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

• 批准号: 10432120
• 负责人: Kamran Avanaki
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432120
• 关键词: Acoustics; Address; Adopted; Age; Allergic Reaction; Animal Model; Autopsy; Birth; Blood; Blood - brain barrier anatomy; Blood capillaries; Brain; Brain Injuries; Brain hemorrhage; Brain imaging; Caliber; Cephalic; Cerebral Palsy; Cerebrum; Classification; Clinical; Clinical Research; Concentration measurement; Contrast Media; Data; Dependence; Detection; Diagnosis; Diagnostic; 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; Lead; 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; 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 outcomes; gray matter; hemodynamics; high risk; imaging detection; imaging modality; imaging probe; imaging system; improved; neonatal brain; neonatal human; neonate; neuroimaging; novel; parametric imaging; photoacoustic imaging; point-of-care diagnosis; point-of-care diagnostics; portability; postnatal; preterm newborn; primipara; relating to nervous system; tissue mapping; tissue oxygenation; ultrasound; vasogenic edema; visual dysfunction; white matter

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.

项目摘要/摘要： 早产和/或低出生体重新生儿有颅内出血（ICH）的高风险 30％-35％。并发症会导致分流依赖性和长期变化：杀伤后脑积水， 周期性白细胞藻，神经胶质病和神经功能障碍。 ICH有很多原因：创伤性交付， 初学或极端多重性，出生时胎龄低。早期检测，分类和诊断 ICH对于减少脑损伤至关重要，这通常导致运动（例如脑瘫），视觉或认知能力 功能障碍。 Transfontanelle超声成像（TFUSI）是婴儿常规的诊断脑成像法 年轻的6个月，其头骨骨头还没有完全融合在一起，并之间有开口。 所谓的“ Fontanelles”。 TFUSI由于其低成本，安全性，可及性和无创性而被广泛使用。 然而，TFUSI的准确性是有限的。 TFUSI不会检测到小于5 mm的出血，并且确实 无法准确检测到CSF中的血液。 TFUSI对出血大小，位置和持续时间的低灵敏度可能导致 揭示常规TFUSI的尸检结果在8-34％的病例中诊断不足。第二阶段诊断 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）具有足够的敏感性和特异性来研究新生儿内部出血，所有这些都需要 将临床上不稳定的新生儿移出NICU，镇静剂与其相关风险（低血压，血液动力学 变化或过敏反应），成本很高。此外，CT使用电离辐射，PET需要一个 发射正常的放射线。近红外光谱法（NIRS）的空间分辨率较差，尤其是对于 小新生儿头和渗透深度差。为了解决当前临床神经影像学的几个局限性， 我们已经开发了一种新型的Transfontanelle多光谱光声成像（TFMPI）方法来研究 病理生理学，并改善新生儿大脑出血的检测，而无需 镇静，辐射或放射线。我们的离体初步结果表明，TFMPI在 比我们更早地检测和定量，具有更高的灵敏度和特异性；并且，地图脑灌注 类似于MRI。该技术允许早期的诊断和治疗，这可能会规避神经并发症， 并改善脑瘫和认知障碍的功能结果。这个长期目标 研究项目将为新生儿提供一个单一的，具有成本效益的，便携式的，即时的护理诊断筛查 潜在的ICH。该提案评估的四个目标中概述了TFMPI检测ICH的可行性 在大型动物模型中，大小与人类新生儿大脑相似，并带有外科手术引起的颅窗 是新生儿Fontanelle的典范。目标1：确定TFMPI灵敏度的下限以检测 CSF及其年龄的血液。目的2：检测核内部出血及其年龄。目标3：测量 脑组织氧饱和度。 AIM 4：由于脑血屏障破坏而检测血管性水肿。