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


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.


CONCLUSIONS
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.
Schmidt
Saskia
S
Muscle Research Unit, Experimental and Clinical Research Center, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Vieweger
Antje
A
Obst
Michael
M
Mueller
Susanne
S
Gross
Volkmar
V
Gutberlet
Matthias
M
Steinbrink
Jens
J
Taubert
Semjon
S
Misselwitz
Bernd
B
Luedemann
Lutz
L
Spuler
Simone
S
D000367:Age Factors; D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D000073939:Dysferlin; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000473:pathology; D005466:Fluorocarbons; D005682:Gadolinium / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000473:pathology*; D009336:Necrosis; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D010865:Pilot Projects
D003287:Contrast Media; C497505:Dysf protein, mouse; D000073939:Dysferlin; D005466:Fluorocarbons; D008565:Membrane Proteins; D009942:Organometallic Compounds; C517961:gadofluorine M; C402765:gadomer 17; D005682:Gadolinium