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

经济实惠的短波红外光谱仪用于镰状细胞病儿童中风风险筛查

• 批准号: 10730967
• 负责人: Seung Yup Lee
• 金额: $ 42.67万
• 依托单位: KENNESAW STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2026-09-20
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10730967
• 关键词: Address; Adult; Africa South of the Sahara; Age; Atlases; Benchmarking; Biophotonics; Blood Transfusion; Blood Vessels; Blood flow; Bluetooth; Brain; Carbon Dioxide; Cerebrovascular Circulation; Cerebrum; Child; Childhood; Clinical; Computer Analysis; Country; Coupled; Data; Devices; Early Diagnosis; Early identification; Engineering; Erythrocytes; Evaluation; Exposure to; Fiber Optics; Flowmeters; Foundations; Germanium; Goals; Head; Heart Diseases; Human Resources; In Vitro; Income; Indium; Inhalation; Institutional Review Boards; Investigation; Lasers; Length; Light; Measures; Methods; Microfabrication; Microfluidics; Modality; Modeling; Monitor; Monte Carlo Method; Near-Infrared Spectroscopy; Nurses; Optics; Patients; Pattern; Penetration; Performance; Perfusion; Photons; Pilot Projects; Procedures; Research; Research Activity; Resource-limited setting; Resources; Risk; Scalp structure; Screening procedure; Series; Short Waves; Sickle Cell; Sickle Cell Anemia; Signal Transduction; Skin; Source; Spectrum Analysis; Stroke; Stroke prevention; Students; Surface; System; Techniques; Technology; Testing; Therapeutic Intervention; Tissues; Training; Transcranial Doppler Ultrasonography; Variant; attenuation; blood flow measurement; cerebrovascular; cohort; community clinic; cost; cost effective; cranium; design; design and construction; diffuse reflectance spectroscopy; experience; fluorescence imaging; gallium arsenide; global health; handheld mobile device; high risk; human subject; improved; in silico; in vivo evaluation; infrared spectroscopy; innovation; instrumentation; medical specialties; neuroimaging; optical fiber; optical imaging; photoacoustic imaging; portability; prototype; recruit; screening; sensor; stroke risk; tool; transmission process; user-friendly; validation studies; wireless communication

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.

项目摘要 患有镰状细胞病（SCD）的儿童中风的风险是巨大的，比健康儿童高300倍 没有SCD和心脏病如果不进行治疗，约11%的SCD患者有临床上明显的卒中， 他们的年龄是20岁，2至5岁之间的风险最大。为了预防中风，早期识别 异常脑灌注的监测对于及时启动治疗干预至关重要。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 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， 由于费用高，在撒哈拉以南非洲等资源贫乏的地区缺乏训练有素的人员， 大多数镰状细胞病患者居住的地方。在这里，我们建议设计一种负担得起的非侵入性光学技术 可以量化小儿镰状细胞病的微血管脑血流量（CBF）。具体来说，我们将 建立了一套工作在短波红外（SWIR或2ND）波段的散斑衬度光谱（SCOS）系统 近红外（NIR）区域，增强了深度灵敏度，SNR提高了10倍，成本降低了10倍 与目前的NIR系统相比。首先，我们将通过计算研究短波红外的高深度灵敏度 SCOS在真实头部模型上使用多层蒙特卡罗模拟。我们还将进行实验性的 使用台式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。将针对NIR SCOS进行基准测试，以表征SNR、深度 模拟分层微血管网络的制造微流体通道的灵敏度和准确度。接下来我们 将探索使用低成本锗基短波红外相机的便携式短波红外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人的CBF来验证所开发的原型。 该提案的科学目标是研究SCOS的SWIR范围，以便评估更深的 组织微血管血流SWIR光学透射窗口具有优于NIR的几个优点 范围（700- 900 nm），包括更低的组织光学衰减、更多的每单位能量光子数和更高的 最大允许暴露于皮肤。由于这些优点，短波红外已被探索用于许多光学成像 和光谱技术，包括荧光或光声成像，以及漫反射 光谱，但还没有在SCOS。更高的深度灵敏度将减轻来自 脑外层（即颅骨/头皮），有助于更准确地估计脑血流量。的 拟议的研究将创建一个便携式深部组织流量计的原型，准备用于临床试验研究， 患有镰状细胞病的儿童。从长远来看，这种设备可以解决神经成像方式的缺乏 在低资源环境中。