Spinal Cord Injury: A Cardiovascular Perspective using Ultrasound - PROJECT SUMMARY The guidelines for the cardiovascular care of spinal cord injury (SCI) have remained essentially unchanged since mean arterial pressure (MAP) management at 85-90 mmHg was recommended 20 years ago. Due to the heterogeneity in SCI, there is a critical need for a precision medicine treatment. A promising target is impaired autoregulation, or the ability of blood vessels to regulate organ blood flow across a wide range of MAP. This results in altered blood flow through the spatial domain, with hypoperfusion at the permanently damaged injury epicenter (umbra) and gradually increasing blood flow in the surrounding vulnerable tissue (penumbra). To capitalize, our team is developing an ultrasound implant to monitor spinal cord blood flow in humans without contrast. Ultrasound is enabled by removal of the posterior aspect of the vertebra via laminectomy, a common procedure after SCI to relieve pressure. Autoregulation can then be measured through metrics such as transfer function analysis (TFA), presenting a diagnostic tool for the acute care physician after SCI, with quantification of injury extent and severity. Therapeutically, the spatial distribution of blood flow can provide feedback for targeted MAP management. We hypothesize that after SCI, autoregulation as measured by ultrasound will be impaired around the injury, extending into the penumbra. Concurrently, systemic MAP management will differentially affect blood flow over distance from injury, with outcomes depending on penumbra flow. We have made progress towards this goal and will address this hypothesis through the following Specific Aims: Preliminary Data: We have developed an algorithm, FlowMorph, which can extract single-vessel flow parameters from ultrasound data and track them over time. We have also implemented a rigorous measure of autoregulation, TFA, and detected the limits of autoregulation capacity in healthy spinal cord. Finally, we have characterized the spatial distribution of blood flow in spinal cord without MAP management. Aim 1: Establish autoregulation as a clinical marker of vascular injury following SCI: We will use the novel techniques listed above to quantify autoregulation through distance from SCI and link it to functional outcomes. Autoregulation as a prognostic marker will reveal the penumbra as a clinically important area vulnerable to MAP changes. Moreover, it will provide mechanistic insight into using MAP management to optimize blood flow. Aim 2: Use MAP management to protect the penumbra: Following SCI, we will treat rats with MAP management at various levels, both pharmacologically- and volume-induced. We will measure the spatial distribution of flow using FlowMorph and relate it to functional outcomes. Different MAP levels will result in variable levels of flow through the umbra, penumbra, and healthy tissue due to altered autoregulation. We expect to find that penumbra flow will be the strongest predictor of outcomes, providing a therapeutic target in the clinic. This study is significant because it will be the first to use metrics of autoregulation as a clinically useful diagnostic tool in SCI. Therapeutically, it will provide a blood flow-based personalized target for MAP management.
