title: Elevated phosphodiester and T2levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients.
abstract: Quantitative MRI and MRS are increasingly important as non-invasive outcome measures in therapy development for Duchenne muscular dystrophy (DMD). Many studies have focussed on individual measures such as fat fraction and metabolite levels in relation to age and functionality, but much less attention has been given to how these indices relate to each other. Here, we assessed spatially resolved metabolic changes in leg muscles of DMD patients, and classified muscles according to the degree of fat replacement compared with healthy controls. Quantitative MRI (three-point Dixon and multi-spin echo without fat suppression and a tri-exponential fit) and 2D-CSI31P MRS scans were obtained from 18 DMD patients and 12 healthy controls using a 3 T and a 7 T MR scanner. Metabolite levels, T2values and fat fraction were individually assessed for five lower leg muscles. In muscles with extensive fat replacement, phosphodiester over adenosine triphosphate (PDE/ATP), inorganic phosphate over phosphocreatine, intracellular tissue pH and T2were significantly increased compared with healthy controls. In contrast, in muscles without extensive fat replacement, only PDE/ATP and T2values were significantly elevated. Overall, our results show that PDE levels and T2values increase prior to the occurrence of fat replacement and remain elevated in later stages of the disease. This suggests that these individual measures could not only function as early markers for muscle damage but also reflect potentially reversible pathology in the more advanced stages.
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Hooijmans
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Niks
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Burakiewicz
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J J G M
authors.initials: JJ
authors.lastname: Verschuuren
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Webb
authors.affiliation: Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H E
authors.identifier: 0000-0002-5772-7177
authors.initials: HE
authors.lastname: Kan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D010758:Phosphorus / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D019275:Radiopharmaceuticals; D010758:Phosphorus; D000255:Adenosine Triphosphate
keywords: Duchenne muscular dystrophy; phosphorus MRS; quantitative MRI; skeletal muscle