1","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3988\/jcn.2021.17.1.52","article-title":"Clinical and Neuroimaging Features in Charcot\u2013Marie\u2010Tooth Patients With GDAP1 Mutations","volume":"17","author":"Kim H. S.","year":"2021","journal-title":"Journal of Clinical Neurology"},{"issue":"3","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/jns.12084","article-title":"Psychometrics Evaluation of Charcot\u2013Marie\u2010Tooth Neuropathy Score (CMTNSv2) Second Version, Using Rasch Analysis","volume":"19","author":"Sadjadi R.","year":"2014","journal-title":"Journal of the Peripheral Nervous System"},{"issue":"5","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1093\/brain\/120.5.813","article-title":"Charcot\u2013Marie\u2013Tooth Disease Type 1A With 17p11.2 Duplication. Clinical and Electrophysiological Phenotype Study and Factors Influencing Disease Severity in 119 Cases","volume":"120","author":"Birouk N.","year":"1997","journal-title":"Brain"},{"issue":"4","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1161\/ATVBAHA.112.301009","article-title":"Intramuscular Fat and Associations With Metabolic Risk Factors in the Framingham Heart Study","volume":"33","author":"Therkelsen K. E.","year":"2013","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology"},{"issue":"1","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12880-017-0185-9","article-title":"Three\u2010Dimensional Comparison of Intramuscular Fat Content Between Young and Old Adults","volume":"17","author":"Yoshiko A.","year":"2017","journal-title":"BMC Medical Imaging"},{"issue":"5","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation Coefficients: Appropriate Use and Interpretation","volume":"126","author":"Schober P.","year":"2018","journal-title":"Anesthesia and Analgesia"},{"issue":"1","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini Y.","year":"1995","journal-title":"Journal of the Royal Statistical Society, Series B: Statistical Methodology"},{"issue":"2","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/mus.26352","article-title":"Magnetic Resonance Imaging of the Anterior Compartment of the Lower Leg Is a Biomarker for Weakness, Disability, and Impaired Gait in Childhood Charcot\u2013Marie\u2013Tooth Disease","volume":"59","author":"Cornett K. M. D.","year":"2019","journal-title":"Muscle & Nerve"},{"issue":"2","key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/S0014-4886(03)00293-0","article-title":"Assessment of Axonal Loss in Charcot\u2013Marie\u2010Tooth Neuropathies","volume":"184","author":"Lawson V. H.","year":"2003","journal-title":"Experimental Neurology"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70430","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70430","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:06:06Z","timestamp":1792645566000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":26,"alternative-id":["10.1002\/mus.70430"],"URL":"https:\/\/doi.org\/10.1002\/mus.70430","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"assertion":[{"value":"2026-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mus.70430"}}