BackgroundMicrowave ablation (MWA) is a minimally invasive alternative for the treatment of unresectable liver tumors. To verify the effectiveness and safety of MWA, it is critical to measure the temperature variation and assess the regions of the microwave‐induced thermal lesions.PurposeRecent studies have indicated that the locations of optimally matched Gabor atoms (LOMGA) from ultrasound radiofrequency (RF) echo signals allow accurate and stable scatterer spacing estimation. Herein, a harmonic‐based LOMGA method is proposed to estimate the scatterer spacing for improving the assessment of microwave‐induced thermal lesions.MethodsThe mean scatterer spacing (MSS) is estimated via the LOMGA method incorporating the selection of concise atoms from separated second‐harmonic RF echo signals with the pulse‐inversion algorithm for thermal lesion evaluation. In vitro experiments, 10 fresh porcine liver samples were ablated at different time nodes during the ablation period, and 200 sets of second‐harmonic and fundamental RF echo signals were randomly selected from the regions of interest in the coagulated liver samples for MSS estimation. The means and standard deviations of the MSSs, as well as the linear regression for the mean MSSs, were calculated from fundamental and second‐harmonic signals for comparison and evaluation, the receiver operating characteristic (ROC) curves for the 200 sets of fundamental‐based and harmonic‐based MSS estimates from the 10 liver samples at five pairs of adjacent time nodes were calculated, and one‐way analysis of variance (ANOVA) tests were performed for the five pairs of adjacent time nodes. The fundamental and harmonic‐based p‐values in the ANOVA tests and the areas under the ROC curves (AUCs) were calculated to statistically analyze the differences in the MSSs between adjacent time nodes.ResultsThe harmonic‐based increments in the intensity variation and coherent components were larger than the fundamental‐based increments with the increasing ablation time. The harmonic‐based MSSs from the 10 liver samples at five pairs of adjacent time nodes were found to be highly statistically significant (p < 0.01). Thus, the harmonic‐based MSSs had greater variations. Compared with the fundamental‐based results, for the five preset ST values, the average increment in the harmonic‐based mean slopes was 69.22% and the average decrement in the mean standard deviations was 11.67% for the linear‐fitting MSS results, and the results were statistically significant (p < 0.05).ConclusionHarmonic‐based MSSs are more sensitive and robust to variations in coagulated tissues, which is advantageous for the assessment of microwave‐induced thermal lesions.