Diffuse optical spectroscopies to assess cerebral hemodynamics in pediatric sickle cell disease

漫反射光谱法评估儿童镰状细胞病的脑血流动力学

• 批准号: 10544168
• 负责人: Erin McGuire Buckley
• 金额: $ 47.92万
• 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: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544168
• 关键词: Accounting; Adverse event; Affect; Age; Anemia; Anesthesia procedures; Blood Flow Velocity; Blood Vessels; Blood flow; Brain; Brain Injuries; Carbon Dioxide; Carrying Capacities; Cell Respiration; Cerebral Infarction; Cerebrovascular Circulation; Cerebrum; Child; Childhood; Clinical; Cognitive deficits; Data; Diffuse; Exhibits; Frequencies; Goals; Hematocrit procedure; Hemoglobin; Impairment; In Vitro; Infarction; Injury; Intervention; Light; Link; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic stress; Metabolism; Modality; Monitor; Near-Infrared Spectroscopy; Optics; Oxygen; Patients; Performance; Perfusion; Physiology; Positron-Emission Tomography; Property; Risk; Risk Reduction; Schools; Screening procedure; Sickle Cell Anemia; Spectrum Analysis; Stimulus; Stroke; Structure; Surface; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Transcranial Doppler Ultrasonography; Transfusion; Treatment Efficacy; Vasodilation; age effect; cerebral artery; cerebral hemodynamics; cerebrovascular; comparison control; cost; cost effective; frontal lobe; gray matter; hemodynamics; high risk; improved; indexing; light intensity; portability; response; routine screening; screening; success; tool; treatment optimization; trend; ultrasound; user-friendly; white matter

Project Summary Silent cerebral infarction is a serious consequence of sickle cell disease (SCD), affecting ~40% of patients by age 15. Although these injuries accumulate occultly, they are linked with cognitive deficits, diminished school performance, and increased risk of overt stroke. Our long-term goal is to develop a low-cost brain monitoring tool that can screen for silent infarct risk in pediatric SCD to facilitate timely therapeutic intervention and that can optimize these interventions to mitigate adverse events. Silent infarcts in SCD are thought to arise from anemia- induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow, vascular reactivity, and/or oxygen extraction may be useful in identifying infarct risk. Indeed, recent MRI studies have shown that SCD children with silent infarcts have globally elevated oxygen extraction in both white and grey matter compared to those without infarct. However, current modalities that quantify microvascular hemodynamic parameters (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children <6y, making them inappropriate as routine screening tools. Transcranial Doppler ultrasound measures of macrovascular blood flow velocity have had great success in reducing the risk of overt strokes of the macrovasculature by <80%; however, ultrasound is not sensitive to silent microvascular infarcts. Thus, there is an unmet clinical need for a low-cost, non-invasive tool sensitive to microvascular, tissue-level cerebral hemodynamic abnormalities in pediatric SCD to detect children at risk for silent infarcts. Diffuse optical spectroscopies (namely frequency domain near-infrared spectroscopy combined with diffuse correlation spectroscopy, FDNIRS/DCS) may provide a user-friendly, cost-effective alternative to current technologies. These non-invasive techniques use near-infrared light to relate measured changes in light intensity detected at the tissue surface to hemodynamic properties of the underlying tissue. Combined, FDNIRS/DCS enable assessment of oxygen extraction, an index of cerebral blood flow, and an index of cerebral oxygen metabolism. Further, using a simple breath hold challenge, FDNIRS/DCS can assess cerebrovascular reactivity, the vasculature’s ability to dilate in response to carbon dioxide. Our preliminary results show that FDNIRS/DCS can detect expected trends in brain oxygen extraction and blood flow in SCD patients (i.e., elevated compared to controls, inverse correlation with hemoglobin). Moreover, we have developed new analytical strategies that improve the accuracy of the DCS-measured blood flow index by accounting for the influence of hematocrit. Building on this preliminary data, the overall objective of this proposal is to validate our DCS hematocrit- correction against “gold-standard” perfusion MRI, to determine if FDNIRS/DCS is sensitive to cerebral hemodynamic abnormalities in patients with silent infarcts, and to demonstrate FDNIRS/DCS can assess real- time changes in cerebral hemodynamics during transfusion, which reduces silent infarct risk in SCD patients.

项目概要 无症状性脑梗死是镰状细胞病 (SCD) 的严重后果，影响约 40% 的患者 15 岁。虽然这些伤害会隐秘地累积，但它们与认知缺陷、学习能力下降有关 表现，并增加明显中风的风险。我们的长期目标是开发低成本的大脑监测 可以筛查儿科 SCD 中无症状梗死风险的工具，以促进及时的治疗干预，并且可以 优化这些干预措施以减轻不良事件。 SCD 中的无症状梗塞被认为是由贫血引起的 诱发微血管灌注异常和随后的脑血管储备减少 不足以满足组织代谢需求。因此，脑微血管异常的量化 血流、血管反应性和/或氧气提取可能有助于识别梗塞风险。确实，最近 MRI 研究表明，患有无症状梗塞的 SCD 儿童的全身氧摄取量均升高 与没有梗塞的白质和灰质相比。然而，目前量化微血管的方式 血流动力学参数（例如 PET、MRI）非常昂贵，可用性有限，并且需要 6 岁以下儿童需要麻醉，因此不适合作为常规筛查工具。经颅多普勒 大血管血流速度的超声测量在降低明显的风险方面取得了巨大成功 大血管中风<80%；然而，超声对无症状微血管梗塞不敏感。 因此，对微血管、组织水平敏感的低成本、非侵入性工具的临床需求尚未得到满足。 儿科 SCD 的脑血流动力学异常，以检测有无症状梗塞风险的儿童。 漫反射光学光谱（即频域近红外光谱与漫反射光谱相结合） 相关光谱、FDNIRS/DCS）可以提供一种用户友好、经济有效的替代方案 技术。这些非侵入性技术使用近红外光来关联测量到的光强度变化 在组织表面检测到下面组织的血流动力学特性。 FDNIRS/DCS 组合 能够评估吸氧量、脑血流量指数和脑氧指数 代谢。此外，使用简单的屏气挑战，FDNIRS/DCS 可以评估脑血管反应性， 脉管系统响应二氧化碳而扩张的能力。我们的初步结果表明 FDNIRS/DCS 可以检测 SCD 患者脑氧提取和血流量的预期趋势（即，与 与对照相比，与血红蛋白呈负相关）。此外，我们还制定了新的分析策略 通过考虑血细胞比容的影响，提高 DCS 测量的血流指数的准确性。 基于这些初步数据，该提案的总体目标是验证我们的 DCS 血细胞比容 针对“金标准”灌注 MRI 进行校正，以确定 FDNIRS/DCS 是否对脑部敏感 无症状梗塞患者的血流动力学异常，并证明 FDNIRS/DCS 可以评估真实的 输血期间脑血流动力学的时间变化，可降低 SCD 患者无症状梗塞的风险。