Quantitative Ultrasound Biomarkers of Testicular Spermatogenic Function

ABSTRACT Introduction Non-obstructive azoospermia (NOA) represents the most severe form of male infertility. Current clinical tools have limited ability to predict sperm production or guide surgical sperm retrieval. Conventional B-mode ultrasound provides qualitative grayscale images and cannot characterize testicular microstructure relevant to spermatogenesis. Quantitative ultrasound (QUS) provides objective parameters from raw radiofrequency data, which quantitatively measure tissue heterogeneity. We hypothesize that men with spermatogenesis will have different QUS features compared to men without spermatogenesis (measured by total motile count, TMC, on semen analysis), with the goal of identifying imaging biomarkers for prognosis and intraoperative guidance. Methods We prospectively analyzed men presenting for infertility evaluation who underwent high-frequency ultrasound imaging and semen analysis. Imaging was performed using a 36-MHz transducer with fixed acquisition parameters. Ninety-two QUS features were extracted from manually annotated testicular regions of interest, including Nakagami distribution parameters (m, ω, k), envelope statistics, and texture features. Univariate associations between each QUS feature and TMC were assessed using Spearman correlation with Bonferroni correction. Top-performing features were evaluated using logistic regression and receiver operating characteristic (ROC) analysis to discriminate sperm presence or absence (TMC>0 vs TMC=0). Results Thirty-seven men (18 azoospermic, 19 with sperm present in the ejaculate) contributed 135 regions of interest. Seventeen of 92 QUS features significantly correlated with TMC after correction. The coefficient of variation of the Nakagami k-factor within the superficial testicular parenchyma (K_Zone1_Cv) demonstrated the strongest correlation (ρ=0.51, corrected p