BRAIN AGING--EVALUATION BY MR SPECTROSCOPIC IMAGING

由于寿命的延长，患神经退行性脑疾病的风险人数正在上升。衰弱的脑部疾病通常与神经元丢失有关。然而，如果神经元也因正常衰老而丢失，这仍然是有争议的。由于目前还没有测量体内神经元密度的诊断技术，也不可能开发出一种早期区分正常脑老化和神经退行性疾病的诊断工具，我们建议使用一种非侵入性的在体1H磁共振波谱成像技术MRSI，它可以测量大脑中神经元标志物N-乙酰天冬氨酸(NAA)和总胆碱(Cho)的浓度，后者在胶质细胞中比在神经元中更丰富。首先，我们建议使用高分辨率的多层磁共振成像技术，在健康的年轻人和老年人之间建立体内NAA和CHO浓度的差异。需要检验的假说是：1.老年脑内选择性脑区NAA浓度低于青年脑，胆碱浓度高于青年脑。较低的NAA浓度将与这些区域较低的神经元密度相一致，较高的胆碱浓度将与较高的胶质细胞密度相一致。2.特定脑区的NAA浓度将与与这些脑区的激活相关的神经心理测试的分数相关。其具体目标是：1.测量4张幕上脑片中多个灰质和白质脑区NAA和总胆碱的绝对浓度，分辨率为0.8毫升。b)确定显示年轻和老年大脑代谢差异的脑区。2.对特定神经心理测验得分与皮质NAA浓度进行相关分析。这项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(通过纵向研究和与定量神经病理学方法的比较)，以监测有发生神经退行性疾病的风险的患者，并在治疗可能成功的早期阶段检测神经退行性疾病。

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.