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
- 来源:
- 关键词:AcademiaAffectAlteplaseAnimal ModelAutopsyBicarbonatesBiological ModelsBlood flowBrainBrain InjuriesCerebral hemisphere hemorrhageCerebrumCitric Acid CycleClinicClinicalClinical TrialsComplementDataDecarboxylationDetectionDevelopmentDiffusionDiffusion Magnetic Resonance ImagingDropsEconomic BurdenEligibility DeterminationEnergy MetabolismEvolutionFamily suidaeFunctional disorderFutureGlucoseGlycolysisGoalsHistologyImageImaging TechniquesImpairmentIndustryInfarctionInjectionsInjuryInterventionIschemiaIschemic StrokeLinkMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMalignant - descriptorMammalsMapsMeasurementMeasuresMechanicsMetabolicMetabolic PathwayMetabolismMethodsMicrodialysisNoiseNuclearOxygenPathologyPatientsPerfusionPlayPopulationProceduresProcessPyruvatePyruvate Metabolism PathwayReperfusion InjuryReperfusion TherapyReportingResolutionRiskRoleScanningSelection for TreatmentsSignal TransductionSocietiesStrokeSurrogate MarkersTherapeuticThrombectomyTimeTissuesTranslatingUreaacute strokebrain tissueclinical careclinically relevantdisabilityimaging modalityimprovedin vivoinnovationinsightischemic injurymetabolic imagingmolecular imagingneuroimagingnovelnovel strategiespharmacologicporcine modelpost strokepyruvate dehydrogenasereal-time imagesresponsespectroscopic imagingstroke modelstroke patientstroke therapystructural imagingtherapeutic evaluationtherapy outcometool
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.
缺血性中风(IS)是导致长期严重残疾的最常见原因,并造成了巨大的生态损失
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
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Miroslaw Janowski其他文献
Miroslaw Janowski的其他文献
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{{ 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:
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