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  • Methodology
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Ultrafast ultrasound imaging reveals altered cerebral blood flow in newborn rats with hypoxic-ischemic encephalopathy

Pediatric Research volume 99, pages 898–908 (2026)Cite this article

Abstract

Background

Hypoxic-ischemic encephalopathy (HIE) leads to poor neurological outcomes without timely treatment, yet early identification remains challenging. While cerebral blood flow (CBF) changes relate to HIE, specific early CBF or cerebral venous drainage (CVD) patterns are unclear. Recently, the advanced multi-angle plane wave high-frequency ultrafast Doppler (HF-μDoppler) imaging has shown promise for neonatal CBF/CVD assessment, aiding early diagnosis and intervention of HIE.

Methods

This study modified the Rice-Vannucci model to enable real-time observation of CBF/CVD changes during HIE. Using HF-μDoppler, we evaluated its feasibility and performance in assessing CBF/CVD under different conditions and stages of HIE, and explored specific early CBF/CVD alterations during HIE onset.

Results

This study validated the feasibility and sensitivity of HF-μDoppler for detecting CBF/CVD anomalies in HIE rats. We identified early-stage HIE-specific retrograde perfusion of the transverse sinus (TS) contralateral to carotid ligation, with reduced velocity and increased diameter on both sides compared to baseline. The contralateral TS showed lower velocity and smaller diameter than the ipsilateral side, with potential explanations discussed.

Conclusion

HF-μDoppler is a promising imaging modality for reliable HIE assessment. The observed retrograde perfusion of TS may serve as a sensitive early biomarker for accurate HIE detection, supporting earlier clinical diagnosis and treatment.

Impacts

  • HF-μDoppler can be used for CBF/CVD evaluation in HIE newborn rats.

  • HF-μDoppler can detect sensitive biomarkers in the early stages of HIE.

  • Transverse sinus’ retrograde perfusion specifically occurs in HIE’ early stages.

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Fig. 1: Experimental process and data processing.
Fig. 2: Results and statistical analysis of HE staining. with n = 8 per group.
Fig. 3: Results and statistical analysis of neurobehavioral analysis. with n = 6 per group.
Fig. 4: Color Doppler imaging of CBF/CVD in newborn rats based on HF-μDoppler under different experimental settings, with n = 8 per group.
Fig. 5: Color Doppler imaging of CBF/CVD in newborn rats at different stages of HIE, based on HF-μDoppler, with n = 8 per group.
Fig. 6: Evaluation of CBF/CVD in HIE newborn rats using different methods, and evaluation of changes in the diameter of the TS throughout the entire process of HIE onset, with n = 8 per group.

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Data availability

Data and software used in this manuscript are available upon reasonable request.

Code availability

Data and software used in this manuscript are available upon reasonable request.

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Acknowledgements

This study was supported by PKU-KJHL Joint Lab for Biomedicine & Data Engineering, Nanjing Jiangbei funding, Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund (2022L222016), General Program of the National Natural Science Foundation of China (82471745), and Key R&D Program of Ningxia Hui Autonomous Region (2024BEG01002). Thanks for manuscript editing by Lin Zhang, Zeming Du and Hui Ni. Thanks for the help in building animal models by Fengtong Ji and Pengting Min.

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  1. These authors contributed equally: Yunlong Zhao, Jiabin Zhang.

Authors and Affiliations

  1. Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Yunlong Zhao, Daichao Chen, Dongdong Liang & Jue Zhang

  2. Children’s Medical Center, Peking University First Hospital, Beijing, China

    Yunlong Zhao, Qianqian Xia, Qiuyue Shen & Xinlin Hou

  3. College of Future Technology, Peking University, Beijing, China

    Jiabin Zhang

  4. College of Engineering, Peking University, Beijing, China

    Jinyu Yang, Yu Xia, Hao Yu & Jue Zhang

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  1. Yunlong Zhao
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Contributions

Yunlong Zhao: Conceptualization, Methodology, Software, Investigation, Formal analysis, Writing - Original Draft. Jiabin Zhang: Conceptualization, Methodology, Software, Investigation, Formal analysis, Writing - Review & Editing. Qianqian Xia: Conceptualization, Methodology, Investigation, Formal analysis, Writing - Original Draft. Jinyu Yang: Software, Investigation. Daichao Chen: Software, Investigation. Yu Xia: Software, Investigation. Hao Yu: Software, Investigation. Qiuyue Shen: Methodology, Investigation. Dongdong Liang: Software, Investigation. Xinlin Hou: Supervision, Funding acquisition, Writing - Review & Editing. Jue Zhang: Supervision, Funding acquisition, Writing - Review & Editing.

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Zhao, Y., Zhang, J., Xia, Q. et al. Ultrafast ultrasound imaging reveals altered cerebral blood flow in newborn rats with hypoxic-ischemic encephalopathy. Pediatr Res 99, 898–908 (2026). https://doi.org/10.1038/s41390-025-04275-8

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