Development of real-time, non-invasive photoacoustic imaging to rapidly detect and track perinatal focal stroke at birth

开发实时、非侵入性光声成像,以快速检测和跟踪出生时的围产期局灶性中风

基本信息

  • 批准号:
    10063016
  • 负责人:
  • 金额:
    $ 42.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-12-18 至 2022-11-30
  • 项目状态:
    已结题

项目摘要

Perinatal arterial ischemic stroke is estimated to occur in 1/2300–1/5000 live births and can result in long-term deficits in motor, cognitive, attention, and executive functions and persistent seizures. Rapid diagnosis of focal ischemic stroke in newborns, the timing of the stroke, and differentiation of perinatal stroke from global hypoxia-ischemia allow more efficient and directed interventions/prognosticacions. In the proposed work, we will develop miniaturized noninvasive photoacoustic imaging for use on the scalp of human fetuses and newborns to dynamically track changes in oxygenation in sagittal sinus venous blood and regional cortical tissue both during and after labor. Using a newborn animal with a large gyrencephalic brain, we will validate the oxygenation measurements against directly measured sagittal sinus O2 saturation during hypoxia-ischemia and against pimonidazole-based measurements of regional tissue hypoxia during focal stroke. Based on these data, we will then develop algorithms for detecting graded progressive ischemia based on tissue hemoglobin content and O2 saturation. We will test the sensitivity and specificity of these algorithms with different size and locations of photothrombotic-induced stroke. Furthermore, secondary injury cascades that transpire in the immature brain after arterial thrombotic stroke may differ from those that transpire in mature brain and likely depend on maturation of connectivity and energy metabolism in specific brain regions. After photothrombosis of the middle cerebral artery, we will contrast dynamic changes in tissue hemoglobin content and O2 saturation in 1) the metabolically active primary sensorimotor cortex, known to be selectively vulnerable to hypoxia- ischemia, 2) the metabolically quiescent secondary sensorimotor cortex known to be resistant to hypoxia- ischemia, and 3) the watershed penumbra. In addition, we will use noninvasive imaging to track tissue uptake of photoacoustically sensitive dyes conjugated to different size molecules and relate regional differences in size-dependent blood brain-barrier permeability to markers of energy metabolism. Finally, we will investigate whether stabilizing anti-inflammatory, anti-epileptic, anti-platelet, pro-vasodilatory, and pro-angiogenic epoxyeicosatrienoic acids with an inhibitor of soluble epoxide hydrolase (sEH) is protective. Though pretreatment with such inhibitors is protective in adult rodent models of transient cerebral ischemia, post- treatment efficacy has not been determined with prolonged ischemia or in immature brain. We will test the concept that a multi-potent sEH inhibitor will attenuate neuroinflammation, blood-brain barrier permeability, perivascular loss of aquaporin-4 channels, ischemia-induced increase in Sur1-TrpM4 channels known to contribute to malignant edema, and the loss of peri-ischemic neurons, while promoting VEGF expression; we will also determine whether an inhibitor of EET synthesis will exert the opposite effects. Therefore, this application will reveal new insights into the mechanisms of injury from perinatal thrombotic ischemia, provide a potential therapeutic target, and enable an innovative technological advance for screening newborns for stroke.
据估计,在1/2300-1/5000的活产婴儿中发生围产期动脉缺血性卒中,并可导致长期的 运动、认知、注意力和执行功能的缺陷以及持续性癫痫发作。快速诊断局灶性 新生儿缺血性卒中、卒中发生时间以及围产期卒中与全身性卒中的鉴别 缺氧-缺血允许更有效和定向的干预/治疗。在工作中,我们 将开发用于人类胎儿头皮的小型化非侵入性光声成像, 新生儿动态跟踪矢状窦静脉血和区域皮质氧合的变化 在分娩过程中和分娩后都是如此。使用一个新生的动物与一个大的脑回,我们将验证 缺氧缺血时矢状窦血氧饱和度的直接测量值 并对抗局灶性中风期间局部组织缺氧的基于哌莫尼达唑的测量。基于这些 数据,然后我们将开发基于组织血红蛋白检测分级进行性缺血的算法 含量和O2饱和度。我们将测试这些算法的灵敏度和特异性, 光凝诱发中风的位置此外,继发性损伤级联,在 动脉血栓性卒中后未成熟脑可能不同于成熟脑中发生的那些, 依赖于特定大脑区域的连接和能量代谢的成熟。光血栓形成后 大脑中动脉,我们将对比组织血红蛋白含量和氧饱和度的动态变化, 1)代谢活跃的初级感觉运动皮层,已知对缺氧有选择性的脆弱性, 缺血,2)已知对缺氧具有抗性的代谢静止的次级感觉运动皮层- 缺血; 3)分水岭半暗带。此外,我们将使用非侵入性成像来跟踪组织摄取 的光声敏感染料共轭到不同大小的分子和相关的区域差异, 大小依赖性血脑屏障对能量代谢标志物的渗透性。最后,我们将调查 无论是稳定抗炎、抗癫痫、抗血小板、促血管扩张和促血管生成 环氧二十碳三烯酸与可溶性环氧化物水解酶(sEH)抑制剂的组合具有保护性。虽然 用这种抑制剂预处理在成年啮齿类动物短暂脑缺血模型中是保护性的, 对于长期缺血或未成熟的脑,治疗效果尚未确定。我们将测试 多能sEH抑制剂将减弱神经炎症,血脑屏障通透性, 水通道蛋白-4通道的血管周围损失,已知缺血诱导的Sur 1-TrpM 4通道增加, 导致恶性水肿和缺血周围神经元的丢失,同时促进VEGF表达;我们 也将决定EET合成的抑制剂是否会发挥相反的作用。因此本 应用将揭示新的见解,从围产期血栓性缺血损伤的机制,提供了一个新的见解, 潜在的治疗靶点,并实现新生儿中风筛查的创新技术进步。

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Embolic occlusion of internal carotid artery in conscious rats: Immediate effects of cerebral ischemia.
  • DOI:
    10.14814/phy2.15613
  • 发表时间:
    2023-02
  • 期刊:
  • 影响因子:
    2.5
  • 作者:
  • 通讯作者:
Photoacoustic assessment of the fetal brain and placenta as a method of non-invasive antepartum and intrapartum monitoring.
  • DOI:
    10.1016/j.expneurol.2021.113898
  • 发表时间:
    2022-01
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Kang J;Koehler RC;Graham EM;Boctor EM
  • 通讯作者:
    Boctor EM
Polynitroxylated PEGylated hemoglobin protects pig brain neocortical gray and white matter after traumatic brain injury and hemorrhagic shock.
  • DOI:
    10.3389/fmedt.2023.1074643
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wang, Jun;Shi, Yanrong;Cao, Suyi;Liu, Xiuyun;Martin, Lee J.;Simoni, Jan;Soltys, Bohdan J.;Hsia, Carleton J. C.;Koehler, Raymond C.
  • 通讯作者:
    Koehler, Raymond C.
Regulation of the Cerebral Circulation During Development.
  • DOI:
    10.1002/cphy.c200028
  • 发表时间:
    2021-09-23
  • 期刊:
  • 影响因子:
    5.8
  • 作者:
    Koehler, Raymond C.
  • 通讯作者:
    Koehler, Raymond C.
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Emad M Boctor其他文献

Photoacoustic Emission Efficiency of Polymer Matrix Nanocomposites for Use in Epiretinal Prosthetics*
用于视网膜前假体的聚合物基质纳米复合材料的光声发射效率*

Emad M Boctor的其他文献

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{{ truncateString('Emad M Boctor', 18)}}的其他基金

5T-IV: photoacoustic needle with beacon pulse for ultrasound guided vascular access with Tool-Tip Tracking and Tissue Typing
5T-IV:带有信标脉冲的光声针,用于通过工具提示跟踪和组织分型进行超声引导血管通路
  • 批准号:
    10677283
  • 财政年份:
    2023
  • 资助金额:
    $ 42.11万
  • 项目类别:
Continuous Photoacoustic Monitoring of Neonatal Stroke in Intensive Care Unit
重症监护病房新生儿中风的连续光声监测
  • 批准号:
    10548689
  • 财政年份:
    2022
  • 资助金额:
    $ 42.11万
  • 项目类别:
A Normal Paradigm to Monitor Perinatal Asphyxia Using A Combined Ultrasound-Neuromodulation and Photoacoustic-Imaging Device
使用超声神经调节和光声成像相结合的设备监测围产期窒息的正常范例
  • 批准号:
    10552231
  • 财政年份:
    2022
  • 资助金额:
    $ 42.11万
  • 项目类别:
Prostate Specific Membrane Antigen Targeted Photoacoustic Imaging for Prostate Cancer
前列腺特异性膜抗原靶向光声成像治疗前列腺癌
  • 批准号:
    9178205
  • 财政年份:
    2016
  • 资助金额:
    $ 42.11万
  • 项目类别:
Prostate Specific Membrane Antigen Targeted Photoacoustic Imaging for Prostate Cancer
前列腺特异性膜抗原靶向光声成像治疗前列腺癌
  • 批准号:
    9279084
  • 财政年份:
    2016
  • 资助金额:
    $ 42.11万
  • 项目类别:
Interventional PhotoAcoustic Surgical System (i-PASS)
介入光声手术系统 (i-PASS)
  • 批准号:
    8509922
  • 财政年份:
    2013
  • 资助金额:
    $ 42.11万
  • 项目类别:
Integrated Photoacoustic Ultrasound Real-time Imaging for Brachytherapy Treatment
用于近距离放射治疗的集成光声超声实时成像
  • 批准号:
    8593128
  • 财政年份:
    2013
  • 资助金额:
    $ 42.11万
  • 项目类别:
Interventional PhotoAcoustic Surgical System (i-PASS)
介入光声手术系统 (i-PASS)
  • 批准号:
    8636019
  • 财政年份:
    2013
  • 资助金额:
    $ 42.11万
  • 项目类别:

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