Quantitative 1H and 23Na muscle MRI in Facioscapulohumeral muscular dystrophy patients

Stefan Schwab,Benjamin Marty,Matthias Türk,Lena V. Gast,Rafael Heiss,Michael Uder,Pierre G. Carlier,Armin M. Nagel,Teresa Gerhalter,Katharina Porzelt

doi:10.1007/s00415-020-10254-2

Abstract

ObjectiveOur aim was to assess the role of quantitative 1H and 23Na MRI methods in providing imaging biomarkers of disease activity and severity in patients with Facioscapulohumeral muscular dystrophy (FSHD).MethodsWe imaged the lower leg muscles of 19 FSHD patients and 12 controls with a multimodal MRI protocol to obtain STIR-T2w images, fat fraction (FF), water T2 (wT2), water T1 (wT1), tissue sodium concentration (TSC), and intracellular-weighted sodium signal (inversion recovery (IR) and triple quantum filter (TQF) sequence). In addition, the FSHD patients underwent muscle strength testing.ResultsImaging biomarkers related with water mobility (wT1 and wT2) and ion homeostasis (TSC, IR, TQF) were increased in muscles of FSHD patients. Muscle groups with FF > 10% had higher wT2, wT1, TSC, IR, and TQF values than muscles with FF < 10%. Muscles with FF < 10% resembled muscles of healthy controls for these MRI disease activity measures. However, wT1 was increased in few muscles without fat replacement. Furthermore, few STIR-negative muscles (n = 11/76) exhibited increased wT1, TSC, IR or TQF. Increased wT1 as well as 23Na signals were also present in muscles with normal wT2. Muscle strength was related to the mean FF and all imaging biomarkers of tibialis anterior except wT2 were correlated with dorsal flexion.ConclusionThe newly evaluated imaging biomarkers related with water mobility (wT1) and ion homeostasis (TSC, IR, TQF) showed different patterns compared to the established markers like FF in muscles of FSHD patients. These quantitative biomarkers could thus contain valuable complementary information for the early characterization of disease progression.

Highlights

MethodsFacioscapulohumeral muscular dystrophy (FSHD) is characterized by a typically asymmetric progression of muscle weakness and wasting including muscular inflammation and fibrotic and fatty replacement [1]
For FSHD patients, the fat fraction as assessed in all analyzed 76 muscles by the Dixon method was significantly increased in the GM, SOL, and TA muscles in contrast to the wT2 values that remained in the normal range in most of the investigated muscles (Fig. 2)
This report presents the initial results of our FSHD study; we showed that sodium anomalies and 1H relaxation time differences are present in FSHD patients and can be measured in vivo on a clinical 3 T scanner

Summary

Introduction

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by a typically asymmetric progression of muscle weakness and wasting including muscular inflammation and fibrotic and fatty replacement [1]. Several clinical trials strive to develop treatment and require reliable and accurate tools to monitor muscle response to interventions [2, 3]. The majority of MRI studies on muscle dystrophies have measured the fat fraction (FF) within the muscle [4]. Clinical trials require biomarkers that detect subtle changes in muscle pathology prior to any irreversible fat replacement [5]. Some muscles without visible fatty replacement have shown T 2 changes reflecting myocyte damage, edema, inflammation and/or hypervascularization [6, 7], and reveal the initial stages of disease expression [8]

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Results

Discussion

Conclusion