BRAIN AGING--EVALUATION BY MR SPECTROSCOPIC IMAGING

脑老化——通过磁共振光谱成像进行评估

• 批准号: 6012385
• 负责人: ALENA HORSKA
• 金额: $ 8.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6012385
• 关键词: Alzheimer's disease; age difference; aging; aspartate; bioimaging /biomedical imaging; biomarker; brain disorder diagnosis; brain electrical activity; brain mapping; brain metabolism; choline; clinical research; diagnosis design /evaluation; glia; human middle age (35-64); human old age (65+); human subject; magnetic resonance imaging; neural degeneration; neuropsychological tests; neuropsychology; periaqueductal gray matter; young adult human (21-34)

Due to increased longevity, the number of people at risk for neurodegenerative brain disease is rising. Debilitating brain diseases are generally associated with neuronal loss. However, it remains controversial if neurons are also lost due to normal aging alone. Since there is no diagnostic technique to measure neuronal density in vivo, early differentiation between normal brain aging and a neurodegenerative disease is not possible To develop a diagnostic tool, we propose using a non-invasive technique of in vivo 1H magnetic resonance spectroscopic imaging, MRSI, which can measure brain concentrations of neuronal marker, N-acetyl aspartate (NAA) and total choline (Cho), which is more abundant in glial cells than in neurons. Initially, we propose to establish in vivo differences in brain concentrations of NAA and Cho between healthy young and aged brain, using high resolution, multi-slice MRSI. The hypotheses to be tested, are: 1. In the aged brain, the NAA concentration in selective brain regions will be lower and choline concentration will be higher than in the young brain. Lower NAA concentration will be consistent with lower neuronal density in those regions and higher choline concentration will be consistent with higher density of glial cells. 2. The NAA concentrations in specific brain regions will correlate with scores of neuropsychological tests that are associated with activation of these brain regions. The specific aims are: 1.a) To measure absolute concentrations of NAA and total choline in multiple gray and white matter brain regions in four supratentorial brain slices, with the resolution of 0.8 ml. b) To identify brain regions that show metabolic differences between young and aged brain. 2. To perform a correlation analysis between specific neuropsychological test scores and cortical NAA concentrations. The study will be performed in two groups of subjects: healthy young (20-40 years old) and healthy old adults (65 years and older). The long-term goal of our research is development and validation of 1H MRSI (by longitudinal studies and comparison with methods of quantitative neuropathology) for monitoring of patients who are at risk for developing neurodegenerative disease and for detection of neurodegenerative diseases at an early stage, at a time, when treatment may be successful.

由于寿命的延长，患有神经退行性脑部疾病的风险人数正在增加。 衰弱性脑部疾病通常与神经元损失有关。 然而，神经元是否仅因正常衰老而丢失仍存在争议。 由于没有测量体内神经元密度的诊断技术，因此不可能早期区分正常大脑衰老和神经退行性疾病。为了开发诊断工具，我们建议使用体内 1H 磁共振波谱成像 (MRSI) 的非侵入性技术，该技术可以测量神经元标记物、N-乙酰天冬氨酸 (NAA) 和总胆碱的大脑浓度 (Cho)，在神经胶质细胞中比在神经元中更丰富。 最初，我们建议使用高分辨率、多切片 MRSI 确定健康年轻人和老年人大脑中 NAA 和 Cho 浓度的体内差异。要检验的假设是： 1. 在老年大脑中，选择性大脑区域的 NAA 浓度将低于年轻大脑，而胆碱浓度将高于年轻大脑。较低的 NAA 浓度将与这些区域中较低的神经元密度一致，而较高的胆碱浓度将与较高的神经胶质细胞密度一致。 2. 特定大脑区域的 NAA 浓度将与与这些大脑区域的激活相关的神经心理学测试分数相关。具体目标是： 1.a) 测量四张幕上脑切片中多个灰质和白质脑区的 NAA 和总胆碱的绝对浓度，分辨率为 0.8 ml。 b) 识别年轻和年老大脑之间表现出代谢差异的大脑区域。 2.进行特定神经心理学测试分数与皮质NAA浓度之间的相关性分析。该研究将在两组受试者中进行：健康年轻人（20-40 岁）和健康老年人（65 岁及以上）。我们研究的长期目标是开发和验证 1H MRSI（通过纵向研究并与定量神经病理学方法进行比较），用于监测有患神经退行性疾病风险的患者，并在治疗可能成功的早期阶段检测神经退行性疾病。