Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy

Alison M. Barnard, Rebecca J. Willcocks, Erika Finanger, Michael J. Daniels, William T. Triplett, William Rooney, Donovan J. Lott, Sean C. Forbes, Dah Jyuu Wang, Claudia R. Senesac, Ann T. Harrington, Richard S. Finkel, Barry S. Russman, Barry J. Byrne, Gihan I. Tennekoon, Glenn A. Walter, H. Lee Sweeney, Krista Vandenborne

Research output: Contribution to journalArticle

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Abstract

Objective To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design. Methods MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests. Results Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation. Discussion Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

Original languageEnglish (US)
Article numbere0194283
JournalPLoS One
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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muscular dystrophy
Duchenne Muscular Dystrophy
Biomarkers
Magnetic resonance
Muscle
skeletal muscle
biomarkers
Skeletal Muscle
Magnetic Resonance Spectroscopy
muscles
Lower Extremity
endpoints
Muscles
Pathology
spectroscopy
image analysis
Quadriceps Muscle
Fats
Spectroscopy
intramuscular fat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy. / Barnard, Alison M.; Willcocks, Rebecca J.; Finanger, Erika; Daniels, Michael J.; Triplett, William T.; Rooney, William; Lott, Donovan J.; Forbes, Sean C.; Wang, Dah Jyuu; Senesac, Claudia R.; Harrington, Ann T.; Finkel, Richard S.; Russman, Barry S.; Byrne, Barry J.; Tennekoon, Gihan I.; Walter, Glenn A.; Sweeney, H. Lee; Vandenborne, Krista.

In: PLoS One, Vol. 13, No. 3, e0194283, 01.03.2018.

Research output: Contribution to journalArticle

Barnard, AM, Willcocks, RJ, Finanger, E, Daniels, MJ, Triplett, WT, Rooney, W, Lott, DJ, Forbes, SC, Wang, DJ, Senesac, CR, Harrington, AT, Finkel, RS, Russman, BS, Byrne, BJ, Tennekoon, GI, Walter, GA, Sweeney, HL & Vandenborne, K 2018, 'Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy', PLoS One, vol. 13, no. 3, e0194283. https://doi.org/10.1371/journal.pone.0194283
Barnard, Alison M. ; Willcocks, Rebecca J. ; Finanger, Erika ; Daniels, Michael J. ; Triplett, William T. ; Rooney, William ; Lott, Donovan J. ; Forbes, Sean C. ; Wang, Dah Jyuu ; Senesac, Claudia R. ; Harrington, Ann T. ; Finkel, Richard S. ; Russman, Barry S. ; Byrne, Barry J. ; Tennekoon, Gihan I. ; Walter, Glenn A. ; Sweeney, H. Lee ; Vandenborne, Krista. / Skeletal muscle magnetic resonance biomarkers correlate with function and sentinel events in Duchenne muscular dystrophy. In: PLoS One. 2018 ; Vol. 13, No. 3.
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abstract = "Objective To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design. Methods MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests. Results Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation. Discussion Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.",
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AU - Barnard, Alison M.

AU - Willcocks, Rebecca J.

AU - Finanger, Erika

AU - Daniels, Michael J.

AU - Triplett, William T.

AU - Rooney, William

AU - Lott, Donovan J.

AU - Forbes, Sean C.

AU - Wang, Dah Jyuu

AU - Senesac, Claudia R.

AU - Harrington, Ann T.

AU - Finkel, Richard S.

AU - Russman, Barry S.

AU - Byrne, Barry J.

AU - Tennekoon, Gihan I.

AU - Walter, Glenn A.

AU - Sweeney, H. Lee

AU - Vandenborne, Krista

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N2 - Objective To provide evidence for quantitative magnetic resonance (qMR) biomarkers in Duchenne muscular dystrophy by investigating the relationship between qMR measures of lower extremity muscle pathology and functional endpoints in a large ambulatory cohort using a multicenter study design. Methods MR spectroscopy and quantitative imaging were implemented to measure intramuscular fat fraction and the transverse magnetization relaxation time constant (T2) in lower extremity muscles of 136 participants with Duchenne muscular dystrophy. Measures were collected at 554 visits over 48 months at one of three imaging sites. Fat fraction was measured in the soleus and vastus lateralis using MR spectroscopy, while T2 was assessed using MRI in eight lower extremity muscles. Ambulatory function was measured using the 10m walk/run, climb four stairs, supine to stand, and six minute walk tests. Results Significant correlations were found between all qMR and functional measures. Vastus lateralis qMR measures correlated most strongly to functional endpoints (|ρ| = 0.68-0.78), although measures in other rapidly progressing muscles including the biceps femoris (|ρ| = 0.63-0.73) and peroneals (|ρ| = 0.59-0.72) also showed strong correlations. Quantitative MR biomarkers were excellent indicators of loss of functional ability and correlated with qualitative measures of function. A VL FF of 0.40 was an approximate lower threshold of muscle pathology associated with loss of ambulation. Discussion Lower extremity qMR biomarkers have a robust relationship to clinically meaningful measures of ambulatory function in Duchenne muscular dystrophy. These results provide strong supporting evidence for qMR biomarkers and set the stage for their potential use as surrogate outcomes in clinical trials.

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