Automated MR Image Analysis in MS: Identification of a Surrogate

多发性硬化症(MS)是一种慢性中枢神经系统疾病，全球有250万患者。 目前，多发性硬化症还没有治愈方法，但一些疾病修改药物已经获得了美国食品和药物管理局的批准 FDA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 可变减刑。这使得MS的临床评估变得困难。最常用的临床应用 用于评估临床状态的仪器灵敏度有限，无法检测到亚临床活动。 因此，需要识别提供客观且可重现的 疾病状态。磁共振成像(Mri)是目前最敏感的无创检查方法。 调查多发性硬化症有可能得出许多基于多模型磁共振成像的指标 反映多发性硬化症不同病理方面的测量，然而，临床之间的相关性 状态和各种MRI衍生的指标充其量是适度的。这至少在一定程度上是因为许多人 相关的研究都是基于几个MRI指标的单一或组合。磁共振成像的组合 包括灰质、白质和脊髓在内的指标有望产生更好的相关性 临床措施。这项建议的主要目标是确定一个代理，它结合了来自 包括大脑和脊髓在内的各种核磁共振测量。这些研究还将确定和量化 多发性硬化症的所谓“正常出现的组织”，已知是病理性的，被认为代表 多发性硬化症的显微或弥漫病理为了实现这一建议的主要目的，我们将开发， 实施和评估许多先进的MRI采集和分析以及图像处理 技巧。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 并确定与临床残疾相关的这些指标的最佳组合，由 扩展残疾状态评分(EDSS)和MS功能评分(MSFC)。建议的多模式磁共振成像和 纵向研究和临床评估应有助于确定合适的替代者(S)，基于 多个MRI派生的指标。与公共卫生相关：多发性硬化症代孕药的确定应彻底改变多发性硬化症临床试验，加快步伐 神经药物的技术转让，并真正节省数百万美元的临床试验费用。这个 系统还应使一般临床医生能够根据以下条件定制对个别患者的管理 有充分根据的合理原则，使用更广泛的定量磁共振成像。虽然主要强调的是 在MS上，这个系统应该很容易适应于调查和管理各种神经疾病 需要准确确定组织体积及其时间变化。

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 surroagte that combines information from various MRI measures that include both brain and spinal cord. These studies will also identify and quantify the 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 bjective of this proposal, we wiil develop, implement, and evaluate a number of 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.