Interstitial pressure sensor to detect fluid status

项目摘要/摘要 心力衰竭(HF)仍然是导致死亡的主要原因，并导致巨大的经济和患者负担。尽管 旨在降低再住院率和改善治疗选择的政策，心衰的住院率 基本保持不变。组织间液体堆积与血管内液体积聚不成比例 积聚在心力衰竭的症状表现和有害后果中起着关键作用，包括 肺水肿和外周水肿。对液体超载的适当管理需要对心衰进行早期干预 在出现症状性拥堵之前的“拥堵级联”。目前用于监测定量的方法 容量状态的变化大多局限于血管内空间，而针对 皮下组织间压(SCIP)的测量无法提供连续、可靠的数据。 需要一种非侵入性的、易于放置的技术，它提供一种清晰的量化度量，从而 医生洞察何时在心力衰竭充血级联中更早地进行医学干预。要解决这一关键问题 未得到满足的需求，NXT开发了IFPx SCIP传感器原型(IFPx)，用于测量间隙中的流体状态 液体舱。我们的长期目标是开发一种可穿戴的、非侵入性的设备来持续监测 SCIP，具有类似于连续血糖监测设备的外形因素。此阶段1应用程序的目标是 是在台式实验和大型动物流体模型中测试我们的NXT IFPx SCIP原型传感器- 超负荷心力衰竭，以证明传感器的可靠性和证明SCIP信号跟踪与标准， 拥塞的侵入性指标。初步原则证明研究表明，所测量的SCIP 根据历史方法，以黄金标准衡量充血，包括左心室舒张期末 液体超负荷心力衰竭猪模型的血压(LVEDP)和中心静脉压(CVP)。AIM中的研究 1旨在提高NXT IFPx SCIP原型的可靠性和重复性。我们将设计、测试、 并迭代不同的压力传感器件，以提高IFPx的可靠性和重复性 原型，通过台式测试进行评估。AIM 2中的研究将主要确认NXT IFPx SCIP传感器 能够可靠地传输和存储数据。然后，从试验台测试中选出的最有希望的候选人将在 AIM 3中的急性心力衰竭动物研究，成功定义为SCIP相关性的变化(阶段调整 相关系数R2&>0.7)或关联(Bland-Altman平均值±2SD)与LVEDP或CVP成功 完成这些研究将启动第二阶段的申请，以进一步开发可穿戴技术在慢性 进行动物研究，并在心力衰竭患者中进行试点临床研究。

Project Summary / Abstract Heart failure (HF) remains a leading cause of death and results in huge economic and patient burden. Despite policies targeted at reducing readmission rates and improved treatment options, hospitalization rates for HF have remained largely the same. Disproportionally greater interstitial fluid accumulation versus intravascular accumulation plays a pivotal role in the symptomatic manifestation and detrimental outcomes of HF, including pulmonary and peripheral edema. Adequate management of fluid overload requires early intervention in the HF “congestion cascade” prior to the onset of symptomatic congestion. Current methods used to monitor quantitative changes in volume status are mostly limited to the intravascular space, and experimental devices targeting the measurement of subcutaneous interstitial pressure (SCIP) have unable to provide continuous, reliable data. There is a need for a non-invasive, easily placed technology that provides a clear quantitative metric that gives physicians insight into when to medically intervene earlier in the HF congestion cascade. To address this critical unmet need, NXT developed a IFPx SCIP sensor prototype (IFPx) that measures fluid status in the interstitial fluid compartment. Our long-term goal is to develop a wearable, non-invasive device to continuously monitor SCIP, with a form-factor like continuous glucose monitoring devices. The objective for this Phase 1 application is to test our NXT IFPx SCIP prototype sensor in benchtop experiments and in a large animal model of fluid- overloaded heart failure to demonstrate sensor reliability and to demonstrate SCIP signal tracking with standard, invasive metrics of congestion. Preliminary proof-of-principle studies demonstrated that the SCIP, as measured by historic methods, tracks with gold standard metrics of congestion, including left ventricular end diastolic pressure (LVEDP) and central venous pressure (CVP) in a porcine model of fluid-overloaded HF. Studies in Aim 1 are designed to improve the reliability and repeatability of the NXT IFPx SCIP prototype. We will design, test, and iterate different pressure sensing transduction devices to improve reliability and repeatability of the IFPx prototype, as assessed by benchtop testing. Studies in Aim 2 will mainly confirm that the NXT IFPx SCIP sensor can transmit and store data reliably. The most promising candidate from bench tests will then be validated in acute HF animal studies in Aim 3 with success defined as changes in SCIP correlates (Phase-adjusted correlation coefficient r2 > 0.7) or associates (Bland-Altman average±2SD) with LVEDP or CVP Successful completion of these studies will initiate a Phase II application to develop wearable technology further in chronic animal studies and to perform pilot clinical studies in patients with HF.