Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus

新生儿脑积水颅内压和脑缺血的新型超声指标

基本信息

批准号：
10680542
负责人：
Misun Hwang
金额：
$ 64.12万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10680542
关键词：
Academy Affect Amendment Animal Model Assessment tool Biological Markers Blood Vessels Brain Brain Injuries Brain Ischemia Brain Neoplasms Brain region Cerebral Ischemia Cerebrospinal Fluid Cerebrovascular Circulation Cerebrum Child Childhood Clinical Clinical Trials Complex Data Data Analyses Diagnosis Dilatation - action Disease Engineering Etiology Evaluation Extracorporeal Membrane Oxygenation FDA approved Future Goals Guidelines Heart Arrest Hemorrhage Histologic Histology Hospitals Hydrocephalus Image Infant Injections International Intervention Intracranial Hypertension Intracranial Pressure Investigational Drugs Judgment Label Lesion Liquid substance Live Birth Liver Measures Meningomyelocele Methods Microbubbles Microcirculation Microspheres Modeling Monitor Neonatal Neurologic Deficit Neurological outcome Non-Invasive Detection Operative Surgical Procedures Outcome Patients Perfusion Population Pre-Clinical Model Protocols documentation Publishing Reference Standards Reproducibility Risk Safety Shunt Device Stenosis Stroke Surgical Management Techniques Testing Time Tissues Traumatic Brain Injury Validation Velocimetries Ventricular Vesico-Ureteral Reflux Work brain health clinical care clinical translation contrast enhanced experience imaging approach improved in vivo indexing intraventricular hemorrhage member meter neonatal brain neonatal care neonate novel particle porcine model pre-clinical prognostication safety assessment standard measure tool ultrasound

项目摘要

Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus Project Summary Neonatal hydrocephalus affects 1-2 of every 1000 live births and results in neurologic deficits in up to 78% treated patients. A wide spectrum of etiologies including intraventricular hemorrhage, congenital aqueduct stenosis, myelomeningocele, and brain tumors cause an abnormal accumulation of cerebral spinal fluid (CSF) in this disease, resulting in cerebral ventricular dilatation and elevated intracranial pressure (ICP). While ventricular shunting is used as surgical treatment for CSF diversion, the decision to shunt is based on ventricular size and clinical judgement which are not sensitive markers of ICP and brain health. Thus, delayed diagnosis of elevated ICP and surgical shunting can result in permanent brain damage and long-term neurologic deficits. Insertion of invasive ICP monitor is not routinely done due to the associated risk of bleeding and regional brain ischemia in the vulnerable neonatal brain. In order to provide a solution to a significant gap in clinical care of neonatal hydrocephalus, we utilize the contrast-enhanced ultrasound (CEUS) technique for noninvasive detection of ICP and brain ischemia in a well-established porcine model of hydrocephalus. CEUS uses intravascular injection of microbubbles of average 2-3 µm in size for assessment of tissue perfusion. With the combined use of the novel particle tracking method (so-called particle intensity and/or tracking velocimetry) and traditional perfusion analysis, the underlying spatial and temporal changes in cerebral microcirculation can be quantified for assessment of elevated ICP and brain ischemia. Note that CEUS has been FDA-approved for pediatric applications in the U.S. as of 2016 for evaluation of focal liver lesions and vesicoureteral reflux, but its application in neonatal brain is off-label. For this, the PI currently spearheads the first FDA regulated, Investigational New Drug (IND)-approved clinical trial applying brain CEUS in infants and published the first imaging guidelines on brain CEUS in infants; the potential for immediate clinical translation of the validated method following the completion of this proposal is therefore significant. The central hypothesis of the proposal is that CEUS will be an accurate biomarker of intracranial pressure and brain ischemia. The overall goal of the proposal is therefore to 1) validate CEUS indices of intracranial pressure and brain ischemia using an already established infant porcine model of hydrocephalus and to 2) assess in vivo safety of the optimized brain CEUS protocol. Our work will set the stage for clinical translation of a new noninvasive tool for assessment of intracranial pressure and brain ischemia in neonatal hydrocephalus, which can ultimately improve the guidance of shunting and long-term neurologic outcomes.

新生儿脑积水颅内压和脑缺血的新型超声指标项目概要每 1000 名活产儿中就有 1-2 人患有新生儿脑积水，并导致高达 78% 的神经功能缺损多种病因的患者，包括脑室内出血、先天性导水管治疗。狭窄、脊髓脊膜膨出和脑肿瘤会导致脑脊液 (CSF) 异常积聚在这种疾病中，导致脑室扩张和颅内压（ICP）升高。脑室分流术作为脑脊液改道的手术治疗，分流的决定是基于心室分流术大小和临床判断不是 ICP 和大脑健康的敏感标志，因此会延迟诊断。颅内压升高和手术分流可导致永久性脑损伤和长期神经功能缺损。由于出血和局部脑损伤的相关风险，插入侵入性 ICP 监测仪并不常规进行脆弱的新生儿大脑缺血，从而为临床护理中的重大差距提供解决方案。新生儿脑积水，我们利用超声造影（CEUS）技术进行无创治疗在完善的猪脑积水模型中检测 ICP 和脑缺血。血管内注射平均大小为 2-3 µm 的微泡，用于评估组织灌注。结合使用新颖的粒子跟踪方法（所谓的粒子强度和/或跟踪测速）和传统的灌注分析可以揭示脑微循环的潜在时空变化量化评估 ICP 升高和脑缺血请注意，CEUS 已获得 FDA 批准用于评估。截至 2016 年，该技术在美国的儿科应用中用于评估局灶性肝脏病变和膀胱输尿管反流，但其在新生儿大脑中的应用是标签外的，PI 目前是第一个 FDA 监管的项目。研究性新药 (IND) 批准的婴儿脑部 CEUS 临床试验并发表第一个婴儿脑部超声造影成像指南；经验证的立即临床转化的潜力因此，完成本提案后的方法具有重要意义。 CEUS将成为颅内压和脑缺血的准确生物标志物的总体目标。因此，建议 1) 使用已经存在的方法验证颅内压和脑缺血的 CEUS 指数建立了婴儿猪脑积水模型，并 2) 评估优化的脑部 CEUS 的体内安全性我们的工作将为用于评估颅内的新无创工具的临床转化奠定基础。新生儿脑积水的压力和脑缺血，最终可以改善分流的指导和长期神经系统结果。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Advanced Neuromonitoring Modalities on the Horizon: Detection and Management of Acute Brain Injury in Children.

DOI：
10.1007/s12028-023-01690-9
发表时间：
2023-06
期刊：
NEUROCRITICAL CARE
影响因子：
3.5
作者：
Ko, Tiffany S.;Catennacio, Eva;Shin, Samuel S.;Stern, Joseph;Massey, Shavonne L.;Kilbaugh, Todd J.;Hwang, Misun
通讯作者：
Hwang, Misun

Superficial anatomy of the neonatal cerebrum - an ultrasonographic roadmap.