gadofluorine-m and Muscular-Dystrophy--Animal

To compare the usefulness of gadofluorine M with that of Gadomer in assessment of dysferlin-deficient muscular dystrophy at 7.0-T magnetic resonance (MR) imaging.. All experiments were approved by local review boards. SJL/J mice (n = 24) with dysferlin-deficient muscular dystrophy and C57BL/6 control mice (n = 24) were imaged at 12-15 weeks (young) or older than 30 weeks (old) by using dynamic contrast material-enhanced imaging with inversion-prepared steady-state free-precession sequence before, during, and after administration of gadofluorine M at 2 micromol or Gadomer at 4 micromol intravenously. After imaging, regions of interest were determined from the upper extremity and left ventricular chamber; fractional extravascular extracellular volume, v(e), and permeability surface tissue density product, PS rho, were measured by using a two-compartment pharmacokinetic model. The natural history of muscular dystrophy was assessed histologically in 70 mice (seven five-mouse groups each of SJL/J mice and of control mice) at 4-week intervals from 8 to 32 weeks. In addition, three SJL/J mice and three control mice at age 33 weeks were sacrificed, and fluorescence microscopy was performed for visualization of intravenously administered carbocyanine-labeled gadofluorine M in muscle cells. Statistical analysis was performed by using the t test.. Gadofluorine M enhancement was significantly greater in skeletal muscle of 30-week-old mice with dysferlin-deficient muscular dystrophy, compared with control mice. Gadofluorine M demonstrated both increased rate of enhancement (PS rho sec(-1) +/- standard error of the mean: 0.004 e(-)(4) +/- 3 vs 0.002 e(-)(4) +/- 3; P < .05) and increased level of enhancement (v(e) +/- standard error of the mean: 0.035 +/- 0.004 vs 0.019 +/- 0.004; P < .05). Gadomer showed no differential enhancement in the two mouse groups. Histologic examination confirmed the presence of labeled gadofluorine M in muscle cells.. Gadofluorine M-enhanced MR imaging may be of value in monitoring dysferlin-deficient muscular dystrophy disease progression in this animal model and could prove to be a useful tool in following the course of chronic muscle diseases in humans.

Topics: Age Factors; Animals; Contrast Media; Dysferlin; Extravasation of Diagnostic and Therapeutic Materials; Fluorocarbons; Gadolinium; Magnetic Resonance Imaging; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Microscopy, Fluorescence; Muscle, Skeletal; Muscular Dystrophy, Animal; Necrosis; Organometallic Compounds; Pilot Projects

Topics: Adolescent; Animals; Child; Child, Preschool; Contrast Media; Disease Progression; Dysferlin; Dystrophin; Fluorocarbons; Humans; Image Enhancement; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Membrane Proteins; Mice; Muscle, Skeletal; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Organometallic Compounds; Sensitivity and Specificity