Development of a rapid, scalable, and deployable point-of-care blood volume diagnostic for monitoring postpartum and trauma-related hemorrhage

摘要 产后出血(PPH)是全球孕产妇死亡的主要原因，占所有产妇死亡的四分之一 与分娩相关的死亡。PPH被描述为累积失血量为1L或更多，并有以下症状 产后24小时内血容量不足。最近，有报道显示，大约53%-93%的PPH- 如果及时实施医疗和干预措施，相关死亡是可以预防的。 目前，妇产科使用对失血量和患者病情的主观视觉评估或半客观评估 对浸血的垫子、窗帘和其他也会吸收羊水、尿液和其他物质的材料的评估 分娩时排泄物和血液一起排出。我们当然可以做得更好：这是一个伟大的未满足和关键的 鉴于目前还没有量化方法来评估血容量或失血量，以确定和 直接PPH治疗决策和干预。为了满足这一需求并直接回应NOT-EB- 21-001，QuantiPort正在开发一种新的快速、可扩展、可部署、易于使用和廉价的点- 美国国立卫生研究院用于测量产后和创伤相关出血的BV诊断仪 SBIR第一阶段应用。为了测量BV，我们的团队开发了一种独特的方法，由非 位于皮肤上、主要血管上方的成像超声换能器，它将量化 注射微泡(MB)示踪剂(Sonazid®，GE Healthcare)的血管内浓度 静脉注射。实际血容量结果可在3分钟内获得，评估可能是 每隔20分钟重复一次，提供随时间推移的定量测量，以确定失血率 或评估治疗干预措施的效果。由于系统设计简单而笨拙，这款小， 轻量级设备可以很容易地适应现有的临床工作流程。建议的甲基溴示踪剂是安全的，非放射性标记的， 具有与红细胞相似的流变学，以消除体积误差，并在室温下稳定 几个月到几年。为了执行拟议的研究，我们对此应用程序的目标包括：1)建立 手动非成像超声系统和优化使用体外血管显像剂检测MB示踪剂 流动体模，以及2)在日本猕猴体内执行BV诊断的概念验证测试 俄勒冈州国家灵长类动物研究中心。这些研究的成功实施将导致 开发一种独特而新颖的超声系统，以快速、便携和低成本的方式准确测量BV。 产后出血和创伤护理的有效方法。我们的目标是确保QuantiPort的设备能够有效地及时引导 改善产妇产后出血的发病率和死亡率的可行干预措施，这是 Not-EB-21-001。

ABSTRACT Postpartum hemorrhage (PPH) is the leading cause of maternal mortality globally, accounting for 1/4th of all delivery-associated deaths. PPH is described as the cumulative blood loss of 1L or more with symptoms of hypovolemia within 24 hours after giving birth. Recently, reports have demonstrated that about 53-93% of PPH- related deaths could have been prevented by administering timely medical treatments and interventions. Currently, OB-GYNs use subjective visual assessments of blood loss and patient condition or semi-objective assessments of blood-soaked pads, drapes, and other materials that also absorb amniotic fluid, urine, and other excretions along with blood at delivery. We can certainly do better: This represents a great unmet and critical need given there is currently no quantitative method of assessing blood volume, or blood loss, to identify and direct PPH treatment decisions and interventions. To address this need and in direct response to NOT-EB- 21-001, QuantiPort is developing a novel rapid, scalable, deployable, easy-to-use, and inexpensive point- of-care BV diagnostic device to measure BV for postpartum and trauma-related hemorrhage in this NIH SBIR Phase I application. To measure BV, our team has developed a unique approach comprised of a non- imaging ultrasound transducer positioned on the skin, over a major blood vessel, which will quantify the intravascular concentration of a microbubble (MB) tracer agent (Sonazoid®, GE Healthcare) injected intravenously. The actual blood volume result can be obtained in under 3 minutes and assessments may be repeated every 20 minutes to provide quantitative measurements over time to determine the rate of blood loss or to assess the efficacy of therapeutic interventions. As the system design is simple and unwieldy, this small, lightweight device can easily fit into existing clinical workflows. The proposed MB tracer is safe, non-radiolabeled, has similar rheology to red blood cells to eliminate volumetric inaccuracies, and is stable at room temperature for months to years. To execute the proposed studies, our objectives for this application include: 1) building a manual non-imaging ultrasound system and optimizing the detection MB tracer agent using an in vitro vascular- flow phantom, and 2) performing proof-of-concept testing of the BV diagnostic in vivo in Japanese macaques at the Oregon National Primate Research Center. Successful execution of these studies will result in the development of a unique and novel ultrasound system to accurately measure BV in a rapid, portable, and cost- effective way for PPH and trauma care. Our goal is to ensure that QuantiPort’s device can effectively guide timely and actionable interventions to improve maternal morbidity and mortality due to PPH, which is a key intention of NOT-EB-21-001.