Spatiotemporal Deep Video-Phenomapping Decodes Microvascular Rarefaction in Middle-Aged and Elder Renovascular Hypertension: A Multi-Modal Study Integrating Spatial Transcriptomics and Mitochondrial Pyroptosis.
Authors
Affiliations (10)
Affiliations (10)
- Department of Sonography, Beijing Hospital, National Center for Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Department of Echocardiography, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
- The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital, National Center for Gerontology, Beijing, China.
- Department of Sonography, Beijing Hospital, National Center for Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China.
- Department of Ultrasound, China-Japan Friendship Hospital; National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
- Department of Ultrasound Medicine, Peking University First Hospital, Beijing 100034, China.
- Department of Ultrasound Medicine, Civil Aviation General Hospital, Beijing, China.
- Department of Vascular Surgery, Beijing Hospital, National Center for Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
- Department of Ultrasound Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
In middle-aged and older atherosclerotic renal artery stenosis (ARAS), the anatomical severity of stenosis is a poor surrogate for microvascular competence, and the renal benefit of revascularization is unpredictable. We developed Renal-Video-AI, a self-supervised deep learning framework (Video Swin Transformer with VideoMAE pretraining) that extracts spatiotemporal hemodynamic features from contrast-enhanced ultrasound, and applied it to a multi-center Discovery Cohort (<i>N</i> = 1,226), an independent External Validation Cohort (<i>N</i> = 122), a prospective Multimodal Cohort with paired 10x Visium spatial transcriptomics (<i>N</i> = 57), and an aged two-kidney-one-clip (2K1C) murine model. Unsupervised phenomapping identified 3 intrinsic hemodynamic phenotypes-Preserved, Delayed, and Rarefied. The Rarefied phenotype predicted major adverse renal events (MAREs) independently of anatomical stenosis [hazard ratio (HR) 4.82, 95% confidence interval (CI) 3.10 to 6.50; Fine-Gray subdistribution HR (sHR) 5.1], and adding the phenotype to a standard clinical model improved the C-statistic from 0.72 to 0.88. A significant phenotype-by-treatment interaction (<i>P</i> < 0.01) showed that stenting reduced events only in the Delayed phenotype (HR 0.52, 95% CI 0.35 to 0.78), not in the Preserved (HR 0.98) or Rarefied (HR 1.05) phenotypes. In absolute terms, stenting reduced the 3-year cumulative incidence of MARE in the Delayed phenotype from 25.4% to 13.2% (absolute risk reduction 12.2%; number needed to treat = 8, 95% CI 6 to 13), with no benefit in the Preserved (8.4% versus 8.0%) or Rarefied (38.6% versus 39.4%) phenotypes. Spatial transcriptomics localized a hypoxia and pyroptosis signature to rarefied tissue, and the aged 2K1C model revealed a mitochondrial reactive oxygen species (ROS)-NLRP3-pyroptosis axis whose pharmacological inhibition (MCC950) restored microvascular perfusion. AI video-phenomapping thus reframes the revascularization decision around microvascular competence rather than anatomy, identifying both therapeutic futility (Rarefied) and a treatable window (Delayed), and nominates NLRP3-driven pyroptosis as a therapeutic target.