3D neonatal Photoacoustic Tomography (3D-nPAT) to detect Hypoxic-Ischemicbrain injury in preterm neonates

项目总结/摘要： 缺氧缺血性脑损伤（Hypoxic-Ischemic Brain Injury，HII）是一种在出生时或出生前后因缺氧而引起的严重脑损伤 早产和/或低出生体重新生儿。尽早识别HII非常重要，因为早期 干预可以改善结果。HII是早产儿死亡和发病的最常见原因之一 发生率约为60%。经历HII的早产儿有发生缺氧缺血性脑病的风险 脑病、脑瘫、脑室周围白质软化和脑积水。基于成像的诊断 识别HII的方法有：颅超声检查的好处是可以在婴儿的床边，但它 由于其不能测量组织氧， 饱和、超出探头范围导致的盲点以及缺乏空间方向以准确定位的2D图像 缺血区相比之下，第二阶段的诊断工具，磁共振成像（MRI），计算机断层扫描 (CT)和正电子发射断层扫描（PET）对于检测脑损伤具有高灵敏度和特异性。 然而，它们并不被用作高危新生儿常规筛查的一线模式，因为MRI需要一段时间， 长时间（~1小时），CT使用电离辐射，PET需要正电子发射放射性核素。小型MRI装置 已经在一些新生儿ICU中安装和测试的设备是昂贵的，并且在成像期间仍然需要镇静。 近红外光谱（NIRS）具有较差的空间分辨率和较差的穿透深度。所有这些模式 需要将临床上不稳定的新生儿从新生儿重症监护室运送出来，通常需要镇静， 与风险（即低血压、血液动力学变化或过敏反应）相关，且成本相对较高。 我们一直在开发一种新型的床旁3D新生儿光声断层扫描（3D-nPAT）仪器， 改善新生儿缺氧缺血性脑损伤的检测和测量， 镇静、辐射或放射性核素。3D-nPAT可用于确定脑损伤的位置和程度， 允许早期治疗，这可以避免各种神经并发症，并改善功能性 脑损伤的后果。该研究项目的长期目标是提供一种快速、便携、即时的 新生儿缺氧缺血性脑损伤的影像学诊断方法。我们的中心前提是， 派对氧合血红蛋白（HbO）和脱氧血红蛋白（HbR）的高敏感性（在两种动物模型中均有充分记录 除了早产儿和/或低出生体重新生儿的非常薄的颅骨（~ 2 mm）之外， 有机会使用光声技术来设计非侵入性3D-nPAT。这件事的直接目标是 本研究拟对现有的3D-nPAT系统进行优化，评估其检测缺氧缺血性脑损伤的可行性 在大型动物模型中，并在临床研究中对10名患者进行评估。拟议的3D-nPAT仪器将 为血管科医生提供了一种负担得起的、快速的、便携式的、非侵入性的血管功能成像工具， 将缺氧缺血性损伤映射到新生儿大脑，目前需要使用多种专业 系统.

PROJECT SUMMARY/ABSTRACT: Hypoxic-Ischemic brain Injury (HII) is a severe injury caused by oxygen deprivation to the brain at or near time of birth in preterm and/or low birth weight newborns. It is very important to recognize HII as soon as possible because early intervention improves outcomes. HII is one of the most common causes of mortality and morbidity in preterm neonates with an occurrence of ~60%. Preterm neonates experiencing HII are at risk for developing hypoxic-ischemic encephalopathy, cerebral palsy, periventricular leukomalacia, and hydrocephalus. The imaging-based diagnostic methods to identify HII are: Cranial ultrasonography has the benefit of being available at the baby’s bedside, but it has a low sensitivity for detecting the anomalies that are caused by HII due to its inability to measure tissue oxygen saturation, blind spots due to being out of probe range, and 2D images that lack spatial orientation to accurately locate ischemic areas. In contrast, second stage diagnostic tools, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET), have high sensitivity and specificity for the detection of brain injuries. However, they are not used as frontline modalities for routine screening of at-risk newborns, because MRI takes a long time (~1 hour), CT is using ionizing radiation, and PET requires a positron-emitting radionuclide. Small MRI units that have been installed and tested in a few neonatal ICUs are expensive and still require sedation during imaging. Near infrared spectroscopy (NIRS) has poor spatial resolution and poor penetration depth. All of these modalities require transporting clinically unstable newborns out of the Neonatal Intensive Care Unit, often require sedation that is associated with risks (i.e. hypotension, hemodynamic changes, or allergic reaction), and have a relatively high cost. We have been developing a novel point-of-care 3D neonatal PhotoAcoustic Tomography (3D-nPAT) instrument to improve the detection and measurement of hypoxic-ischemic brain injury in neonates without the need for sedation, radiation or radionuclides. 3D-nPAT can be used to determine the location and extent of brain injury, allowing for earlier treatment which may circumvent a variety of neural complications, and improve the functional outcome from cerebral injuries. The long-term goal of this research project is to provide a fast, portable, point-of-care diagnostic imaging method for neonates suspected of hypoxic-ischemic brain injury. Our central premise is that the high sensitivity of PAI to oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) (well documented in both animal models and humans), in addition to the very thin skull (~ 2mm) in preterm and/or low birth weight neonates, provides an opportunity to use photoacoustic technology to design the non-invasive 3D-nPAT. The immediate objective of this proposal is to optimize the current 3D-nPAT system, assess the feasibility of it to detect hypoxic-ischemic brain injury in a large animal model, and evaluate it on 10 patients in a clinical study. The proposed 3D-nPAT instrument, will provide neonatologists with an affordable, fast, portable, non-invasive, vascular functional imaging tool to map hypoxic-ischemic injuries to the neonatal brain that currently require the use of multiple specialized systems.