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

摘要 监测颅内压（ICP）是严重脑损伤后的全球标准治疗。的目标 监测和治疗ICP升高是为了维持足够的脑血流量（CBF），从而防止 继发性脑损伤颅内压是通过一个小的压力敏感探头插入头骨测量的， 颅内出血和感染，因此仅用于最危重的患者。更重要的是， 探头不直接测量CBF和临界闭合压力（CrCP），即血流停止时的压力， 这是正确评估脑灌注压（CPP）所需要的。因此，目前无法 将良性ICP升高与限流压力峰值分开。颅内压、脑血流量和肌酐的无创监测 能够进行有针对性的干预，直接优化脑灌注， ICP监测的潜在用例。扩散相关光谱（DCS）已经成为一种可行的工具， 监测CBF、CrCP和ICP。为了测量CBF，DCS量化了 相干的、扩散传播的近红外光，其由红细胞的运动驱动。DCS 基于脉动血流（pCBFi）的形态测量ICP，并通过以下方式估计CrCP： 脉动血压和pCBFi之间的线性回归方法。虽然成功的概念验证 我们的研究小组和其他人已经进行了研究，目前成人DCS的临床翻译是 受到平衡对高大脑灵敏度的需求的挑战的阻碍，这需要大量的来源- 探测器分离，以及在高采集速率下需要高信噪比（SNR）来捕获详细的 脉动血流数据。目前的DCS装置在785 - 850 nm处操作，并且限于2.5 cm的间隔， 提供相对较低的大脑敏感性，表面生理污染的高风险，并且需要脉搏- 由于SNR有限，50-60个心动周期的门控平均值可以提取干净的pCBFi信号。CBF定量 受头皮血流和精确量化所需的重要形态学信息的强烈影响 CrCP和ICP在取平均值期间丢失。为了克服这些局限性，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 一个紧凑的，低声和热发射8通道SNSPD单元，设计成本，可制造性和 考虑到可扩展性，我们将与最先进的1064 nm激光系统集成，外差检测， 快速FPGA相关器提供3.5 cm处的双侧DCS监测（大脑灵敏度增加>50%）， 相对于当前785 - 850 nm DCS技术，SNR增加了200倍以上。我们将展示 SNSPD-DCS在50例神经ICU患者中的可行性和初步临床效用，并验证了我们的CBF、CrCP和 根据TCD、侵入性ICP、Hemedex和患者结局进行ICP估计。成功实现这一点 最先进的非侵入性脑灌注和压力监测将能够指导患者的管理 从而改善神经学结果。

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.