Probing the Intracellular Environment in Normal Aging Using Magnetic Resonance

使用磁共振探测正常衰老过程中的细胞内环境

• 批准号: 9131605
• 负责人: MALGORZATA MARJANSKA
• 金额: $ 19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9131605
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Biochemistry; Blood; Body Size; Brain; Brain region; Cell Size; Cell physiology; Cells; Cerebral cortex; Chemicals; Choline; Clinic; Clinical; Cognitive aging; Cognitive deficits; Computer software; Coupled; Creatine; Data Analyses; Diffusion; Disease Progression; Early Diagnosis; Elderly; Environment; Extracellular Fluid; Extracellular Space; Glutamates; Goals; Health; Human; Human body; Immune; Individual; Inositol; Intracellular Space; Iron; Lead; Learning; Length; Life; Link; Location; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Modification; Molecular; Molecular Probes; Monitor; N-acetylaspartate; Nerve Degeneration; Neurodegenerative Disorders; Neuroglia; Neurons; Occipital lobe; Organelles; Pattern; Physical Performance; Play; Positron-Emission Tomography; Prefrontal Cortex; Process; Protocols documentation; Psyche structure; Relaxation; Reproducibility; Research; Role; Sensitivity and Specificity; Synapses; System; Techniques; Testing; Therapeutic; Time; Tissues; Translating; Viscosity; Water; Work; age effect; age related; aging brain; base; brain cell; brain metabolism; cell type; cingulate cortex; clinically relevant; cognitive performance; computerized data processing; extracellular; imaging biomarker; meetings; neuroimaging; non-invasive imaging; normal aging; novel; pathological aging; regional difference; research clinical testing; senescence; tool

DESCRIPTION (provided by applicant): This project proposes to identify intracellular molecular probes that are sensitive to changes that take place on the cellular level during aging in the human brain. The cellular changes include shrinkage in cell size, decrease in total dendritic length, and total number of dendritic segments. MR measurement of transverse relaxation (T2) is sensitive to reduction in cell body size, modification in the intracellular macromolecular and organelle composition, and iron content. Another, MR measure, the apparent diffusion coefficients (ADC), is sensitive to decrease in neuronal space and changes in viscosity. Metabolites present in the human brain are predominantly intracellular, and some are cell specific, such as N-acetylaspartate that is located in neurons and myo-inositol located in glia. By measuring the T2 and ADC values of several metabolites, the approach will specifically probe differing cellular and subcellular compartments. The T2 and ADC values of N- acetylaspartate, total creatine, total choline, glutamate and myo-inositol will be measured noninvasively in multiple brain regions that may or may not be affected by aging. One aim is to measure T2 values of those metabolites in three brain regions in young and elderly subjects to determine whether recently found lower T2 values in cognitively normal elderly subjects are more widespread than the occipital cortex. A complementary specific aim is to measure ADC values of the metabolites in the same brain regions. The measurements will be performed at the clinically relevant field strength of 3 T. The acquisition protocols for measuring T2 and ADC values of J-coupled metabolites, such as glutamate and myo-inositol, will be optimized as sub aims. The data processing and analysis will be fully automated using commercially available software. Successful completion of this project will determine whether low T2 and ADC values are widespread in the elder human brain. Additionally, we will learn if the T2 and ADC measurements for metabolites are sensitive and specific to cellular changes that take place in aging. Long term, this proposal has the potential to lead towards the discovery of quantitative, non-invasive, intracellular imaging biomarkers which can play an important role in clinical evaluation for early diagnosis, monitoring of disease progression, and testing of therapeutic approaches for neurodegenerative disorders, such as Alzheimer's disease.

描述（由申请人提供）：本项目旨在鉴定对人脑老化过程中细胞水平发生的变化敏感的细胞内分子探针。细胞变化包括细胞大小的收缩、总树突长度和树突节段总数的减少。横向弛豫（T2）的MR测量对细胞体大小的减小、细胞内大分子和细胞器组成的改变以及铁含量敏感。另一个MR测量，表观扩散系数（ADC），对神经元空间的减少和粘度的变化敏感。存在于人脑中的代谢物主要是细胞内的，并且一些是细胞特异性的，例如位于神经元中的N-乙酰天冬氨酸和位于神经胶质中的肌醇。通过测量几种代谢物的T2和ADC值，该方法将特异性地探测不同的细胞和亚细胞区室。将在可能或可能不受老化影响的多个脑区中无创测量N-乙酰天冬氨酸、总肌酸、总胆碱、谷氨酸和肌醇的T2和ADC值。一个目的是测量年轻和老年受试者三个脑区中这些代谢物的T2值，以确定最近发现的认知正常老年受试者中较低的T2值是否比枕叶皮质更广泛。补充的具体目标是测量相同脑区域中代谢物的ADC值。将在临床相关场强3 T下进行测量。作为子目标，将优化用于测量J-偶联代谢物（如谷氨酸和肌醇）的T2和ADC值的采集方案。数据处理和分析将使用商业软件完全自动化。该项目的成功完成将确定低T2和ADC值是否广泛存在于老年人大脑中。此外，我们将了解代谢物的T2和ADC测量是否对衰老中发生的细胞变化敏感和特异。从长远来看，这一提议有可能导致发现定量的、非侵入性的、细胞内成像生物标志物，这些生物标志物可以在早期诊断的临床评价、疾病进展的监测和神经退行性疾病（如阿尔茨海默病）的治疗方法的测试中发挥重要作用。