【作者】 陈薇；

【导师】 张云亭；

【作者基本信息】 天津医科大学 ， 影像医学与核医学， 2011， 博士

【摘要】 研究背景及目的：Alzheimer病(Alzheimer’s disease, AD)是以认知功能障碍、情感障碍及行为异常为主要表现的神经退行性病变,是造成痴呆最常见的原因。组织学上以老年斑、神经元纤维缠结、神经元丧失和淀粉样血管病变的出现为特点。最初的神经病理学改变位于内侧颞叶,晚期可扩展至颞顶叶和额叶等相关皮层,初级感觉中枢和运动中枢一般不受累。功能神经影像学,能够在疾病亚临床期检测AD患者脑功能及血流动力学的改变,实现早期诊断,使患者能够获得及时有效的治疗,延缓病程,提高生活质量。本研究目的在于利用高场MR获得早期AD患者在静息态及记忆任务刺激下的脑血流动力学及功能异常。研究方法：研究对象为临床诊为早期AD的志愿者12人(平均年龄72.3±7.9岁)和年龄匹配的正常对照组12人(平均年龄73.7±5.5岁)。在4T MR采用动脉自旋标记(arterial spin labeling, ASL)灌注技术,对所有受试者在静息态下行MR灌注扫描,并采用ASL及血氧水平依赖(blood oxygenation level dependent, BOLD)对比分别在记忆编码及记忆提取任务下行功能成像。数据后处理应用FSL和SPM软件,统计学处理采用SPSS 19.0。结果：静息状态下,AD患者脑血流灌注主要分布于右侧额叶、左侧颞、枕叶及前扣带回。与对照组相比,AD组在双侧额叶、左顶叶楔回、右侧颞上回及后扣带回出现了散在的低灌注区,同时在双侧前额叶皮层(包括前额叶背外侧皮层和前额叶腹外侧皮层)、右顶叶及前扣带回出现了显著的灌注增高区。执行记忆编码和提取任务时,AD组除在双侧额叶和运动区出现低灌注/激活区外,在双侧前额叶皮层(包括双侧前额叶背外侧皮层、前额叶腹外侧皮层、额极)和前扣带回可见显著的高灌注/激活区。结论：4TMR下,早期AD患者在静息态及认知状态下,脑内均存在一定的灌注损伤。同时,双侧前额叶皮层均出现了神经代偿反应。ASL和BOLD两种成像方式在检测AD静息态及认知状态下的脑血流灌注及功能活动方面具有可比性。更多还原

【Abstract】 Background and objective:Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairments and is the most common reason for dementia. The histological changes are characterized by senile plaque, neurofibrillary tangles, neuron loss and granulovacuolar degeneration. Brain damage begins in the medial temporal lobe in the early stage of AD and extends gradually to the entire neocortex. Neuroimaging techniques have played an important role in diagnosing AD, especially in finding functional abnormalities in early stage of the disease. The purpose of this study was to detect brain hemodynamic and functional changes in subjects with AD at both resting state and during cognitive tasks.Methods:Twelve subjects with early AD (mean age=72.3±7.9 yrs, females=5) and 12 age-matched cognitively normal (CN, mean age=73.7±5.5yrs, females=9) subjects were recruited for this study. Perfusion-weighted imaging with arterial spin labeling (ASL) was employed to study the hemodynamic abnormalities in AD at resting state. ASL-based fMRI was used to investigate brain functional changes during cognitive states including both encoding and retrieval tasks in AD. Blood oxygenation level dependent (BOLD)-functional MRI (fMRI) was also conducted for comparison. Data post-processing was performed with SPM and FSL software package. SPSS versoin19.0 was used for statistics.Results:During the resting state, brain perfusion was located in AD in the right frontal lobe, left temporal and occipital lobes, and anterior cingulate cortex (ACC). In comparison with the CN group, hypoperfusion occurred in AD in the bilateral prefrontal cortex, left precuneus and posterior cingulate cortex. Hyperperfusion was also found in the bilateral prefrontal cortex (including the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC) and ACC in subjects with AD. During the memory task performance, the AD group showed significantly greater perfusion/activation than the normal controls in bilateral prefrontal cortex (including the DLPFC and VLPFC), as well as the ACC under both encoding and retrieval tasks.Conclus i on:Hypoperfusion occurred in multiple areas in AD at both resting state and under memory tasks, reflecting perfusion damage in early AD. Meanwhile, hyperperfusion/hyperactivation was also found in bilateral prefrontal cortex in subjects with AD in both resting state and under task performance, suggesting the neurocompensatory response in these areas. ASL and BOLD are comparable in detecting brain hemodynamic changes in AD with 4T MR.更多还原