Ultrasound attenuation imaging as a strategy for evaluation of early and late ambulatory functions in Duchenne muscular dystrophy

Abstract Background Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that leads to mobility loss and life‐threatening cardiac or respiratory complications. Quantitative ultrasound (QUS) envelope statistics imaging, which characterizes fat infiltration and fibrosis in muscles, has been extensively used for DMD evaluations. Purpose Notably, changes in muscle microstructures also result in acoustic attenuation, potentially serving as another crucial imaging biomarker for DMD. Expanding upon the reference frequency method (RFM), this study contributes to the field by introducing the robust RFM (RRFM) as a novel approach for ultrasound attenuation imaging in DMD. Methods The RRFM algorithm was developed using an iterative reweighted least squares technique. We conducted standard phantom measurements with a clinical ultrasound system equipped with a linear array transducer to assess the improvement in attenuation estimation bias by RRFM. Additionally, 161 DMD patients, included in both a validation dataset ( n = 130) and a testing dataset ( n = 31), underwent ultrasound scanning of the gastrocnemius for RRFM‐based attenuation imaging. The diagnostic performances for ambulatory functions and discrimination between early and late ambulatory stages were evaluated and compared with those of QUS envelope statistics imaging (involving Nakagami distribution, homodyned K distribution, and entropy values) using the area under the receiver operating characteristic curve (AUROC). Results The results indicated that the RRFM method more closely matched the actual attenuation properties of the phantom, reducing measurement bias by 50% compared to conventional RFM. The AUROCs for RRFM‐based attenuation imaging, used to discriminate between early and late ambulatory stages, were 0.88 and 0.92 for the validation and testing datasets, respectively. These performances significantly surpassed those of QUS envelope statistics imaging ( p < 0.05). Conclusions Ultrasound attenuation imaging employing RRFM may serve as a sensitive tool for evaluating the progression of ambulatory function deterioration, offering substantial potential for the health management and follow‐up care of DMD patients.