Assessing CSF flow dynamics in pediatric hemorrhagic hydrocephalus

小儿脑积水每年影响全世界40万新生儿。主要病因是 在发达国家，新生儿出血后脑积水（PHH）影响约1/16的早产儿 29周以下出生的婴儿由于最初的脑室内出血， 神经炎症和脉络丛上皮破坏，PHH表现为进行性 心室扩张和颅内压升高。PHH可能导致严重残疾，甚至 死亡 对脑脊液（CSF）流动动力学的不完整和不断发展的理解限制了其发展 预防和治疗PHH的改进策略。传统的大量CSF流量模型认为脑积水 可能是脑脊液生成率和颅外流出率不匹配的管道问题。几 临床前研究已经表明神经炎症破坏CSF-淋巴颅外流出。我们 假设在PHH的婴儿中，颅外CSF流出到外周动脉的受损 导致神经炎症增加的恶性循环，这可能是初始治疗的原因 失败和渐进性损伤，确保不可逆转的脑损伤。 在这个试点项目中，我们将部署一种新的技术，称为荧光，基于帽的经颅光学 断层扫描（fCTOT）以了解脑室和淋巴CSF动力学之间的关系， 神经炎症指标，标准治疗CSF分流术以及内镜下第三次 脑室造口术和脉络丛凝固。我们的具体目标是： (1)对患有以下疾病的婴儿进行心室肌花青绿色（ICG）-CSF动力学的床旁fCTOT成像 PHH进展; (2)通过床旁、无创漫反射测量ICG-CSF清除到淋巴/血液中 使用NIRF-LI进行测量;以及 (3)关联fCTOT衍生的ICG-CSF动力学、ICG-CSF清除至淋巴/血液和CSF生物标志物 炎症与治疗结果的关系。 如果成功，该应用将提供关于CSF动力学在治疗中的作用的新的关键信息。 制定PHH的未来预防、进展和治疗策略。该研究将共同指导 作者：Manish Shah，医学博士，一位监督大量PHH患者护理的神经外科医生;作者：伊娃塞维克， 博士，生物医学工程师和近红外荧光光学断层扫描的早期先驱; Banghe Zhu，博士，一位光学工程师，他将非对比度与CTOT转换为快速，全脑 PHH婴儿的断层扫描。

Pediatric hydrocephalus affects 400,000 new children annually around the world. The primary etiology in the developed world is neonatal post-hemorrhagic hydrocephalus (PHH), affecting around 1 in 16 premature babies born at less than 29 weeks. Arising from the initial insult of intraventricular hemorrhage, subsequent neuroinflammation, and disruption of the choroid plexus epithelium, PHH is manifested by progressive ventricular dilation and increased intracranial pressure. PHH that can lead to significant disability and even death. The incomplete and evolving understanding of cerebrospinal fluid (CSF) flow dynamics limit the development of improved strategies to prevent and treat PHH. Traditional bulk CSF flow models consider hydrocephalus to be a plumbing problem with a mismatch in the rate of CSF generation and extracranial outflow. Several preclinical studies have shown that neuroinflammation disrupts CSF-lymphatic extracranial outflow. We hypothesize that in infants with PHH, impaired extracranial CSF outflow into the peripheral lymphatics contributes to a vicious cycle of increasing neuroinflammation that may be responsible for initial treatment failures and progressive insults that ensure irreversible brain injury. In this pilot project, we will deploy a new technique, called fluorescence, cap-based transcranial optical tomography (fCTOT) to understand the relationship between ventricular and lymphatic CSF dynamics, measures of neuroinflammation, and outcomes to standard-of-care CSF diversion as well as endoscopic third ventriculostomy and choroid plexus coagulation. Our specific aims are to: (1) Conduct point-of-care, fCTOT imaging of ventricular Inodcyanine green (ICG)-CSF dynamics in infants with progressing PHH; (2) Measure ICG-CSF clearance into lymph/blood from point-of-care, non-invasive diffuse reflectance measurements using NIRF-LI; and (3) Correlate fCTOT-derived ICG-CSF dynamics, ICG-CSF clearance into lymph/blood, and CSF biomarkers of inflammation with treatment outcomes. If successful, this application will provide novel, critical information on the role of CSF dynamics for the development of future prevention, progression, and treatment strategies for PHH. The study will be co-directed by Manish Shah, MD, a neurosurgeon overseeing the care of a large PHH patient population; by Eva Sevick, PhD., a biomedical engineer and early pioneer of near-infrared fluorescence optical tomography; and by Banghe Zhu, PhD., an optical engineer who translated a non-contrast versus CTOT for rapid, whole-brain tomography of PHH infants.