{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:03:26Z","timestamp":1784887406360,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007873","name":"Heimer Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003417","name":"Deutsche Gesetzliche Unfallversicherung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003417","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Late\u2010onset Pompe disease (LOPD) is a progressive metabolic myopathy characterised by lysosomal glycogen accumulation and leading to secondary disruptions in autophagy and cellular energy metabolism. While enzyme replacement therapy (ERT) has improved outcomes, early detection remains critical, because irreversible muscle damage often precedes overt clinical symptoms. This study investigates whether quantitative MRI (qMRI) can detect subclinical disease progression and correlate with clinical decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Over a 2\u2010year period, 25 participants (10 LOPD (disease duration 131\u2009\u00b1\u2009127\u2009months; ERT 76\u2009\u00b1\u200972\u2009months; two dropouts) and 15 age\/sex\u2010matched controls) underwent longitudinal clinical and MRI assessments at intervals of ~4\u2009months (\u00b1\u20094\u2009weeks; T1\u2013T7). Clinical tests included strength measurements (Medical Research Council, MRC), the Quick Motor Function Measure (QMFM), patient\u2010reported outcomes (ACTIVLIM; Neuromuscular Symptom Score\u2014NSS) and gait analysis. The 3.0T lower extremity MRI included multi\u2010echo, gradient\u2010echo, a Dixon\u2010based sequence for fat quantification (fat fraction [FF]), a multi\u2010echo, spin\u2010echo sequence for T2 mapping (wT2) and a spin\u2010echo EPI diffusion\u2010weighted sequence. Baseline differences in quantitative MRI (qMRI) metrics between patients and controls were assessed using multivariate analysis of variance. Longitudinal changes and associations with clinical outcomes were evaluated using linear mixed\u2010effects models (LMMs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Group differences were found for ACTIVLIM (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.027), NSS (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.001) and MRC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090,027) from T6\/T7. Baseline differences of qMRI metrics between groups were found for FF (mean difference\u2009=\u20090.071,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), wT2 (mean difference\u2009=\u20091.925,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and fractional anisotropy (mean difference\u2009=\u20090.010,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029). In muscles with FF\u2009&lt;\u200910%, diffusion metrics did not differ (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2265\u20090.332), whereas wT2 remained elevated in LOPD (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). LMMs revealed a significant increase in FF in LOPD patients from T4 onward (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.029), particularly in thigh muscles, while wT2 and diffusion metrics remained stable over time. LMMs demonstrated significant associations between thigh muscle qMRI metrics and clinical outcomes, for example between FF and QMFM (estimate: \u22125.16;\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.76;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) or wT2 and QMFM (estimate: \u22120.64;\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.83;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Interestingly, wT2 showed a modest positive association over time for ACTIVLIM (estimate: 0.005;\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.517;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.010).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although muscle function is measurable clinically, qMRI captured alterations beyond clinical detection; its correlation with clinical scores supports qMRI as a more sensitive surrogate marker. Our findings indicate that FF changes preceded alterations in clinical outcome, highlighting sensitivity to early disease progression. The lack of a consistent temporal pattern in wT2 and diffusion metrics warrants further studies to fully understand underlying mechanisms in LOPD. Larger, long\u2010term studies are needed to validate qMRI for monitoring disease progression and therapeutic response in LOPD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70304","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:41:33Z","timestamp":1780321293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal Assessment of Muscle Involvement in Late\u2010Onset Pompe Disease Using Quantitative MRI: A Prospective Cohort Study"],"prefix":"10.1002","volume":"17","author":[{"given":"Alice","family":"De Lorenzo","sequence":"first","affiliation":[{"name":"Department of Neurology, BG\u2010University Hospital Bergmannsheil Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Heimer Institute for Muscle Research BG\u2010University Hospital Bergmannsheil  Bochum 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Enax\u2010Krumova","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG\u2010University Hospital Bergmannsheil Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Heimer Institute for Muscle Research BG\u2010University Hospital Bergmannsheil  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Kleefeld","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG\u2010University Hospital Bergmannsheil Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Heimer Institute for Muscle Research BG\u2010University Hospital Bergmannsheil  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menekse","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Neurology, BG\u2010University Hospital Bergmannsheil Ruhr\u2010University Bochum  Bochum 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Bergmannsheil Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Heimer Institute for Muscle Research BG\u2010University Hospital Bergmannsheil  Bochum Germany"},{"name":"Department of Neuropediatrics and Social Pediatrics, University Hospital of Pediatrics and Adolescent Medicine, St. Josef\u2010Hospital Ruhr\u2010University Bochum  Bochum Germany"},{"name":"Department of Information Technology Dortmund University of Applied Sciences and Arts  Dortmund Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103794"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20807"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.12.006"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31322"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6636-x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13285"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00241-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00331-8"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0580"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-024-04837-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52143-6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29091"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9825-9"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27021"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10928"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.675781"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13071958"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-49971-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.02.013"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9388-3"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312303292704"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.5172"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4119"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01204"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21890"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.08.016"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.05.028"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26259"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20624"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3459"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3427"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23972-6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008441"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004711"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12555"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29170-7"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.05.013"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4111"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-022-08862-9"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27099"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T09:18:55Z","timestamp":1784884735000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/jcsm.70304"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70304","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2025-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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