{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:44:19Z","timestamp":1783338259631,"version":"3.54.6"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["113302001"],"award-info":[{"award-number":["113302001"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Replacement of muscle tissue by fat in patients with Becker muscular dystrophy (BMD), as measured by quantitative muscle MRI, has been shown to reflect disease progression, but this process is considered irreversible. To monitor treatment effects in healthy\u2010appearing muscles, biomarkers reflecting disease activity are needed. Here, we compare several candidate biomarkers for disease activity between patients with BMD and controls: intracellular ionised magnesium ([Mg<jats:sup>2+<\/jats:sup>]), phosphodiesters (PDE), and weighted pH measures from phosphorus\u2010(<jats:sup>31<\/jats:sup>P)\u2010MRS; and membrane permeability derived from the random permeable barrier model (RBPM), as applied to diffusion\u2010tensor\u2010(DT)\u2010MRI data. We performed 7\u2009T <jats:sup>31<\/jats:sup>P\u2010MRS and 3\u2009T DT\u2010MRI in the left lower leg of 23 participants with BMD (mean [range] age: 41.1 [18.8\u201366.2] years) and 14 healthy controls (mean [range] age: 43.0 [21.2\u201363.6] years), estimating [Mg<jats:sup>2+<\/jats:sup>], PDE\/\u03b3\u2010ATP, weighted pH and RPBM permeability. Follow\u2010up scans at 24\u2009months were performed in a subset of these participants. Muscles in patients with BMD were regarded as likely to be \u2018preserved\u2019 (BMD<jats:sub>pre<\/jats:sub>) with fat fractions \u2264\u200913.5% and as \u2018progressing\u2019 (BMD<jats:sub>prog<\/jats:sub>) with 13.5%\u2009&lt;\u2009fat fraction &lt;\u200981.5%. Muscles with fat fractions\u2009\u2265\u200981.5% were excluded from further analyses. We observed decreased [Mg<jats:sup>2+<\/jats:sup>] in BMD<jats:sub>pre<\/jats:sub> and BMD<jats:sub>prog<\/jats:sub> compared to healthy controls, whereas PDE\/\u03b3\u2010ATP and weighted pH were increased in these muscles. RBPM\u2010measured permeability did not differ between groups. We observed no longitudinal changes in [Mg<jats:sup>2+<\/jats:sup>], PDE\/\u03b3\u2010ATP or weighted pH. Only [Mg<jats:sup>2+<\/jats:sup>] continued to show group differences on inclusion of longitudinal data, and weighted pH demonstrated inter\u2010muscle differences. In patients with BMD, <jats:sup>31<\/jats:sup>P\u2010MRS demonstrates reduced [Mg<jats:sup>2+<\/jats:sup>] and increased weighted pH in the lower leg muscles versus controls, suggesting greater membrane permeability\u2014a potential disease activity biomarker independent of the disease phase. PDE\/\u03b3\u2010ATP was also significantly increased in progressing and preserved muscle. Incorporating <jats:sup>31<\/jats:sup>P\u2010MRS in therapeutic trials will help to further establish its use as a response biomarker.<\/jats:p>","DOI":"10.1002\/nbm.70155","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T06:56:44Z","timestamp":1759906604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Skeletal Muscle Membrane Permeability Markers Derived From <sup>31<\/sup>P\u2010MRS May Reflect Disease Activity in Becker Muscular Dystrophy"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3716-6584","authenticated-orcid":false,"given":"Esther\u00a0J.","family":"Schrama","sequence":"first","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Duchenne Center Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-1383","authenticated-orcid":false,"given":"Melissa\u00a0T.","family":"Hooijmans","sequence":"additional","affiliation":[{"name":"Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences VU University  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-130X","authenticated-orcid":false,"given":"Nienke\u00a0M.","family":"van de Velde","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Duchenne Center Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-5143","authenticated-orcid":false,"given":"Erik\u00a0H.","family":"Niks","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Duchenne Center Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5772-7177","authenticated-orcid":false,"given":"Hermien\u00a0E.","family":"Kan","sequence":"additional","affiliation":[{"name":"Duchenne Center Netherlands"},{"name":"C.J. Gorter MRI Center, Department of Radiology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9841-6909","authenticated-orcid":false,"given":"Donnie","family":"Cameron","sequence":"additional","affiliation":[{"name":"C.J. Gorter MRI Center, Department of Radiology Leiden University Medical Center  Leiden the Netherlands"},{"name":"Department of Medical Imaging Radboud University Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"U.S. Food & Drug Administration.Table of Surrogate Endpoints That Were the Basis of Drug Approval or Licensure [updated 17 December 20244 April 2025]. Available from:https:\/\/www.fda.gov\/drugs\/development\u2010resources\/table\u2010surrogate\u2010endpoints\u2010were\u2010basis\u2010drug\u2010approval\u2010or\u2010licensure."},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201000130"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25804"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-160145"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301247"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1522-2594(200010)44:4<655::AID-MRM22>3.0.CO;2-T"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2004.08.004"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.11.005"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3839"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4115"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(79)85162-0"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nphys1936"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3087"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3612"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4534"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13242"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3199"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4385"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-240061"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmr.b.20195"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20024"},{"key":"e_1_2_13_23_1","first-page":"121","volume-title":"Handbook of Magnetic Resonance Spectroscopy In\u00a0Vivo","author":"Schar M.","year":"2016"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26655"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01454"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28630"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10858-013-9718-x"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1090-7807(02)00069-1"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1999.00063.x"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1940050202"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1940050506"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22057"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.891"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4691"},{"key":"e_1_2_13_35_1","volume-title":"Mosby's Diagnostic and Laboratory Test Reference","author":"Pagana K. D.","year":"2019"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10109"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.29231"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910330403"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1522-2594(199902)41:2<400::AID-MRM26>3.0.CO;2-E"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6793-2-6"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00667a015"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3667"},{"key":"e_1_2_13_43_1","first-page":"4510","volume-title":"Proc Intl Soc Mag Reson Med Hawai'i, USA","author":"Forbes S.","year":"2025"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182086"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2018.09.020"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(92)90167-J"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.22181"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.02.009"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012233"}],"container-title":["NMR in Biomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nbm.70155","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:43:46Z","timestamp":1760939026000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/nbm.70155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":48,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/nbm.70155"],"URL":"https:\/\/doi.org\/10.1002\/nbm.70155","archive":["Portico"],"relation":{},"ISSN":["0952-3480","1099-1492"],"issn-type":[{"value":"0952-3480","type":"print"},{"value":"1099-1492","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"2025-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70155"}}