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

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）。在这种无情的渐进条件下，控制肌肉的运动神经纤维死亡，导致虚弱并最终瘫痪。早期诊断可以让患者接受延长生命的治疗，但目前的临床测试只对疾病的后期阶段敏感，到那时这些测试可能已经太晚了。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前肌肉微小区域的特征性抽搐（称为肌束震颤）。这些区域被称为运动单位。我们能够证明我们的新技术，我们称之为运动单位MRI（MUMRI），检测到MND患者腿部肌肉中的数百个肌束震颤，但在健康受试者中没有。这是非常令人兴奋的，因为这是第一次使用MRI检测到肌束震颤，它可能提供一种灵敏，快速和完全无痛的方法来诊断和监测患有MND和其他疾病的患者。该项目的目的是：利用这些有希望的早期结果，并将其开发成一种工具，可用于重复研究同一肌肉区域;然后使用改进的技术来回答关于疾病如何发展的基本问题;并产生一个“全身”版本，可用于临床研究患者。我们将要求MND患者在两年的时间内接受多次扫描。除了拍摄MUMRI图像外，我们还将进行目前使用的测试，如肌肉MRI，超声和肌肉电测试。这将使我们能够看到MUMRI上看到的变化何时首次出现，这些变化是否在疾病中比目前可用的测试更早发生，以及随着疾病的进展变化如何发展。MUMRI的一个巨大优势是它可以检测单个运动神经纤维水平的活动。这在人类身上是不可能的，它使我们能够回答一些关于MND如何发展的基本问题。例如，我们不知道开始表现出肌束震颤的运动单位是否即将死亡，或者实际上这些运动单位是否正在尽最大努力来补偿周围发生的损伤。我们也不知道这种疾病是从整个肌肉开始，还是在传播之前从几个运动单位开始。由于我们可以重复成像相同的运动单位与MUMRI我们可以开始回答这些问题，并反过来了解更多关于疾病本身.最后，我们将开发新的方法使用MUMRI在肌肉以外的腿.这一点很重要，因为MND可以影响身体的任何地方，这是MUMRI在临床环境中使用的重要步骤。它还将使我们能够研究肌束震颤如何在MND中遍布全身，补充早期对了解疾病起源的工作。我们的团队包括研究物理学家，神经生理学家，放射科医生和神经学家。这使我们能够汇集广泛的技术来研究MND。它还有助于我们与广泛的利益相关者进行接触，从基础科学到新成像技术的参与者，应用这些技术诊断和治疗患者的临床医生，以及患者本身。这为我们提供了将这种有前途的新技术转化为临床的最佳机会，同时确保我们的结果是相关的和可接受的。

项目成果

Editorial For "Quantitative MRI Predicts Electromyography Severity Grades of Denervated Muscle in Neuropathy of the Brachial Plexus".

“定量 MRI 预测臂丛神经病变中失神经肌肉的肌电图严重程度”的社论。

• DOI: 10.1002/jmri.28181
• 发表时间: 2022
• 期刊: JMRI
• 作者: Blamire AM

In vivo 3D imaging of human motor units in upper and lower limb muscles

人体上肢和下肢肌肉运动单位的体内 3D 成像

• DOI: 10.1016/j.clinph.2022.05.018
• 发表时间: 2022
• 期刊: Clinical Neurophysiology
• 影响因子: 4.7
• 作者: Heskamp L

Ultrasound-guided motor unit scanning electromyography.

• DOI: 10.1002/mus.27720
• 发表时间: 2022-12
• 期刊: MUSCLE & NERVE
• 影响因子: 3.4
• 作者: Maitland, Stuart;Hall, Julie;McNeill, Andrew;Stenberg, Ben;Schofield, Ian;Whittaker, Roger
• 通讯作者: Whittaker, Roger