Prehospital Diagnostic Biomarker for Large Vessel Occlusion

背景：大血管急性缺血性卒中（AIS）的发病率估计为 在美国，每年约有250，000名患者，是残疾的主要原因， 主要死因尽管存在介入（支架取栓器）和药物（tPA）治疗， 大血管闭塞（LVO），其使用是有限的，因为这些症状发作的时间窗短， 治疗被指示在中施用。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，这已显示在几个方面取得了更好的结果。 全球RCT为了使干预取得成功，需要一个标准化、量化、基于实地的（预 医院）诊断工具，以提高LVO识别，并确保快速转移到一个有能力的医疗 设施。目前，脑卒中诊断的金标准是CT血管造影（CTA），但仅限于医院内 使用或少量的移动的中风救护车，所有这些都花费数百万美元，需要专家 操作员和静脉注射富碘造影剂。此外，临床卒中评估量表 (RACE、LAMS、CPSS），尽管成本低且无创，但由于 培训要求和低固有精度，在最近的研究中，SEN和SPE的范围为0.50-0.64 0.83-0.92。 项目目标和广泛的具体目标：可测量的LVO评估生物标志物 并显示了一个全自动的，非侵入性的，经颅多普勒（TCD）机器人系统， 达到或超过90% ROC-AUC（目标SEN和SPE大于90%）的标准治疗性能 显像完成一项临床研究，其中第1组证明了该系统在急性卒中中的技术可行性 第2组证明了安全性，对标准治疗无不利变化，并收集了稳健的数据， 向FDA提交IFU扩展，以使用我们的机器人系统和生物标志物推动临床护理。的 这项工作的最终和未来的目标是使用自动化设备和经验证的VCI生物标志物， 由于改善了院前分诊，卒中发作后的临床结局得到改善。 这项工作对于首先根据金标准CTA验证生物标志物至关重要，必须在 医院，最终用于院前环境。 长期目标：CTA在综合性卒中中心不会被取代，我们不打算使用我们的 在综合中心使用CTA技术来实现这一点。相反，我们的技术将在 没有CTA或MRA，最终在院前环境中。我们公司的目标是表明， 我们的低成本、便携式、非侵入性技术可用于测量大血管的有效生物标志物 可以在综合中风中心之外进行的闭塞。第一步是验证 生物标志物，在一个中心与CTA作为金标准，这是这项工作的最终目标。

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.