Radiological Biomarkers for Frontotemporal Lobar Degeneration

描述（由申请人提供）：本提案旨在发展UT西南大学神经病学和精神病学助理教授Kyle B. Womack医学博士以患者为导向的研究事业。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。在这个奖项的支持下，他将能够发展必要的生物统计学技能和先进的神经成像程序，如磁共振扩散张量成像（DTI）。凭借该奖项获得的额外研究经验、技能和动力，他将在以患者为导向的研究中扩展他的职业生涯，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通常被认为是一组退行性疾病，导致特定皮质区域的神经元丢失和萎缩，但最近的研究表明，除了皮质萎缩外，白质病变也存在。本研究的目的是通过识别FTLD中这类病理的生物标志物来探索白质/轴突损伤的作用和本质。Womack博士将评估DTI作为FTLD生物标志物的效用，在FTLD患者和正常对照组的横断面研究中，确定可以区分这两组的放射学特征。还将在3年后进行纵向研究，随访DTI扫描，以确定DTI措施对跟踪疾病进展的效用。将对在研究过程中死亡的患者进行死后评估，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物，它可以提高对该疾病患者的诊断准确性。它是一个相对较短的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于辐射。此外，疾病进展的生物标志物可能会提高相对较小、较短的治疗试验的效果。

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.