Noninvasive Noncontact High-Density Optical Imaging of Neonatal Intraventricular Hemorrhage

新生儿脑室内出血的无创非接触式高密度光学成像

• 批准号: 10609485
• 负责人: Guoqiang Yu
• 金额: $ 53.74万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-10 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609485
• 关键词: Acute; Aftercare; Algorithms; Autopsy; Biological Markers; Birth; Blood; Blood Vessels; Brain; Brain Injuries; Brain imaging; Calibration; Case Study; Cephalic; Cerebral Ventricles; Cerebrospinal Fluid; Cerebrospinal fluid shunts procedure; Cerebrovascular Circulation; Cerebrum; Chronic Phase; Clinical; Clinical assessments; Complication; Coupled; Coupling; Critical Care; Critical Illness; Detection; Development; Devices; Diffuse; Dimensions; Effectiveness of Interventions; Evaluation; Fiber; Functional Imaging; Goals; Guidelines; Harm Reduction; Head; Histologic; Homeostasis; Human; Hydrocephalus; Image; Imaging Device; Imaging Techniques; Impairment; Inflammation; Injury; Intervention; Intracranial Hypertension; Intracranial Pressure; Ischemic Brain Injury; Laboratories; Legal patent; Magnetic Resonance Imaging; Measurement; Measures; Medical; Metabolic; Metabolism; Methodology; Methods; Modeling; Monitor; Multi-modal optical imaging; Mus; Near-Infrared Spectroscopy; Neonatal; Neonatal Brain Injury; Neonatal Intensive Care Units; Neonatology; Neurologic Deficit; Neurological outcome; Neurosciences Research; Observational Study; Optics; Outcome; Outcome Measure; Outcome Study; Oxygen; Oxygen Consumption; Premature Birth; Premature Infant; Property; Rattus; Recovery; Research; Resolution; Safety; Scalp structure; Signal Transduction; Source; Survival Rate; System; Technology; Testing; Three-Dimensional Imaging; Tissues; Ultrasonography; Very Low Birth Weight Infant; brain health; brain tissue; cerebral hemodynamics; cerebrovascular; clinical application; cranium; density; design; detector; functional disability; high risk; human imaging; imager; imaging modality; improved; in vivo; innovation; intraventricular hemorrhage; metabolic rate; multimodality; neonatal brain; neonate; neuroimaging; novel; optical imaging; portability; pre-clinical; premature; preservation; preterm newborn; prevent; standard care; standard of care; tissue injury; tissue phantom; tomography; tool

ABSTRACT Germinal matrix-intraventricular hemorrhage (GM-IVH) is a major complication of premature birth, occurring in up to 45% of very low birthweight neonates (<1500 g) due to fragility of immature blood vessels within the germinal matrix. GM-IVH can also lead to hydrocephalus (HCP) and increased intracranial pressure, which further induces inflammation and brain tissue injury. Though neonatal GM-IVH and HCP are increasingly common due to the rising survival rate of preterm births, there are no established biomarkers or guidelines for their treatments to prevent brain injury. Preterm infants with GM-IVH/HCP are vulnerable to alterations in cerebral blood flow (CBF) because they have impaired cerebrovascular autoregulation. However, there are no reliable functional imaging methods at the bedside of neonatal intensive care units (NICUs) for repeatedly assessing either degree of cerebral injury or effectiveness of interventions. Near-infrared spectroscopy and tomography technologies have been used for decades as noninvasive bedside tools for continuous monitoring of cerebral blood oxygen saturation (StO2). However, most systems lack the combination of spatial resolution and wide field- of-view (FOV) to image distributed brain functions and discriminate the brain signal from overlaying scalp and skull. A few high-density tomographic systems use numerous discrete sources and detectors coupled with fiber bundles to a head cap. However, adjusting and maintaining a stable optical coupling of numerous fibers to a small fragile neonatal head (i.e., a contact measurement) is labor-intensive and poses great challenges to head cap design with safety concern. To overcome these limitations, we propose to develop a novel, noncontact, high-density-detection (using a CCD/CMOS camera), multi-wavelength speckle contrast diffuse correlation tomography (MW-scDCT) system to accommodate fast, high-resolution, functional imaging of both CBF and StO2 over a large FOV on the neonatal head. The MW-scDCT will be rigorously calibrated and optimized using standard tissue phantoms (Aim 1). In vivo calibration/evaluation will be conducted against MRI and histological examination in an IVH/HCP model of neonatal piglets who preserve great similarities with human neonates (Aim 2). A pilot clinical observational study will be performed in preterm neonates with GM-IVH/HCP under standard of care in the NICU (Aim 3). Cerebral hemodynamics/metabolism, cerebrovascular autoregulation, and cerebral functional connectivity will be analyzed from serial functional images taken over several weeks after birth. We hypothesize that cerebral hemodynamic/metabolic alterations detected by MW-scDCT correlate with progression of brain injury after GM-IVH/HCP and recovery after treatment. Multiple parameters will provide more comprehensive assessments of neonatal brain injury/recovery compared to a single parameter alone. This study will fulfill a critical need in the field of neonatology to provide objective measures/biomarkers to guide timing of treatment for GM-IVH and HCP. We anticipate that noninvasive, repeated, and longitudinal cerebral monitoring for the guidance of interventions could be eventually implemented as standard of care in NICUs.

抽象的 生发基质脑室内出血（GM-IVH）是早产的主要并发症，发生在 由于体内血管未成熟的脆弱性，高达 45% 的极低出生体重新生儿（<1500 g） 生发基质。 GM-IVH 还可导致脑积水 (HCP) 和颅内压升高，从而导致 进一步诱发炎症和脑组织损伤。尽管新生儿 GM-IVH 和 HCP 越来越多 由于早产存活率不断上升，这种情况很常见，但目前还没有确定的生物标志物或指南 他们的治疗方法是为了预防脑损伤。患有 GM-IVH/HCP 的早产儿很容易受到大脑功能的改变 血流量（CBF），因为他们的脑血管自动调节受损。但目前还没有可靠的 新生儿重症监护病房 (NICU) 床边的功能成像方法用于反复评估 脑损伤的程度或干预措施的有效性。近红外光谱和断层扫描 几十年来，技术一直被用作连续监测脑功能的无创床边工具。 血氧饱和度 (StO2)。然而，大多数系统缺乏空间分辨率和宽视场的结合。 视野 (FOV) 对分布的大脑功能进行成像，并区分来自覆盖头皮和区域的大脑信号 颅骨。一些高密度断层扫描系统使用大量离散源和探测器与光纤耦合 束至头帽。然而，调整和维持大量光纤到一个稳定的光耦合 新生儿头部小且脆弱（即接触式测量）是劳动密集型的，对头部造成很大的挑战 瓶盖设计考虑安全性。为了克服这些限制，我们建议开发一种新颖的、非接触式的、 高密度检测（使用 CCD/CMOS 相机）、多波长散斑对比度漫相关 断层扫描 (MW-scDCT) 系统可对 CBF 和 CBF 进行快速、高分辨率、功能性成像 新生儿头部大视场上的 StO2。 MW-scDCT 将使用严格的校准和优化 标准组织模型（目标 1）。将针对 MRI 和组织学进行体内校准/评估 对新生仔猪的 IVH/HCP 模型进行检查，该模型与人类新生儿保持高度相似性（目的 2）。将在标准条件下对 GM-IVH/HCP 早产儿进行一项试点临床观察研究 NICU 的护理（目标 3）。脑血流动力学/代谢、脑血管自动调节和脑 功能连接性将根据出生后几周内拍摄的系列功能图像进行分析。我们 假设 MW-scDCT 检测到的脑血流动力学/代谢改变与 GM-IVH/HCP 后脑损伤的进展以及治疗后的恢复。将提供多个参数 与单独的单个参数相比，对新生儿脑损伤/恢复进行更全面的评估。这 研究将满足新生儿学领域的关键需求，提供客观的测量/生物标志物来指导时机 GM-IVH 和 HCP 的治疗。我们预计无创、重复和纵向脑监测 干预措施的指导最终可以作为 NICU 的护理标准实施。