Purpose: The relationship between fat fractions (FFs) determined based on multiple TE, unipolar gradient echo images and H-1 magnetic resonance spectroscopy (MRS) was evaluated using different models for fat-water decomposition, signal-to-noise ratios, and excitation flip angles.Methods: A combination of single-voxel proton spectroscopy(H-1-MRS) and gradient echo imaging was used to determine muscle FFs in both normal and dystrophic muscles. In order to cover a large range of FFs, the soleus and vastus lateralis muscles of 22 unaffected control subjects, 16 subjects with collagen VI deficiency (COL6), and 71 subjects with Duchenne muscular dystrophy (DMD) were studied. H-1-MRS-based FF were corrected for the increased muscle (H2OT1)-H-1 and T-2 values observed in dystrophic muscles.Results: Excellent agreement was found between coregistered FFs derived from gradient echo images fit to a multipeak model with noise bias correction and the relaxation-corrected H-1-MRS FFs (y = 0.93x + 0.003; R-2 = 0.96) across the full range of FFs. Relaxation-corrected H-1-MRS FFs and imaging-based FFs were significantly elevated (P < 0.01) in the muscles of COL6 and DMD subjects.Conclusion: FFs, T-2, and T-1 were all sensitive to muscle involvement in dystrophic muscle. MRI offered an additional advantage over single-voxel spectroscopy in that the tissue heterogeneity in FFs could be readily determined. (C) 2013 Wiley Periodicals, Inc.

PURPOSE To validate a multicenter protocol that examines lower extremity skeletal muscles of children with Duchenne muscular dystrophy (DMD) by using magnetic resonance (MR) imaging and MR spectroscopy in terms of reproducibility of these measurements within and across centers. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review boards of all participating centers, and informed consent was obtained from each participant or a guardian. Standardized procedures with MR operator training and quality assurance assessments were implemented, and data were acquired at three centers by using different 3-T MR imaging instruments. Measures of maximal cross-sectional area (CSAmax), transverse relaxation time constant (T2), and lipid fraction were compared among centers in two-compartment coaxial phantoms and in two unaffected adult subjects who visited each center. Also, repeat MR measures were acquired twice on separate days in 30 boys with DMD (10 per center) and 10 unaffected boys. Coefficients of variation (CVs) were computed to examine the repeated-measure variabilities within and across centers. RESULTS CSAmax, T2 from MR imaging and MR spectroscopy, and lipid fraction were consistent across centers in the phantom (CV, <3%) and in the adult subjects who traveled to each site (CV, 2%-7%). High day-to-day reproducibility in MR measures was observed in boys with DMD (CSAmax, CV = 3.7% [25th percentile, 1.3%; 75th percentile, 5.1%]; contractile area, CV = 4.2% [25th percentile, 0.8%; 75th percentile, 4.9%]; MR imaging T2, CV = 3.1% [25th percentile, 1.2%; 75th percentile, 4.7%]; MR spectroscopy T2, CV = 3.9% [25th percentile, 1.5%; 75th percentile, 5.1%]; and lipid fraction, CV = 4.7% [25th percentile, 1.0%; 75th percentile, 5.3%]). CONCLUSION The MR protocol implemented in this multicenter study achieved highly reproducible measures of lower extremity muscles across centers and from day to day in ambulatory boys with DMD.

A multi-center study is being implemented to evaluate the potential of magnetic resonance imaging (MRI) and spectroscopy (MRS) to monitor the progression of disease in children with Duchenne muscular dystrophy (DMD) and ultimately to serve as a surrogate outcome measure for clinical trials. Longitudinal MRI/MRS measures are being acquired over five years at three geographically distributed sites with a centralized data analysis center. In addition to MR, a battery of timed functional tests and muscle strength are assessed and immortalized fibroblasts deposited in tissue repositories. Initial efforts of this study have focused on establishing quality assurance procedures and minimizing variability in MR measures across sites, and from day-to-day. This has been accomplished using two-compartment coaxial phantoms and human subjects that visited each site. To date, 21 children have been enrolled in the study: 5 controls (9.2 ± 2.4 years, 29.2 ± 6.7 kg) and 16 ambulatory boys with DMD (9.3 ± 2.0 years, 32.4 ± 9.6 kg). MR scans include fat suppressed and unsuppressed transaxial 3D-gradient echo and spin echo images as well as localized 1H-spectroscopy. During the initial visit MR measures are being performed twice on separate days to test reproducibility. The MR data acquisition is performed on a Philips 3T Achieva, Siemens Verio, or Siemens TIM Trio system. Reproducibility of the MR measures have been evaluated for the soleus using MRI-T2 (Day 1: 43 ± 9 ms, Day 2: 44 ± 9 ms; CV 2.2 ± 1.9%), T2 of 1H2O from spectroscopic relaxometry (Day 1: 30.3 ± 2.6 ms, Day 2: 30.4 ± 2.9 ms; CV 2.1 ± 1.5%), and the ratio of lipid/(lipid + water) using 1H-spectroscopy (Day 1: 0.32 ± 0.23 ms, Day 2: 0.32 ± 0.22 ms; CV 4.8 ± 2.8%). In summary, the MR measures implemented in this multisite study are highly reproducible in children with DMD and controls. These noninvasive measures show promise for evaluating disease progression and treatment in DMD subjects, and are continuing to be evaluated in this multi-center study.