Characterization of brain atrophy in Huntington?s disease mouse model

描述(申请人提供)：亨廷顿病小鼠模型脑萎缩的特征该研究的目的是开发新的图像分析技术来表征亨廷顿病小鼠模型R6/2小鼠的脑萎缩。特定大脑结构的萎缩被认为是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，例如萎缩和运动障碍，并已广泛用于临床前治疗试验。虽然已有R6/2系的组织病理学和行为学数据，但脑萎缩的关键方面，如其空间和时间分布，还没有得到充分的研究。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。这项研究中提出的技术基于三项主要技术创新：(I)用于数据采集的在体MR“微成像”，(Ii)用于对大脑结构进行一致分割的发育小鼠大脑的详细神经解剖图谱，以及(Iii)用于量化萎缩和结构变形的最先进的计算神经解剖学。在这项应用中，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。公共卫生相关性：在这个项目中，将开发基于磁共振成像的新分析技术，以表征广泛使用的亨廷顿病模型R6/2小鼠脑萎缩的空间和时间分布。萎缩和神经退行性变之间的联系以及肌酸治疗的效果也将被调查。

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.