Examination Of Natural History And Therapy Of Multiple Sclerosis Using MRI

使用 MRI 检查多发性硬化症的自然史和治疗

• 批准号: 7594666
• 负责人: Henry F McFarland
• 金额: $ 113.58万
• 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/7594666
• 关键词: Acute; Acute Disease; Appearance; Autoimmune Diseases; Clinical; Clinical Trials; Collaborations; Daclizumab; Data Collection; Depth; Diffusion weighted imaging; Disease; Effectiveness; Enhancing Lesion; Event; Evolution; Image; Imaging Techniques; Inflammation; Inflammatory; Interferon-beta; Investigational Therapies; Lead; Lesion; Magnetic Resonance Imaging; Measures; Motor; Motor Cortex; Multiple Sclerosis; Multiple Sclerosis Lesions; Natural History; Neuraxis; Outcome; Outcome Measure; Patients; Phase; Prefrontal Cortex; Process; Protons; Relapse; Relapsing-Remitting Multiple Sclerosis; Research Personnel; Sample Size; Spectrum Analysis; Staging; Testing; Thalamic structure; Tissues; Weight; Work; cohort; disability; disease natural history; gray matter; medical schools; tool; white matter

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. Examining the evidence of involvement of gray matter in the disease process 4. Examining 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. Studies in the NIB have shown that the evolution of the MS lesion using imaging techniques that measure tissue destruction such as T1 hypointensities and alterations in magnetization transfer ratios is variable suggesting that distinct mechanisms may contribute to lesion progression. 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. In addition to the studies of the natural history of the acute lesion in MS, the usefulness of T1 hypointensities as an outcome measure in clinical trials has also been examined and the large data collection available in the NDS has been used to estimate sample sizes needed for clinical trials. Recent studies have begun to examine the degree to which MRI can demonstrate tissue damage in either the deep gray matter or the cortex in patients with MS. Pathological studies have indicated that involvement of gray matter is not uncommon although the pathological appearance differs from that in white matter in that there is less inflammation. The demonstration of damage in gray matter using MRI has been largely unsuccessful. Studies in the NDS have now shown that several imaging approaches can be used to reproducibly demonstrate lesions in the cortex. Further, in collaboration with investigators at Harvard School of Medicine, significant thinning of the cortex, especially the prefrontal cortex and motor cortex is seen in patients even those early in the disease process. A correlation with clinical motor function also has been seen indicating that the cortical involvement may by one component of the clinical disability in MS. Damage to deep gray matter has also been demonstrated using regional MTR analysis. In addition diffusion weighted imaging has been used to study involvement of deep gray matter especially the thalamus. Finally, MRI continues to be an important part of clinical trials in the NIB. Studies of daclizumab using contrast enhancing lesions as the primary outcome in patients who have failed conventional therapy with interferon beta have successfully demonstrated the effectiveness of this therapy. A current study is examining the value of the therapy as an initial treatment in a cohort of patients. The findings from the NDS studies have now resulted in multicenter phase II testing the therapy.

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。检查灰质参与疾病过程的证据4。检查MRI测量的新疗法对MS疾病活动的影响。 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中的研究表明，使用成像技术的MS病变的演变，这些技术测量了组织破坏（例如T1的低敏度）和磁化转移比的变化，这表明不同的机制可能有助于病变的进展。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，对比增强病变存在定性差异。结果表明，组织破坏的机制可能是与引发病变的事件区分开的。除了研究MS急性病变的自然史外，还研究了T1低敏度作为临床试验中的结果指标的有用性，并且使用NDS中可用的大量数据收集用于估计临床试验所需的样本大小。 最近的研究已经开始研究MRI可以证明MS患者的深灰质或皮质的组织损​​伤的程度。病理研究表明，灰质的参与并不少见，尽管病理外观与白质的不同之处在于炎症较少。使用MRI在灰质中损害的证明在很大程度上没有成功。 NDS中的研究现已表明，可以使用几种成像方法可重复地证明皮质中的病变。此外，在哈佛医学院的研究人员合作，皮质大幅度稀疏，尤其是在疾病早期的患者中，患者也可以看到前额叶皮层和运动皮质。还可以看到与临床运动功能的相关性，表明皮质受累可能是MS中临床障碍的一个组成部分。还使用区域MTR分析证明了对深灰质的损害。此外，扩散加权成像已用于研究深灰质尤其是丘脑的参与。 最后，MRI仍然是NIB临床试验的重要组成部分。使用造影剂增强病变的Daclizumab的研究是对干扰素β常规疗法失败的患者的主要结果，已成功证明了这种疗法的有效性。当前的研究正在研究该治疗的价值作为患者队列中的初始治疗。 NDS研究的发现已导致多中心II期测试该疗法。