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.

新生儿脑积水中颅内压和脑缺血的新型超声指数项目摘要新生儿脑积水会影响每1000个活产的1-2个，并导致神经系统缺陷多达78％治疗的患者。广泛的病因，包括脑室出血，先天性渡槽狭窄，脊髓脑膨出和脑肿瘤引起脑脊髓液（CSF）异常积累在这种疾病中，导致脑室膨胀和颅内压升高（ICP）。尽管心室分流用作CSF转移的手术治疗，决定分流的决定是基于心室的大小和临床判断不是ICP和大脑健康的敏感标记。那是延迟的诊断 ICP和手术分流升高会导致永久性脑损伤和长期神经系统缺陷。由于出血和区域大脑的相关风险，插入侵入性ICP监视器的插入不可行脆弱的新生儿大脑中的缺血。为了提供解决临床护理显着差距的解决方案新生儿脑积水，我们利用对比增强的超声（CEU）技术无创在公认的脑积水模型中检测ICP和脑缺血。 CEUS使用血管内注射平均2-3 µm的微泡评估组织灌注。与新型粒子跟踪方法的联合使用（所谓的粒子强度和/或跟踪速度法）和传统的灌注分析，脑微循环的潜在空间和暂时变化可以是量化以评估ICP升高和脑缺血。请注意，CEU已被FDA批准截至2016年，美国的儿科应用评估局灶性肝脏病变和囊泡反射术，但在新生儿大脑中的应用是标签外。为此，PI当前率领第一个FDA受监管，研究性新药（IND）批准了在婴儿中应用脑CEU的临床试验，并发表了第一个婴儿脑CEU的成像指南；验证的立即临床翻译的潜力因此，该提案完成后的方法很重要。提案的中心假设 CEUS将是颅内压和脑缺血的准确生物标志物。总体目标因此，建议是1）验证颅内压和脑缺血的CEU指数已建立的脑积水的婴儿猪模型和2）评估优化的脑CEUS的体内安全性协议。我们的工作将为临床上的临床翻译奠定了阶段，以评估颅内。新生儿脑积水中的压力和脑缺血，最终可以改善分流的指导和长期神经结局。

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.