Assessing cerebral capillary function and stalling using single capillary reporters in ultrasound localization microscopy
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 SCaRes ability to resolve immune responses to injury at the single capillary level, markedly broadening research avenues for exploring microvascular dysfunction across diverse neurological conditions.
SIGNIFICANCE
Growing evidence indicates that the brains microvascular system plays a key role in neurological diseases and aging. This is especially true for capillaries, the smallest blood vessels, that interact directly with neurons. However, imaging and measuring the function of these tiny vessels through the skull remains extremely challenging. Here, we introduce single capillary reporters (SCaRe), statistically derived biomarkers that track the movement of individual microbubbles to directly image and assess single capillaries in ultrasound localization microscopy. SCaRe surpasses the spatial and temporal limitations of current techniques, enabling the extraction of markers that reflect capillary function in both healthy and diseased brains. These biomarkers reveal immune-related responses to brain injury with single capillary precision.
Web | DOI | PDF | Proceedings of the National Academy of Sciences | Open Access
Lee, Stephen A; Leconte, Alexis; Wu, Alice; Kinugasa, Joshua; Palacios, Gerardo Ramos; Porée, Jonathan; Sadikot, Abbas F; Linninger, Andreas; Provost, Jean
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 SCaRes ability to resolve immune responses to injury at the single capillary level, markedly broadening research avenues for exploring microvascular dysfunction across diverse neurological conditions.
SIGNIFICANCE
Growing evidence indicates that the brains microvascular system plays a key role in neurological diseases and aging. This is especially true for capillaries, the smallest blood vessels, that interact directly with neurons. However, imaging and measuring the function of these tiny vessels through the skull remains extremely challenging. Here, we introduce single capillary reporters (SCaRe), statistically derived biomarkers that track the movement of individual microbubbles to directly image and assess single capillaries in ultrasound localization microscopy. SCaRe surpasses the spatial and temporal limitations of current techniques, enabling the extraction of markers that reflect capillary function in both healthy and diseased brains. These biomarkers reveal immune-related responses to brain injury with single capillary precision.
Web | DOI | PDF | Proceedings of the National Academy of Sciences | Open Access