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

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 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.

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 (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.

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.

• Authors: Saskia Schmidt, Antje Vieweger, Michael Obst, Susanne Mueller, Volkmar Gross, Matthias Gutberlet, Jens Steinbrink, Semjon Taubert, Bernd Misselwitz, Lutz Luedemann, Simone Spuler
• Journal: Radiology (Radiology) Vol. 250 Issue 1 Pg. 87-94 (Jan 2009) ISSN: 1527-1315 [Electronic] United States
• PMID: 19001151 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) RSNA, 2008.

Chemical References

• Contrast Media
• Dysf protein, mouse
• Dysferlin
• Fluorocarbons
• Membrane Proteins
• Organometallic Compounds
• gadofluorine M
• gadomer 17
• Gadolinium

Topics

• Age Factors
• Animals
• Contrast Media (pharmacokinetics)
• Dysferlin
• Extravasation of Diagnostic and Therapeutic Materials (pathology)
• Fluorocarbons
• Gadolinium (pharmacokinetics)
• Magnetic Resonance Imaging
• Membrane Proteins (deficiency, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred Strains
• Microscopy, Fluorescence
• Muscle, Skeletal (pathology)
• Muscular Dystrophy, Animal (pathology)
• Necrosis
• Organometallic Compounds (pharmacokinetics)
• Pilot Projects