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Herein, we establish a mechanism-driven stratification framework integrating ultrasound localization microscopy (ULM) with multi-omics profiling. Using murine models representing diverse etiologies, high-frame-rate ULM following intravenous microbubble administration (acquiring over 120,000 compounded frames at 1000 Hz) overcomes the spatial-resolution limit of conventional ultrasound to achieve in vivo quantitative mapping of the testicular microvasculature. Super-resolution maps unveil distinct etiology-specific microvascular phenotypes: NOA models showed fragmented and hypoperfused vascular networks with reduced larger intratesticular vessel diameter (BU:166 \u00b1 9.9\u03bcm, p &lt; 0.01; Pnldc1:175\u00b1 4.9\u03bcm, p &lt; 0.05), whereas OA displayed increased vessel density (7.944 \u00b1 0.52; p &lt; 0.01), mean vessel diameter (43.99 \u00b1 1.168 \u03bcm; p &lt; 0.01), and mean flow velocity (8.333 \u00b1 0.523 mm\/s; p&lt;0.001). Transcriptomic and metabolomic analyses linked these imaging phenotypes to angiogenesis, extracellular matrix remodeling, lipid peroxidation, and energy-metabolism rewiring. In a small preliminary human cohort, clinical ULM showed concordant differences in vascular morphology and mean vessel diameter between NOA and OA. These findings support ULM as a candidate contrast-enhanced imaging adjunct for mechanism-informed azoospermia stratification, requiring further validation in larger prospective cohorts.<\/jats:p>","DOI":"10.1177\/15579883261468072","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:09:11Z","timestamp":1785424151000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated Ultrasound Localization Microscopy and Multi-Omics for Mechanism-Driven Stratification of Azoospermia"],"prefix":"10.1177","volume":"20","author":[{"given":"Chujun","family":"Ye","sequence":"first","affiliation":[{"name":"Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine"},{"name":"Shanghai Institute of Ultrasound in Medicine"},{"name":"Shanghai Key Laboratory of Neuro-Ultrasound for Diagnosis and Treatment, Shanghai, 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