Reducing Spectral Oscillations for Robust Reference Frequency-Based Ultrasound Attenuation Estimation in Harmonic...

Ultrasound attenuation coefficient estimation (ACE) has emerged as a quantitative imaging biomarker for noninvasive assessment of hepatic steatosis. A system-independent technique based on spectral normalization, known as the reference frequency method (RFM), was previously proposed to estimate ACE without requiring a well-calibrated reference phantom. Furthermore, incorporating harmonic imaging can significantly suppress reverberation signals. In previous clinical study, RFM has achieved high correlation with MRI-PDFF, demonstrating its potential for clinical application. However, a major challenge of RFM is the presence of oscillations in the frequency power-ratio decay curves (FPDCs), which can distort the linear fitting used to estimate the attenuation coefficient and consequently degrade ACE accuracy. These oscillations arise from constructive and destructive interference among backscattered echoes, resulting in oscillatory fluctuations in the measured power spectrum that propagate into the FPDCs. We propose a transmission scheme combining multiple frequencies and steering angles to mitigate oscillations in the FPDCs. Averaging these FPDCs suppresses the interference-induced oscillations while preserving the attenuation-dependent decay trend, thereby improving linearity and the accuracy of ACE results. In in-vitro experiments using calibrated phantoms (0.5 and 0.76 dB/cm/MHz) demonstrated that the proposed method improved FPDC linearity and ACE accuracy, achieving an R2 of 0.99 and attenuation coefficient estimates of 0.51 and 0.77 dB/cm/MHz, versus an R2 of 0.89 and estimates of 0.56 and 0.70 dB/cm/MHz for conventional RFM. The proposed method also demonstrated superior performance in a pilot patient study (n=15), achieving a stronger correlation with MRI-PDFF (R = 0.89 vs. 0.83) while reducing inter-measurement variability, indicating improved robustness and clinical potential.