Non-contrast MR imaging of blood-brain-barrier permeability in Alzheimer's disease
阿尔茨海默病血脑屏障通透性的非对比磁共振成像
基本信息
- 批准号:10621142
- 负责人:
- 金额:$ 63.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAffectAlbuminsAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAmyloidAmyloid ProteinsAnimal ModelAreaAstrocytesAutopsyBacteriaBenchmarkingBiochemicalBiological AssayBloodBlood - brain barrier anatomyBolus InfusionBrainBrain DiseasesCellsCentral Nervous SystemCerebrospinal FluidCerebrovascular CirculationClinicalClinical TrialsCognitionContrast MediaDevelopmentDextransDiseaseElderlyExtravasationFoot ProcessGadoliniumGenetic RiskGoalsHumanImaging TechniquesIndividualInflammatory ResponseInjuryLabelLinkLiteratureMagnetic Resonance ImagingMeasurementMeasuresMethodsMicroscopyModalityModelingMonitorMulticenter TrialsNerve DegenerationNeurodegenerative DisordersNeuronsNeurotoxinsOsmosisOutcomePathogenesisPatientsPericytesPermeabilityPersonsPhasePhysiologic pulsePhysiologicalProceduresProcessProteinsProtocols documentationRattusResearchRestSamplingScanningSchemeSenile PlaquesSignal TransductionSiteSpinal PunctureSurfaceTechniquesTestingTimeTissuesTranslatingVascular Endothelial CellVascular EndotheliumVeinsVenousWaterWorkapolipoprotein E-4arterial spin labelingblood-brain barrier crossingblood-brain barrier functionblood-brain barrier permeabilizationcerebral atrophyclinical applicationcognitive functioncontrast enhanceddesignin vivoindexinginterestmacromoleculenew therapeutic targetnovelpathogenscreeningvascular injuryverification and validationβ-amyloid burden
项目摘要
Project Summary/Abstract:
Because of disappointing outcomes of recent clinical trials of anti-amyloid therapy in Alzheimer’s Disease
(AD), the field is increasingly interested in elucidating alternative disease mechanisms which may lead to new
therapeutic targets that are complementary to anti-amyloid treatment. Extensive literature using post-mortem
tissue has suggested that damage to the blood-brain-barrier (BBB) is intricately involved in the pathogenesis of
AD. Furthermore, recent studies in animal models suggested a direct link between BBB damage and
accumulation of amyloid plaques, in that aggregation of the amyloid protein may be part of an inflammatory
response of the brain to pathogen entry, presumably following BBB leakage.
However, in vivo studies of BBB in AD are scarce. A method commonly used to evaluate BBB permeability
in humans is by administering Gadolinium (Gd) based contrast agent while measuring and modeling dynamic
contrast-enhanced (DCE) MRI signal. However, contrast-enhanced MRI is not a common procedure in AD
research and has not been used in large-scale or multi-site studies. Therefore, a non-contrast technique to
assess BBB permeability is of particular importance in AD research and, if successful, can feasibly translate to
clinical screening and monitoring of treatment.
The central goal of this application is to develop an MRI technique to measure BBB permeability to water,
without using any exogenous agent. MRI can probe water BBB permeability by determining what fraction of the
incoming arterial water enters the brain and what fraction remains in the vessel and drains to the vein. This
project consists of three logical aims. Aim 1 will develop novel MRI pulse sequences to quantitatively evaluate
permeability-surface-area product (PS) of BBB in both global and regional fashion. Aim 2 will validate the non-
contrast method with Gd-contrast based technique in humans and with fluorescent microscopy in animal
models following osmotic opening of BBB. Aim 3 will conduct clinical application of the technique in elderly
individuals who have an established genetic risk to develop Alzheimer’s Disease (AD), i.e. APOE4-carriers. We
will compare BBB permeability with amyloid burden and cognitive function, and study their causal relationship
through a mediational model analysis. We will also compare the non-contrast permeability results to those
using an invasive method of CSF sampling as well as using DCE MRI.
The impact of this work is that we will develop a novel non-contrast technique to evaluate BBB permeability
in humans. The technique can be completed within 5 minutes on a standard 3T MRI. The outcome of the
measurement is in physiological unit of ml water/100g brain/min, thus can be feasibly compared across sites or
modalities. This technique will have broad clinical utility, as injury of BBB is implicated in many brain diseases.
In this application, we will demonstrate the utility of this technique in AD.
项目总结/文摘:
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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Hanzhang Lu其他文献
Hanzhang Lu的其他文献
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{{ truncateString('Hanzhang Lu', 18)}}的其他基金
ISMRM Workshop on Perfusion MRI: From Head to Toe
ISMRM 灌注 MRI 研讨会:从头到脚
- 批准号:
10391735 - 财政年份:2022
- 资助金额:
$ 63.04万 - 项目类别:
TRD1: Quantitative Imaging of Physiological Markers
TRD1:生理标志物的定量成像
- 批准号:
10614608 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers
生理、代谢和解剖生物标志物的 MRI 资源
- 批准号:
10614604 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers
生理、代谢和解剖生物标志物的 MRI 资源
- 批准号:
10439901 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
TRD1: Quantitative Imaging of Physiological Markers
TRD1:生理标志物的定量成像
- 批准号:
10439903 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
TRD1: Quantitative Imaging of Physiological Markers
TRD1:生理标志物的定量成像
- 批准号:
10270098 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
MRI Resource for Physiologic, Metabolic and Anatomic Biomarkers
生理、代谢和解剖生物标志物的 MRI 资源
- 批准号:
10270096 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
Blood-brain barrier dysfunction in Alzheimer's disease: from humans to animal models
阿尔茨海默病的血脑屏障功能障碍:从人类到动物模型
- 批准号:
10178195 - 财政年份:2021
- 资助金额:
$ 63.04万 - 项目类别:
Non-contrast MR imaging of blood-brain-barrier permeability in Alzheimer's disease
阿尔茨海默病血脑屏障通透性的非对比磁共振成像
- 批准号:
10390475 - 财政年份:2020
- 资助金额:
$ 63.04万 - 项目类别:
An integrated vascular MR imaging suite in brain diseases
脑部疾病的综合血管 MR 成像套件
- 批准号:
10330590 - 财政年份:2018
- 资助金额:
$ 63.04万 - 项目类别:
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