Serial Brain 3D 1H MR Spectroscopy in Multiple Sclerosis

串行脑 3D 1H 磁共振波谱在多发性硬化症中的应用

• 批准号: 6970076
• 负责人: ODED GONEN
• 金额: $ 53.95万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6970076
• 关键词: bioimaging /biomedical imaging; brain disorder diagnosis; brain imaging /visualization /scanning; brain metabolism; clinical research; diagnosis design /evaluation; gray matter; human subject; multiple sclerosis; nuclear magnetic resonance spectroscopy; patient oriented research; prognosis; three dimensional imaging /topography; white matter

Clinical T2 and contrast-enhanced Tl-weighted magnetic resonance imaging (MRI) have become the diagnostic modalities of choice in the evaluation of multiple sclerosis (MS) due to their sensitivity to acute, often subclinical events in the brain and their ability to measure the accumulation of the disease over time. MRI, however, lacks specificity, in that to date, there are conflicting reports concerning the number and volume of these lesions, "the load of the disease," and the associated neurological deficits. Furthermore, clinical MRI is completely blind to occult white matter (WM) and most gray matter (GM) pathology. The need for more reliable surrogate markers frequently leads to proton magnetic resonance spectroscopy 1HMRS being used to probe the underlying metabolism of normal appearing WM (NAWM) and the lesions in it. Since MS pathogenesis starts on molecular cellular levels, we propose to use state of the art, short echotime, three-dimensional high-spatial resolution local and global 1H-MRS methods to examine three hypotheses: HI: That MS lesions develop in WM regions which are already metabolically abnormal; H2: Abnormal metabolic activity persists in NAWM and lesions even absent Gd-enhancement (the current marker of "activity"); and H3: That global whole-brain quantification of the decline rate of the neuronal cell marker N-acetylaspartate (NAA) reflects the aggressiveness of a patient's disease, and therefore, could forecast its future course in that individual. These hypotheses will be tested by following a cohort of 25 relapsingremitting (RR) MS patients and 25 matched controls, for 5 years, with three Specific Aims: Specific Aim 1 is to perform longitudinal follow-up of the overall metabolites levels in the NAWM to establish markers for current MRI-occult disease activity. Specific Aim 2 is to follow localized metabolism in NAWM to determine what focal changes preceded lesion formation and determine those lesions' outcome - to repair or become chronic. Specific Aim 3 is to correlate the NAA levels of the whole brain and its WM and GM fractions with the patients' clinical deficits to establish the NAA as a forecaster of disease severity and future course. The health relatedness of this study is its potential to establish, quantify and validate non-invasive radiological metabolic surrogate markers of RR MS progression that will enable us to: (i) Gauge current level of disease activity, thereby, (ii) increase our capability to forecast its future course for these (young) patients; and consequently (iii) lead to improved monitoring of response in drug and treatment trials.

临床T2和对比增强tl加权磁共振成像（MRI）已成为评估多发性硬化症（MS）的首选诊断方式，因为它们对大脑中急性、通常是亚临床事件的敏感性，以及它们随时间推移测量疾病积累的能力。然而，MRI缺乏特异性，迄今为止，关于这些病变的数量和体积、“疾病负荷”以及相关的神经功能缺陷，存在相互矛盾的报道。此外，临床MRI对隐匿性白质（WM）和大多数灰质（GM）病理完全视而不见。对更可靠的替代标记物的需求经常导致质子磁共振波谱（hmrs）被用于探测正常外观WM （NAWM）及其病变的潜在代谢。由于MS发病机制始于分子细胞水平，我们建议使用最先进的、短回声时间、三维高空间分辨率的局部和全局1H-MRS方法来检验三个假设：HI: MS病变发生在已经代谢异常的WM区域；H2: NAWM和病变中持续存在异常代谢活性，即使没有gd增强（目前的“活性”标志）；和H3：神经元细胞标记物n -乙酰天冬氨酸（NAA）下降率的全球全脑量化反映了患者疾病的侵袭性，因此可以预测该个体的未来病程。这些假设将通过跟踪25名复发缓解型（RR） MS患者和25名匹配对照者的队列进行验证，为期5年，有三个特定目的：特定目的1是对NAWM中总体代谢物水平进行纵向随访，以建立当前mri隐匿性疾病活动的标志物。特异性目标2是跟踪NAWM的局部代谢，以确定病变形成之前的局灶性变化，并确定这些病变的结果——是修复还是变成慢性病变。具体目标3是将全脑及其WM和GM部分的NAA水平与患者的临床缺陷联系起来，以建立NAA作为疾病严重程度和未来病程的预测指标。该研究的健康相关性在于其建立、量化和验证RR MS进展的非侵入性放射代谢替代标志物的潜力，这将使我们能够：(i)衡量当前的疾病活动水平，从而（ii）提高我们预测这些（年轻）患者未来病程的能力；因此（iii）可以改善对药物和治疗试验反应的监测。