Prehospital Diagnostic Biomarker for Large Vessel Occlusion

背景：据估计，大血管急性缺血性卒中(AIS)的发生率为 在美国每年约有25万名患者，是导致残疾的主要原因，排名第五 头号死因。尽管存在介入性(支架)和药物(TPA)治疗 大血管闭塞(LVO)，它们的使用受到限制，因为从症状开始的时间窗口很短，这些 治疗被指定为在。此外，最近的估计表明，只有大约10%的 符合条件的患者接受介入治疗，已证明在几个患者中导致了更好的结果 世界范围内的RCT。为了使干预成功，标准化的、定量的、以现场为基础的(预审) 医院)需要诊断工具来改进LVO识别并确保快速转移到有能力的医生 设施。目前，中风诊断的金标准是CT血管造影(CTA)，这仅限于住院期间 使用或数量较少的移动中风救护车，所有费用都在数百万美元，需要专家 操作人员和静脉注射富碘对比剂。此外，临床卒中评估量表 (RACE、LAMS、CPSS)虽然成本低且非侵入性，但由于以下原因已被证明不可靠 训练要求和低固有精度，在最近的一项研究中，SEN和SPE的范围在0.50-0.64之间 和0.83-0.92。 项目目标和广泛的特定目标：验证可测量的LVO评估的生物标记物 并通过全自动、非侵入性、经颅多普勒(TCD)机器人系统进行显示 达到或超过90%ROC-AUC(目标SEN和SPE大于90%)的性能达到护理标准 成像。完成一项临床研究，其中ARM 1展示了该系统在急性卒中中的技术可行性 设置和ARM 2展示了安全性，没有对护理标准进行有害更改，并收集了可靠的数据以 向FDA提交IFU扩展，以使用我们的机器人系统和生物标记物推动临床护理。这个 这项工作的最终和未来目标是将自动化设备和经过验证的VCI生物标记物用于 院前设置，以显示由于改善了院前分诊，中风发作后临床结果的改善。 这项工作对于首先对照黄金标准CTA验证生物标记物至关重要，必须在 医院，最终将在院前环境中使用。 长期目标：CTA不会在综合性卒中中心被取代，我们也不打算使用我们的 与CTA一起在综合中心实现这一点的技术。相反，我们的技术将在中心提供 没有CTA或MRA，最终是在院前环境中。我们公司的目标是展示 我们的低成本、便携式、非侵入性技术可以用来测量大型血管的有效生物标志物。 可以在全面的卒中中心之外执行的遮挡。第一步是验证 BioMarker，在一个以CTA为黄金标准的中心，这是本工作的最终目标。

Background: The incidence of Large Vessel Acute Ischemic Stroke (AIS) has been estimated to be approximately 250,000 patients per year in the United States and is the leading cause of disability and fifth leading cause of death. Although interventional (stentriever) and pharmaceutical (tPA) treatments exist for large vessel occlusion (LVO), their use is limited due to the short time window from symptom onset that these treatments are indicated to be administered in. Moreover, recent estimates suggest only approximately 10% of eligible patients receive interventional treatment which has shown to lead to better outcomes in several worldwide RCTs. In order for intervention to be successful, a standardized, quantitative, field based (pre- hospital) diagnostic tool is needed to improve LVO identification and ensure rapid transfer to a capable medical facility. Currently, the gold standard for stroke diagnosis is CT angiogram (CTA) which is limited to in-hospital use or a low number of mobile stroke ambulances, all costing multi-millions of dollars, requiring expert operators and IV injection of iodine-rich contrast material. Additionally, the clinical stroke assessment scales (RACE, LAMS, CPSS) used in the field although low cost and non-invasive have proven unreliable due to training requirements and low inherent accuracies, with SEN and SPE ranging in a recent study from 0.50-0.64 and 0.83-0.92, respectively. Project Goals and Broad Specific Aims: Validate a biomarker for LVO assessment which can be measured and displayed with a fully automated, non-invasive, transcranial Doppler (TCD) robotic system with performance at or exceeding 90% ROC–AUC (targeting SEN & SPE greater than 90%) to standard of care imaging. Complete a clinical study where Arm 1 demonstrates technical feasibility of the system in acute stroke settings and Arm 2 demonstrates safety, no detrimental change to standard of care, and collect robust data to submit to the FDA an IFU expansion to drive clinical care using our robotic system and the biomarker. The ultimate and future goal of this work is to use the automated device and validated VCI biomarker in a prehospital setting to show improved clinical outcomes after stroke onset due to improved prehospital triage. This work is critical to first validate the biomarker against gold standard CTA, which must be completed in a hospital, to ultimately be used in the pre-hospital setting. Longterm Objective: CTA will not be replaced in comprehensive stroke centers and we do not aim to use our technology to do this in comprehensive centers with CTA. Instead, our technology will be available in centers without CTA or MRA and ultimately in the prehospital environment. The goal of our company is to show that our lower cost, portable, non invasive technology can be used to measure a valid biomarker of large vessel occlusion that can be performed outside of a comprehensive stroke center. The first step is to validate the biomarker, in a center with CTA as a gold standard, which is the ultimate goal of this work.