Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy.
The purpose of this study was to explore the use of iterative decomposition of water and fat with echo asymmetry and least-squares estimation Carr-Purcell-Meiboom-Gill (IDEAL-CPMG) to simultaneously measure skeletal muscle apparent fat fraction and water T2(T2,w) in patients with Duchenne muscular dystrophy (DMD). In twenty healthy volunteer boys and thirteen subjects with DMD, thigh muscle apparent fat fraction was measured by Dixon and IDEAL-CPMG, with the IDEAL-CPMG also providing T2,was a measure of muscle inflammatory activity. A subset of subjects with DMD was followed up during a 48-week clinical study. The study was in compliance with the Patient Privacy Act and approved by the Institutional Review Board. Apparent fat fraction in the thigh muscles of subjects with DMD was significantly increased compared to healthy volunteer boys (p <0.001). There was a strong correlation between Dixon and IDEAL-CPMG apparent fat fraction. Muscle T2,wmeasured by IDEAL-CPMG was independent of changes in apparent fat fraction. Muscle T2,wwas higher in the biceps femoris and vastus lateralis muscles of subjects with DMD (p <0.05). There was a strong correlation (p <0.004) between apparent fat fraction in all thigh muscles and six-minute walk distance (6MWD) in subjects with DMD. IDEAL-CPMG allowed independent and simultaneous quantification of skeletal muscle fatty degeneration and disease activity in DMD. IDEAL-CPMG apparent fat fraction and T2,wmay be useful as biomarkers in clinical trials of DMD as the technique disentangles two competing biological processes.
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: Ami.Mankodi@nih.gov.
Ami
A
Mankodi
Imanova Centre for Imaging Sciences, Hammersmith Hospital, London W12 0NN, UK.
Courtney A
CA
Bishop
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Sungyoung
S
Auh
Imanova Centre for Imaging Sciences, Hammersmith Hospital, London W12 0NN, UK.
Rexford D
RD
Newbould
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Kenneth H
KH
Fischbeck
Experimental Medicine Imaging, Experimental Medicine Unit, GlaxoSmithKline, Middlesex UB11 1BT, UK.
Robert L
RL
Janiczek
D000273:Adipose Tissue / Q000000981:diagnostic imaging*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D016018:Least-Squares Analysis; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D009841:Oligonucleotides / Q000627:therapeutic use; D013848:Thigh / Q000000981:diagnostic imaging; D016896:Treatment Outcome; D000070857:Walk Test; D016138:Walking
D009841:Oligonucleotides; C525434:PRO051
Apparent fat fraction; Duchenne muscular dystrophy; Fatty degeneration; IDEAL-CPMG; Magnetic resonance imaging; Skeletal muscle; T(2) relaxation times; Water T(2)