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: 7658167
• 负责人: ODED GONEN
• 金额: $ 58.92万
• 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 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658167
• 关键词: 3-Dimensional; Acute; Address; Affect; Age; Arts; Atrophic; Blood - brain barrier anatomy; Brain; Cells; Choline; Chronic; Clinical; Clinical Trials; Clinical/Radiologic; Cognitive deficits; Conflict (Psychology); Corpus Callosum; Creatine; Development; Diagnostic; Disease; Evaluation; Event; Evolution; Feedback; Fingerprint; Future; Gender; Health; Histocompatibility Testing; Image; Impaired cognition; Impairment; Individual; Injury; Inositol; Lead; Lesion; Link; Lipids; Location; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolic; Metabolism; Methods; Metric; Microscopic; Modality; Molecular; Monitor; Motor; Multiple Sclerosis; Multiple Sclerosis Lesions; N-acetylaspartate; Nature; Neurologic; Neurons; Newly Diagnosed; Outcome; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Protons; Recording of previous events; Relapse; Relative (related person); Reporting; Research Personnel; Resolution; Severity of illness; Specificity; Surrogate Markers; Symptoms; Techniques; Testing; Time; Tissues; Translating; Virulence; Weight; activity marker; analog; blind; cohort; cranium; disability; follow-up; gray matter; improved; interest; nervous system disorder; novel; repaired; response; tool; trait; treatment trial; 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 T1 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，因为它们对大脑中的急性、通常是亚临床事件敏感，并且能够测量疾病随着时间的推移而积累。然而，MRI 缺乏特异性，迄今为止，关于这些病变的数量和体积、“疾病的负荷”以及相关的神经功能缺损的报告相互矛盾。此外，临床 MRI 对隐匿性白质 (WM) 和大多数灰质 (GM) 病理情况完全视而不见。由于需要更可靠的替代标记，质子磁共振波谱 1HMRS 经常被用来探测正常 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，因此我们建议使用最先进的、短回波时间、三维高空间分辨率局部和全局 1H-MRS 方法来检查三个假设： HI：MS 病变发生在 WM 区域，其中代谢已经异常； H2：即使没有 Gd 增强（当前的“活性”标记），NAWM 和病变中仍然存在异常代谢活动； 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未来的病程。这些假设将通过对 25 名复发性多发性硬化症 (RR) 患者和 25 名匹配对照者进行为期 5 年的跟踪测试，并具有三个具体目标：具体目标 1 是对 NAWM 中的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记。 具体目标 2 是跟踪 NAWM 中的局部代谢，以确定病变形成之前的病灶变化，并确定这些病变的结果 - 修复或变成慢性。 具体目标 3 是将全脑及其 WM 和 GM 分数的 NAA 水平与患者的临床缺陷相关联，以将 NAA 确立为疾病严重程度和未来病程的预测因子。这项研究与健康的相关性在于它有可能建立、量化和验证 RR MS 进展的非侵入性放射代谢替代标记，这将使我们能够：(i) 衡量当前的疾病活动水平，从而 (ii) 提高我们的能力预测这些（年轻）患者未来的病程；从而 (iii) 改善对药物和治疗试验反应的监测。