Radiological Biomarkers for Frontotemporal Lobar Degeneration

描述(由申请人提供)：这项建议是为了发展凯尔·B·沃马克医学博士的以患者为中心的研究生涯，他是德克萨斯大学西南分校的神经学和精神病学助理教授。沃马克博士接受过普通神经学、分子生物学以及最近的行为和认知神经学方面的培训。在该奖项的支持下，他将能够在生物统计学和高级神经成像程序(如磁共振扩散张量成像(DTI))方面发展必要的技能。凭借这一奖项的额外研究经验、技能和势头，他将扩大他在以患者为导向的研究方面的职业生涯，利用神经成像技术，专注于额颞叶变性(FTLD)以及其他神经退行性痴呆。FTLD通常被概念化为一组退行性疾病，导致神经元丢失和特定皮质区域的萎缩，但最近的研究表明，除了皮质萎缩外，还存在白质损害。本研究的目的是通过确定FTLD中白质/轴索损伤的生物标志物来探讨白质/轴索损伤的作用和性质。沃马克博士将在一组特征良好的FTLD患者和正常对照的横断面研究中，评估DTI作为FTLD生物标记物的实用性，确定可以区分这两组人的放射学特征。还将进行一项纵向研究，并在3年后进行跟踪DTI扫描，以确定DTI措施跟踪疾病进展的有效性。将对那些在研究过程中死亡的患者进行尸检评估，以确认临床诊断，并将轴突密度的定量测量与同一区域的DTI结果相关联。如果DTI被证明是FTLD的一个可靠和敏感的标志，它可以提高对这种疾病患者的诊断准确性。这是一个相对较短的MRI序列，可以添加到临床MRI的标准序列中，并且不需要静脉注射或暴露在辐射中。此外，疾病进展的生物标记物可能会提高相对较小、简短的治疗试验的能力。

DESCRIPTION (provided by applicant): This proposal is for development of the patient oriented research career of Kyle B. Womack, MD, an assistant professor of Neurology and Psychiatry at UT Southwestern. Dr. Womack has received training in general neurology, molecular biology and, most recently, in behavioral and cognitive neurology. With the support from this award, he will be able to develop necessary skills in biostatistics and advanced neuroimaging procedures such as magnetic resonance diffusion tensor imaging (DTI). With the additional research experience, skills and momentum from this award, he will expand his career in patient oriented research, utilizing neuroimaging techniques and focusing on frontotemporal lobar degeneration (FTLD) as well as other neurodegenerative dementias. FTLD is usually conceptualized as a group of degenerative diseases resulting in neuronal loss and atrophy of specific cortical regions, but recent work has demonstrated white matter lesions are also present in addition to cortical atrophy. The purpose of this study is to explore the role and nature of white matter/axonal damage by identifying biomarkers for this type of pathology in FTLD. Dr. Womack will evaluate the utility of DTI, as a biomarker for FTLD in a cross sectional study of a cohort of well characterized FTLD patients and normal controls, identifying radiological characteristics that can distinguish these two groups. There will also be a longitudinal study with a follow up DTI scan after 3 years to ascertain the utility of DTI measures to follow disease progression. Post mortem evaluations will be sought on those who expire over the course of the study to both confirm the clinical diagnoses and to correlate quantitative measures of axon density with the DTI results from the same region. If DTI turns out to be a reliable and sensitive marker for FTLD it could improve the diagnostic accuracy for patients with this disorder. It is a relatively short MRI sequence that can be added onto the standard sequences in a clinical MRI, and requires no intravenous injections or exposure to radiation. Furthermore, a biomarker of disease progression may improve the power of relatively small, brief therapeutic trials.