Characterization of brain atrophy in Huntington?s disease mouse model

亨廷顿病小鼠模型脑萎缩的特征

基本信息

批准号：
7895049
负责人：
JIANGYANG ZHANG
金额：
$ 24.39万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-16 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7895049
关键词：
Adverse effects Alzheimer&apos s Disease Arts Atlases Atrophic Behavioral Brain Brain region Characteristics Complex Corpus striatum structure Creatine Creatine Supplement Data Detection Development Diagnosis Diffusion Magnetic Resonance Imaging Disease Disease Progression Gold Huntington Disease Image Image Analysis Investigation Longitudinal Studies Magnetic Resonance Imaging Measurement Measures Methods Modeling Monitor Motor Mus Nature Nerve Degeneration Neuroanatomy Neurodegenerative Disorders Pathogenesis Patients Performance Phenotype Play Process Research Role Shapes Staging Structure Surrogate Markers Symptoms Techniques Testing Therapy Clinical Trials Time Treatment Efficacy abstracting base cerebral atrophy cost data acquisition drug development improved in vivo innovation longitudinal analysis motor deficit mouse model novel palliative postnatal pre-clinical preclinical study public health relevance treatment planning white matter

项目摘要

DESCRIPTION (provided by applicant): Characterization of brain atrophy in Huntington's disease mouse model Abstract The proposed study is aimed at developing new image analysis techniques to characterize brain atrophy in the R6/2 mouse line, a mouse model of Huntington's disease (HD). Atrophy of specific brain structures is known to be an important marker of HD and other neurodegenerative diseases. The R6/2 line has progressive HD-like phenotypes, e.g. atrophy and motor deficits, and has been widely used in preclinical therapeutic trials. Although there exist histo-pathological and behavioral data of the R6/2 line, key aspects of atrophy in the brain, such as its spatial and temporal profiles, have not been full investigated. The information is important to understand the mechanism of disease progression and to develop new treatment. The technique proposed in this study is based on three major technical innovations: (i) in vivo MR "micro-imaging" for data acquisition, (ii) a detailed neuro-anatomical atlas of developing mouse brains for consistent parcellation of brain structures, and (iii) state-of-the-art computational neuroanatomy for quantification of atrophy and structural deformation. In this application, we will first validate the techniques and then apply the techniques to characterize atrophy in R6/2 mice and the effect of creatine treatment on atrophy, through in vivo longitudinal studies. PUBLIC HEALTH RELEVANCE: In this project, novel magnetic resonance imaging based analysis techniques will be developed to characterize the spatial and temporal profiles of atrophy in R6/2 mouse brain, a widely used model of Huntington's disease. Association between atrophy and neurodegeneration and the effect of creatine treatment will also be investigated.

描述（由申请人提供）：亨廷顿病小鼠模型中脑萎缩的表征摘要所提议的研究旨在开发新的图像分析技术来表征 R6/2 小鼠系（亨廷顿病（HD）的小鼠模型）中的脑萎缩特征。已知特定大脑结构的萎缩是 HD 和其他神经退行性疾病的重要标志。 R6/2 系具有进行性 HD 样表型，例如萎缩和运动缺陷，并已广泛用于临床前治疗试验。尽管存在 R6/2 系的组织病理学和行为数据，但大脑萎缩的关键方面，例如其空间和时间特征，尚未得到充分研究。这些信息对于了解疾病进展的机制和开发新的治疗方法非常重要。本研究提出的技术基于三项主要技术创新：(i) 用于数据采集的体内 MR“显微成像”，(ii) 发育中小鼠大脑的详细神经解剖图谱，以实现大脑结构的一致分割，以及(iii) 最先进的计算神经解剖学，用于量化萎缩和结构变形。在此应用中，我们将首先验证这些技术，然后通过体内纵向研究应用这些技术来表征 R6/2 小鼠的萎缩以及肌酸治疗对萎缩的影响。公共健康相关性：在该项目中，将开发基于磁共振成像的新型分析技术，以表征 R6/2 小鼠大脑（一种广泛使用的亨廷顿病模型）萎缩的空间和时间特征。还将研究萎缩和神经变性之间的关联以及肌酸治疗的效果。