Assessing CSF flow dynamics in pediatric hemorrhagic hydrocephalus

评估小儿出血性脑积水的脑脊液流动动力学

• 批准号: 10420486
• 负责人: Eva M. Sevick-Muraca
• 金额: $ 59.9万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10420486
• 关键词: Affect; Age; Arachnoid mater; Biological Markers; Biomedical Engineering; Birth Rate; Blood; Blood Circulation; Brain; Brain Injuries; Caring; Cerebrospinal Fluid; Cessation of life; Child; Childhood; Choroid Plexus Epithelium; Clinical Research; Clinical Trials Data Monitoring Committees; Coagulation Process; Creation of ventriculo-peritoneal shunt; Cytoplasmic Granules; Development; Developmental Disabilities; Diagnosis; Diffuse; Doctor of Philosophy; Engineering; Ensure; Etiology; Failure; Fluorescence; Fourth ventricle structure; Functional disorder; Future; Generations; Healthcare; Hemorrhage; Hydrocephalus; Image; Impairment; Indocyanine Green; Infant; Inflammation; Institutional Review Boards; Intracranial Hypertension; Intraventricular; Investigation; Lead; Lymph; Lymphatic; Macaca fascicularis; Measurement; Measures; Mediating; Minimal Risk Study; Modeling; Neonatal; Neurosurgeon; Operative Surgical Procedures; Optical Tomography; Optics; Outcome; Peripheral; Pilot Projects; Play; Plumbing; Premature Birth; Premature Infant; Prevention; Production; Prognosis; Research; Rodent; Role; Spinal Cord; Structure of choroid plexus; Subarachnoid Space; System; Techniques; Third ventricle structure; Time; Translating; Translations; Treatment Failure; Treatment outcome; Ventricular; Ventriculostomy; base; care burden; cerebrospinal fluid flow; disability; draining lymph node; experience; fluorescence imaging; improved; intraventricular hemorrhage; lateral ventricle; lymphatic imaging; neuroinflammation; novel; patient population; point of care; pre-clinical; preclinical study; prenatal; prevent; socioeconomic disadvantage; standard of care; temporal measurement; therapeutic target; tomography; tool; treatment response; treatment strategy; wasting

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.

全世界每年有 400,000 名新生儿受到小儿脑积水的影响。主要病因学在 发达国家是新生儿出血后脑积水 (PHH)，影响大约十分之一的早产儿 出生小于 29 周的婴儿。由脑室内出血的最初损伤引起，随后 神经炎症和脉络丛上皮细胞的破坏，PHH 表现为进行性 心室扩张和颅内压增高。 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。传统的大量脑脊液流量模型将脑积水视为 可能是管道问题，导致脑脊液生成速率和颅外流出速率不匹配。一些 临床前研究表明，神经炎症会扰乱脑脊液淋巴液的颅外流出。我们 假设患有 PHH 的婴儿颅外脑脊液流入外周淋巴管受损 导致神经炎症增加的恶性循环，这可能是初始治疗的原因 失败和进行性侮辱导致不可逆转的脑损伤。 在这个试点项目中，我们将部署一种新技术，称为荧光、基于帽的经颅光学 断层扫描（fCTOT）以了解脑室和淋巴脑脊液动力学之间的关系， 神经炎症的测量以及标准护理脑脊液分流以及内窥镜第三次治疗的结果 脑室造口术和脉络丛凝固术。我们的具体目标是： (1) 对患有以下疾病的婴儿进行床旁 fCTOT 成像：心室吲哚菁绿 (ICG)-CSF 动态 进展性PHH； (2) 从护理点、非侵入性漫反射测量 ICG-CSF 进入淋巴/血液的清除率 使用 NIRF-LI 进行测量；和 (3) 将 fCTOT 衍生的 ICG-CSF 动力学、ICG-CSF 清除到淋巴/血液以及 CSF 生物标志物相关联 炎症与治疗结果的关系。 如果成功，该应用将为 CSF 动力学的作用提供新颖的关键信息。 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，一名神经外科医生，负责监督大量 PHH 患者的护理；通过伊娃·塞维克， 博士，生物医学工程师，近红外荧光光学断层扫描的早期先驱；并由 Banghe Zhu 博士，光学工程师，将非对比与 CTOT 转化为快速、全脑 PHH 婴儿的断层扫描。