Platelet Expression of FcgammaRIIa and Arterial Hemodynamics to Predict Recurrent Stroke in Intracranial Atherosclerosis
FcgammaRIIa 的血小板表达和动脉血流动力学预测颅内动脉粥样硬化复发性中风
基本信息
- 批准号:10444288
- 负责人:
- 金额:$ 71.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccountingAcuteAddressAgeAgonistAngiographyArchitectureArteriesBiologicalBiological AssayBiologyBlood PlateletsBlood flowBlood specimenBrainBrain InjuriesCardiovascular systemCerebral IschemiaClinicalCollaborationsCore FacilityCoronary ArteriosclerosisCoronary CirculationDataDiagnosticDistalEligibility DeterminationEnrollmentEthnic OriginEventExposure toFunctional disorderGeographyGoalsHeterogeneityHourHypertensionImageIncidenceIndividualIndividual DifferencesInjuryIntracranial Atherosclerotic DiseaseIschemiaIschemic StrokeLiquid substanceMagnetic Resonance ImagingMeasurementMinorModelingMulticenter StudiesObservational StudyOutcomeParticipantPathologyPatientsPatternPharmaceutical PreparationsPlatelet ActivationPlatelet aggregationPopulation HeterogeneityPublic HealthRaceRecording of previous eventsRecurrenceResearchResearch InfrastructureRiskRisk FactorsRoleSerial Magnetic Resonance ImagingSiteStatistical ModelsStenosisStimulusStratificationStrokeStroke preventionSymptomsThrombosisTimeTransient Ischemic AttackUniversitiesVermontWorkadjudicationbasebrain magnetic resonance imagingcerebrovascularclinical translationcomorbiditydata managementdisabilitydisease diagnosisethnic diversityhemodynamicsindexingindividualized medicineischemic injurymechanical forceneurovascularnovelnovel strategiespost strokeprecision medicinepreventrecruitresponsesexshear stressstatisticsstroke riskstroke therapysynergism
项目摘要
PROJECT SUMMARY/ABSTRACT
The overall goal of this proposal is to determine the potentially pivotal and interactive roles of individual
platelet expression of FcγRIIa [SA-1] and wall shear stress (WSS) calculated from patient-specific CT
angiography (CTA) computational fluid dynamics (CFD) [SA-2] to explain recurrent ischemia after minor
stroke or TIA due to ICAD. A precision model is developed [SA-3] to quantify risk of recurrent ischemic injury,
accounting for FcγRIIa, WSS, anti-platelet therapies and platelet reactivity, across a diverse population of
stroke and TIA patients with ICAD. Our central hypothesis is that high FcγRIIa plus high shear force pose
individual and synergistic risk of stroke recurrence, providing a rational basis for the precision medicine of
stroke prevention in ICAD. Our preliminary data reveal that greater platelet FcγRIIa expression identifies
patients at greater risk of recurrent cardiovascular events including stroke and that high WSS on CTA CFD
predicts recurrent stroke due to ICAD at 1 year. Our three independent specific aims leverage an established
research infrastructure and ICAD network of 6 geographically distinct enrolling sites with race-ethnic diverse
populations and a longstanding history of productive collaboration to recruit 250 participants with acute
cerebral ischemia within 72 hours from symptom onset. The multicenter, observational study will enroll stroke
or TIA patients due to 50-99% ICAD diagnosed on routinely acquired CTA and obtain brain MRI and blood
sampling for FcγRIIa and platelet assays within 72 hours and again at 1 year after onset. Clinical outcomes will
be ascertained at 90 days and at 1 year, with co-registration of serial MRI to quantify interval silent and
symptomatic ischemic injury. The Platelet Biology Core at University of Vermont will quantify platelet FcγRIIa
expression. The Neurovascular Imaging Research Core at UCLA will conduct central imaging analyses,
including CTA CFD quantification of WSS, serial MRI co-registration and imaging adjudication of eligibility
and interval endpoints. The Statistical Core will coordinate data management from 6 enrolling sites and the
core facilities, conducting predictive statistics, stratification of key biological variables and novel application of
clustering analytic strategies to maximally inform a precision model of ICAD stroke risk at 1 year. This timely
culmination of synergistic work on shear stress-induced platelet activation in ICAD leverages our robust
preliminary data on FcγRIIa, CTA CFD of WSS and precision medicine analytics in stroke, layered on a
successful track record of multicenter, observational studies of the most common cause of recurrent stroke.
Measurement of individual differences in FcγRIIa and shear stress induced by heterogenous arterial stenoses
inform a logical precision medicine strategy to avert stroke. This novel strategy of using diagnostic data easily
acquired shortly after stroke or TIA due to ICAD has clear implications for clinical translation via precision
medicine enabling individualized stroke treatment, focused on mechanisms of platelet pathophysiology while
addressing clinical events and silent, insidious brain damage due to recurrent ischemia distal to the plaque.
项目总结/文摘
项目成果
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{{ truncateString('DAVID SIGMUND LIEBESKIND', 18)}}的其他基金
Platelet Expression of FcgammaRIIa and Arterial Hemodynamics to Predict Recurrent Stroke in Intracranial Atherosclerosis
FcgammaRIIa 的血小板表达和动脉血流动力学预测颅内动脉粥样硬化复发性中风
- 批准号:
10588179 - 财政年份:2022
- 资助金额:
$ 71.27万 - 项目类别:
8th International Symposium on Collaterals to the Brain
第八届脑络国际研讨会
- 批准号:
10318759 - 财政年份:2021
- 资助金额:
$ 71.27万 - 项目类别:
6th International Symposium on Collaterals to the Brain
第六届脑络国际研讨会
- 批准号:
9914738 - 财政年份:2019
- 资助金额:
$ 71.27万 - 项目类别:
Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease
颅内动脉粥样硬化疾病早期复发的机制
- 批准号:
9222819 - 财政年份:2014
- 资助金额:
$ 71.27万 - 项目类别:
Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease
颅内动脉粥样硬化疾病早期复发的机制
- 批准号:
9008083 - 财政年份:2014
- 资助金额:
$ 71.27万 - 项目类别:
2nd International Symposium on Collaterals to the Brain
第二届脑络国际研讨会
- 批准号:
8785972 - 财政年份:2014
- 资助金额:
$ 71.27万 - 项目类别:
Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza
急性脑卒中低体温与血运重建的溶栓影像学评估
- 批准号:
8401815 - 财政年份:2012
- 资助金额:
$ 71.27万 - 项目类别:
International Symposium on Collaterals to the Brain
大脑络脉国际研讨会
- 批准号:
8458827 - 财政年份:2012
- 资助金额:
$ 71.27万 - 项目类别:
Hypothermia in Acute Stroke with Thrombolysis Imaging Evaluation of Revasculariza
急性脑卒中低体温与血运重建的溶栓影像学评估
- 批准号:
8536969 - 财政年份:2012
- 资助金额:
$ 71.27万 - 项目类别:
Modeling of Collateral Perfusion in the Ischemic Brain
缺血性脑部侧支灌注的建模
- 批准号:
8337308 - 财政年份:2011
- 资助金额:
$ 71.27万 - 项目类别:
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