Noninvasive Noncontact High-Density Optical Imaging of Neonatal Intraventricular Hemorrhage

摘要 生发基质脑室出血(GM-IVH)是早产的主要并发症，发生于 高达45%的极低出生体重儿(&lt；1500克)是由于体内未成熟血管的脆弱所致 生发矩阵。GM-IVH还可导致脑积水(HCP)和颅内压升高，这 进一步导致炎症和脑组织损伤。尽管新生儿GM-IVH和HCP越来越多 由于早产存活率的上升，目前还没有确定的生物标记物或指南 他们预防脑损伤的治疗方法。GM-IVH/HCP早产儿易受脑部改变的影响 血流(CBF)，因为它们损害了脑血管的自我调节。然而，目前还没有可靠的 新生儿重症监护病房(NICU)床边重复评估的功能成像方法 无论是脑损伤的程度还是干预的有效性。近红外光谱分析和层析成像 几十年来，这些技术一直被用作连续监测大脑的无创床边工具 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- Of-view(FOV)成像分布式大脑功能并区分大脑信号与覆盖的头皮和 头骨。一些高密度层析成像系统使用大量与光纤耦合的分立源和探测器 捆绑在一顶头帽上。然而，调整和保持大量光纤到光纤的稳定光耦合 小而脆弱的新生儿头部(即接触式测量)是劳动密集型的，对头部构成巨大挑战 考虑到安全问题的盖子设计。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)，多波长散斑对比漫射相关 体层摄影术(MW-scDCT)系统，支持快速、高分辨率的CBF和 血氧饱和度超过新生儿头部的大视野。MW-scDCT将经过严格的校准和优化，使用 标准组织模体(目标1)。体内校准/评估将对照MRI和组织学进行 对与人类新生儿有很大相似性的新生仔猪进行IVH/HCP模型的检查(目的 2)。对符合标准的早产儿GM-IVH/HCP进行先导性临床观察研究 在NICU的护理(目标3)。脑血流动力学/代谢、脑血管自动调节和脑 功能连接将从出生后几周拍摄的连续功能图像中进行分析。我们 假设MW-SCDCT检测到的脑血流动力学/代谢改变与 GM-IVH/HCP后脑损伤的进展及治疗后的恢复多个参数将提供 与单一参数相比，对新生儿脑损伤/恢复的评估更全面。这 这项研究将满足新生儿学领域的一个关键需求，即提供客观的措施/生物标志物来指导时机 对GM-IVH和HCP的治疗。我们预计，无创的、重复的和纵向的大脑监测 对于干预措施的指导，最终可以作为新生儿重症监护病房的护理标准来实施。

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.