Dysferlin-deficient Muscular Dystrophy: Gadofluorine M Suitability at MR Imaging in a Mouse Model

doi:10.1148/radiol.2501080180

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Dysferlin-deficient Muscular Dystrophy: Gadofluorine M Suitability at MR Imaging in a Mouse Model¹

Saskia Schmidt, MD, Antje Vieweger, MD, Michael Obst, PhD, Susanne Mueller, MSc, Volkmar Gross, PhD, Matthias Gutberlet, MD, Jens Steinbrink, MD, Semjon Taubert, MD, Bernd Misselwitz, PhD, Lutz Luedemann, MD, and Simone Spuler, MD

¹ From the Muscle Research Unit, Experimental and Clinical Research Center (S. Schmidt, A.V., S.T., S. Spuler), Berlin Neuro Image Center (S.M., J.S.), Department of Radiology, Nuclear Medicine and Radiooncology (M.G., L.L.), Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany; Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany (M.O., V.G.); and Research Laboratories, Bayer Schering Pharma, Berlin, Germany (B.M.). Received January 28, 2008; revision requested April 5; revision received May 12; accepted June 18; final version accepted July 30. S. Spuler supported by a grant from the German Research Foundation (Sp 1152-8/1, KFO 192). Address correspondence to S. Spuler (e-mail: simone.spuler{at}charite.de).

Purpose: To compare the usefulness of gadofluorine M with that ofGadomer in assessment of dysferlin-deficient muscular dystrophy at7.0-T magnetic resonance (MR) imaging.

Materials and Methods: All experiments were approved by local reviewboards. SJL/J mice (n = 24) with dysferlin-deficient muscular dystrophyand C57BL/6 control mice (n = 24) were imaged at 12–15 weeks(young) or older than 30 weeks (old) by using dynamic contrast material–enhancedimaging with inversion-prepared steady-state free-precession sequencebefore, during, and after administration of gadofluorine M at 2 µmolor Gadomer at 4 µmol intravenously. After imaging, regionsof interest were determined from the upper extremity and left ventricularchamber; fractional extravascular extracellular volume, v_e, and permeabilitysurface tissue density product, PS ${rho}$ , were measured by using a two-compartmentpharmacokinetic model. The natural history of muscular dystrophywas assessed histologically in 70 mice (seven five-mouse groups eachof SJL/J mice and of control mice) at 4-week intervals from 8 to32 weeks. In addition, three SJL/J mice and three control mice atage 33 weeks were sacrificed, and fluorescence microscopy was performedfor visualization of intravenously administered carbocyanine-labeledgadofluorine M in muscle cells. Statistical analysis was performedby using the t test.

Results: Gadofluorine M enhancement was significantly greater inskeletal muscle of 30-week-old mice with dysferlin-deficient musculardystrophy, compared with control mice. Gadofluorine M demonstratedboth increased rate of enhancement (PS ${rho}$ sec^–1 ± standarderror of the mean: 0.004e^–⁴ ± 3 vs 0.002e^–⁴ ±3; P < .05) and increased level of enhancement (v_e ± standarderror of the mean: 0.035 ± 0.004 vs 0.019 ± 0.004;P < .05). Gadomer showed no differential enhancement in the twomouse groups. Histologic examination confirmed the presence of labeledgadofluorine M in muscle cells.

Conclusion: Gadofluorine M–enhanced MR imaging may be of valuein monitoring dysferlin-deficient muscular dystrophy disease progressionin this animal model and could prove to be a useful tool in followingthe course of chronic muscle diseases in humans.

Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2501080180/DC1

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