LONGITUDINAL FEATURES OF STIR BRIGHT SIGNAL IN FSHD 1 SETH D. FRIEDMAN, PhD, 1 SANDRA L. POLIACHIK, PhD, 1 RANDOLPH K. OTTO, MD, 1,2 GREGORY T. CARTER, MD, 3 CHRISTOPHER B. BUDECH, BA, 1 THOMAS D. BIRD, MD, 4 DANIEL G. MILLER, MD, PhD, 5 and DENNIS W.W. SHAW, MD 1,2 1 Seattle Children’s Hospital, Department of Radiology, 4800 Sandpoint Way, Room: L-Shaped MA.6.226, Seattle, Washington 98105, USA 2 University of Washington School of Medicine, Department of Radiology, Seattle, Washington, USA 3 University of Washington School of Medicine, Department of Rehabilitation, Seattle, Washington, USA 4 University of Washington School of Medicine, Department of Neurology, Seattle, Washington, USA 5 University of Washington School of Medicine, Department of Genetics, Seattle, Washington, USA Accepted 13 May 2013 ABSTRACT: Introduction: Magnetic resonance imaging of mus- cle shows short tau-inversion recovery (STIR) brightness in autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1) suggestive of active inflammation/injury. We measured the longitudinal stability/progression of this potential disease bio- marker. Methods: Nine subjects underwent calf MRI imaging over 2 years. Two radiologists evaluated qualitative muscle changes. Results: In 3/9 subjects, calf muscles demonstrated moderate/severe STIR hyperintensity at Time 1 that had pro- gressed to fatty replacement 2 years later (Time 2). In the remaining subjects, moderate/severe muscle STIR abnormal- ities, when present, were consistent between exams. Mild STIR1 elevations had roughly similar patterns between exams. Conclusions: Moderate/severe STIR hyperintensities often fore- shadow fatty replacement over a 2-year interval. Whether longer time courses are required to observe muscle degeneration and fatty replacement in some subjects remains to be explored. Muscle Nerve 49: 257–260, 2014 Facioscapulohumeral muscular dystrophy 1 (FSHD1) is associated with D4Z4 array contraction on a specific, commonly occurring chromosome 4 1 haplotype that contains a polyadenylation signal for the DUX4 gene. 2 Disease severity is related to allele size with strong epigenetic components. 3 Muscle injury is thought to be related directly to the pathological expression of DUX4. 4 Using MRI, short tau-inversion recovery sequen- ces (STIR) demonstrate areas in muscle of increased signal intensity (STIR1), suggestive of edema and/or inflammation. 5,6 Elevated cytokines in tissue/serum 7 and transcriptional alterations accompany STIR1 signal, 8 whereas muscles that appear to be normal by MRI do not demonstrate pathological characteristics (cytokine 7 , energetics, 9 and electromyographic changes 10 ). STIR1 features may foreshadow fatty replacement, effectively giving it relevance as a disease/treatment indicator. To confirm that STIR1 signal leads to fatty replace- ment, and evaluate issues related to rate and pattern of STIR1 changes, a longitudinal sample was evaluated. MATERIALS AND METHODS Recruitment. Institutional Review Board approval was obtained from Seattle Children’s Hospital for this study. Fifteen FSHD1 subjects were recruited from sur- rounding clinics for a 1-year longitudinal MRI study evaluating thigh and calf. Of this cohort, 9 subjects had been enrolled in a former study that included calf imaging 2 years previously (Time 1). 5 These baseline scans were compared with the first scan of this new study (Time 2) to form the basis of this report. MRI. The initial MRI examination (Time 1) used a knee coil centered on the mid-calf (3T Philips scan- ner running software version 2.5.3). 5 Parameters included T1 (turbo spin echo, echo time [TE] 5 6.9 ms, repetition time [TR] 5 575 ms, 640 3 640, 4 mm thick, 18 slices) and STIR sequences (TE 5 60 ms, TR 5 4200 ms, same resolution). One follow-up scan used this same equipment, and all others were performed on a 3T Siemens Trio scanner running software VB17. Siemens sequences were acquired using flexible array coils (to acquire both legs simul- taneously) and parameters as follows: 3-plane local- izers, T1 (TE 5 8.9 ms, TR 5 510 ms, 320 3 224, 5 mm thick, 40 slices), and STIR (same resolution, TE 5 37 ms, TR 5 6120, flip 150  ). This report describes T1/STIR qualitative results; subsequent reports will include longitudinal thigh data (of which the follow-up data have not been collected). Rating. Two of the authors blinded to clinical find- ings (D.W.W.S., R.O.) assessed muscle change in the calf using a previously described rating scale for fat. 11,12 Briefly, the rating scale can be summarized as 0 5 normal appearance; 1 5 scattered small areas of abnormality, 2a: numerous discrete areas of increased signal intensity, less than 30% of the mus- cle volume, 2b: numerous discrete areas with early confluence, 30–60% volume, 3: >60% with patchy loss of fascial structure, or 4: pronounced fatty replacement throughout with complete fascial struc- ture loss. In addition, the STIR1 intensity was rated This work was funded by the Pacific Northwest Friends of FSH Research. Abbreviations: D4Z4, tandem repeat sequence; DUX4, double homeo- box 4; FSHD, Facioscapulohumeral Muscular Dystrophy; MRI, magnetic resonance imaging; STIR, short tau inversion recovery; TE, echo time; TR, repetition time Key words: facioscapulohumeral muscular dystrophy; longitudinal; mag- netic resonance; Muscular dystrophy; muscle Correspondence to: S.D. Friedman; e-mail: sethdfriedman@gmail.com V C 2013 Wiley Periodicals, Inc. Published online 29 May 2013 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.23911 Longitudinal Features of STIR1 in FSHD MUSCLE & NERVE February 2014 257