In vivo MRI Biomarkers of Microstructural Correlates of Brain Pathology in Preclinical and Early Alzheimer Disease
临床前和早期阿尔茨海默病脑病理学微观结构相关的体内 MRI 生物标志物
基本信息
- 批准号:9908038
- 负责人:
- 金额:$ 54.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAddressAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease diagnosisAlzheimer&aposs disease pathologyAlzheimer&aposs disease therapyAmyloidApplications GrantsAutopsyBiological MarkersBrainBrain PathologyCellular StructuresClinicalCognitionCognitiveCognitive deficitsCountryDataDementiaDevelopmentDiseaseDisease ProgressionEarly identificationEvaluationFailureFemaleGoalsGoldHealthHippocampus (Brain)HumanImaging TechniquesImmunohistochemistryImpaired cognitionImpairmentIndividualInterventionInvestigational TherapiesLaboratoriesMRI ScansMagnetic Resonance ImagingMeasurementMeasuresMental disordersMethodsModelingMolecularMonitorMultiple SclerosisNatureNeurodegenerative DisordersNeurofibrillary TanglesNormal RangeParticipantPathologicPathologic ProcessesPathologyPatient RecruitmentsPatternPerformancePharmaceutical PreparationsPopulationPositron-Emission TomographyPrevention trialPropertyProtocols documentationRadiation exposureRelaxationReproducibilityResearchResolutionRoleSignal TransductionStructureSurrogate MarkersSymptomsTechniquesTestingTherapeutic InterventionTimeTissuesTracerTreatment EfficacyUnited States National Institutes of HealthUniversitiesVisitWashingtonabeta accumulationbasebrain tissuecognitive performancecontrast imagingdisorder preventionfollow-uphistological stainsin vivoin vivo evaluationinnovationinsightmagnetic resonance imaging biomarkermalemild cognitive impairmentneuron lossneuropathologypre-clinicalpreventscreeningsymptom treatmenttau Proteins
项目摘要
This grant application addresses a significant health problem - Alzheimer’s disease (AD) - that affects ~5.3 million
people in the US and 20-30 million worldwide. As the population ages, these numbers are anticipated to rise,
stimulating an intense search for disease prevention and treatment therapies as well as for biomarkers allowing
early identification of AD. The latter is very important due to the existence of a long pre-symptomatic period that
can be used for the initiation of prevention trials of disease-modifying therapies in asymptomatic individuals, with
the goal of preventing cognitive decline as opposed to treating of symptoms that are already present.
The main goal of this study is to provide a groundwork for using the innovative MRI-based Gradient Echo
Plural Contrast Imaging (GEPCI) technique for in vivo identifying early pathological changes in the AD brain.
This technique, GEPCI, developed in our laboratory, provides surrogates for quantitative assessments of
changes in the brain tissue structure at the cellular level and has been already successfully applied to evaluating
tissue damage in multiple sclerosis and some psychiatric diseases.
Our preliminary data, obtained on well-characterized research participants recruited from studies of aging
and dementia at the Washington University Knight Alzheimer’s Disease Research Center, allowed us to
demonstrate for the first time that in vivo MRI-based measurements obtained on a clinical MRI scanner can
provide information on brain amyloid-β accumulation in human participants, and to distinguish between healthy
control, preclinical and mild AD stages. Based on these results, we plan to achieve the following Specific Aims:
1. Our Aim 1 is to develop a readily available, non-invasive quantitative in vivo MRI-based biomarker that can
serve as a surrogate for amyloid-β accumulation in the brain (a primary role of Aβ in the development of
Alzheimer's disease is now almost universally accepted).
2. Our Aim 2 is to establish specific quantitative and spatial patterns of GEPCI metrics abnormalities that would
distinguish between normal brain, preclinical AD, and very mild AD.
3. Our Aim 3 is to establish the effect of early AD-related brain tissue damage (defined by GEPCI surrogate
biomarkers) on cognitive performance and to test the hypothesis that the GEPCI metrics and/or changes in
GEPCI metrics can be predictors of the disease progression.
4. Our Aim 4 is to validate GEPCI measurements against direct neuropathology.
The overarching goal of this proposal is to establish GEPCI as an in vivo non-invasive MRI technique
available in a conventional clinical setting for screening population for preclinical AD pathology and clinical drug
trials. GEPCI data are quantitative, reproducible and MRI scanner independent, thus allowing multi-center
applications. The non-invasive nature of our approach is especially important since most of currently available
biomarkers for identifying AD “are invasive, to one degree or another (NIH PAR-15-359)”.
这项拨款申请解决了一个重大的健康问题——阿尔茨海默病(AD)——影响着约530万人
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
DMITRIY A YABLONSKIY其他文献
DMITRIY A YABLONSKIY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('DMITRIY A YABLONSKIY', 18)}}的其他基金
In vivo Identification of Pre-Atrophic Brain Neurodegeneration in Prodromal Alzheimer Disease with Quantitative Gradient Recalled Echo MRI
利用定量梯度回忆回波 MRI 体内鉴定阿尔茨海默病前驱期的萎缩前脑神经变性
- 批准号:
10448152 - 财政年份:2022
- 资助金额:
$ 54.85万 - 项目类别:
In vivo MRI Biomarkers of Microstructural Correlates of Brain Pathology in Preclinical and Early Alzheimer Disease
临床前和早期阿尔茨海默病脑病理学微观结构相关的体内 MRI 生物标志物
- 批准号:
9381996 - 财政年份:2017
- 资助金额:
$ 54.85万 - 项目类别:
In vivo human lung morphometry with hyperpolarized 3He MRI and CT: effects of aging, smoking, and COPD
使用超极化 3He MRI 和 CT 进行体内人肺形态测量:衰老、吸烟和 COPD 的影响
- 批准号:
9340827 - 财政年份:2016
- 资助金额:
$ 54.85万 - 项目类别:
QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE
健康与疾病的定量大胆对比
- 批准号:
8016613 - 财政年份:2008
- 资助金额:
$ 54.85万 - 项目类别:
QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE
健康与疾病的定量大胆对比
- 批准号:
7766923 - 财政年份:2008
- 资助金额:
$ 54.85万 - 项目类别:
QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE
健康与疾病的定量大胆对比
- 批准号:
8212451 - 财政年份:2008
- 资助金额:
$ 54.85万 - 项目类别:
QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE
健康与疾病的定量大胆对比
- 批准号:
7372884 - 财政年份:2008
- 资助金额:
$ 54.85万 - 项目类别:
QUANTITATIVE BOLD CONTRAST IN HEALTH AND DISEASE
健康与疾病的定量大胆对比
- 批准号:
7560322 - 财政年份:2008
- 资助金额:
$ 54.85万 - 项目类别:
Brain Temperature Control During Functional Activation
功能激活期间的大脑温度控制
- 批准号:
6621700 - 财政年份:2002
- 资助金额:
$ 54.85万 - 项目类别:
Brain Temperature Control During Functional Activation
功能激活期间的大脑温度控制
- 批准号:
6689533 - 财政年份:2002
- 资助金额:
$ 54.85万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 54.85万 - 项目类别:
Research Grant