title: Quantitative T2 combined with texture analysis of nuclear magnetic resonance images identify different degrees of muscle involvement in three mouse models of muscle dystrophy: mdx, Largemyd and mdx/Largemyd.
abstract: Quantitative nuclear magnetic resonance imaging (MRI) has been considered a promising non-invasive tool for monitoring therapeutic essays in small size mouse models of muscular dystrophies. Here, we combined MRI (anatomical images and transverse relaxation time constant-T2-measurements) to texture analyses in the study of four mouse strains covering a wide range of dystrophic phenotypes. Two still unexplored mouse models of muscular dystrophies were analyzed: The severely affected Largemyd mouse and the recently generated and worst double mutant mdx/Largemyd mouse, as compared to the mildly affected mdx and normal mice. The results were compared to histopathological findings. MRI showed increased intermuscular fat and higher muscle T2 in the three dystrophic mouse models when compared to the wild-type mice (T2: mdx/Largemyd: 37.6±2.8 ms; mdx: 35.2±4.5 ms; Largemyd: 36.6±4.0 ms; wild-type: 29.1±1.8 ms, p<0.05), in addition to higher muscle T2 in the mdx/Largemyd mice when compared to mdx (p<0.05). The areas with increased muscle T2 in the MRI correlated spatially with the identified histopathological alterations such as necrosis, inflammation, degeneration and regeneration foci. Nevertheless, muscle T2 values were not correlated with the severity of the phenotype in the 3 dystrophic mouse strains, since the severely affected Largemyd showed similar values than both the mild mdx and worst mdx/Largemyd lineages. On the other hand, all studied mouse strains could be unambiguously identified with texture analysis, which reflected the observed differences in the distribution of signals in muscle MRI. Thus, combined T2 intensity maps and texture analysis is a powerful approach for the characterization and differentiation of dystrophic muscles with diverse genotypes and phenotypes. These new findings provide important noninvasive tools in the evaluation of the efficacy of new therapies, and most importantly, can be directly applied in human translational research.
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil; NMR Laboratory, Institute of Myology, Paris, France.
authors.forename: Aurea B
authors.initials: AB
authors.lastname: Martins-Bach
authors.affiliation: Centro de Imagens e Espectroscopia in vivo por Ressonância Magnética-CIERMag. Instituto de Física de São Carlos, Universidade de São Paulo-IFSC-USP, São Paulo, São Paulo, Brazil; Departamento de Fisiologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, São Paulo, Brazil.
authors.forename: Jackeline
authors.initials: J
authors.lastname: Malheiros
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, I²BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Matot
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil.
authors.forename: Poliana C M
authors.initials: PC
authors.lastname: Martins
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil.
authors.forename: Camila F
authors.initials: CF
authors.lastname: Almeida
authors.affiliation: Laboratório de Microscopia Eletrônica, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil.
authors.forename: Waldir
authors.initials: W
authors.lastname: Caldeira
authors.affiliation: Laboratório de Microscopia Eletrônica, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil.
authors.forename: Alberto F
authors.initials: AF
authors.lastname: Ribeiro
authors.affiliation: Université de Strasbourg, CNRS, ICube (UMR 7357), FMTS, Strasbourg, France; NMR Laboratory, Institute of Myology, Paris, France; CEA, I²BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: Paulo
authors.initials: P
authors.lastname: Loureiro de Sousa
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, I²BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: Noura
authors.initials: N
authors.lastname: Azzabou
authors.affiliation: Centro de Imagens e Espectroscopia in vivo por Ressonância Magnética-CIERMag. Instituto de Física de São Carlos, Universidade de São Paulo-IFSC-USP, São Paulo, São Paulo, Brazil.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tannús
authors.affiliation: NMR Laboratory, Institute of Myology, Paris, France; CEA, I²BM, MIRCen, NMR Laboratory, Paris, France.
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Carlier
authors.affiliation: Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo-IB-USP, São Paulo, São Paulo, Brazil.
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000000981:diagnostic imaging* / Q000473:pathology; D011859:Radiography