Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy

Rebecca J. Willcocks; Alison M. Barnard; Michael J. Daniels; Sean C. Forbes; William T. Triplett; John F. Brandsema; Erika L. Finanger; William D. Rooney; Sarah Kim; Dah Jyuu Wang; Donovan J. Lott; Claudia R. Senesac; Glenn A. Walter; H. Lee Sweeney; Krista Vandenborne

doi:10.1002/acn3.51933

Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy

Rebecca J. Willcocks
, Alison M. Barnard
, Michael J. Daniels
, Sean C. Forbes
, William T. Triplett
, John F. Brandsema
, Erika L. Finanger
, William D. Rooney
, Sarah Kim
, Dah Jyuu Wang
, Donovan J. Lott
, Claudia R. Senesac
, Glenn A. Walter
, H. Lee Sweeney
, Krista Vandenborne

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

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-T₂), 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-T₂. Interpretation: MR measures of FF and MRI T₂ 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.

Original language	English (US)
Pages (from-to)	67-78
Number of pages	12
Journal	Annals of Clinical and Translational Neurology
Volume	11
Issue number	1
DOIs	https://doi.org/10.1002/acn3.51933
State	Published - Jan 1 2024

Funding

This study was supported by grant funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01‐AR056973 and U54‐AR052646). MRI data was collected in the McKnight Brain Institute at the National High Magnetic Field Laboratory's Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) Facility, which is supported by National Science Foundation Cooperative Agreement No. DMR‐1644779 and DMR‐1157490 and the State of Florida, and in OHSU's Advanced Imaging Research Center, supported by NIH S10OD021701 for the 3T Siemens Prisma MRI instrument. AMB was supported by a Rehabilitation Research Career Development Award (NIH K12 HD055929). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders. We are very grateful to the study participants and their families.

Funders	Funder number
Author National Science Foundation National Science Foundation National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health National Science Foundation National Science Foundation	DMR‐1644779, DMR‐1157490
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	K12 HD055929, R01‐AR056973, U54‐AR052646, S10OD021701
National Institute of Neurological Disorders and Stroke
National Institute for Arthritis and Musculoskeletal and Skin Diseases
Florida State University

ASJC Scopus subject areas

General Neuroscience
Clinical Neurology

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10.1002/acn3.51933

Cite this

Willcocks, R. J., Barnard, A. M., Daniels, M. J., Forbes, S. C., Triplett, W. T., Brandsema, J. F., Finanger, E. L., Rooney, W. D., Kim, S., Wang, D. J., Lott, D. J., Senesac, C. R., Walter, G. A., Sweeney, H. L., & Vandenborne, K. (2024). Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy. Annals of Clinical and Translational Neurology, 11(1), 67-78. https://doi.org/10.1002/acn3.51933

Willcocks, RJ, Barnard, AM, Daniels, MJ, Forbes, SC, Triplett, WT, Brandsema, JF, Finanger, EL , Rooney, WD, Kim, S, Wang, DJ, Lott, DJ, Senesac, CR, Walter, GA, Sweeney, HL & Vandenborne, K 2024, 'Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy', Annals of Clinical and Translational Neurology, vol. 11, no. 1, pp. 67-78. https://doi.org/10.1002/acn3.51933

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title = "Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy",

abstract = "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-T2), 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-T2. Interpretation: MR measures of FF and MRI T2 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.",

author = "Willcocks, \{Rebecca J.\} and Barnard, \{Alison M.\} and Daniels, \{Michael J.\} and Forbes, \{Sean C.\} and Triplett, \{William T.\} and Brandsema, \{John F.\} and Finanger, \{Erika L.\} and Rooney, \{William D.\} and Sarah Kim and Wang, \{Dah Jyuu\} and Lott, \{Donovan J.\} and Senesac, \{Claudia R.\} and Walter, \{Glenn A.\} and Sweeney, \{H. Lee\} and Krista Vandenborne",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.",

year = "2024",

month = jan,

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doi = "10.1002/acn3.51933",

language = "English (US)",

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T1 - Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy

AU - Willcocks, Rebecca J.

AU - Barnard, Alison M.

AU - Daniels, Michael J.

AU - Forbes, Sean C.

AU - Triplett, William T.

AU - Brandsema, John F.

AU - Finanger, Erika L.

AU - Rooney, William D.

AU - Kim, Sarah

AU - Wang, Dah Jyuu

AU - Lott, Donovan J.

AU - Senesac, Claudia R.

AU - Walter, Glenn A.

AU - Sweeney, H. Lee

AU - Vandenborne, Krista

PY - 2024/1/1

Y1 - 2024/1/1

N2 - 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-T2), 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-T2. Interpretation: MR measures of FF and MRI T2 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.

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-T2), 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-T2. Interpretation: MR measures of FF and MRI T2 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.

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JO - Annals of Clinical and Translational Neurology

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Clinical importance of changes in magnetic resonance biomarkers for Duchenne muscular dystrophy

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