PMID- 37932907 OWN - NLM STAT- MEDLINE DCOM- 20240117 LR - 20240221 IS - 2328-9503 (Electronic) IS - 2328-9503 (Linking) VI - 11 IP - 1 DP - 2024 Jan TI - Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy. PG - 67-78 LID - 10.1002/acn3.51933 [doi] AB - OBJECTIVE: Magnetic resonance (MR) measures of muscle quality are highly sensitive to disease progression and predictive of meaningful functional milestones in Duchenne muscular dystrophy (DMD). This investigation aimed to establish the reproducibility, responsiveness to disease progression, and minimum clinically important difference (MCID) for multiple MR biomarkers at different disease stages in DMD using a large natural history dataset. METHODS: Longitudinal MR imaging and spectroscopy outcomes and ambulatory function were measured in 180 individuals with DMD at three sites, including repeated measurements on two separate days (within 1 week) in 111 participants. These data were used to calculate day-to-day reproducibility, responsiveness (standardized response mean, SRM), minimum detectable change, and MCID. A survey of experts was also performed. RESULTS: MR spectroscopy fat fraction (FF), as well as MR imaging transverse relaxation time (MRI-T(2) ), measures performed in multiple leg muscles, and had high reproducibility (Pearson's R > 0.95). Responsiveness to disease progression varied by disease stage across muscles. The average FF from upper and lower leg muscles was highly responsive (SRM > 0.9) in both ambulatory and nonambulatory individuals. MCID estimated from the distribution of scores, by anchoring to function, and via expert opinion was between 0.01 and 0.05 for FF and between 0.8 and 3.7 ms for MRI-T(2) . INTERPRETATION: MR measures of FF and MRI T(2) are reliable and highly responsive to disease progression. The MCID for MR measures is less than or equal to the typical annualized change. These results confirm the suitability of these measures for use in DMD and potentially other muscular dystrophies. CI - (c) 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. FAU - Willcocks, Rebecca J AU - Willcocks RJ AUID- ORCID: 0000-0003-3383-0759 AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Barnard, Alison M AU - Barnard AM AUID- ORCID: 0000-0001-7715-0865 AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Daniels, Michael J AU - Daniels MJ AD - Department of Statistics, University of Florida, Gainesville, Florida, USA. FAU - Forbes, Sean C AU - Forbes SC AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Triplett, William T AU - Triplett WT AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Brandsema, John F AU - Brandsema JF AD - Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. FAU - Finanger, Erika L AU - Finanger EL AD - Department of Pediatrics and Neurology, Oregon Health & Science University, Portland, Oregon, USA. FAU - Rooney, William D AU - Rooney WD AD - Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, USA. FAU - Kim, Sarah AU - Kim S AUID- ORCID: 0000-0002-9179-0735 AD - Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Wang, Dah-Jyuu AU - Wang DJ AD - Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. FAU - Lott, Donovan J AU - Lott DJ AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Senesac, Claudia R AU - Senesac CR AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. FAU - Walter, Glenn A AU - Walter GA AD - Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Sweeney, H Lee AU - Sweeney HL AD - Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Vandenborne, Krista AU - Vandenborne K AD - Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA. LA - eng GR - S10 OD021701/OD/NIH HHS/United States GR - K12 HD055929/HD/NICHD NIH HHS/United States GR - P50 AR052646/AR/NIAMS NIH HHS/United States GR - R01 AR056973/AR/NIAMS NIH HHS/United States GR - R01-AR056973/AR/NIAMS NIH HHS/United States GR - U54-AR052646/AR/NIAMS NIH HHS/United States GR - NIH S10OD021701/NH/NIH HHS/United States GR - U54 AR052646/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20231106 PL - United States TA - Ann Clin Transl Neurol JT - Annals of clinical and translational neurology JID - 101623278 RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Muscular Dystrophy, Duchenne/diagnostic imaging MH - Clinical Relevance MH - Reproducibility of Results MH - Magnetic Resonance Spectroscopy/methods MH - Magnetic Resonance Imaging/methods MH - Biomarkers MH - Disease Progression PMC - PMC10791017 COIS- The authors do not report any conflicts of interest that are directly relevant to this study. EDAT- 2023/11/07 06:46 MHDA- 2024/01/17 06:42 PMCR- 2023/11/06 CRDT- 2023/11/07 00:13 PHST- 2023/10/03 00:00 [revised] PHST- 2023/04/17 00:00 [received] PHST- 2023/10/08 00:00 [accepted] PHST- 2024/01/17 06:42 [medline] PHST- 2023/11/07 06:46 [pubmed] PHST- 2023/11/07 00:13 [entrez] PHST- 2023/11/06 00:00 [pmc-release] AID - ACN351933 [pii] AID - 10.1002/acn3.51933 [doi] PST - ppublish SO - Ann Clin Transl Neurol. 2024 Jan;11(1):67-78. doi: 10.1002/acn3.51933. Epub 2023 Nov 6.