Innovative Non-Invasive Imaging of Traumatic Brain Injury
创伤性脑损伤的创新非侵入性成像
基本信息
- 批准号:10527640
- 负责人:
- 金额:$ 40.07万
- 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:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAgingAnatomyAnimal ModelAttenuatedAxonBiodistributionBiological MarkersBiomechanicsBlood - brain barrier anatomyBlood CirculationBlood Circulation TimeBlood VesselsBrainBrain EdemaBrain InjuriesCellular MembraneCerebrovascular CirculationCerebrovascular systemCessation of lifeChronicClinicalComputers and Advanced InstrumentationContusionsDetectionDiagnosisDiffuseDiffusion Magnetic Resonance ImagingDoseEmergency SituationFerritinFloridaFunctional disorderHalf-LifeHemoglobinHemorrhageHistologicHospitalizationHumanImageImaging DeviceImaging technologyIndividualInjuryIonizing radiationIronIschemiaLifeLinkLiquid substanceMagnetic Resonance ImagingMagnetismMeasuresMethodsMicroscopicMonitorMorbidity - disease rateNoiseOperative Surgical ProceduresOxygenPathologyPatientsPenetrationPerformancePersonsPhysiologicalPre-Clinical ModelPrincipal InvestigatorPrognosisPropertyQuantitative EvaluationsRecording of previous eventsRecoveryReportingResearchResearch PersonnelResolutionRodent ModelSecondary toSeveritiesSignal TransductionSiteSkull FracturesSurvivorsSwellingT2 weighted imagingTestingTimeTissuesTracerTraumatic Brain InjuryUniversitiesWorkX-Ray Computed Tomographybiomaterial compatibilityblood-brain barrier disruptionclinical imagingcohortcontrolled cortical impactdensitydisabilityimagerimaging capabilitiesimaging detectionimaging modalityimprovedin vivoinnovationinstrumentationiron oxidemagnetic fieldmechanical forcemild traumatic brain injurymolecular imagingmouse modelnanoparticleneurophysiologynon-invasive imagingoptical imagingparticlepre-clinicalquantitative imagingroutine imagingspectroscopic imagingsuperparamagnetismtoolwhite matterwhite matter damage
项目摘要
Project Summary
Traumatic brain injury (TBI) occurs due to the transient application of mechanical force to the brain, which
causes damage to cellular membranes, axons, and brain vasculature. TBI affects millions of people in the US
each year, resulting in hundreds of thousands of hospitalizations, thousands of deaths, and significant disability
in survivors. In addition to acute injury, TBI leads to progressive pathophysiology, including focal bleeding and
transient opening of the blood brain barrier (BBB). Accurate and fast diagnosis of severity of TBI is necessary to
better prescribe treatments and reduce associated death, morbidity, and disability. However, diagnosis of TBI
often relies on patient history, subjective complaints, and neurophysiological status, and classifying severity
remains challenging. Computed tomography and magnetic resonance imaging are fast and accurate for injuries
requiring emergency surgery but are limited to chronic issues such as excessive brain bleeding and swelling.
Magnetic resonance imaging (MRI) can evaluate white matter micropathology of TBI in cohorts but fail to
evaluate TBI in individuals. Therefore, innovative non-invasive imaging technologies are necessary to
improve TBI diagnosis and accelerate research at the clinical and pre-clinical stage.
This proposal will apply an innovative imaging modality called magnetic particle imaging (MPI) to monitor
vascular pathophysiology of TBI. MPI enables non-invasive, unambiguous, and quantitative imaging of the
biodistribution of biocompatible superparamagnetic iron oxide (SPION) tracers. Application of MPI to monitor
TBI consists of systemic administration of SPIONs that accumulate at sites of local BBB disruption, resulting in
a signal that is proportional to SPION MPI performance, rate of accumulation, and accumulation time. The PI
developed a new synthesis method resulting in SPIONs with enhanced MPI performance and preliminary results
demonstrate these SPIONs are superior to commercially available nanoparticles and possess long blood
circulation half-life. The PI hypothesizes that MPI using SPIONs optimized for sensitivity and blood circulation
time will be a powerful non-invasive complementary imaging tool to study TBI in pre-clinical rodent models. This
hypothesis will be tested through two specific aims. Studies in Aim 1 will determine SPION accumulation in a
controlled cortical impact (CCI) injury mouse model of TBI as a function of dose and time of administration and
will establish histological factors linked to MPI measures of SPION accumulation. Studies in Aim 2 will compare
MPI measures of SPION accumulation in the CCI injury mouse model against MRI measures of SPION
accumulation and other changes associated with TBI. Together, the proposed studies will test the potential of
MPI for non-invasive, sensitive, and quantitative evaluation of TBI in pre-clinical models by comparison to ground
truth and established non-invasive imaging modalities. The proposed work is supported by a diverse team of
investigators with complementary expertise and access to state-of-the-art MPI and MRI instrumentation.
项目摘要
创伤性脑损伤(TBI)的发生是由于机械力对脑的瞬时施加,
会对细胞膜轴突和脑血管造成损伤TBI影响美国数百万人
每年都有数十万人住院,数千人死亡,
幸存者。除了急性损伤,TBI导致进行性病理生理学,包括局灶性出血和
血脑屏障(BBB)的短暂开放。准确、快速地诊断TBI的严重程度是必要的,
更好地制定治疗方案,减少相关的死亡、发病率和残疾。然而,TBI的诊断
通常依赖于患者病史、主观主诉和神经生理状态,并对严重程度进行分类
仍然具有挑战性。计算机断层扫描和磁共振成像是快速和准确的伤害
需要紧急手术,但仅限于慢性问题,如过度脑出血和肿胀。
磁共振成像(MRI)可以评价队列中TBI的白色微病理学,但不能
评估个体TBI。因此,需要创新的非侵入性成像技术,
改善创伤性脑损伤的诊断,加速临床和临床前阶段的研究。
该提案将采用一种称为磁粒子成像(MPI)的创新成像方式来监测
TBI的血管病理生理学。MPI能够实现非侵入性、明确和定量成像,
生物相容性超顺磁性氧化铁(SPION)示踪剂的生物分布。MPI在监控中的应用
TBI包括SPION的全身给药,SPION在局部BBB破坏部位积聚,导致
与SPION MPI性能、累积速率和累积时间成比例的信号。的PI
开发了一种新的合成方法,使SPION具有增强的MPI性能和初步结果
证明这些SPION比市售纳米颗粒更上级,
循环半衰期PI假设使用SPION的MPI优化了灵敏度和血液循环
时间将是一个强大的非侵入性的补充成像工具,研究TBI的临床前啮齿动物模型。这
我们将通过两个具体目标来检验这一假设。目标1中的研究将确定SPION在
TBI的受控皮质撞击(CCI)损伤小鼠模型作为给药剂量和时间的函数,
将建立与SPION蓄积的MPI测量相关的组织学因素。目标2中的研究将比较
CCI损伤小鼠模型中SPION蓄积的MPI测量与SPION的MRI测量
与TBI相关的累积和其他变化。总之,拟议中的研究将测试
MPI用于临床前模型中TBI的无创、灵敏和定量评估,与地面相比
真实性和已建立的非侵入性成像模式。拟议的工作得到了一个多元化的团队的支持,
具有互补专业知识的研究人员,并可使用最先进的MPI和MRI仪器。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Carlos M Rinaldi-Ramos其他文献
Carlos M Rinaldi-Ramos的其他文献
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{{ truncateString('Carlos M Rinaldi-Ramos', 18)}}的其他基金
NIH Administrative Supplement to Promote Diversity in Health Related Research
NIH 促进健康相关研究多样性的行政补充
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10876754 - 财政年份:2023
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Nanoparticles for In Vivo Labeling of T Cells During Cancer Immunotherapy
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10450938 - 财政年份:2022
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Nanoparticles to Track T Cell Immunotherapy Using Magnetic Particle Imaging
使用磁粒子成像追踪 T 细胞免疫治疗的纳米粒子
- 批准号:
10365339 - 财政年份:2022
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Nanoparticles for In Vivo Labeling of T Cells During Cancer Immunotherapy
用于癌症免疫治疗期间 T 细胞体内标记的纳米颗粒
- 批准号:
10634620 - 财政年份:2022
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Nanoparticles to Track T Cell Immunotherapy Using Magnetic Particle Imaging
使用磁粒子成像追踪 T 细胞免疫治疗的纳米粒子
- 批准号:
10621153 - 财政年份:2022
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$ 40.07万 - 项目类别:
Magnetically Templated Regeneration Scaffolds for Nerve Injury Repair
用于神经损伤修复的磁模板再生支架
- 批准号:
8954155 - 财政年份:2015
- 资助金额:
$ 40.07万 - 项目类别:
Modeling of the Magnetic Particle Imaging Signal Due to Magnetic Nanoparticles
磁性纳米粒子产生的磁性粒子成像信号的建模
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9024525 - 财政年份:2015
- 资助金额:
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Magnetically Templated Regeneration Scaffolds for Nerve Injury Repair
用于神经损伤修复的磁模板再生支架
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9086452 - 财政年份:2015
- 资助金额:
$ 40.07万 - 项目类别:
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