Microvascular Cerebral Blood Flow Monitoring with Diffuse Correlation Spectroscopy in Sickle Cell Anemia Children

镰状细胞性贫血儿童的弥散相关光谱微血管脑血流监测

• 批准号: 10597513
• 负责人: Eashani Sathialingam
• 金额: $ 1.85万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597513
• 关键词: Abnormal Red Blood Cell; Adult; Affect; Age; Agreement; Algorithms; Anemia; Arteries; Blood; Blood Flow Velocity; Blood Vessels; Blood flow; Brain; Brain Injuries; Caliber; Cell Density; Cerebrovascular Circulation; Child; Childhood; Chronic; Clinical; Clinical Data; Complement; Complication; Contrast Media; Data; Diffuse; Erythrocytes; Face; Gold; Hematocrit procedure; Hematological Disease; Hemoglobin; Hyperemia; In Vitro; Infarction; Light; Linear Regressions; Literature; Magnetic Resonance Imaging; Measurement; Measures; Metabolism; Microfluidics; Modality; Modeling; Monitor; Neurocognitive Deficit; Optics; Oxygen; Patients; Perfusion; Physiological; Positron-Emission Tomography; Property; Publications; Publishing; Radiation; Reporting; Rest; Risk; Scanning; Screening procedure; Sedation procedure; Sickle Cell; Sickle Cell Anemia; Specificity; Spectrum Analysis; Stenosis; Stroke; Symptoms; Techniques; Testing; Time; Tissues; Transcranial Doppler Ultrasonography; Transfusion; arterial spin labeling; arteriole; blood flow measurement; cell motility; cohort; cost; design; experience; experimental study; feeding; imaging modality; improved; in vivo; indexing; neuroimaging; neurovascular; pediatric patients; prognostic tool; screening; sickling; stroke risk; tool; trend; validation studies

Project Summary/Abstract Stroke is a devastating complication of sickle cell anemia (SCA), a blood disorder, where SCA pediatric patients are 250 times more likely to have a stroke than age-matched healthy controls. Red blood cell abnormalities contribute to vascular occlusion, significantly increasing the risk of stroke. By age 20, 11% of SCA pediatric patients will experience an overt stroke, and by age 14, approximately 40% will have a silent infarct. Silent infarcts do not present with clinically apparent symptoms; they can only be visualized on neuroimaging scans. Early transcranial Doppler ultrasound (TCD) screening of SCA patients, with rapid initiation of transfusion therapy, has resulted in successful reduction of overt strokes. However, TCD suffers from poor specificity to overt stroke (i.e., some TCD deemed low-risk patients still develop a stroke), and it is completely insensitive to silent infarct risk. Microvascular measurements of blood flow show promise as a complementary tool to TCD measurements. Yet, current imaging modalities that measure microvascular perfusion (i.e., MRI, PET) are not applicable for routine use due to need for contrast and/or radiation, high costs, and/or sedation in children <6y. Thus, there is a clinical need for a low-cost tool that measures microvascular cerebral blood flow in a routine manner to detect any abnormalities in cerebral blood flow to ultimately mitigate stroke risk. Diffuse correlation spectroscopy (DCS) is an emerging low-cost (<$50k), non-invasive optical modality that utilizes near-infrared light to directly sense red blood cell movement and measure microvascular cerebral blood flow. To date, we have demonstrated that DCS measures a higher resting state cerebral blood flow (by 3x) in sickle cell children in comparison to healthy controls. However, this increase is not comparable to the commonly reported ~1.5x increase from MRI/PET. Since these SCA patients experience moderate to severe anemia and DCS is sensitive to red blood cell movement and density, I hypothesize that this quantitative difference in DCS blood flow measurements may be attributed to anemia. To test this hypothesis, I designed, developed, and validated a microfluidic tissue-simulating platform, with hundreds of embedded microchannels. This platform allows me to systematically manipulate flow rate, hematocrit, and vessel size for both healthy and sickle blood. My preliminary data with healthy blood demonstrates the confounding influence of hematocrit on DCS blood flow measurements. I used my preliminary data to develop an initial linear regression model, applied it to my published clinical data, and now observe a ~1.7x increase between sickle cell and healthy controls. In this proposal, I will use my microfluidic tissue-simulating platform to determine the effects of hematocrit on the DCS blood flow index (Aim 1). Next, I will develop and validate DCS correction algorithms against a “gold- standard” perfusion modality, arterial spin-labeled (ASL) MRI to reliably quantify cerebral blood flow in SCA patients (Aim 2). Upon completion of the proposed aims, I will have sufficient in vitro and clinical data to support further experiments that will explore the clinical utility of DCS.

项目摘要/摘要 中风是镰状细胞性贫血(SCA)的毁灭性并发症，SCA是一种血液疾病，SCA儿童患者 中风的可能性是年龄匹配的健康对照组的250倍。红细胞异常 导致血管闭塞，显著增加中风的风险。到20岁时，11%的SCA儿童 患者将经历明显的中风，到14岁时，大约40%的患者将出现无症状脑梗塞。静默 梗塞没有明显的临床症状；它们只能在神经成像扫描中被可视化。 快速输血的SCA患者的早期经颅多普勒超声(TCD)筛查 治疗，已经成功地减少了明显的中风。然而，TCD的特异性较差。 明显的中风(即，一些被认为是低风险的TCD患者仍然会发生中风)，而且它对 无声的脑梗塞风险。微血管血流测量有望成为TCD的补充工具 测量。然而，目前测量微血管血流的成像方式(即磁共振成像、正电子发射计算机断层扫描)并不是 适用于需要对比剂和/或放射、高成本和/或镇静剂的6岁儿童的常规使用。 因此，临床上需要一种常规测量微血管脑血流量的低成本工具 检测脑血流的任何异常以最终降低中风风险的方式。 漫反射相关光谱(DCS)是一种新兴的低成本(5万美元)的非侵入性光学检查手段 它利用近红外光直接感知红细胞运动并测量脑微血管 血液流动。到目前为止，我们已经证明了DCS测量了更高的静息状态脑血流量(通过 3x)，与健康对照组比较。然而，这一增长无法与 通常报告比MRI/PET增加约1.5倍。由于这些SCA患者经历了中度到重度 贫血和DCs对红细胞运动和密度很敏感，我假设这一数量 DCs血流测量的差异可能归因于贫血。为了验证这一假设，我设计了， 开发并验证了一个具有数百个嵌入微通道的微流控组织模拟平台。 这个平台使我能够系统地控制流速、红细胞压积和血管大小， 镰刀血。我用健康血液的初步数据显示了红细胞压积对 Dcs血流量测量。我使用我的初步数据开发了一个初始的线性回归模型，应用 这与我发表的临床数据一致，现在观察到镰状细胞与健康对照组之间增加了约1.7倍。 在这项提案中，我将使用我的微流控组织模拟平台来确定红细胞压积的影响 对DCs血流指数(目标1)的影响。接下来，我将针对“黄金--”开发和验证分布式控制系统校正算法 动脉自旋标记(ASL)MRI“标准”灌注模式可靠地定量SCA的脑血流量 患者(目标2)。在完成建议的目标后，我将有足够的体外和临床数据来支持 进一步的实验，将探索分布式控制系统的临床应用。

项目成果

Accuracy of diffuse correlation spectroscopy measurements of cerebral blood flow when using a three-layer analytical model.

使用三层分析模型时脑血流的扩散相关光谱测量的准确性。

• DOI: 10.1364/boe.438303
• 发表时间: 2021
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Zhao,Hongting;Sathialingam,Eashani;Buckley,ErinM
• 通讯作者: Buckley,ErinM

Quantifying the Cerebral Hemometabolic Response to Blood Transfusion in Pediatric Sickle Cell Disease With Diffuse Optical Spectroscopies.

• DOI: 10.3389/fneur.2022.869117
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROLOGY
• 影响因子: 3.4
• 作者: Lee, Seung Yup;Brothers, Rowan O.;Turrentine, Katherine B.;Quadri, Ayesha;Sathialingam, Eashani;Cowdrick, Kyle R.;Gillespie, Scott;Bai, Shasha;Goldman-Yassen, Adam E.;Joiner, Clinton H.;Brown, R. Clark;Buckley, Erin M.
• 通讯作者: Buckley, Erin M.