Assessing cerebral capillary function and stalling using single capillary reporters in ultrasound localization microscopy

• 成果类型: Article
• 署名作者: Lee, Stephen A.; Leconte, Alexis; Wu, Alice; Kinugasa, Joshua; Palacios, Gerardo Ramos; Poree, Jonathan; Sadikot, Abbas F.; Linninger, Andreas; Provost, Jean
• 署名单位: Universite de Montreal; Polytechnique Montreal; Chiba University; McGill University; University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; Universite de Montreal
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2509564123
• 发表日期: 2026-01-13
• 页码: 2509564123
• 关键词: ultrasound localization microscopy; capillary stalling; microvasculature; neuroimaging; blood-flow; doppler; BIAS

摘要

While transcranial neuroimaging of individual capillary function holds transformative potential for diagnostics, it has proven difficult to achieve. Superresolution ultrasound, while capable of achieving micron-scale resolution, relies on the accumulation of multiple microbubble events, a method inherently limited by the exceedingly low probability of observing such events within capillaries. We present single capillary reporters (SCaRe), a paradigm-shifting approach that utilizes the complete flow trajectory information extracted from individual microbubbles to directly image single capillaries. This method allows for transcranial reconstruction and functional assessment of deep capillary networks in the entire brain. We employed computational simulations and pathological neuroinflammation models to quantify and validate metrics such as capillary transit-time and capillary stalling. Importantly, we demonstrated SCaRe's ability to resolve immune responses to injury at the single capillary level, markedly broadening research avenues for exploring microvascular dysfunction across diverse neurological conditions.