Fasciculation IN Amyotrophic Lateral Sclerosis Using MUMRI (FINALSUM)

新的和更好的治疗方法正在改变运动神经元疾病（MND）患者的前景。为了有效，这些必须尽早给予，但患者通常在症状发作和诊断之间等待12个月。关键因素是看神经科医生的时间;此时可以做出诊断，开始延长生命的治疗，并招募患者进行临床试验。我们需要的是一种快速，准确和广泛可用的筛查测试，对疾病的最早阶段敏感，以便正确的患者可以快速跟踪到神经科医生，而不会压倒这种有限的资源。绝大多数患者在看神经科医生之前的某个时间点进行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。我们已经开发出一种快速和完全无痛的基于MRI的方法，该方法对称为肌束震颤的肌肉抽搐非常敏感。肌束震颤是MND的有用筛查，因为它发生在疾病的早期，并且在进行性运动无力的背景下高度提示该疾病。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只要求受试者放松地躺在扫描仪中，每个身体区域只增加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来执行。目前检测肌束震颤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）。最近，我们开发了一种“全身”版本，可以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9/9例典型MND患者至少一个身体部位的肌束震颤率显著增加。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，并已成功地在我们当地的NHS Trust的西门子扫描仪上实施。然而，我们需要测试MUMRI是否可以在整个NHS中推广到MRI扫描仪。为此，我们将：1）测试MUMRI是否可以在3种最常见的MRI扫描仪上实现; 2）比较MUMRI在不同磁场强度的扫描仪上检测肌束震颤的灵敏度。为了做到这一点，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伦敦，每年总共有超过1,000名MND患者。这些中心使用3家主要MRI扫描供应商（Philips、GE和Siemens），磁体强度为3 T和1.5T。该项目的第一阶段是访问每个中心，并在其当地扫描仪上执行MUMRI协议。第二阶段是在每个中心招募12名最近诊断为ALS的患者，并邀请他们在常规临床成像期间接受MUMRI扫描。第三阶段是比较每种类型的扫描仪之间的肌束震颤检测率，以确定MUMRI是否可以成功地在整个NHS及其他地区推广。该项目的目的是确定：1）MUMRI是否可以应用于任何品牌，型号和磁强度的MRI扫描仪。2）建立该技术在ALS患者中的诊断准确性。

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.