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。为了发挥作用，必须尽早给予这些药物，但患者在症状出现和诊断之间通常仍需要等待 12 个月。关键因素是看神经科医生的时间；此时即可做出诊断，开始延长生命的治疗，并招募患者参加临床试验。我们需要一种快速、准确且广泛可用的对疾病最早阶段敏感的筛查测试，以便可以快速跟踪正确的患者去看神经科医生，而不会压垮这一有限的资源。绝大多数患者在看神经科医生之前都会进行 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。我们开发了一种基于 MRI 的快速且完全无痛的方法，该方法对称为肌束颤动的肌肉抽搐非常敏感。肌束颤动是 MND 的有用筛查，因为它发生在疾病早期，并且在进行性运动无力的情况下高度提示该疾病。我们将这种技术称为运动单位 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 仅要求受试者放松地躺在扫描仪中，每个身体区域仅增加 1 分钟的额外扫描时间，并且不需要额外的扫描仪软件或硬件即可执行。目前检测肌束颤动的方法要么是侵入性的（针肌电图），要么是耗时的（超声），要么是仅对浅表肌肉进行采样（表面肌电图）。在对 4 名 MND 患者进行的一项初步研究中，我们检测到下肢肌束颤动增加了 10 倍以上。四肢与对照相比。最近，我们开发了一种“全身”版本，可在一次扫描中对头部、上肢、胸部和下肢进行成像。我们发现，与对照组相比，MUMRI 检测到 9 名典型 MND 患者中有 9 名的至少一个身体区域的肌束颤动率显着增加。为了成为一种有用的筛查测试，MUMRI 必须适用于尽可能广泛的 MRI 扫描仪。我们在飞利浦 MRI 扫描仪上开发了 MUMRI，并已在当地 NHS Trust 的西门子扫描仪上成功实施。然而，我们需要测试 MUMRI 是否可以推广到整个 NHS 的 MRI 扫描仪。为此，我们将：1) 测试 MUMRI 是否可以在 3 种最常见品牌的 MRI 扫描仪上实施，以及； 2) 比较 MUMRI 在不同磁场强度的扫描仪上检测肌束颤动的灵敏度。为此，我们与英国 4 个主要的 ALS 中心合作；利兹、谢菲尔德、牛津和伦敦国王学院每年收治超过 1,000 名 MND 患者。这些中心使用 3 个主要 MRI 扫描供应商（飞利浦、GE 和西门子）的 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。第二阶段是在每个中心招募 12 名新近诊断的 ALS 患者，并邀请他们在常规临床影像过程中接受 MUMRI 扫描。第三阶段是比较每种类型扫描仪之间的肌束颤动检测率，以确定 MUMRI 是否可以在整个 NHS 及其他地区成功推广。该项目的目的是确定；1) MUMRI 是否可以应用于任何品牌、型号和磁体强度的 MRI 扫描仪。2) 确定该技术对 ALS 患者的诊断准确性。