MR Image Analysis in MS: Identification of a Surrogate

描述(申请人提供)：多发性硬化症(MS)是人类最常见的脱髓鞘疾病，有一个复杂的临床过程，包括不可预测的复发和不同的缓解。这使得MS的临床评估变得困难。因此，目前的临床试验设计必须纳入大量长期随访的患者。这些设计非常昂贵，可能会剥夺患者及时获得有效治疗的机会。使用具有预测价值的稳健的替代标记物(S)可以减少新药评估中的问题，并改善对个别患者的管理。基于MRI的测量，如病变体积、黑洞、对比度增强、萎缩和磁化转移率，有望作为可靠的替代指标。然而，许多研究表明，这些MR指标与临床评分之间的相关性很弱。我们假设，这种弱相关性的部分原因是使用了稳健图像量化所必需的不正确的图像分析工具，部分原因是未能定义正确的MRI替代物。在这些研究中，我们建议开发一个综合的图像分析包，它是健壮的和自动的，用于准确地定量组织体积。这一分析包的一个重要特征是它能够使用过多的MR序列分析在广泛的MR扫描仪上获取的图像，从而极大地扩展了其用途。这个程序包使我们能够跟踪单个病变的时间变化，以及当前使用的全球变化。这一分析包将使用一个广泛的数据库进行严格的评估，该数据库包含2000多名多发性硬化症患者的图像，并在几年内进行跟踪。利用这个数据库，我们提出了基于单独的或一些组合的磁共振测量来识别代孕(S)。最后，该软件将被分发到几个精选的中心进行多中心评估。虽然主要的重点是多发性硬化，但这个系统应该很容易适应于调查和处理各种神经疾病，这些疾病需要准确地确定组织体积及其时间变化。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is the most common demyelinating disease in humans and has a complex clinical course that includes unpredictable relapses and variable remissions. This makes clinical evaluation of MS difficult. Therefore, current clinical trial designs must incorporate large numbers of patients followed over long periods. These designs are expensive and may deprive patients of timely access to effective treatment. The use of robust surrogate marker(s) that have predictive value could reduce problems in evaluating new drugs and improve the management of individual patients. MRI-based measures such as volumes of lesions, black holes, contrast enhancements, atrophy, and magnetization transfer ratios, are expected to serve as robust surrogates. However, a number of studies have shown that the correlation between these MR measures and clinical score is weak. We hypothesize that this weak correlation is in part due to the use of improper image analysis tools necessary for robust image quantitation and in part due to failure to define the correct MRI surrogate. In these studies we propose to develop an integrated image analysis package that is robust and automatic for accurate quantitation of tissue volumes. An important feature of this analysis package is its ability to analyze images acquired on a wide range of MR scanners using a plethora of MR sequences, greatly extending its utility. This package allows us to follow temporal changes in individual lesions, as well as currently used global changes. This analysis package will be rigorously evaluated using an extensive database that contains images on more than 2,000 MS patients, followed over several years. Using this database, we propose to identify surrogate(s) based on individual or some combination of MRI-measures. Finally, this software will be distributed to a few select centers for multicenter evaluation. While the main emphasis is on MS, this system should be readily adaptable to investigate and manage various neurological disorders that require accurate determination of tissue volumes and their temporal change.