Automated MR Image Analysis in MS: Identification of a Surrogate

描述（由申请人提供）：多发性硬化症（MS）是一种慢性中枢神经系统疾病，影响全球250万患者。目前，还没有治愈多发性硬化症的药物，但一些疾病改善药物已经被FDA批准或正在进行临床试验。多发性硬化症有一个复杂的临床过程，包括不可预测的复发和可变的缓解。这使得MS的临床评估变得困难。评估临床状态最常用的临床仪器灵敏度有限，不能检测亚临床活动。因此，有必要确定一种替代物，提供疾病状态的客观和可重复的测量。磁共振成像（MRI）是无创研究多发性硬化症最敏感的成像方式，可以根据多模型MRI测量得出许多指标，这些指标反映了多发性硬化症的不同病理方面。然而，临床状态与各种MRI衍生指标之间的相关性充其量是适度的。这至少在一定程度上是由于许多相关研究都是基于单个或几个MRI指标的组合。包括灰质、白质和脊髓在内的MRI指标的组合有望与临床测量结果产生更好的相关性。本提案的主要目的是确定一种结合了包括脑和脊髓在内的各种MRI测量信息的替代物。这些研究还将识别和量化MS中所谓的“正常组织”，这些组织已知是病理的，被认为代表MS的微观或弥漫性病理。为了实现本提案的主要目标，我们将开发，实施和评估一些先进的MRI采集和分析以及图像处理技术。我们将在一组多发性硬化症患者中确定mri衍生指标的纵向变化，并通过扩展残疾状态评分（EDSS）和多发性硬化症功能评分（MSFC）评估与临床残疾相关的这些指标的最佳组合。拟议的多模型MRI和纵向研究以及临床评估应该有助于根据多个MRI衍生指标确定合适的替代指标。与公共卫生相关：在多发性硬化症中鉴定替代物将彻底改变多发性硬化症的临床试验，加快神经药物的技术转移，并节省数百万美元的临床试验费用。该系统还应使临床医生能够根据更广泛使用的定量MRI的良好原则，对个别患者进行定制化管理。虽然主要的重点是MS，但该系统应该很容易适应于调查和管理各种需要准确测定组织体积及其时间变化的神经系统疾病。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a chronic central nervous system disease that affects 2.5 million patients worldwide. Currently, there is no cure for MS, but a number of disease modifying drugs have been either approved by the FDA or undergoing clinical trials. MS has a complex clinical course that includes unpredictable relapses and variable remissions. This makes clinical evaluation of MS difficult. The most commonly used clinical instruments for assessing the clinical status are limited in their sensitivity and can not detect subclinical activity. Thus, there is a need for identifying a surrogate that provides an objective and reproducible measure of the disease state. Magnetic resonance imaging (MRI) is the most sensitive imaging modality for noninvasively investigating MS. It is possible to derive a number of metrics that are based on multi-model MRI measurements that reflect different pathological aspects of MS. However, the correlation between the clinical status and various MRI-derived metrics is, at best, modest. This is, at least, in part due to the fact that many of the correlative studies are based on a single or a combination of a few MRI metric. A combination of MRI metrics that include gray matter, white matter, and spinal cord is expected to result in better correlation with clinical measures. The main objective of this proposal is to identify a surrogate that combines information from various MRI measures that include both brain and spinal cord. These studies will also identify and quantify the so called "normal appearing tissue" in MS that is known to be pathological and thought to represent microscopic or diffuse pathology in MS. In order to realize the main objective of this proposal, we will develop, implement, and evaluate a number of advanced MRI acquisition and analysis, and image processing techniques. We will determine the longitudinal changes in the MRI-derived metrics in a cohort of MS patients and identify an optimum combination of these metrics that correlate with clinical disability as assessed by the extended disability status score (EDSS) and MS functional score (MSFC). The proposed multi-model MRI and longitudinal studies along with clinical evaluation should help identify appropriate surrogate(s), based on multiple MRI-derived metrics. Relevance to Public Health: Identification of surrogate in MS should revolutionize MS clinical trials, expedite technology transfer in neuropharmaceuticals and literally save millions of dollars in clinical trial expenses. The system should also empower clinicians in general to customize management of individual patients based on well-founded sound principles of the use of more widely available quantitative MRI. 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.