SNSPD-DCS at 1064 nm for non-invasive monitoring of cerebral perfusion and intracranial pressure in the ICU

1064 nm 的 SNSPD-DCS 用于 ICU 脑灌注和颅内压的无创监测

• 批准号: 10628070
• 负责人: Maria Angela Franceschini
• 金额: $ 67.13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10628070
• 关键词: Acoustics; Adult; Affect; Algorithms; Benign; Bilateral; Blood Pressure; Blood flow; Brain; Brain Injuries; Cardiac; Caring; Cerebral perfusion pressure; Cerebrovascular Circulation; Cerebrum; Clinical; Clinical Investigator; Computer software; Critical Illness; Data; Detection; Devices; Diameter; Diffuse; Environment; Erythrocytes; Fiber; General Hospitals; Goals; Hospitals; Infection; Intervention; Intracranial Hemorrhages; Intracranial Hypertension; Intracranial Pressure; Lasers; Light; Lighting; Linear Regressions; Massachusetts; Measures; Microcirculation; Mind; Monitor; Morphology; Motion; Nerve Sheaths; Neurological outcome; Noise; Optic Nerve; Optics; Oxygen saturation measurement; Parameter Estimation; Patient-Focused Outcomes; Patients; Performance; Perfusion; Physiologic pulse; Physiology; Pilot Projects; Risk; Role; Scalp structure; Signal Transduction; Source; Spectrum Analysis; System; Technology; Time; Training; Transcranial Doppler Ultrasonography; Traumatic Brain Injury; Tympanic membrane; Visualization; Woman; Work; brain parenchyma; brain surgery; clinical care; clinical translation; commercialization; cost; cranium; design; detector; heterodyning; high risk; improved; improved outcome; indexing; instrument; light weight; machine learning algorithm; manufacturability; nanowire; non-invasive monitor; operation; personalized medicine; photon-counting detector; portability; pressure; prevent; prototype; quantum; response; sensor; software development; standard of care; technology development; tool

Abstract Monitoring intracranial pressure (ICP) is the global standard of care following severe brain injury. The goal of monitoring and treating rises in ICP is to maintain adequate cerebral blood flow (CBF), thereby preventing secondary brain injury. ICP is measured by a small pressure-sensitive probe inserted through the skull, with risk of intracranial hemorrhage and infection, hence used only in the most critically ill patients. More importantly, ICP probes do not directly measure CBF and critical closing pressure (CrCP), the pressure where blood flow ceases, which is needed to correctly assess cerebral perfusion pressure (CPP). Therefore it is not currently possible to separate benign ICP elevations from flow-limiting pressure spikes. A non-invasive monitor of ICP, CBF and CrCP would enable targeted interventions that directly optimize cerebral perfusion and significantly expand the potential use cases for ICP monitoring. Diffuse correlation spectroscopy (DCS) has emerged as a viable tool to monitor CBF, CrCP and ICP. To measure CBF, DCS quantify the timescale of fluctuations in the intensity of coherent, diffusely propagating near-infrared light, which are driven by the motion of red blood cells. DCS measures ICP based on the morphology of the pulsatile blood flow (pCBFi) and it estimates CrCP by means of a linear regression approach between pulsatile blood pressure and pCBFi. While successful proof of concept studies have been conducted by our group and others, the clinical translation of DCS in adults is currently hampered by the challenge of balancing the requirement for high brain sensitivity, which requires large source- detector separations, and the need for high signal to noise ratio (SNR) at high acquisition rates to capture detailed pulsatile blood flow data. Current DCS devices operate at 785 - 850 nm and are limited to separations of 2.5 cm, offering relatively low brain sensitivity, high risk of superficial physiology contamination, and requiring pulse- gated averages of 50-60 cardiac cycles to extract clean pCBFi signals due to limited SNR. Quantification of CBF is strongly affected by scalp blood flow and important morphological information needed to accurately quantify CrCP and ICP is lost during the averaging. To overcome these limitations, we propose to partner with one of the pioneers of superconducting nanowire single photon detectors (SNSPD) technology, Quantum Opus, to develop a compact, low sonic and thermal emission 8 channel SNSPD unit, designed with costs, manufacturability and scalability in mind, that we will integrate with a state-of-the art 1064 nm laser system, heterodyne detection, and fast FPGA correlator to offer bilateral DCS monitoring at 3.5 cm (>50% increase in brain sensitivity) with more than 200-fold increase in SNR with respect to current 785 - 850 nm DCS technology. We will demonstrate the feasibility and initial clinical utility of the SNSPD-DCS in 50 neuro-ICU patients and validate our CBF, CrCP and ICP estimates against TCD, invasive ICP, Hemedex, and patient outcomes. The successful realization of this state-of-the-art non-invasive cerebral perfusion and pressure monitor will enable guided management of patients resulting in improved neurological outcomes.

摘要 监测颅内压是重型颅脑损伤后的全球护理标准。的目标是 监测和治疗颅内压升高是为了维持充足的脑血流量，从而防止 继发性脑损伤。通过插入颅骨的小型压力敏感探头测量颅内压是有风险的 治疗颅内出血和感染，因此只用于最危重的病人。更重要的是，国际比较方案 探头不直接测量CBF和临界关闭压(CrCP)，即血流停止处的压力， 这是正确评估脑灌注压(CPP)所必需的。因此，目前不可能 将良性的颅内压升高与限流压力峰值分开。无创性监测颅内压、脑血流量和肌钙蛋白 将允许有针对性的干预，直接优化脑血流灌注，并显著扩大 国际比较方案监测的潜在用例。漫相关光谱分析已经成为一种可行的工具 监测CBF、CRCP和颅内压。为了测量CBF，分布式控制系统将波动的时间尺度量化为 由红血球运动驱动的相干、漫反射的近红外光。集散控制系统 根据脉动血流形态(PCBFi)测量颅内压，并通过以下方法估计CRCP 脉动血压与pCBFi的线性回归分析。在成功证明概念的同时 我们小组和其他人已经进行了研究，目前在成人中的临床翻译是 受制于平衡高大脑敏感度要求的挑战，这需要大量的来源- 探测器分离，以及在高采集率下需要高信噪比(SNR)以捕获详细信息 脉动血流数据。当前的分布式控制系统设备工作在785-850 nm并且限制为2.5 cm的间隔， 大脑敏感度相对较低，表面生理污染的风险较高，需要脉搏- 由于有限的信噪比，用于提取干净的pCBFi信号的50-60个心动周期的门控平均值。脑血流量的量化 受头皮血流和精确量化所需的重要形态信息的强烈影响 CrCP和ICP值在平均过程中丢失。为了克服这些限制，我们建议与 超导纳米线单光子探测器(SNSPD)技术的先驱Quantum Opus将开发 一种紧凑型、低音速和低热发射的8通道SNSPD单元，设计具有成本、可制造性和 考虑到可扩展性，我们将与最先进的1064 nm激光系统、外差检测和 快速的现场可编程门阵列相关器可在3.5厘米处提供双边的分布式控制系统监控(大脑敏感度提高50%) 与当前的785-850 nm分布式控制系统技术相比，信噪比提高了200多倍。我们将演示 SNSPD-DCS在50例神经ICU患者中的可行性和初步临床应用并验证我们的CBF、CrCP和 根据经颅多普勒超声、侵袭性颅内压、血液动力学和患者预后评估颅内压。这一点的成功实现 最先进的非侵入性脑血流灌注和压力监测器将使患者能够进行指导管理 从而改善了神经学结果。