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

基本信息

批准号：
8819375
负责人：
MALGORZATA MARJANSKA
金额：
$ 22.8万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8819375
关键词：
Affect Age Aging Alzheimer&apos 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 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 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 neuronal cell body non-invasive imaging normal aging novel pathological aging public health relevance regional difference research clinical testing senescence tool

项目摘要

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）：该项目提议识别对人脑衰老期间细胞水平发生的变化敏感的细胞内分子探针。细胞的变化包括细胞大小的收缩，树突长度的减少和树突段的总数。横向松弛（T2）的MR测量对细胞体大小的减小，细胞内大分子组成和细胞器组成的修饰以及铁含量敏感。另一个MR测量，明显的扩散系数（ADC）对降低神经元空间和粘度的变化敏感。人脑中存在的代谢产物主要是细胞内的，有些是细胞特异性的，例如位于神经元中的神经元和肌醇中的N-乙酰天冬氨酸。通过测量几种代谢产物的T2和ADC值，该方法将特别探测不同的细胞和亚细胞隔室。 N-乙酰天冬氨酸，总肌酸，总胆碱，谷氨酸和肌醇的T2和ADC值将在可能受老化影响或可能不会影响的多个大脑区域中进行无创测量。一个目的是测量年轻和老年受试者三个大脑区域中这些代谢产物的T2值，以确定最近在认知正常的老年受试者中发现T2值较低的T2值比枕骨皮质更广泛。互补的特定目的是测量同一大脑区域中代谢产物的ADC值。测量结果将在3 t的临床相关场强度下进行。用于测量J耦合代谢物（例如谷氨酸和肌醇）的T2和ADC值的采集方案将作为子目标进行优化。数据处理和分析将使用市售软件充分自动化。该项目的成功完成将确定低T2和ADC值在人类大脑中是否普遍存在。此外，我们将学习代谢物的T2和ADC测量是否敏感且特定于衰老中发生的细胞变化。从长远来看，该提案有可能导致发现定量，无创，细胞内成像生物标志物，这些生物标志物可以在早期诊断，监测疾病进展和测试神经退行性疾病的治疗方法（例如阿尔茨海默氏病）中发挥重要作用。