Hyperpolarized 13C metabolic imaging in an endovascular swine model of ischemic stroke

缺血性中风血管内猪模型的超极化 13C 代谢成像

基本信息

  • 批准号:
    10726555
  • 负责人:
  • 金额:
    $ 19.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-21 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Ischemic stroke (IS) is the most frequent cause of long-term severe disability, and places an enormous eco- nomic burden on society. One of the primary goals in clinical care of acute stroke is to salvage the so-called penumbra, i.e., tissue that is at risk of irreversible infarction, but is still viable. This can be achieved through various strategies that re-establish the perfusion of the affected tissue. However, there is a tight time window for intervention as well as a risk of cerebral hemorrhage during the establishment of reperfusion and it requires an accurate assessment of the extend of injury as benefits from reperfusion have to be weighed against potential complications arising from treatment. The most widely used tool in identifying the penumbra is magnetic resonance imaging (MRI) and exploiting the “mismatch” in abnormalities as measured with perfusion-weighted and diffusion-weighted MRI. However, multiple studies have found that these surrogate markers have mischaracterized irreversibly infarcted and salvageable tissue and the inaccuracy of these markers may have contributed to both inconclusive results from clinical trials and negative therapeutic outcomes. To this end, a more accurate identification of penumbra and ischemic core that could expand the patient pool that benefit from treatment is needed. The reduced delivery of oxygen and glucose following IS leads to impaired energy metabolism within the affected tissue, one of the hallmarks of the pathology. Therefore, new approaches for quantitative and spatially precise assessment of brain energy metabolism could lead to improved assessment of injury following IS. The recent development of hyperpolarized 13C magnetic resonance spectroscopy and spectroscopic imaging enables for the first time the real-time non-invasive measurement of critical dynamic metabolic processes in vivo. Given pyruvate’s central role in energy metabolism as the link between glycolysis and the Krebs cycle, we propose to use metabolic imaging of co-polarized pyruvate (Pyr) and urea for noninvasive assessment of brain energy metabolism and perfusion in a novel swine IS model. Specifically, we will use injections of co-polarized [1-13C]Pyr and [13C,15N2]urea to quantify cellular energy metabolism and brain perfusion at the time of IS completion in order to identify regions of ischemic core, penumbra, and healthy tissue using histology as the gold standard (Aim 1). Secondly, we will expand our study to include multiple time points during stroke evolution as well as after reperfusion. This will further characterize the temporal and spatial extent of metabolic changes in IS and allow the comparison with the time course of abnormalities as measured with diffusion-weighted MRI (Aim 2). The proposed combination of a novel endovascular swine model of IS and metabolic imaging of hyperpolarized substrates is a unique model system to study the pathophysiology of IS and develop new treatments prior to clinical trials. It also represents the first step in developing a novel neuroimaging approach for assessing ischemic injury in patients and improving treatment selection.
缺血性卒中(IS)是导致长期严重残疾的最常见原因,对人类健康造成巨大的生态危害。 社会的经济负担。急性卒中临床护理的主要目标之一是挽救所谓的 半影区,即有不可逆性脑梗塞风险,但仍可存活的组织。这可以通过以下方式实现 重建受影响组织的灌注的各种策略。然而,有一个紧凑的时间窗口用于 在建立再灌流期间进行干预以及脑出血的风险,这需要 准确评估损伤的程度,因为必须权衡再灌注的益处和潜在的损伤程度 治疗过程中出现的并发症。最广泛使用的识别半影的工具是磁力 磁共振成像(MRI)和利用灌注加权测量的异常中的“失配” 弥散加权磁共振成像。然而,多项研究发现,这些替代标记具有 错误地描述了不可逆转的梗塞和可挽救的组织,并且这些标志物的不准确可能 导致临床试验结果不确定和治疗结果为阴性。为此,一个 更准确地识别半暗带和缺血核心,从而扩大受益于 治疗是必要的。 随后氧和葡萄糖的输送减少导致体内能量代谢受损。 受累组织,这是病理的标志之一。因此,定量和空间分析的新方法 对大脑能量代谢的准确评估可以改善对IS后损伤的评估。这个 超极化~(13)C磁共振波谱和光谱成像的最新进展 首次实现了对体内关键动态代谢过程的实时无创测量。vt.给出 丙酮酸在能量代谢中的中心作用,作为糖酵解和Krebs循环之间的纽带,我们建议 利用共极化丙酮酸(PYR)和尿素的代谢成像无创性评估脑能量 一种新型猪的代谢和灌流模型。具体地说,我们将使用共极化的[1-13C]PYR注入 和[~(13)C,~(15)N]尿素依次定量细胞能量代谢和脑血流灌注 以组织学为金标准,确定缺血核心、半暗带和健康组织的区域(目标1)。 其次,我们将扩大我们的研究范围,包括中风演变过程中和之后的多个时间点 再灌流。这将进一步表征IS代谢变化的时间和空间范围,并允许 与磁共振弥散加权成像(AIM 2)测量的异常时间进程进行比较。 一种新的猪血管内IS模型和代谢成像的组合 超极化底物是研究IS病理生理学和开发新的模型系统的独特模型系统。 临床试验前的治疗。这也是开发新的神经成像方法的第一步。 用于评估患者的缺血性损伤和改进治疗选择。

项目成果

期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mesenchymal stem cell-derived exosomes: Shaping the next era of stroke treatment.
  • DOI:
    10.1002/nep3.30
  • 发表时间:
    2023-12
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Arshi Waseem;Saudamini;Rizwanul Haque;Miroslaw Janowski;Syed Shadab Raza
  • 通讯作者:
    Arshi Waseem;Saudamini;Rizwanul Haque;Miroslaw Janowski;Syed Shadab Raza
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Miroslaw Janowski其他文献

Miroslaw Janowski的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Miroslaw Janowski', 18)}}的其他基金

Image-guided, intra-arterial delivery of antibodies to the central nervous system
图像引导、动脉内将抗体输送至中枢神经系统
  • 批准号:
    10383753
  • 财政年份:
    2021
  • 资助金额:
    $ 19.31万
  • 项目类别:
Image-guided, intra-arterial delivery of antibodies to the central nervous system
图像引导、动脉内将抗体输送至中枢神经系统
  • 批准号:
    10604318
  • 财政年份:
    2021
  • 资助金额:
    $ 19.31万
  • 项目类别:
Image-guided, intra-arterial delivery of antibodies to the central nervous system
图像引导、动脉内将抗体输送至中枢神经系统
  • 批准号:
    10176254
  • 财政年份:
    2021
  • 资助金额:
    $ 19.31万
  • 项目类别:
CEST/FLEX MRI for the Detection of the Host Immune Response to CNS Grafts
CEST/FLEX MRI 用于检测宿主对中枢神经系统移植物的免疫反应
  • 批准号:
    8672704
  • 财政年份:
    2013
  • 资助金额:
    $ 19.31万
  • 项目类别:
CEST/FLEX MRI for the Detection of the Host Immune Response to CNS Grafts
CEST/FLEX MRI 用于检测宿主对中枢神经系统移植物的免疫反应
  • 批准号:
    8583591
  • 财政年份:
    2013
  • 资助金额:
    $ 19.31万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 19.31万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了