Human Brain Interferometers for Better Blood Flow Monitoring

摘要： 创伤性脑损伤（TBI）管理的主要目标是优化脑血流（CBF）， 受伤后数天至数周。然而，目前还没有成熟的、非侵入性的方法来连续地 监测成人CBF。基于动态扩散光学血流仪（DOF）监测脑血流的方法 尽管在研究中使用近红外（NIR）光的散射，但是这些方法遭受基本的限制。 首先，它们需要昂贵的光子计数，这严格限制了可实现的速度，大脑特异性和大脑功能。 覆盖其次，它们缺乏深度辨别，导致浅表组织中血流的污染。 第三，它们需要对光学特性进行假设，而这些特性在个体之间或整个大脑中可能会有所不同 地区第四，它们对来自环境光的噪声敏感。 为了解决这些局限性，我们将干涉测量引入到人类漫射光学中，创建了一类新的近红外光谱， 基于光的监测工具，称为干涉漫射光谱（iDOS）。首先，我们证明， CMOS传感器可以取代光子计数，并使弱漫射光的测量并行化 波动揭示了CBF。这一进步将光吞吐量与成本比提高了约100倍。因此，我们可以 更多的测量（改善大脑覆盖），更大的源收集器分离（改善大脑 特异性）。然后，我们表明，通过快速调谐光源波长，我们也实现了飞行时间 (TOF)分辨率这种额外的TOF维度更好地将大脑与浅表组织区分开，并且还提供了 光学性质的估计，提高量化。最后，干涉测量方法基本上 不受环境光线的影响。 基于我们在成年人中的有希望的结果，我们将开发，优化和验证iDOS的定量， 快速、可靠的CBF监测。我们将确定iDOS相对于 常规方法。最后，我们将在本研究中对严重TBI患者进行观察性CBF监测。 神经重症监护病房（neuro-ICU），测试我们的非侵入性CBF测量预测月经周期的能力 缺氧。

Abstract: A major goal in the management of traumatic brain injury (TBI) is to optimize cerebral blood flow (CBF) over the days to weeks following injury. Yet, there is currently no well-established, non-invasive method to continuously monitor CBF in adults. Though diffuse optical flowmetry (DOF) methods for monitoring CBF based on dynamic scattering of near-infrared (NIR) light are used in research, these methods suffer from fundamental limitations. First, they require costly photon counting, which strictly constrains achievable speed, brain specificity, and brain coverage. Second, they lack depth discrimination, leading to contamination from blood flow in superficial tissues. Third, they require assumptions about optical properties, which can vary between individuals or across brain regions. Fourth, they are sensitive to noise from ambient light. To address these limitations, we introduce interferometry to human diffuse optics, creating a new class of NIR light-based monitoring tools, called interferometric Diffuse Optical Spectroscopy (iDOS). First, we show that with interferometry, a CMOS sensor can replace photon counting and parallelize measurements of weak diffuse light fluctuations that reveal CBF. This advance improves light throughput-to-cost ratio by ~100x. We can thus take more measurements (improving brain coverage) with larger source collector separations (improving brain specificity). Then, we show that by rapidly tuning the light source wavelength, we also achieve time-of-flight (TOF) resolution. This extra TOF dimension better distinguishes brain from superficial tissue, and also provides estimates of optical properties, improving quantification. Finally, interferometric methods are essentially unaffected by ambient light. Building on our promising results in adult humans, we will develop, optimize, and validate iDOS for quantitative, rapid, and robust CBF monitoring. We will identify the advantages and weaknesses of iDOS relative to conventional methods. Finally, we will perform observational CBF monitoring in severe TBI patients in the neurointensive care unit (neuro-ICU), testing the ability of our non-invasive CBF measurements to predict periods of hypoxia.