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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：
10097438
负责人：
Misun Hwang
金额：
$ 66.12万
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/10097438
关键词：
Academy Affect Animal Model Assessment tool Biological Markers Brain Brain Injuries Brain Ischemia Brain Neoplasms 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 Family suidae Future Goals Guidelines Heart Arrest Hemorrhage Histologic Histology Hospitals Hydrocephalus Image Infant Injections International Intervention Intracranial Hypertension Intracranial Pressure Investigational Drugs Judgment Label Lead Lesion Liquid substance Live Birth Liver Measures Meningomyelocele Methods Microbubbles Microcirculation Microspheres Modeling Monitor Neonatal Neurologic Deficit Neurological outcome Non-Invasive Cancer Detection Operative Surgical Procedures Outcome Patients Perfusion Population Pre-Clinical Model Protocols documentation Publishing Reference Standards Risk Safety Shunt Device Stenosis Stroke Surgical Management Techniques Testing Time Tissues Traumatic Brain Injury Ultrasonography Validation Velocimetries Ventricular Vesico-Ureteral Reflux Work base brain health clinical care clinical translation clinically translatable contrast enhanced experience imaging approach improved in vivo indexing intraventricular hemorrhage member neonatal brain neonatal care neonate novel particle pre-clinical standard measure tool

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