Novel MRI Biomarkers in Neuromuscular Disease

神经肌肉疾病的新型 MRI 生物标志物

• 批准号: MR/T005483/1
• 负责人: Julie Hall
• 金额: $ 14.95万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT005483%2F1
• 关键词: Novel; MRI; Biomarkers; Neuromuscular; Disease; Novel; MRI; Biomarkers; Neuromuscular; Disease

More than 2,000 people a year die of motor neuron disease (MND). In this relentlessly progressive condition, the motor nerve fibres that control the muscles die off, resulting in weakness and eventually paralysis. Early diagnosis allows patients to receive life-prolonging treatment, but current clinical tests are only sensitive to the later stages of the disease by which time it may be too late for these to work.We have recently developed an entirely new way to detect early changes in the muscles of patients with MND. This uses a type of MRI scanning that can detect characteristic twitches in tiny regions of the muscles (called fasciculation) that occur before the nerve fibres have died. These regions are called motor units. We were able to show that our new technique, which we call Motor Unit MRI (MUMRI), detected hundreds of fasciculations in the leg muscles of patients with MND but not in healthy subjects. This is very exciting as it is the first time that fasciculation has been detected using MRI, and it potentially offers a sensitive, quick, and entirely pain-free way to diagnose and monitor patients with MND and other diseases.The aims of this project are: to take these promising early results and develop them into a tool that can be used to study the same muscle region repeatedly; to then use the refined technique to answer fundamental questions about how the disease develops; and to produce a 'whole-body' version that can be used to study patients in the clinic.We will ask patients with MND to undergo several scans over a two-year period. As well as taking the MUMRI images, we will also perform currently used tests such as muscle MRI, ultrasound, and electrical muscle tests. This will allow us to see when the changes seen on MUMRI first appear, whether these occur earlier in the disease than currently available tests, and how the changes develop as the disease progresses.A great strength of MUMRI is that it detects activity at the level of individual motor nerve fibres. This has never before been possible in humans, and it allows us to answer some fundamental questions about how MND develops. For example, we do not know if motor units that start to show fasciculation are about to die, or whether in fact these are the healthy ones doing their best to compensate for the damage occuring around them. We also do not know if the disease starts throughout the muscle, or start in just a few motor units before spreading. Since we can repeatedly image the same motor units with MUMRI we can begin to answer these questions, and in turn learn more about the disease itself.Finally, we will develop new ways to use MUMRI in muscles other than the legs. This is important since MND can affect anywhere in the body, and this is an essential step to MUMRI being used in the clinical setting. It will also allow us to study how fasciculation spreads throughout the body in MND, complimenting the earlier work on understanding how the disease originates.Our team includes research physicists, neurophysiologists, radiologists and neurologists. This gives us the ability to bring together a broad range of techniques to study MND. It also helps us to engage with a wide range of stakeholders from people involved in basic science into new imaging techniques, clinicians who apply these to diagnose and treat patients, and patients themselves. This gives us the best opportunity to translate this promising new technique into the clinic, whilst ensuring that our results are relevant and acceptable.

每年有2,000多人死于运动神经元疾病（MND）。在这种无情的渐进状态下，控制肌肉的运动神经纤维死亡，导致无力和最终瘫痪。早期诊断允许患者接受生命的治疗，但是当前的临床检查仅对疾病的后期敏感，此时可能为时已晚。我们最近开发了一种全新的方法来检测MND患者肌肉的早期变化。这使用了一种MRI扫描，可以检测到神经纤维死亡之前发生的肌肉小区域（称为fassication）的特征抽搐。这些区域称为电动机单元。我们能够证明我们称之为运动单元MRI（MUMRI）的新技术检测到MND患者的腿部肌肉中数百次症状，但在健康受试者中没有发现。这是非常令人兴奋的，因为这是第一次使用MRI检测到着迷，并且有可能提供一种敏感，快速且完全无痛的方法来诊断和监测MND和其他疾病的患者。该项目的目的是：将这些有前途的早期结果并发展为可以重复研究相同肌肉区域的工具；然后使用精致的技术回答有关疾病如何发展的基本问题；并生产可用于研究诊所患者的“全身”版本。我们将要求MND患者在两年内接受多次扫描。除了拍摄Mumri图像外，我们还将执行当前使用的测试，例如肌肉MRI，超声和电肌测试。这将使我们能够查看何时出现在Mumri上的变化，这些变化是否比当前可用的测试更早，以及随着疾病进展的变化如何发展。Mumri的强大强度是，它在单个运动神经纤维的水平上检测到活性。在人类中，这从来没有做到这一点，它使我们能够回答有关MND如何发展的一些基本问题。例如，我们不知道开始表现出迷恋的电动机是否即将死亡，或者实际上这些是健康的电动机，是否是健康的，以弥补周围造成的损害。我们也不知道该疾病是在整个肌肉中开始的，还是在扩散之前仅在几个电动机单元中开始。由于我们可以与Mumri反复对相同的电机单元进行成像，因此我们可以开始回答这些问题，进而了解更多有关疾病本身的问题。在本文中，我们将开发新的方法来在腿以外的其他肌肉中使用Mumri。这很重要，因为MND会影响体内任何地方，这是在临床环境中使用Mumri的重要步骤。它还将使我们能够研究迷象在MND中如何在整个身体中传播，从而赞美早期的工作，以了解该疾病的起源方式。我们的团队包括研究物理学家，神经生理学家，放射学家和神经病学家。这使我们能够将广泛的技术汇集在一起​​研究MND。它还可以帮助我们与参与基础科学的人们的广泛利益相关者互动，以新成像技术，将其应用于诊断和治疗患者以及患者本身的临床医生。这为我们提供了将这种有希望的新技术转化为诊所的最佳机会，同时确保我们的结果相关且可以接受。