Quantification of Thalamic Atrophy and Connectivity in Medial Temporal Lobe Epile

描述(由申请者提供)：该奖学金的目标是让申请者(Daniel S.Barron)学习先进的神经影像研究方法，并获得大量临床癫痫治疗机会。申请者将接受结构、功能和弥散磁共振图像分析方法的培训；他将使用这些方法对内侧颞叶癫痫(MTLE)的海马区外病理进行量化。MTLE是转诊至外科中心的最常见的癫痫类型，也是成人中最常见的定位相关癫痫。(Tellez-Zenteno等人，2012年)。MTLE最常见的病理是海马区硬化症(HS)。(Wieser，2004)当它是磁共振图像肉眼观察到的唯一病理时，HS是阳性手术结果的预测因子。(Engel，2008)相反，海马区外病理是较差预后的预测指标，实际上也是手术的禁忌症。(Thom等人，2010)海马区外的病理通常是微妙的，在手术前的评估中在视觉上是不被发现的，因此海马区外的病理继续导致手术失败。(Thom等人，2010)定量、有针对性地分析 海马区外的病理学可以指导手术前的评估，提供新的治疗措施，减少手术失败。到目前为止，这样的尝试取得的成功有限，是改善手术前评估和患者护理的关键障碍。我们近期的研究目标是确定MTLE-HS的海马区外病理区域，长期目标是了解手术失败。我们最近对24个基于体素的形态计量学实验(审稿中)的荟萃分析表明，MTLE海马区外病理最一致的区域是丘脑内侧背核(MDN)。我们假设MTLE与MDN的选择性组织损伤有关，MDN和海马体之间的功能和解剖连接增加。为了验证这一假设，我们将对MTLE-HS患者数据进行以下分析： 目的1.我们将使用结构性磁共振数据来测量MDN体积的变化。 目的2.我们将使用扩散磁共振数据测量连接海马体和MDN的白质束的解剖连接性。 目的3.我们将使用静息状态功能磁共振数据的区域种子分析来测量海马区和MDN之间的功能连通性。 为了学习这些神经影像分析方法，申请者将利用壁内和壁外课程和合作。申请人还将有临床接触的病理生理学，临床护理和手术治疗的MTLE。这项研究培训将允许申请者学习他将作为神经成像研究人员和癫痫专家使用的神经成像分析方法。

DESCRIPTION (provided by applicant): The goal of this fellowship is for the applicant (Daniel S. Barron) to learn advanced neuroimaging research methods and to gain significant exposure to clinical epilepsy care. The applicant will receive training in structural, functional, and diffuion magnetic resonance image analysis methods; he will use these methods to quantify extra-hippocampal pathology in medial temporal lobe epilepsy (MTLE). MTLE is the most common type of epilepsy referred to surgical centers and the most common localization- related epilepsy in adults. (Tellez-Zenteno et al., 2012). The most common pathology in MTLE is hippocampal sclerosis (HS). (Wieser, 2004) When it is the sole pathology observed on visual inspection of magnetic resonance images, HS is a predictor of positive surgical outcome. (Engel, 2008) Conversely, extra-hippocampal pathology is a predictor of poorer outcome and is, in fact, a contraindication for surgery. (Thom et al., 2010) Extra-hippocampal pathology is often subtle and goes visually undetected on the pre-surgical evaluation, thus extra-hippocampal pathology continues to contribute to surgical failure. (Thom et al., 2010) Quantitative, targeted analyses of extrahippocampal pathology could guide the pre-surgical evaluation, inform new therapeutic interventions, and mitigate surgical failure. Thus far such attempts have met with limited success and represent a critical barrier to improved pre-surgical evaluation and patient care. Our immediate research goal is to define regions of extra-hippocampal pathology in MTLE-HS with the long- term goal of understanding surgical failure. Our recent meta-analysis of 24 voxel-based morphometry experiments (manuscript in review) demonstrated the most consistent area of extra-hippocampal pathology in MTLE is the medial dorsal nucleus of the thalamus (MDN). We hypothesize that MTLE is associated with selective tissue damage in the MDN related to increased functional and anatomical connectivity between the MDN and the hippocampus. To test this hypothesis we will perform the following analyses on MTLE-HS patient data: Aim 1. We will measure changes in MDN volume using structural MR data. Aim 2. We will measure anatomic connectivity in white matter tracts connecting the hippocampus and MDN using diffusion MR data. Aim 3. We will measure functional connectivity between the hippocampus and MDN using region-seeded analyses of resting-state functional MR data. To learn these neuroimaging analysis methods, the applicant will leverage intra-mural and extra-mural courses and collaborations. The applicant will also have clinical exposure to the pathophysiology, clinical care, and surgical treatment of MTLE. This research training will allow the applicant to learn neuroimaging analysis methods he will use as a neuroimaging researcher and epileptologist.