Affordable Shortwave Infrared Spectroscopy for Stroke Risk Screening in Children with Sickle Cell Disease

项目总结 患有镰状细胞病(SCD)的儿童中风的风险是巨大的，大约是健康儿童的300倍 没有SCD和心脏病。在没有治疗的情况下，约11%的SCD患者通过以下方式出现临床明显中风 他们的年龄在20岁，风险在2岁到5岁之间最显著。为了预防中风，及早识别 异常脑血流灌注对于启动及时的治疗干预是至关重要的。现行标准 筛查工具是经颅超声多普勒(TCD)。在高资源环境中，TCD筛查紧随其后 通过输血治疗，中风的风险降低了92%。不幸的是，TCD筛查并不广泛 由于成本高，在撒哈拉以南非洲等资源匮乏的环境中缺乏训练有素的人员 大多数镰状细胞病人都住在那里。在这里，我们建议设计一种负担得起的非侵入性光学技术 可以量化儿童镰状细胞疾病的微血管脑血流量(CBF)。具体来说，我们将 建立工作在短波红外(SWIR或第二波段)的散斑对比光学光谱(SCOS)系统 近红外(NIR)区域，用于增强深度灵敏度，以较低的成本(减少×10)获得更高的信噪比×10 与目前的近红外系统相比。首先，我们将对SWIR的高深度敏感性进行计算研究 在一个逼真的头部模型上使用多层蒙特卡罗模拟的SCOS。我们还将进行实验性的 利用台式SWIR SCOS系统进行验证，该系统包括SWIR长相干激光器和现成的 InGaAs相机。基准测试将在近红外SCOS上执行，以表征SNR、深度 在模拟层状微血管网络的制造的微流体通道上的灵敏度和准确性。接下来，我们 将探索使用低成本的基于锗的SWIR相机的便携式SWIR SCOS系统的可行性 并通过测量经历高碳酸血症挑战的健康成年人的脑血流来验证所开发的原型。 这项建议的科学目标是研究SCOS使能评估更深层次的SWIR范围 组织微血管血流。与近红外相比，SWIR光学传输窗口具有几个优点 范围(700-900 nm)，包括较低的组织光学衰减、更多的单位能量光子数和更高的 对皮肤的最大允许暴露。基于这些优点，SWIR在许多光学成像领域得到了广泛的应用 以及光谱技术，包括荧光或光声成像和漫反射 分光镜，但还没有进入SCOS。更高的深度敏感度将减少信号污染 脑外层(即头骨/头皮)，有助于更准确地估计脑血流量。这个 拟议的研究将创建便携式深部组织血流计的原型，准备在#年进行临床先导研究 患有镰状细胞病的儿童。从长远来看，这种设备可能会解决神经成像手段的匮乏。 在资源不足的情况下。

PROJECT SUMMARY The risk of stroke in children with sickle cell disease (SCD) is enormous, ~300 times higher than healthy children without SCD and heart disease. Without treatment, ~11% of SCD patients have clinically apparent stroke by their age of 20 and the risk is the most significant between ages 2 and 5. For stroke prevention, early identification of abnormal cerebral perfusion is critical to initiating a timely therapeutic intervention. The current standard screening tool is a transcranial ultrasound doppler (TCD). In high-resource settings, the TCD screening followed by blood transfusion therapy has reduced the risk of stroke by 92%. Unfortunately, TCD screening is not widely available due to a high cost and a lack of trained personnel in low resource settings such as sub-Saharan Africa where most sickle cell patients live. Here we propose to engineer an affordable non-invasive optical technique that can quantify microvascular cerebral blood flow (CBF) in pediatric sickle cell disease. Specifically, we will build a speckle contrast optical spectroscopy (SCOS) system working in the shortwave infrared (SWIR or 2nd near-infrared, NIR) region for the enhanced depth sensitivity with ×10 higher SNR at a lower cost (×10 less) compared to the current NIR system. First, we will computationally investigate the high depth-sensitivity of SWIR SCOS using a multi-layer Monte Carlo simulation on a realistic head model. We will also perform experimental verification using a benchtop SWIR SCOS system comprising a SWIR long-coherence laser and an off-the-shelf InGaAs camera. The benchmark tests will be performed against NIR SCOS to characterize SNR, depth sensitivity and accuracy on fabricated microfluidic channels mimicking layered microvascular networks. Next, we will explore the feasibility of a portable SWIR SCOS system using a low-cost Germanium-based SWIR camera and validate the developed protype by measuring CBF of healthy adults undergoing a hypercapnic challenge. The scientific goal of this proposal is to study the SWIR range for SCOS enabling assessment of deeper tissue microvascular blood flow. The SWIR optical transmission window has several advantages over the NIR range (700-900nm) including lower tissue optical attenuation, more photon numbers per unit energy and higher maximum permissible exposure to skin. With these benefits, SWIR has been explored in many optical imaging and spectroscopic techniques including fluorescence or photoacoustic imaging, and diffuse reflectance spectroscopies but not yet in SCOS. The higher depth-sensitivity will mitigate signal contamination from the extracerebral layers (i.e. skull/scalp), contributing to more accurate estimation of cerebral blood flow. The proposed research will create a prototype of a portable deep tissue flowmeter ready for a clinical pilot study in children with sickle cell disease. In the long-term, this device may address the paucity of neuroimaging modalities in the low-resource settings.