Estimation of Plaque Burden in Alzheimer's Mouse Models using SPECT Imaging
使用 SPECT 成像估计阿尔茨海默病小鼠模型中的斑块负担
基本信息
- 批准号:8241054
- 负责人:
- 金额:$ 9.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-15 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AlgorithmsAlzheimer&aposs DiseaseAmyloid beta-ProteinAnimal ModelAnimalsBiological ModelsBrainCharacteristicsClassificationCollimatorComputational TechniqueComputational algorithmComputing MethodologiesDataDetectionDevelopmentEvaluationGoalsHistologyHumanImageKnowledgeLaboratoriesMentorsMethodsModelingMusNeurosciencesNoiseNuclearPattern RecognitionPharmaceutical PreparationsPhasePhotonsPositron-Emission TomographyResearchResolutionScanningScientistSignal TransductionSimulateSpecificityStagingStructureSupervisionSystemTechniquesTheoretical StudiesTherapeuticTracerTrainingTransgenic MiceTranslatingValidationWorkage groupbasecomputer studiesdesigndrug testingexperiencefallsimage reconstructionimaging modalityin vivoinstrumentationmolecular imagingmouse modelneuropathologynovelpublic health relevanceradiotracerresearch studysimulationsingle photon emission computed tomographyskillstool
项目摘要
DESCRIPTION (provided by applicant): The overall goal of the proposed research is to develop in vivo imaging methods for plaque detection and classification in transgenic mice using SPECT or alternative nuclear imaging modalities. The reduction of beta-amyloid (A2) plaque burden is one of the main therapeutic objectives for the treatment of Alzheimer's disease (AD). Transgenic mouse models of AD have been created, and in vivo imaging of A2 in a mouse brain would facilitate the study of plaque development and testing of drugs that could potentially cure AD in human. However, the heterogeneous plaque structure of micro-scale range makes an in vivo approach to detecting and quantifying the plaque distribution challenging due to insufficient sensitivity and/or resolution of imaging systems or a lack of good contrast mechanism or radiotracer specificity. These problems can be largely overcome by using novel computational algorithms based on mathematical observers and stochastic object models as an alternative technique to image reconstruction. These algorithms take advantage of prior knowledge about plaque distributions and the noise characteristics of an imaging system to make classification decisions that are based on the best match between the observed data and the underlying stage of plaque burden. The candidate's training in the K99 phase will provide skills to establish herself in this interdisciplinary field, and is also a logical extension of her past experiences in SPECT/PET instrumentation and image reconstruction. This training is adapted to the candidate's needs in acquiring knowledge and skills in neuroscience. In addition to didactic training, she will obtain laboratory training in plaque studies and small-animal imaging of transgenic mouse models of AD under the supervision of mentors at Vanderbilt. This training is well-coordinated with the current research of these mentors, and will be carried out as a part of specific aim I.a, where the stereological plaque studies will help to define a statistical object model of plaque distributions. Specific aim I.a will also include computational studies of binary classification methods to detect the presence of simulated plaque distributions from noisy projection data. The objective of aim I.b is to further advance the candidate's skill in developing system models for SPECT scanners. This training together with he past training in PET systems will allow her to perform the R00 research with the most suitable SPECT or, alternatively, PET systems. By the end of the K99 phase, she will have the skills for developing object models and classification methods. Specific aims II.a and II.b outline R00 studies to explore the feasibility of using a three-class observer analysis with both experimental phantoms and animal scans. The ultimate goal of this study is to acquire scans of transgenic mice from different age groups and to accurately classify the stage of plaque burden. The candidate's long-term goal is to develop signal detection and pattern recognition tools to overcome the practical limitations of current radiotracers while maintaining her focus on their implementation in AD research.
PUBLIC HEALTH RELEVANCE: My studies propose new computational techniques for conducting molecular imaging of Alzheimer's disease (AD) using transgenic mouse models. These techniques are likely to be applicable for studying new radiotracers and therapies for AD. There is a potential for translating these methods to human for detecting AD at very early stages.
描述(由申请人提供):拟议研究的总体目标是开发使用SPECT或替代核成像模式进行转基因小鼠中斑块检测和分类的体内成像方法。减少β-淀粉样蛋白(A2)斑块负荷是治疗阿尔茨海默病(AD)的主要治疗目标之一。已经建立了AD的转基因小鼠模型,并且小鼠脑中A2的体内成像将促进斑块发展的研究和可能治愈人类AD的药物的测试。然而,由于成像系统的灵敏度和/或分辨率不足或缺乏良好的对比机制或放射性示踪剂特异性,微尺度范围的异质斑块结构使得检测和量化斑块分布的体内方法具有挑战性。这些问题可以在很大程度上克服使用新的计算算法的基础上的数学观察员和随机对象模型作为一种替代技术,图像重建。这些算法利用关于斑块分布和成像系统的噪声特性的先验知识来进行分类决策,所述分类决策基于观察到的数据与斑块负担的基础阶段之间的最佳匹配。候选人在K99阶段的培训将提供在这个跨学科领域建立自己的技能,也是她过去在SPECT/PET仪器和图像重建方面经验的逻辑延伸。这种培训是适应候选人在获取神经科学知识和技能的需求。除了教学培训外,她还将在范德比尔特导师的监督下获得斑块研究和AD转基因小鼠模型小动物成像的实验室培训。该培训与这些导师目前的研究协调良好,并将作为具体目标I. a的一部分进行,其中体视学斑块研究将有助于定义斑块分布的统计对象模型。具体目标I. a还将包括二元分类方法的计算研究,以从噪声投影数据中检测模拟斑块分布的存在。目标I.B的目的是进一步提高候选人开发SPECT扫描仪系统模型的技能。该培训与过去的PET系统培训一起,将使她能够使用最合适的SPECT或PET系统进行R 00研究。到K99阶段结束时,她将拥有开发对象模型和分类方法的技能。具体目标二. a和二.B概述了R 00研究,以探索使用三级观察者分析与实验体模和动物扫描的可行性。本研究的最终目标是获得不同年龄组转基因小鼠的扫描结果,并准确分类斑块负荷的阶段。候选人的长期目标是开发信号检测和模式识别工具,以克服当前放射性示踪剂的实际局限性,同时保持她对AD研究实施的关注。
公共卫生关系:我的研究提出了新的计算技术进行分子成像阿尔茨海默病(AD)使用转基因小鼠模型。这些技术可能适用于研究新的放射性示踪剂和治疗AD。有可能将这些方法转化为人类在非常早期阶段检测AD。
项目成果
期刊论文数量(0)
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Sepideh Shokouhi其他文献
Sepideh Shokouhi的其他文献
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{{ truncateString('Sepideh Shokouhi', 18)}}的其他基金
In vivo Amyloid-Beta Imaging in Mouse Brain Using Stochastic Object Models
使用随机对象模型对小鼠大脑进行体内β-淀粉样蛋白成像
- 批准号:
9248782 - 财政年份:2014
- 资助金额:
$ 9.01万 - 项目类别:
In vivo Amyloid-Beta Imaging in Mouse Brain Using Stochastic Object Models
使用随机对象模型对小鼠大脑进行体内β-淀粉样蛋白成像
- 批准号:
9002044 - 财政年份:2014
- 资助金额:
$ 9.01万 - 项目类别:
In vivo Amyloid-Beta Imaging in Mouse Brain Using Stochastic Object Models
使用随机对象模型对小鼠大脑进行体内β-淀粉样蛋白成像
- 批准号:
8792447 - 财政年份:2014
- 资助金额:
$ 9.01万 - 项目类别:
In vivo Amyloid-Beta Imaging in Mouse Brain Using Stochastic Object Models
使用随机对象模型对小鼠大脑进行体内β-淀粉样蛋白成像
- 批准号:
8795175 - 财政年份:2014
- 资助金额:
$ 9.01万 - 项目类别:
Estimation of Plaque Burden in Alzheimer's Mouse Models using SPECT Imaging
使用 SPECT 成像估计阿尔茨海默病小鼠模型中的斑块负担
- 批准号:
8047059 - 财政年份:2011
- 资助金额:
$ 9.01万 - 项目类别: