Development and validation of quantitative MRI techniques for CNS tissue

磁共振成像(MRI)是研究组织基本特性的最通用的成像技术之一。尤其重要的是可以测量物理参数的定量MRI技术，它可以提供更准确和客观的方法来表征感兴趣的组织属性。许多定量磁共振成像(QMRI)技术已被成功地应用于中枢神经系统组织的研究，其中最引人注目的是：弥散磁共振成像、定量T2磁共振成像、定量磁化率成像(QSM)，以及最近的非均匀磁化转移(IhMT)。在目前的应用中，我们建议进一步开发、测试和验证这些qMRI技术，以便更好地表征啮齿动物中枢神经组织的生物物理特性。*拟议研究计划的长期目标是开发、验证和应用定量核磁共振技术来研究动物中枢神经组织的生物物理特性。*拟议研究的短期目标是：*1.研究啮齿动物中枢神经系统组织中非均匀磁化传递(IhMT)的基本特征和局限性。*我们将在体内和体外建立ihMT比值与温度、T1D滤波和磁场取向的依赖关系。我们还将通过研究固定时间对ihMT比值的影响来研究组织固定对ihMT测量的影响。2.在大鼠脊髓进行MWI+ihMT联合测量。*我们将优化结合定量T2和ihMT方法的脉冲序列。这将允许分别测量ihMT对髓鞘和轴突内/外水室的影响。这些测量将在体内和体外的正常和损伤的大鼠脊髓中进行。*3.比较MWI、QSM、扩散磁共振和ihMT在测量髓鞘含量和区分功能性髓鞘和髓鞘碎片方面的能力。*这些测量将在正常和损伤的大鼠脊髓中进行，包括体内和体外，核磁共振结果将与组织学和透射电子显微镜(TEM)相关联。*拟议研究的意义：*拟议计划旨在进一步扩大动物体内中枢神经系统组织非侵入性研究领域的研究能力。在整个项目中开发的定量、非侵入性成像技术将有助于扩大我们对动物中枢神经系统生物学和生理学的理解。此外，该方案将为在跨学科环境中培训研究生和博士后研究员提供极好的机会。

Magnetic Resonance Imaging (MRI) is one of the most versatile imaging techniques for studying fundamental properties of tissue. Of particular significance are quantitative MRI techniques that can measure physical parameters, which can provide more accurate and objective way of characterizing tissue properties of interest. A number of quantitative MRI (qMRI) techniques have been successfully applied to study CNS tissue, most notably: diffusion MRI, quantitative T2 MRI, Quantitative Susceptibility Mapping (QSM), and more recently inhomogeneous Magnetization Transfer (ihMT). In the current application we propose to further develop, test and validate these qMRI techniques to allow better characterization of biophysical properties of the rodent CNS tissue. ******Long term objective of the proposed research programme is the development, validation and application of quantitative MRI techniques to study biophysical properties of CNS tissue in animals. ******Short term objectives of the proposed research are:***1. To study fundamental characteristics and limitations of inhomogeneous Magnetization Transfer (ihMT) in rodent CNS tissue.***We will establish the dependence of ihMT ratio values on the temperature, T1d filtering and orientation with regards to the magnetic field, both in vivo and ex vivo. We will also study the effect of tissue fixation on ihMT measurements by studying the effect of fixation time on the ihMT ratio values.******2. To carry out a combined MWI + ihMT measurements in rat spinal cord.***We will optimize a pulse sequence that combines both quantitative T2 and ihMT methods. This will allow measurement of ihMT effect separately on myelin and intra-/extra-axonal water compartments. These measurements will be carried out in normal and injured rat spinal cords both in-vivo and ex-vivo.******3. To compare MWI, QSM, diffusion MRI, and ihMT in their ability to measure myelin content and distinguish between functional myelin and myelin debris.***The measurements will be carried in in normal and injured rat spinal cords, both in-vivo and ex-vivo, and the MRI results will be correlated with histology and Transmission Electron Microscopy (TEM).******Significance of the proposed research:***The proposed programme aims to further expand research capabilities in the area of non-invasive studies of CNS tissue in animals in vivo. Quantitative, non-invasive imaging technology developed throughout this programme will help to broaden our understanding of animal CNS biology and physiology. In addition this programme will provide excellent opportunities for training graduate students and post-doctoral fellows in an interdisciplinary environment.**