Histologically validated structural MR imaging biomarkers for Alzheimers Disease

经组织学验证的阿尔茨海默病结构磁共振成像生物标志物

• 批准号: 7976213
• 负责人: Jonathan J. Wisco
• 金额: $ 14.68万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7976213
• 关键词: Affect; Age; Agreement; Alzheimer' s Disease; Anisotropy; Anterior; Anterior Nuclear Group; Area; Atlases; Attenuated; Autopsy; Biological Markers; Brain; Clinical; Data Set; Degenerative Disorder; Dementia; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Exhibits; Fiber; Fingerprint; Frequencies; Functional disorder; Hippocampus (Brain); Histologic; Human; Image; Imaging Techniques; Impaired cognition; Individual; Internal Capsule; Left; Limb structure; Limbic System; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Methods; Metric; Mind; Monitor; Morphology; Neurofibrillary Tangles; Neurons; Onset of illness; Outcome Measure; Parahippocampal Gyrus; Parietal Lobe; Pathology; Patient Care; Patients; Pattern; Perforant Pathway; Physicians; Public Health; Radial; Resolution; Scanning; Senile Plaques; Short-Term Memory; Side; Specimen; Staging; Structure; Structure of superior temporal sulcus; Techniques; Temporal Lobe; Thick; Time; Tissues; Validation; Weight; Work; aged; brain tissue; cingulate gyrus; density; entorhinal cortex; experience; frontal lobe; gray matter; hippocampal atrophy; human very old age (85+); improved; in vivo; innovation; long term memory; male; mild neurocognitive impairment; neurochemistry; normal aging; outcome forecast; pre-clinical; primary outcome; prognostic; reconstruction; tau Proteins; tissue processing; tool; white matter; white matter change

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is one of the most common and devastating degenerative diseases. Dementia doubles in frequency every five years after age 60, afflicting 1% of those aged 60-64 but rising to 30-40% percent of those 85 years and older. Examination at autopsy remains the only definitive method to diagnosis AD, leaving no reliable method during a patient's lifetime to know the onset of the disease, its progression or prognosis. Studies using Magnetic Resonance Imaging (MRI) have detected some areas of the brain that show gray matter and/or white matter structural changes in morphology and/or integrity, but none of these studies have been validated using corresponding histological analysis. Establishing a reliable imaging biomarker for the disease that is correlated with underlying pathology could provide a means by which physicians can provide a clear diagnosis and monitor micro and macrostructural changes in the brain that are associated with the different stages of dementia. In essence, a validated biomarker could be used as a tool to identify a "fingerprint" for the different stages of cognitive decline and help physicians find the appropriate treatment options for their afflicted patients. In this proposal, we will develop a histologically validated imaging biomarker for T1-weighted and Diffusion Tensor Imaging (DTI) of the hippocampus, entorhinal cortex of the parahippocampal gyrus, and cingulate gyrus from cadaveric control brain tissue and autopsy brain specimens. In general, this is an important innovation for determining the ground truth for imaging studies and for characterizing the true underlying cause of gray and white matter changes seen in AD. PUBLIC HEALTH RELEVANCE: Alzheimer's Disease (AD) looms as the greatest threat to public health in the first half of the 21st Century, yet its definitive diagnosis remains limited autopsy examination. Using structural imaging and corresponding histological validation, this project will construct a validated imaging biomarker of the hippocampus, entorhinal cortex of the parahippocampal gyrus, and cingulate gyrus, all areas of the brain that are affected pathologically in the earliest stages of Alzheimer's disease (AD) dementia and throughout the course of the disease. We expect that the validated biomarker created through this project will assist with the diagnosis and prognosis of AD, thereby facilitating more treatment options for patients who are afflicted.

描述（由申请人提供）：阿尔茨海默氏病（AD）是最常见和毁灭性的退行性疾病之一。痴呆症在60岁以后每五岁五岁每五岁一次，年龄在60-64岁的人中有1％，但在85岁及以上的年龄段中却增加到30-40％。尸检的检查仍然是诊断AD的唯一明确方法，在患者一生中没有可靠的方法来了解疾病的发作，其进展或预后。使用磁共振成像（MRI）的研究检测到了大脑的某些区域，这些区域表现出灰质和/或白质结构的形态和/或完整性的结构变化，但是这些研究都没有使用相应的组织学分析来验证。建立与潜在病理相关的疾病的可靠成像生物标志物可以提供一种手段，医生可以在大脑中提供明确的诊断并监测与痴呆症不同阶段有关的大脑中的微观和宏观结构变化。从本质上讲，经过验证的生物标志物可以用作确定认知能力下降的不同阶段的“指纹”工具，并帮助医生为患病患者找到适当的治疗选择。在此提案中，我们将开发一种经过组织学验证的成像生物标志物，用于用于T1加权和扩散张量张量成像（DTI），海马，帕拉希公水回的内嗅皮层，以及从尸体控制脑组织和自动性脑脑标志物中扣紧回去的回去。通常，这是确定成像研究的基础真理以及表征AD中看到的灰色和白质变化的真正根本原因的重要创新。 公共卫生相关性：阿尔茨海默氏病（AD）笼罩着21世纪上半叶对公共卫生的最大威胁，但其明确的诊断仍然有限。使用结构成像和相应的组织学验证，该项目将构建一个经过验证的成像生物标志物，海马，帕拉希波卡宫帕拉希波卡宫的肠系膜皮层以及扣带回的回旋，这是大脑的所有领域，这些区域在病理上受到病理的所有阶段。我们预计，通过该项目创建的经过验证的生物标志物将有助于AD的诊断和预后，从而促进患病患者的更多治疗选择。