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，能够识别和监测受轻度认知障碍（MCI）影响的患者。 MCI 通常被定义为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进行诊断。这种过渡状态的一个标志特征是大脑生物化学的早期变化，可以通过 1H MRS 技术进行非侵入性检测。此类技术还有可能在记忆障碍症状出现之前提供更快、更有效的 MCI 治疗监测和疾病检测。我们将仔细优化 1H MRS 数据采集技术，以准确测量据报道其浓度在 MCI 中发生变化的两种代谢物：肌醇 (mL)（神经胶质细胞数量的标记）和 N-乙酰天冬氨酸 (NAA)（神经元完整性的标记）。通过模拟，我们将通过过滤掉据报道在疾病中恒定的代谢物，同时保留光谱中感兴趣的两种代谢物，定制脉冲序列以获得简化的体内光谱。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再现性并检测可归因于疾病或治疗的较小变化。我们将在 3T 临床扫描仪上实施最成功的脉冲序列，并进行体外实验以验证感兴趣代谢物的测量重现性的改进。通过 GE 全球研究中心和奥尔巴尼医学中心之间的全面合作，我们还将比较新开发的方法将一组 MCI 患者与一组年龄匹配的正常对照分开的敏感性。定制脉冲序列以实现准确的 NAA 和 mI 检测可能会显着改善 MCI 诊断和监测。这项研究的结果是可以降低疾病诊断成本以及更有效地监测疾病，从而降低涉及 MCI 患者的临床试验成本。此外，这项研究的直接结果，即代谢物定制脉冲序列，有可能有益于其他疾病的检测和监测，其中报道了 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.