Fasciculation IN Amyotrophic Lateral Sclerosis Using MUMRI (FINALSUM)

使用 MUMRI 治疗肌萎缩侧索硬化症的肌束颤动 (FINALSUM)

• 批准号: MR/Y503502/1
• 负责人: Roger Whittaker
• 金额: $ 27.11万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY503502%2F1
• 关键词: Fasciculation; Amyotrophic; Lateral; Sclerosis; Using

New and better therapies are transforming the outlook for patients with Motor Neuron Disease (MND). To be effective these must be given as early as possible, but patients still typically wait 12 months between symptom onset and diagnosis. The critical factor is the time to see a neurologist; at this point the diagnosis can be made, life-prolonging therapy started, and patients recruited to clinical trials. What is needed is a quick, accurate and widely available screening test sensitive to the earliest stages of the disease so that the correct patients can be fast-tracked to see a neurologist without overwhelming this limited resource. The vast majority of patients have an MRI scan at some point prior to seeing a neurologist, so improving the ability of MRI to detect key features of early MND would be an important advancement for patient stratification. We have developed a rapid and entirely pain-free MRI based method which is exquisitely sensitive to muscle twitching called fasciculation. Fasciculation is a useful screen for MND since it occurs early in the disease and in the context of progressive motor weakness is highly suggestive of the disease. We call this technique motor unit MRI, or MUMRI. MUMRI uses a variation of a type of imaging available on any modern MRI scanner. MUMRI requires only that the subject lies relaxed in the scanner, adds only 1 minute extra scanning time per body region, and needs no additional scanner software or hardware to perform. Current methods of detecting fasciculation are either invasive (needle electromyography), time consuming (ultrasound) or sample only superficial muscles (surface electromyography).In a pilot study of 4 MND patients we detected a greater than 10-fold increase in fasciculation in the lower limbs compared to controls. More recently, we have developed a 'whole-body' version which images the head, upper limbs, thorax and lower limbs in a single scan session. We showed MUMRI detected significantly increased fasciculation rates in at least one body region in 9 out of 9 patients with typical MND compared to controls. To be a useful screening test, MUMRI must be applicable on as wide a range of MRI scanners as possible. We developed MUMRI on a Philips MRI scanner, and have successfully implemented it on our local NHS Trust's Siemens scanners. However, we need to test whether MUMRI can be rolled out to MRI scanners throughout the NHS. To do this we will: 1) test whether MUMRI can be implemented on the 3 most common makes of MRI scanner, and; 2) compare the sensitivity of MUMRI in detecting fasciculation on scanners with different magnetic strengths.To do this we have partnered with 4 major ALS centres around the UK; Leeds, Sheffield, Oxford and King's College London which together see over 1,000 MND patients per year. These centres use the 3 major MRI scan vendors (Philips, GE and Siemens) with both 3T and 1.5T magnet strengths. Phase 1 of the project is to visit each centre and implement the MUMRI protocol on their local scanners. Phase 2 is to recruit 12 patients with recently diagnosed ALS in each centre and invite them to undergo MUMRI scanning during their routine clinical imaging. Phase 3 is to compare fasciculation detection rates between each type of scanner to establish whether or not MUMRI can successfully be rolled-out throughout the NHS and beyond. The aim of this project is to determine;1) Whether MUMRI can be applied on any make, model, and magnet strength of MRI scanner.2) To establish the diagnostic accuracy of the technique in patients with ALS.

新的，更好的疗法正在改变运动神经元疾病（MND）患者的前景。为了有效，必须尽早给予这些，但是在症状发作和诊断之间，患者通常仍会等待12个月。关键因素是去看神经科医生的时候了。在这一点上，可以进行诊断，开始生命疗法，并招募患者参加临床试验。需要的是快速，准确且可广泛可用的筛查测试对疾病的最早阶段敏感，因此可以快速训练正确的患者来查看神经科医生，而不会压倒这种有限的资源。绝大多数患者在看到神经科医生之前进行了MRI扫描，因此提高MRI检测早期MND关键特征的能力将是患者分层的重要进步。我们已经开发了一种快速且完全无疼痛的基于MRI的方法，该方法对称为fassicution的肌肉抽搐非常敏感。着迷是MND的有用屏幕，因为它发生在疾病的早期，而在进行性运动无力的背景下，它极大地暗示了该疾病。我们称此技术电动机单元MRI或Mumri。 Mumri使用任何现代MRI扫描仪上可用的成像类型的变体。 Mumri仅要求主题在扫描仪中放松，每个身体区域的额外扫描时间仅增加1分钟，并且不需要其他扫描仪软件或硬件才能执行。当前检测诱变的方法是侵入性（针肌电图），耗时（超声）或仅样品浅表肌肉（表面肌电图）。与对照组相比，在4个MND患者的初步研究中，我们发现在4 MND患者的诱惑性研究中，偶像增加了10倍以上。最近，我们开发了一个“全身”版本，该版本在单个扫描过程中为头部，上肢，胸部和下肢映射。我们显示，与对照组相比，在9个典型MND患者中，有9例中至少有9个身体区域发现Mumri显着提高了诱因率。为了进行有用的筛选测试，Mumri必须适用于尽可能宽的MRI扫描仪。我们在飞利浦MRI扫描仪上开发了Mumri，并在我们当地的NHS Trust的西门子扫描仪上成功实施了它。但是，我们需要测试是否可以在整个NHS中将MUMRI推出到MRI扫描仪上。为此，我们将：1）测试是否可以对MRI扫描仪最常见的三个制造者实施Mumri，并且； 2）比较Mumri在检测具有不同磁性强度的扫描仪中的敏感性。要做到这一点，我们与英国各地的4个主要ALS中心合作；利兹，谢菲尔德，牛津大学和伦敦国王学院，每年共享1,000多名MND患者。这些中心使用3个主要的MRI扫描供应商（Philips，GE和Siemens）具有3T和1.5T磁铁强度。该项目的第一阶段是访问每个中心并在其本地扫描仪上实施Mumri协议。第2阶段是在每个中心招募12例最近被诊断为ALS的患者，并邀请他们在常规临床成像中进行Mumri扫描。第3阶段是要比较每种类型的扫描仪之间的诱因检测率，以确定是否可以在整个NHS及以后成功推出Mumri。该项目的目的是确定; 1）是否可以在MRI扫描仪的任何品牌，模型和磁力强度上应用Mumri。2）在ALS患者中确定该技术的诊断准确性。