Oscillating gradient diffusion MRI and quantitative susceptibility mapping in the epileptogenic brain

总结 癫痫是一种严重的神经系统疾病，涉及使人衰弱的癫痫发作，影响超过1%（6500万）的人。 世界人口。导致癫痫的大脑结构和生理变化的级联仍在继续 仍然不为人所知。由于癫痫是在癫痫发作后才被发现的， 癫痫发生过程中大脑中引发的病理变化，包括神经变性，神经胶质增生， 钙化和树突状损伤几乎完全来自已建立的啮齿动物模型。一个主要 早期诊断和靶向干预的发展的局限性是缺乏可靠的标志物， 致癫痫过程，终点组织学对癫痫进展的了解严重有限。 引起癫痫的变化该R21提案旨在研究体内定量MR 对比机制，1）振荡梯度扩散MRI（OG-dMRI）;和2）定量磁共振成像（MRI）。 药敏图（QSM），实现非侵入性、敏感性和靶向检测特异性 在癫痫持续状态的毛果芸香碱大鼠模型中，整个大脑的微结构癫痫后遗症。 此外，结合3D扫描电子显微镜，我们将阐明 OG-dMRI和QSM结果验证MR对比机制作为特异性癫痫发生的标志物- 诱发病理性后遗症。 我们将在三个具体目标中瞄准这些目标：1）研究振荡和脉冲梯度dMRI， 海马神经元和树突变性的检测，这是一个主要的标志， 癫痫发生; 2）研究进行性钙化和铁沉积的体内检测 致癫痫丘脑使用QSM;和，3）阐明OG-dMRI的显微结构基础和起源， 使用3D连续块面扫描电子显微镜和组织病理学分析的QSM结果。的 在这个R21项目中开发的关键创新技术将建立高度具体的，定量的， 基于MRI的内源性标记物，用于靶向检测大脑中的微观结构过程， 允许癫痫发生过程中发生的进行性病理变化的非侵入性成像。这个项目 将产生关键的技术和数据，以提供洞察癫痫的发展和进展， 大脑，并进一步阐明在大脑中dMRI和QSM结果的潜在病理学相关性。 致癫痫的大脑

Summary Epilepsy is a severe neurological disorder involving debilitating seizures that affects over 1% (65 million) of the world’s population. The cascade of alterations in brain structure and physiology leading to epilepsy continues to remain poorly understood. Since epilepsy is not detected in patients until after the onset of seizures, insights into pathologic changes triggered in the brain during epileptogenesis, which include neurodegeneration, gliosis, calcification, and dendritic damage, are almost exclusively gained from established rodent models. A major limitation in early diagnosis and development of targeted intervention is the lack of reliable markers of the epileptogenic process, with end-point histology providing severely limited insight into the progression of epileptogenic changes across brain areas. This R21 proposal aims to investigate in vivo quantitative MR contrast mechanisms using, 1) oscillating gradient diffusion MRI (OG-dMRI); and 2) quantitative magnetic susceptibility mapping (QSM), to achieve non-invasive, sensitive, and targeted detection of specific microstructural epileptogenic sequelae across the brain in the pilocarpine rat model of status epilepticus. Further, in combination with 3D scanning electron microscopy, we will elucidate the microstructural basis of OG-dMRI and QSM findings to validate the MR contrast mechanisms as markers of specific epileptogenesis- induced pathologic sequelae. We will target these goals in three specific aims: 1) to investigate oscillating- and pulsed-gradient dMRI for detection of hippocampal neuronal and dendritic degeneration, which is one of the main hallmarks of epileptogenesis; 2) to investigate in vivo detection of progressive calcification and iron deposits in the epileptogenic thalamus using QSM; and, 3) to elucidate the microstructural basis and origins of OG-dMRI and QSM findings using 3D serial block-face scanning electron microscopy and histopathological analyses. The key innovative techniques developed in this R21 project will establish highly-specific, quantitative, and endogenous MRI-based markers for targeted detection of microstructural processes in the brain, which will allow non-invasive imaging of progressive pathological changes occurring during epileptogenesis. This project will produce techniques and data crucial to afford insights into the development and progression of epilepsy in the brain, and further, to elucidate the underlying pathological correlates of both dMRI and QSM findings in the epileptogenic brain.