IMAGING

影像学

基本信息

批准号：
7264455
负责人：
Michael A Weiner
金额：
$ 14.93万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7264455
关键词：
Accounting Aging Alzheimer&apos s Disease Anterior Atrophic Autopsy Boxing Brain Brain region COMT gene Catechol O-Methyltransferase Cerebral cortex Cerebrovascular Circulation Clinical dementia rating scale Cognition Cognitive Corpus striatum structure Diagnosis Clinical Trials Diffusion Magnetic Resonance Imaging Disease Elderly Emotional Emotions Enrollment Frontotemporal Dementia Frontotemporal Lobar Degenerations Future Goals Grant Gray unit of radiation dose Hand Hippocampus (Brain)Image Impaired cognition Impairment Lead Lesion Magnetic Resonance Imaging Measurement Measures Medial Modeling N-acetylaspartate Patients Pattern Perfusion Personality Primary Lateral Sclerosis Rate Relative (related person)Resolution Scanning Severity of illness Spin Labels Structure Sum Temporal Lobe Testing Thalamic structure Thick Thinking Ubiquitin apolipoprotein E-4 base cingulate cortex executive function gray matter hippocampal atrophy interest mild neurocognitive impairment morphometry neuroimaging normal aging progressive neurodegeneration tau Proteins white matter

项目摘要

PROVIDED. The overall goals of this project are to determine the changes in the brain that occur in early frontotemporal dementia (FTD)and to use amyotropic lateral sclerosis (ALS)as a model for understanding the earliest manifestation of FTD. Four groups of subjects (20/group) will be studied on a 4 Tesla Bruker/Siemens MRI scanner: (1) patients with early FTD (CDR 0.5),(2) ALS patients with mild personality or executive function impairment, (3) patients with MCI or early AD and (4) cognitively normal age-matched controls. The'following measurements will be obtained: 1) Atrophy patterns in cerebral cortex, using tensor based morphometry, and subcortical structures, including hippocampal subfields, detected with high resolution MRI. 2) Cerebral blood flow in gray matter (GM) and white matter (WM) quantified with arterial spin-labeled perfusion MRI. 3) Integrity of WM tracts thought to be involved in FTD, ALS, and early AD, as measured by fractional anisotrophy (FA)from diffusion tensor imaging (DTI). We will also assess progressive neurodegeneration in FTD and ALS relative to patients with MCI or early AD using longitudinal MRI, perfusion, and DTI measurements. These goals Will be accomplished by testing the following hypotheses: 1) ALS and early FTD show GM loss and reduced perfusion in the frontal insular and anterior cingulate cortex compared to controls. There will be reduced FA for the following WM tracts: uncinate, thalamic-frontal, striatal frontal, anterior callosm, superior longitudinal fasciculus and cingulum. The posterior callosum and Meyer's loop will serve as control tracts because they are not expected to change with these diseases. 2) ALS and FTD involve the frontal insular and anterior cingulate cortex compared to amnestic MCI/early AD, who will show greater hippocampal atrophy, especially in posterior hippocampus, and reduced FA in posterior cingulum and posterior callosal tracts. Differential effects between ALS and FTD versus MCI/early AD will be explored in hippocampal subfield thickness. 3) Rates of change in FTD and ALS involving frontal insular and anterior cingulate cortex is greater than that compared to 20 amnestic MCI/early AD and 20 controls. MCI/early AD show greater hippocampal atrophy and reduced FA in cingulum than FTD/ALS longitudinally. 4) We will further explore our preliminary findings of greater medial temporal lobe atrophy in ubiquitin-positive than tau-positive patients, and greater general cortical thinning, caudate atrophy, and WM lesions in tau-positive than ubiquitin-positive patients. The results of this project will provide new information concerning brain changes that occur in early FTD, and will help distinguish early FTD from early AD. These results should be directly applicable to future clinical trials and diagnosis of subjects with cognitive impairments.

假如。该项目的总体目标是确定早期额颞叶发生的大脑变化痴呆（FTD），并使用肌动性侧面硬化症（ALS）作为最早理解的模型 FTD的表现。将在4个Tesla Bruker/Siemens MRI上研究四组受试者（20/组）扫描仪：（1）早期FTD患者（CDR 0.5），（2）ALS患者的性格轻度或执行功能受损，（3）MCI或早期AD的患者以及（4）认知正常的年龄匹配对照。下列将获得测量值：1）使用基于张量的形态计量学和大脑皮层中的萎缩模式和皮层结构，包括海马子场，用高分辨率MRI检测到。 2）脑血流用动脉自旋标记的灌注MRI定量的灰质（GM）和白质（WM）。 3）WM的完整性根据分数各向异性（FA）的测量，认为与FTD，ALS和早期AD有关的区域涉及。扩散张量成像（DTI）。我们还将评估FTD和ALS中的进行性神经退行性相对于使用纵向MRI，灌注和DTI测量值的MCI或早期AD的患者。这些目标将是通过检验以下假设来完成： 1）ALS和早期FTD表现出GM损失，并减少了额叶和前扣带回皮质的灌注与对照组相比。以下WM区域将减少FA：uncinate，thalamic-frontal，纹状体额叶，前call骨，上等纵向筋膜和cing。后callos和迈耶的循环将作为控制区，因为预计它们不会随着这些疾病而改变。 2）ALS和FTD涉及额叶岛的额叶和前扣带回皮层，而Amnestic MCI/早期AD（谁）将显示出更大的海马萎缩，尤其是在后海马中，并减少后FA 扣带和后callosal区。 ALS和FTD与MCI/早期广告之间的差异效应将是在海马子场厚度中探索。 3）FTD和ALS的变化发生率涉及额叶岛额和前扣带回皮层的变化率大于相比之下，有20个敏感的MCI/早期AD和20个对照。 MCI/早期广告显示出更大的海马萎缩和与FTD/ALS纵向相比，扣带的FA降低。 4）我们将进一步探讨泛素阳性中更大的内侧颞叶萎缩的初步发现 tau阳性患者和tau阳性中的一般皮质稀疏，尾状萎缩和WM病变比泛素阳性患者。该项目的结果将提供有关大脑变化的新信息发生在FTD早期，将有助于将早期FTD与早期AD区分开。这些结果应直接适用对未来的临床试验和认知障碍受试者的诊断。