title: Anatomical and mesoscopic characterization of the dystrophic diaphragm: An in vivo nuclear magnetic resonance imaging study in the Golden retriever muscular dystrophy dog.
abstract: Because respiratory failure remains a major issue in Duchenne Muscular Dystrophy patients, respiratory muscles are a key target of systemic therapies. In the Golden Retriever Muscular Dystrophy (GRMD) dogs, the disease shows strong clinical and histological similarities with the human pathology, making it a valuable model for preclinical therapeutic trials. We report here the first nuclear magnetic resonance (NMR) imaging anatomical study of the diaphragm in GRMD dogs and healthy controls. Both T1- and T2-weighted images of the diaphragm of seven healthy and thirteen GRMD dogs, from 3 to 36 months of age, were acquired on a 3 tesla NMR scanner. Abnormalities of texture and shape were revealed and consisted of increases in signal intensity on T2-weighted images and in signal heterogeneity on both T1- and T2-weighted images of the dystrophic diaphragm. These abnormalities were associated with a significant thickening of the muscle and we identified a clear 8-mm-threshold distinguishing clinically preserved GRMD dogs from those more severely affected. In this study, we demonstrated the feasibility of NMR imaging of the diaphragm and depicted several anatomical and mesoscopic anomalies in the dystrophic diaphragm. NMR imaging of the diaphragm shows a promise as an outcome measure in preclinical trials using GRMD dogs.
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; Inserm U955-E10, IMRB, Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort 94700, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Thibaud
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, DRF, I(2)BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Matot
authors.affiliation: Inserm U955-E10, IMRB, Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort 94700, France.
authors.forename: I
authors.initials: I
authors.lastname: Barthélémy
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, DRF, I(2)BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Fromes
authors.affiliation: Inserm U955-E10, IMRB, Université Paris Est, Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort 94700, France.
authors.forename: S
authors.initials: S
authors.lastname: Blot
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, DRF, I(2)BM, MIRCen, NMR Laboratory, Paris, France. Electronic address: p.carlier@institut-myologie.org.
authors.forename: P G
authors.initials: PG
authors.lastname: Carlier
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000000981:diagnostic imaging*; D004285:Dogs; D016189:Dystrophin / Q000172:deficiency; D008279:Magnetic Resonance Imaging; D009137:Muscular Dystrophy, Animal / Q000000981:diagnostic imaging*
chemical_list: D016189:Dystrophin
keywords: Diaphragm; Dog; Dystrophin; GRMD; Imaging; MRI; NMR