Background and Objective:Ultrasound information entropy imaging is an emerging quantitative ultrasound technique for characterizing local tissue scatterer concentrations and arrangements. However, the commonly used ultrasound Shannon entropy imaging based on histogram-derived discrete probability estimation suffers from the drawbacks of histogram settings dependence and unknown estimator performance. In this paper, we introduced the information-theoretic cumulative residual entropy (CRE) defined in a continuous distribution of cumulative distribution functions as a new entropy measure of ultrasound backscatter envelope uncertainty or complexity, and proposed ultrasound CRE imaging for tissue characterization. Methods:We theoretically analyzed the CRE for Rayleigh and Nakagami distributions and proposed a normalized CRE for characterizing scatterer distribution patterns. We proposed a method based on an empirical cumulative distribution function estimator and a trapezoidal numerical integration for estimating the normalized CRE from ultrasound backscatter envelope signals. We presented an ultrasound normalized CRE imaging scheme based on the normalized CRE estimator and the parallel computation technique. We also conducted theoretical analysis of the differential entropy which is an extension of the Shannon entropy to a continuous distribution, and introduced a method for ultrasound differential entropy estimation and imaging. Monte-Carlo simulation experiments were performed to evaluate the estimation accuracy of the normalized CRE and differential entropy estimators. Phantom simulation and clinical experiments were conducted to evaluate the performance of the proposed normalized CRE imaging in characterizing scatterer concentrations and hepatic steatosis (n = 204), respectively. Results:The theoretical normalized CRE for the Rayleigh distribution was π/4, corresponding to the case where there were ≥10 randomly distributed scatterers within the resolution cell of an ultrasound transducer. The theoretical normalized CRE for the Nakagami distribution decreased as the Nakagami parameter m increased, corresponding to that the ultrasound backscattered statistics varied from pre-Rayleigh to Rayleigh and to post-Rayleigh distributions. Monte-Carlo simulation experiments showed that the proposed normalized CRE and differential entropy estimators can produce a satisfying estimation accuracy even when the size of the test samples is small. Phantom simulation experiments showed that the proposed normalized CRE and differential entropy imaging can characterize scatterer concentrations. Clinical experiments showed that the proposed ultrasound normalized CRE imaging is capable to quantitatively characterize hepatic steatosis, outperforming ultrasound differential entropy imaging and being comparable to ultrasound Shannon entropy and Nakagami imaging. Conclusion:This study sheds light on the theory and methodology of ultrasound normalized CRE. The proposed ultrasound normalized CRE can serve as a new, flexible quantitative ultrasound envelope statistics parameter. The proposed ultrasound normalized CRE imaging may find applications in quantified characterization of biological tissues. Our code will be made available publicly at https://github.com/zhouzhuhuang.