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.

项目概要/摘要 中风是镰状细胞性贫血 (SCA) 的一种破坏性并发症，这是一种血液疾病，SCA 儿科患者 中风的可能性比年龄匹配的健康对照组高 250 倍。红细胞异常 导致血管闭塞，显着增加中风的风险。到 20 岁时，11% 的 SCA 儿童 患者会经历明显的中风，到 14 岁时，大约 40% 的人会出现无症状的梗塞。沉默的 梗塞没有明显的临床症状；它们只能通过神经影像扫描才能看到。 对 SCA 患者进行早期经颅多普勒超声 (TCD) 筛查，并快速开始输血 治疗，已成功减少明显的中风。然而，TCD 的特异性较差。 明显的中风（即一些被认为低风险的 TCD 患者仍然会发生中风），并且它对以下因素完全不敏感： 无症状梗塞风险。血流的微血管测量有望成为 TCD 的补充工具 测量。然而，目前测量微血管灌注的成像方式（即 MRI、PET）并不能 由于需要对比剂和/或放射、高成本和/或 6 岁以下儿童的镇静作用，适用于常规使用。 因此，临床需要一种低成本的工具来常规测量微血管脑血流量 检测脑血流异常的方法，最终降低中风风险。 漫相关光谱 (DCS) 是一种新兴的低成本（<5 万美元）、非侵入性光学模式 利用近红外光直接感知红细胞运动并测量脑微血管 血流（量。迄今为止，我们已经证明 DCS 可以测量更高的静息状态脑血流量（通过 3x）在镰状细胞儿童中与健康对照相比。但这一增幅无法与 据报道，与 MRI/PET 相比，增加约 1.5 倍。由于这些 SCA 患者经历中度至重度 贫血和 DCS 对红细胞运动和密度敏感，我假设这种定量 DCS 血流测量值的差异可能归因于贫血。为了检验这个假设，我设计了， 开发并验证了一个微流体组织模拟平台，具有数百个嵌入式微通道。 这个平台使我能够系统地控制流速、血细胞比容和血管尺寸，以确保健康和健康。 镰刀血。我对健康血液的初步数据证明了血细胞比容对 DCS 血流测量。我用我的初步数据开发了一个初始线性回归模型，应用 根据我发表的临床数据，现在观察到镰状细胞和健康对照之间增加了约 1.7 倍。 在这个提案中，我将使用我的微流体组织模拟平台来确定血细胞比容的影响 DCS 血流指数（目标 1）。接下来，我将针对“黄金- 标准”灌注方式，动脉自旋标记 (ASL) MRI，可可靠量化 SCA 中的脑血流量 患者（目标 2）。完成拟议的目标后，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 DCS 的临床效用。

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.