Susceptibility MRI as a marker for diagnosis and clinical disability in MS

描述（由申请人提供）：多发性硬化症（MS）是一种慢性致残性疾病。在世界范围内，有超过250万人患有这种疾病，仅在美国就有40多万人。虽然没有已知的治愈MS的方法，但有一些疗法可以有效地减缓疾病。这些治疗方案的主要目的是控制症状和防止进一步的损害。为了使这一策略有效，我们需要早期诊断疾病并准确描述其特征。然而，在早期阶段，MS很难诊断，因为症状可以模仿许多其他神经系统疾病的症状。在过去的十年中，脑和脊柱MRI的使用大大提高了诊断的准确性。然而，越来越清楚的是，目前的临床MRI方案仅显示了MS病理学的一部分，未能揭示微观水平上发生的重要变化。此外，现在认识到标准MRI方案不能反映临床症状的严重程度。例如，我们经常看到MR结果没有变化，即使临床恶化已经发生。与此同时，临床试验和新兴治疗越来越多地关注预防CNS损伤和促进从已经发生的损伤中恢复。因此，迫切需要改进的诊断和预后成像工具，可以更准确地评估疾病状态。多发性硬化症的标志是髓鞘的损失，髓鞘保护轴突并促进神经信号的传递。最近的研究表明，髓磷脂具有独特的磁化率，可以通过MRI测量。这种独特的磁性降低了MRI信号衰减率（R2*），并在脱髓鞘发生时引起正频移。如果这种磁性可以被准确地量化，它可以被用作一个强大的标记，以启动早期治疗和监测治疗结果。我们正在开发新的、准确的和临床可行的技术，以高空间分辨率成像和量化组织磁化率。在拟议的项目中，我们将进一步开发和优化这种新技术;我们将确定易感性和MS病理之间的关系;我们将表征MS大脑病变和正常出现的白色物质和灰质的易感性特性;我们将确定易感性是否可用作预测疾病进展和临床残疾的标志物。预期的结果将有助于翻译这种新技术的MS的临床管理。除了MS，该技术在许多其他神经系统疾病和障碍的成像具有广泛的适用性。

DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is a chronic and disabling disease. Worldwide, there are over 2.5 million people suffering from it, with more than 400,000 in the US alone. Although there is no known cure for MS, there are therapies that can effectively slow down the disease. These therapeutic regimens mainly aim to control symptoms and prevent further damages. For this strategy to be effective, we need to diagnose the disease early and characterize it accurately. However, at its early stage, MS is difficult to diagnose as is symptoms can mimic those of many other nervous system disorders. In the past decade, the use of brain and spinal MRI has greatly improved the diagnostic accuracy. However, it has also become increasingly clear that current clinical MRI protocols show only part of MS pathology, failing to reveal important changes occurring at the microscopic level. Furthermore, it is now recognized that standard MRI protocols do not reflect the severity of clinical symptoms. For example, we often see no change in MR findings even though clinical worsening has occurred. At the same time, clinical trials and emerging treatments are focusing increasingly on prevention of CNS injury and promotion of recovery from damages already occurred. Therefore, there is an urgent need for improved diagnostic and prognostic imaging tools that can evaluate the disease status more accurately. The hallmark of MS is loss of myelin which protects the axons and facilitates the transmission of nerve signals. Recent studies suggested that myelin has a unique magnetic susceptibility that can be measured by MRI. This unique magnetic property reduces the rate of MRI signal decay (R2*) and causes a positive frequency shift when demyelination occurs. If this magnetic property can be quantified accurately, it can be used as a powerful marker to initiate early treatment and to monitor treatment outcome. We are developing novel, accurate and clinical feasible techniques to image and quantify tissue magnetic susceptibility with high spatial resolution. In the proposed project, we will further develop and optimize this novel technique; we will determine the relationship between susceptibility and MS pathology; we will characterize susceptibility properties of MS brains in lesions and normal appearing white matter and gray matter; we will determine if susceptibility can be used as a marker for predicting disease progression and clinical disability. The expected outcome will facilitate the translation o this novel technique to the clinical management of MS. In addition to MS, the technique has a broad applicability in the imaging of many other neurological diseases and disorders.