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: 10591523
• 负责人: Eva M. Sevick-Muraca
• 金额: $ 55.63万
• 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/10591523
• 关键词: Affect; Age; Arachnoid mater; Biological Markers; Biomedical Engineering; Birth Rate; Blood; Brain; Brain Injuries; Caring; Cephalic; Cerebrospinal Fluid; Cessation of life; Child; Childhood; Choroid Plexus Epithelium; Circulation; Clinical Research; Clinical Trials Data Monitoring Committees; Coagulation Process; Creation of ventriculo-peritoneal shunt; Development; Developmental Disabilities; Diagnosis; Diffuse; Doctor of Philosophy; Economically Deprived Population; 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; 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; Second Look Surgery; Spinal Cord; Structure of choroid plexus; Subarachnoid Space; System; Techniques; Third ventricle structure; Time; Translating; Translations; Treatment Failure; Treatment outcome; Ventricular; Ventriculostomy; absorption; care burden; cerebrospinal fluid flow; disability; draining lymph node; experience; fluorescence imaging; imaging detection; 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.

儿童脑积水每年影响全球40万名新儿童。本病的主要病因学 发达国家是新生儿出血性脑积水(PHH)，每16名早产儿中就有1名受到影响。 出生时不到29周的婴儿。起因于最初的脑室出血，随后 神经炎症和脉络丛上皮破坏，PHH表现为进行性 脑室扩张和颅内压升高。PHH会导致严重的残疾，甚至 死亡。 对脑脊液(CSF)流动动力学的不完全和不断发展的认识限制了发展 改进了预防和治疗PHH的策略。传统的脑脊液流量模型认为脑积水 脑脊液生成率和颅外流出量不匹配的管道问题。几个 临床前研究表明，神经炎症破坏了脑脊液淋巴流出颅外。我们 假设在PHH的婴儿中，颅外脑脊液流出受损进入外周淋巴管 导致神经炎症增加的恶性循环，这可能是最初治疗的原因 失败和循序渐进的侮辱，确保了不可逆转的脑损伤。 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 体层摄影术(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和内窥镜检查的结果 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脑室异位蓝绿(ICG)-脑脊液(CSF)动态监测。 进展性PHH； (2)从护理点无创漫反射测量icg-csf对淋巴/血液的清除 使用NIRF-Li进行测量；以及 (3)fCTOT衍生的ICG-CSF动力学、ICG-CSF淋巴/血液清除率和脑脊液生物标记物之间的相关性 炎症与治疗结果的关系。 如果成功，这项应用将为脑脊液动力学的作用提供新的、关键的信息 PHH未来预防、进展和治疗策略的发展。这项研究将是共同指导的 Manish Shah医学博士，一位神经外科医生，负责管理一大批PHH患者的护理；Eva Sevick， 博士，生物医学工程师和近红外荧光光学断层成像的早期先驱； 朱邦和博士，一位光学工程师，他将非对比度与CTOT转换为快速、全脑 PHH婴儿的体层摄影术。