title: Muscle MRS detects elevated PDE/ATP ratios prior to fatty infiltration in Becker muscular dystrophy.
abstract: Becker muscular dystrophy (BMD) is characterized by progressive muscle weakness. Muscles show structural changes (fatty infiltration, fibrosis) and metabolic changes, both of which can be assessed using MRI and MRS. It is unknown at what stage of the disease process metabolic changes arise and how this might vary for different metabolites. In this study we assessed metabolic changes in skeletal muscles of Becker patients, both with and without fatty infiltration, quantified via Dixon MRI and (31) P MRS. MRI and (31) P MRS scans were obtained from 25 Becker patients and 14 healthy controls using a 7 T MR scanner. Five lower-leg muscles were individually assessed for fat and muscle metabolite levels. In the peroneus, soleus and anterior tibialis muscles with non-increased fat levels, PDE/ATP ratios were higher (P < 0.02) compared with controls, whereas in all muscles with increased fat levels PDE/ATP ratios were higher compared with healthy controls (P ≤ 0.05). The Pi /ATP ratio in the peroneus muscles was higher in muscles with increased fat fractions (P = 0.005), and the PCr/ATP ratio was lower in the anterior tibialis muscles with increased fat fractions (P = 0.005). There were no other significant changes in metabolites, but an increase in tissue pH was found in all muscles of the total group of BMD patients in comparison with healthy controls (P < 0.05). These findings suggest that (31) P MRS can be used to detect early changes in individual muscles of BMD patients, which are present before the onset of fatty infiltration.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: B H
authors.initials: BH
authors.lastname: Wokke
authors.forename: M T
authors.initials: MT
authors.lastname: Hooijmans
authors.forename: J C
authors.initials: JC
authors.lastname: van den Bergen
authors.forename: A G
authors.initials: AG
authors.lastname: Webb
authors.forename: J J
authors.initials: JJ
authors.lastname: Verschuuren
authors.forename: H E
authors.initials: HE
authors.lastname: Kan
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis*; D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004185:Disability Evaluation; D018450:Disease Progression; D016189:Dystrophin / Q000235:genetics; D005260:Female; D020404:Glycerophospholipids / Q000032:analysis*; D005997:Glycerylphosphorylcholine / Q000032:analysis*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010759:Phosphorus Isotopes; D011522:Protons; D055815:Young Adult
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D020404:Glycerophospholipids; D010759:Phosphorus Isotopes; D011522:Protons; C000599355:glycerol 3-phosphoethanolamine; D005997:Glycerylphosphorylcholine; D000255:Adenosine Triphosphate
keywords: Becker muscular dystrophy; MRS; PDE; phosphor spectroscopy