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

描述(申请人提供)：多发性硬化症(MS)是一种慢性致残性疾病。在全球范围内，有超过250万人患有此病，仅美国就有40多万人。尽管目前还没有治愈多发性硬化症的已知方法，但有一些疗法可以有效地减缓疾病的发展。这些治疗方案主要是为了控制症状和防止进一步的损害。为了使这一策略有效，我们需要及早诊断疾病并准确地描述它的特征。然而，在其早期阶段，MS很难诊断，因为它的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的使用极大地提高了诊断的准确性。然而，也越来越清楚的是，目前的临床MRI只显示了MS病理的一部分，未能揭示发生在微观水平上的重要变化。此外，现在人们认识到，标准的MRI方案不能反映临床症状的严重程度。例如，我们经常看到，即使临床恶化，MR检查结果也没有变化。与此同时，临床试验和新兴的治疗方法越来越注重预防中枢神经系统损伤和促进已经发生的损伤的恢复。因此，迫切需要改进的诊断和预后成像工具，以便更准确地评估疾病状态。多发性硬化症的特点是髓鞘丢失，髓鞘保护轴突，促进神经信号的传递。最近的研究表明，髓鞘具有一种独特的磁化率，可以通过核磁共振来测量。这种独特的磁性可降低MRI信号衰减率(R2*)，并在发生脱髓鞘时引起正频移。如果这种磁性能够被准确地量化，它可以被用作启动早期治疗和监测治疗结果的强有力的标记。我们正在开发新的、准确的和临床上可行的技术来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项新技术；我们将确定敏感度与MS病理之间的关系；我们将表征MS大脑病变和正常外观白质和灰质的敏感度特性；我们将确定敏感度是否可以用作预测疾病进展和临床残疾的标志。预期的结果将有助于将这一新技术转化为多发性硬化症的临床治疗。除多发性硬化症外，该技术在许多其他神经系统疾病和障碍的成像中具有广泛的适用性。

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.