Examination Of Natural History & Therapy Of MS Using MRI

自然历史检验

• 批准号: 6842529
• 负责人: Henry F McFarland
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6842529
• 关键词: T lymphocyte; bioimaging /biomedical imaging; clinical research; clinical trials; contrast media; diagnosis quality /standard; histopathology; human subject; human therapy evaluation; immunotherapy; insulinlike growth factor; interferon beta; longitudinal human study; magnetic resonance imaging; multiple sclerosis; myelin basic proteins; nervous system disorder chemotherapy; oligodendroglia; outcomes research; pathologic process; prognosis; protein structure function; relapse /recurrence; remission /regression; spectrometry

Over the past decade, the use of MRI to study multiple sclerosis (MS) has lead to substantial advances in understanding the disease process. Disease activity as detected by new lesions on T2-weighted images or contrast-enhancing lesions on T1-weighted images have established that the level of activity seen on MRI is considerably greater than that seen clinically. Further, MRI has become an important and powerful tool for the assessment of the effect of new experimental therapies in MS. Recent work continues to focus on defining the natural history of the disease using MRI and in examining the effect of experimental treatments on disease activity as measured by MRI. Specifically, recent studies have focused on the following; 1. Defining the natural history of the MS lesion using both conventional imaging as well as advanced imaging techniques including magnetization transfer imaging, proton spectroscopy and measures of T1 hypointensities. 2. Defining the level of new disease activity seen in patients who are early in the relapsing remitting course of the disease? 3. Defining the long term effect of treatment with interferon beta 1b on disease activity as measured by MRI. 4. Examination of the effect of new therapies on disease activity in MS as measured by MRI. Serial studies of patients with early, relapsing-remitting MS using contrast enhanced MRI have shown that nearly two thirds of the patients have evidence of active new lesion formation. Recent studies in the NIB have examined the evolution of the MS lesion using imaging techniques that measure tissue destruction such as lesion load on T2-weighted images or T1 hypointensities, alterations in magnetization transfer ratios and alterations seen using proton spectroscopy. Findings have demonstrated that progression of disease as measured by overall burden of disease increases during the early phase of the disease. However, only a modest correlation can be found between the frequency of acute enhancing lesions and the level of accumulated disease burden suggesting that distinct mechanisms may contribute to lesion progression. In addition, some patients showing a marked reduction in new disease activity as measured by contrast enhancing lesions continue to have progression of disease as measured by T2 lesion load or T1 hypointensities. Recent results indicate that the extent of tissue damage varies in acute contrast enhancing lesions. Recent evidence has shown that the persistence of a lesion as a T1 hypointensities is related to the duration of contrast enhancement. Those lesions that enhance for longer than 2 months have a greater chance of developing into a persistent T1 hypointensity indicating tissue damage. This evidence indicates that qualitative differences exist in contrast enhancing lesions The results indicate that mechanisms of tissue destruction may be, in part distinguished from the events that initiate the lesion. Attention continues to focus on the value of MRI as a predictor of future clinical course and disability. A major effort has been made over the past year to reevaluate all patients seen by the NIB between 8 and 5 years previously. Results of these efforts indicate that the magnitude of disease as seen on MRI early in the disease course does have some ability to predict the level of clinical disease. Consistent with the studies of T1 hypointensities, the results of the follow-up study indicate that while contrast enhancing lesions are related to clinical disease early in the disease course, measures that reflect destruction such as T1 hypointensities correlate with clinical disability at follow-up. Findings derived from this retrospective evaluation should have substantial influence on our understanding of MRI as a possible surrogate for clinical disability.

在过去的十年中，使用MRI来研究多发性硬化症（MS）已导致理解疾病过程的重大进展。新病变在T2加权图像上发现的疾病活性或T1加权图像上的对比度增强病变已经确定，在MRI上看到的活性水平比临床上所见。此外，MRI已成为评估MS新实验疗法效果的重要和强大的工具。最近的工作继续专注于使用MRI定义疾病的自然历史，并在检查实验治疗对MRI衡量的疾病活动的影响时。具体而言，最近的研究集中在以下方面。 1。使用常规成像和先进的成像技术定义MS病变的自然历史，包括磁化转移成像，质子光谱和T1低敏感性的测量。 2。定义在疾病复发过程中早期的患者中看到的新疾病活动水平？ 3。定义干扰素β1B治疗对MRI测量的疾病活动的长期影响。 4。通过MRI测量的新疗法对MS疾病活动的影响的检查。使用对比度增强的MRI对早期复发的MS患者的序列研究表明，近三分之二的患者有活跃的新病变形成的证据。 NIB中的最新研究使用了测量组织破坏的成像技术（例如在T2加权图像上的病变负载）或T1低敏感性，磁化转移比例的改变以及使用质子光谱观察到的改变。研究结果表明，疾病的总负担在疾病早期阶段的总体负担增加了疾病的进展。但是，在急性增强病变的频率与累积疾病负担水平之间只能发现适度的相关性，这表明不同的机制可能有助于病变的进展。此外，通过T2病变负荷或T1低敏度测量的对比性增强病变测量，一些患者表现出明显减少的新疾病活性降低。最近的结果表明，急性对比度增强病变的组织损伤程度有所不同。最近的证据表明，病变作为T1低敏感性的持久性与对比度增强的持续时间有关。增强超过2个月的病变有更大的机会发展成持续的T1高压，表明组织损伤。该证据表明，定性差异存在与增强病变的对比，结果表明，组织破坏的机制可能部分与启动病变的事件区分开。注意力继续关注MRI的价值，作为未来临床过程和残疾的预测指标。在过去的一年中，已经做出了重大努力，以重新评估8至5年前的所有患者。这些努力的结果表明，疾病早期在MRI中看到的疾病的大小确实具有预测临床疾病水平的能力。与对T1高敏度的研究一致，后续研究的结果表明，虽然疾病早期的对比度增强病变与临床疾病有关，但反映了破坏性的措施，例如T1的低敏度与随访时的临床残疾相关。从这种回顾性评估中得出的结果应该对我们对MRI的理解有重大影响，因为MRI可能是临床障碍的替代物。