Optimizing MRS to Detect Mild Cognitive Impairment

描述（由申请人提供）：拟议研究的长期目标是开发新型磁共振波谱（MRS）数据采集技术，能够识别和监测轻度认知障碍（MCI）患者。MCI通常被定义为介于正常衰老和痴呆之间的过渡状态，目前通过广泛的神经心理学测试来诊断。这种过渡状态的一个标志性特征是大脑生化的早期变化，这可以通过1H MRS技术无创地检测到。这些技术也有可能提供更快、更有效的MCI治疗监测和记忆损伤症状发作前的疾病检测。我们将仔细优化1H MRS数据采集技术，以准确测量两种代谢物的浓度，这两种代谢物的浓度在MCI中发生了变化：肌醇(mI) -胶质细胞数量的标志-和n -乙酰天冬氨酸(NAA)-神经元完整性的标志。通过模拟，我们将调整脉冲序列以获得简化的体内光谱，通过过滤掉在疾病中报告不变的代谢物，同时保留光谱中感兴趣的两种代谢物。我们假设，在通过拟合量化数据时，更简单的光谱将留下更少的误差空间，因此可以提高测量的可重复性，并检测到可归因于疾病或治疗的较小变化。我们将在3T临床扫描仪上实现最成功的脉冲序列，并进行体外实验来验证改进的代谢物测量再现性。通过GE全球研究中心和奥尔巴尼医学中心的全面合作，我们还将比较新开发的方法在将MCI患者队列与年龄匹配的正常对照队列分开时的敏感性。为精确检测NAA和mI而调整脉冲序列可以显著改善MCI的诊断和监测。由于这项研究，可以降低疾病诊断成本，以及更有效的疾病监测，从而降低涉及MCI患者的临床试验成本。此外，该研究的直接结果，即代谢物定制脉冲序列，有可能有利于检测和监测其他疾病，其中报告了NAA或mI的上调或下调，包括多发性硬化症，急性脑损伤或肝性脑病。

DESCRIPTION (provided by applicant): The long term goal of the proposed research is to develop novel magnetic resonance spectroscopy (MRS) data acquisition techniques, capable to identify and monitor patients affected by mild cognitive impairment (MCI). MCI is generally defined as a transitional state between normal aging and dementia, and is currently diagnosed through extensive neuropsychological testing. A hallmark characteristic of this transitional state is an early change in the brain biochemistry, which can be non-invasively detected through 1H MRS techniques. Such techniques also have the potential to provide faster, more efficient treatment monitoring in MCI and disease detection prior to the onset of memory impairment symptoms. We will carefully optimize 1H MRS data acquisition techniques, to accurately measure two metabolites whose concentrations are reported to change in MCI: myo-Inositol (mI) -a marker of glial cell numbers- and N-acetyl aspartate (NAA)-a marker of neuronal integrity. Through simulations, we will tailor pulse sequences to acquire simplified in vivo spectra, by filtering out metabolites reported to be constant in the disease, while maintaining the two metabolites of interest in the spectrum. We hypothesize that simpler spectra will leave less room for error while quantifying data through fitting, therefore allowing increased measurement reproducibility and the detection of smaller changes that can be attributed to disease or treatment. We will implement the most successful pulse sequences on a 3T clinical scanner, and perform in vitro experiments to validate the improved measurement reproducibility for the metabolites of interest. Through a comprehensive partnership between GE Global Research and Albany Medical Center, we will also compare the sensitivities of the newly developed methods in separating a cohort of MCI patients from a cohort of age-matched normal controls. Tailoring pulse sequences for accurate NAA and mI detection may significantly improving MCI diagnosis and monitoring. Decreased disease diagnosis costs, as well as more efficient monitoring of disease, leading to lower clinical trial costs involving MCI patients, can be obtained as a consequence of this study. Moreover, the direct results of this study, i.e., metabolite tailored pulse sequences, have the potential to benefit detection and monitoring of other diseases, in which up- or down- regulation of NAA or mI are reported including multiple sclerosis, acute brain injury, or hepatic encephalopathy.