Transfontanelle photoacoustic imaging to study pathophysiology of neonatal braininjury

经囟门光声成像研究新生儿脑损伤的病理生理学

基本信息

批准号：
10541907
负责人：
Kamran Avanaki
金额：
$ 37.41万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-15 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10541907
关键词：
Acoustics Address Adopted Age Allergic Reaction Animal Model Autopsy Birth Blood Blood - brain barrier anatomy Blood capillaries Brain Injuries Brain Mapping Brain hemorrhage Brain imaging Cephalic Cerebral Palsy Cerebrum Classification Clinical Clinical Research Concentration measurement Contrast Media Data Dependence Detection Diagnosis Diagnostic Diameter Early Diagnosis Early treatment Evans blue stain Exhibits Fiber Optics Functional Magnetic Resonance Imaging Functional disorder Gestational Age Gliosis Goals Head Hemorrhage Hydrocephalus Hypotension Image Imaging technology Impaired cognition Incidence Infant Institutional Review Boards Intervention Intracranial Hemorrhages Intraventricular Ionizing radiation Ischemia Lesion Location Low Birth Weight Infant Magnetic Resonance Imaging Maps Measures Modeling Motor Multiparity Nature Near-Infrared Spectroscopy Neonatal Neonatal Intensive Care Units Neurologic Dysfunctions Newborn Infant Operative Surgical Procedures Outcome Oxygen Penetration Perfusion Periventricular Leukomalacia Positron Positron-Emission Tomography Radiation Radioisotopes Reperfusion Injury Reporting Research Project Grants Resolution Risk Safety Sedation procedure Sensitivity and Specificity Severities Sheep Shunt Device Special Education Structure of fontanel of skull Surface Survivors Techniques Testing Ultrasonography Ventricular X-Ray Computed Tomography blood oxygen level dependent blood-brain barrier disruption bone brain tissue clinical translation clinically relevant cortex mapping cost cost effective cranium diagnostic screening diagnostic tool functional improvement gray matter hemodynamics high risk imaging detection imaging modality imaging probe imaging system improved neonatal brain neonatal human neonate neural neuroimaging novel optical fiber parametric imaging photoacoustic imaging point-of-care diagnosis point-of-care diagnostics portability postnatal preterm newborn primipara tissue mapping tissue oxygenation ultrasound vasogenic edema visual dysfunction white matter

项目摘要

PROJECT SUMMARY/ABSTRACT: Preterm and/or low birth weight neonates are at high risk for intracranial hemorrhage (ICH) with an incidence of 30%-35%. Complications result in shunt dependence and long-term changes: post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. ICH has many causes: traumatic delivery, primiparity or extreme multiparity, and low gestational age at birth. Early detection, classification and diagnosis of ICH is essential to reduce brain injury which often leads to motor (e.g., cerebral palsy), visual or cognitive dysfunction. TransFontanelle Ultrasound Imaging (TFUSI) is a routine diagnostic brain imaging method for infants younger than 6 months, whose skull bones have not completely fused together and have openings between them; so-called ‘fontanelles’. TFUSI is widely used due to its low cost, safety, accessibility, and noninvasive nature. Nevertheless, the accuracy of TFUSI is limited; TFUSI does not detect hemorrhages smaller than 5 mm and does not accurately detect blood in CSF. The low sensitivity of TFUSI to bleed size, location and duration may lead to autopsy findings that reveal conventional TFUSI underdiagnoses ICH in 8–34% of cases. Second stage diagnostic tools like magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) have sufficient sensitivity and specificity to study neonatal intracranial hemorrhage, however, all require moving clinically unstable newborns out of the NICU, sedation with its associated risks (hypotension, hemodynamic changes, or allergic reaction), and have high cost. Moreover, CT uses ionizing radiation and PET requires a positron-emitting radionuclide. Near InfraRed Spectroscopy (NIRS) has poor spatial resolution, especially for the small neonate head, and poor penetration depth. To address several limitations of current clinical neuroimaging, we have developed a novel TransFontanelle Multispectral Photoacoustic Imaging (TFMPI) method to study pathophysiology, and to improve the detection of brain hemorrhage in neonates without the need for sedation, radiation or radionuclides. Our ex vivo preliminary results show the surpassing capability of TFMPI in detection and quantification ICH earlier, with higher sensitivity and specificity than US; and, maps brain perfusion similar to MRI. This technique allows earlier diagnosis and treatment which may circumvent neural complications, and improve functional outcomes from cerebral palsy and cognitive impairments. The long-term goal of this research project is to provide a single, cost-effective, portable, point-of-care diagnostic screening for neonates with potential ICH. Studies outlined in the four aims of this proposal assess the feasibility of TFMPI for detection of ICH in a large animal model, similar in size to a human neonatal brain, with a surgically-induced cranial window that serves as a model for neonate’s fontanelle. Aim 1: To determine the lower limits of sensitivity of TFMPI to detect blood in CSF and its age. Aim 2: To detect intraparenchymal hemorrhages and their age. Aim 3: To measure the brain tissue oxygen saturation. Aim 4: To detect vasogenic edema due to brain blood barrier disruption.

项目概要/摘要：早产儿和/或低出生体重新生儿发生颅内出血 (ICH) 的风险较高，发生率 30%-35% 并发症导致分流依赖性和长期变化：出血后脑积水、脑室周围白质软化、神经胶质增生和神经功能障碍有多种原因：创伤性分娩、初产或极度多产以及出生时低胎龄的早期发现、分类和诊断。 ICH 对于减少脑损伤至关重要，脑损伤通常会导致运动（例如脑瘫）、视觉或认知障碍经囟门超声成像 (TFUSI) 是一种针对婴儿的常规诊断脑成像方法。 6个月以下，颅骨尚未完全融合，且颅骨之间有开口；所谓的“囟门”由于其低成本、安全性、可及性和非侵入性而被广泛使用。然而，TFUSI 的准确性是有限的；TFUSI 不能检测小于 5 毫米的出血，但可以检测到。 TFUSI 对出血量、位置和持续时间的低敏感性可能导致无法准确检测脑脊液中的血液。尸检结果显示，第二阶段诊断中 8-34% 的病例传统 TFUSI 未能诊断出 ICH。磁共振成像 (MRI)、计算机断层扫描 (CT) 和正电子发射断层扫描等工具（PET）对于研究新生儿颅内出血有足够的敏感性和特异性，但是，所有这些都需要将临床不稳定的新生儿移出 NICU、镇静及其相关风险（低血压、血流动力学）变化，或过敏反应），而且成本高，而且CT使用电离辐射，而PET需要一个。近红外光谱（NIRS）的空间分辨率较差，尤其是对于正电子发射放射性核素。新生儿头部较小，穿透深度较差。为了解决当前临床神经影像学的一些局限性，我们开发了一种新颖的跨囟门多光谱光声成像（TFMPI）方法来研究病理生理学，并改进新生儿脑出血的检测，而无需我们的体外初步结果表明 TFMPI 在镇静、辐射或放射性核素方面具有卓越的能力。更早地检测和量化 ICH，比 US 具有更高的灵敏度和特异性，并且绘制脑灌注图；与 MRI 类似，该技术可以进行早期诊断和治疗，从而避免神经并发症，并改善脑瘫和认知障碍的功能结果。这是该项目的长期目标。研究项目旨在为患有以下疾病的新生儿提供单一的、具有成本效益的、便携式的护理点诊断筛查该提案的四个目标中概述的研究评估了 TFMPI 检测 ICH 的可行性。在大型动物模型中，其大小与人类新生儿大脑相似，具有手术诱导的颅窗作为新生儿囟门的模型目标 1：确定 TFMPI 检测的灵敏度下限。脑脊液中的血液及其年龄目标 2：检测实质内出血及其年龄目标 3：测量脑脊液中的血液及其年龄。目标 4：检测由于脑血屏障破坏引起的血管源性水肿。