Diffusional Kurtosis Assessment of the Cuprizone Mouse Model of Demylination

描述（由申请人提供）：弥散张量成像（DTI）已被证明是研究与许多中枢神经系统（CNS）疾病相关的白质变化的重要工具[Sullivan and Pfefferbaum, 2003；Salat et al., 2005；Assaf and Pasternak, 2008]。近年来，一种新的弥散性MRI成像方法被称为弥散峰度成像（diffusion Kurtosis imaging， DKI） [Jensen and Helpern, 2003；Jensen et al., 2005；Lu et al.， 2006]已经开发。DKI能够量化水扩散的非高斯行为。最近的DKI研究表明，平均峰度（MK）在检测与神经系统疾病相关的脑微结构变化方面提供了与传统DTI不同的有用和独特的信息。[Falangola et al., 2008；Helpern et al., 2007；Ramani et al., 2007]。然而，在这个时间点上，在少数已发表的DKI动物研究中未发现组织学相关性[Falangola et al., 2007；张et al., 2008]；bbb10等人，2008b]， DKI指标的定量解释仍有待验证。该项目的总体目标是通过研究这些测量与脱髓鞘和髓鞘再生模型（铜zone小鼠模型）中轴突和髓鞘损伤之间的关系，验证和理解这些新的MRI扩散指数，主要是DKI测量的平均峰度、轴向（K//）和径向（K4）峰度，在组织水平上反映了什么。通过将DK指标和常规DTI指标与铜酮小鼠模型胼胝体脱髓鞘和再髓鞘脱髓鞘过程中髓磷脂丢失、轴突损伤和胶质细胞积累的组织学标志物进行比较，将实现这一目标。本提案所解决的问题是，一种新的磁共振成像（MRI）扩散技术，称为扩散峰度成像（DKI），是否可以准确和适合于定量评估大脑微观结构的变化。与任何新的MR技术一样，验证和理解建议的MRI指数在组织水平上反映的内容对于表征疾病集的正常形态学方面和潜在病理是必不可少的。为了验证这一点，我们将使用铜zone小鼠脱髓鞘和再脱髓鞘模型。本课题的意义在于试图验证和理解这些新的MRI弥散指标在脑形态学水平上的反映。

DESCRIPTION (provided by applicant): Diffusion tensor imaging (DTI) has proven to be an important tool for investigating white matter changes associated with many central nervous system (CNS) diseases [Sullivan and Pfefferbaum, 2003; Salat et al., 2005; Assaf and Pasternak, 2008]. Recently, a new diffusion MRI imaging method called Diffusional Kurtosis Imaging (DKI) [Jensen and Helpern, 2003; Jensen et al., 2005; Lu et al., 2006] has been developed. DKI is capable of quantifying the non-Gaussian behavior of water diffusion. Recent DKI studies have demonstrated that mean kurtosis (MK) yields useful and distinct information from that provided by conventional DTI in detecting changes in brain microstructure associated with neurological diseases. [Falangola et al., 2008; Helpern et al., 2007; Ramani et al., 2007]. However, at this point in time, no histological correlation has been performed in the few published DKI animal studies [Falangola et al., 2007, Cheung et al., 2008a; Cheung et al., 2008b] and the quantitative interpretation of DKI metrics remains to be validated. The overall goal of this project is to validate and understand what these new MRI indices of diffusion, mainly the DKI measurements of Mean Kurtosis, axial (K//) and radial (K4) kurtosis, reflect at the tissue level by investigating the relationship between these measurements and axonal and myelin damage in a model of demyelination and remyelination, the cuprizone mouse model. This goal will be achieved by comparing indices of DK metrics and conventional DTI metrics with histological markers of myelin loss, axonal damage and glial cells accumulation during the process of demyelination and remyelination that occur in the corpus callosum of the cuprizone mouse model PUBLIC HEALTH RELEVANCE: The questions addressed in this proposal are whether a new Magnetic Resonance Imaging (MRI) diffusion technique, called Diffusional Kurtosis Imaging (DKI), can be accurate and suitable for quantitative evaluation of brain microstructure changes. As with any new MR technique, the validation and understanding of what the proposed MRI indices reflect at the tissue level is essential for characterizing the normal morphological aspects and the underlying pathology on a disease set. For this validation we will use the cuprizone mouse model of demyelination and remyelination. The significance of this project is to try to validate and understand what these new MRI indices of diffusion reflect at the brain morphological level.