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Published on: May 27, 2022
Integrated Ultrasound Localization Microscopy and Multi-Omics for Mechanism-Driven Stratification of Azoospermia
Chujun Ye1,2, Qijie Lu1,2, Keke Yang3,4
1Department of Ultrasound in Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai, China.
Ultrasound localization microscopy (ULM) combined with multi-omics profiling offers a non-invasive method to differentiate non-obstructive azoospermia (NOA) from obstructive azoospermia (OA). This approach reveals distinct microvascular phenotypes, aiding in diagnosis and therapeutic decisions.
Area of Science:
- Reproductive Medicine
- Medical Imaging
- Genomics and Proteomics
Background:
- Accurate diagnosis of non-obstructive azoospermia (NOA) versus obstructive azoospermia (OA) is critical for male infertility treatment.
- Current diagnostic methods often rely on invasive testicular biopsy, necessitating less invasive alternatives.
Purpose of the Study:
- To develop and validate a mechanism-driven stratification framework for azoospermia using ultrasound localization microscopy (ULM) and multi-omics profiling.
- To identify distinct in vivo microvascular phenotypes associated with different azoospermia etiologies.
Main Methods:
- High-frame-rate ultrasound localization microscopy (ULM) with microbubble contrast agents for quantitative mapping of testicular microvasculature.
- Integration of ULM imaging with transcriptomic and metabolomic analyses in murine models.
- Preliminary validation in a small human cohort.
Main Results:
- ULM revealed distinct microvascular phenotypes: NOA models showed fragmented, hypoperfused networks with reduced vessel diameter, while OA models exhibited increased vessel density, diameter, and flow velocity.
- Multi-omics data correlated imaging phenotypes with biological pathways including angiogenesis and metabolism.
- Clinical ULM demonstrated concordant differences between NOA and OA in human subjects.
Conclusions:
- ULM serves as a promising non-invasive imaging adjunct for mechanism-informed azoospermia stratification.
- This approach has the potential to guide therapeutic decision-making in male infertility.
- Further validation in larger prospective human studies is warranted.
