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Dysferlin-deficient muscular dystrophy: Gadofluorine M suitability at MR imaging in a mouse model

Item Type:Article
Title:Dysferlin-deficient muscular dystrophy: Gadofluorine M suitability at MR imaging in a mouse model
Creators Name:Schmidt, S. and Vieweger, A. and Obst, M. and Mueller, S. and Gross, V. and Gutberlet, M. and Steinbrink, J. and Taubert, S. and Misselwitz, B. and Luedemann, L. and Spuler, S.
Abstract:Purpose: 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. Materials and Methods: 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 mumol or Gadomer at 4 mumol 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, PSrho, 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. Results: 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 (PSrho sec(-1) +/- standard error of the mean: 0.004e(-)(4) +/- 3 vs 0.002e(-)(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. Conclusion: 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.
Keywords:Age Factors, Contrast Media, Extravasation of Diagnostic and Therapeutic Materials, Gadolinium, Magnetic Resonance Imaging, Membrane Proteins, Inbred C57BL Mice, Inbred Strains Mice, Fluorescence Microscopy, Skeletal Muscle, Animal Muscular Dystrophy, Necrosis, Organometallic Compounds, Pilot Projects, Animals, Mice
Publisher:Radiological Society of North America
Page Range:87-94
Date:January 2009
Official Publication:https://doi.org/10.1148/radiol.2501080180
PubMed:View item in PubMed

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