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In vivo plaque characterization is an important research field in interventional cardiology. We will study the realistic challenges to this goal by deploying 40 MHz single-element, mechanically rotating transducers. The intrinsic variability among the transducers' spectral parameters as well as tissue signals will be demonstrated. Subsequently, we will show that global data normalization is not suited for data calibration, due to the aforementioned variations as well as the stringent characteristics of spectral features. We will describe the sensitivity of an existing feature extraction algorithm based on eight spectral signatures (integrated backscatter coefficient, slope, midband-fit (MBF), intercept, and maximum and minimum powers and their relative frequencies) to a number of factors, such as the window size and order of the autoregressive (AR) model. It will be further demonstrated that the variations in the transducer's …