Sensitive and reproducible techniques for spinal cord morphometry on magnetic resonance images with application to multiple sclerosis

多发性硬化症（MS）攻击大脑和脊髓，可导致严重的残疾。磁共振成像（MRI）是一种高度敏感的观察MS体内损伤的工具，因此在大多数临床试验中用于评估MS新疗法的疗效。为了了解多发性硬化症的复杂病理，必须研究并尽可能精确地测量大脑和脊髓中疾病引起的变化。然而，虽然用于测量大脑结构变化的精确图像分析算法通常用于MS研究，并且特定大脑结构的形态测量仍然是一个非常活跃的研究领域，但脊髓分析算法的发展似乎滞后。该项目的主要目标是提高MRI脊髓形态测量的灵敏度和可重复性，用于研究多发性硬化症。我们将设计和实施新的软件方法来解决我们已经确定的一些技术问题。试验数据将在健康志愿者身上收集，用于新算法的初步开发，随后将在MS/MRI研究小组的真实临床数据上进行验证。MS/MRI研究小组是不列颠哥伦比亚大学的一个跨学科小组，在MS临床试验中应用神经成像生物标志物方面具有丰富的经验。MS/MRI研究小组的主要任务是开发更好的试验方法，以改善神经系统疾病患者的生活。多发性硬化症每年给加拿大经济造成超过10亿美元的损失，包括处方药、医疗服务和收入损失。我们认为，提高脊髓MRI生物标志物的敏感性将对开发新的多发性硬化症药物的成本效益产生重大影响，这将直接使制药业和加拿大卫生保健系统受益。通过提高药物开发过程的效率，更好的药物可以更快地进入市场，并且可以减轻多发性硬化症对加拿大患者和经济的负担。

Multiple sclerosis (MS) attacks the brain and spinal cord, which can lead to severe disability. Magnetic resonance imaging (MRI) is a highly sensitive tool for observing MS damage in vivo, and is therefore used in the majority of clinical trials evaluating the efficacy of new MS therapies. To understand the complex pathology of MS, the disease-induced changes in both the brain and the spinal cord must be studied and precisely measured where possible. However, while accurate image analysis algorithms for measuring structural changes in the brain are commonly used in MS studies, and the morphometry of specific brain structures remains a very active area of research, the development of algorithms for spinal cord analysis seems to be lagging. The main objective of the proposed project is to improve the sensitivity and reproducibility of spinal cord morphometry on MRI for studying MS. We will design and implement new software methods to address a number of technical issues that we have identified. Pilot data will be collected on healthy volunteers for initial development of the new algorithms, with subsequent validation performed on real clinical data from the MS/MRI Research Group, an interdisciplinary group at the University of British Columbia with extensive experience in the application of neuroimaging biomarkers in MS clinical trials. The primary mandate of the MS/MRI Research Group is to develop better trial methodologies to improve the lives of patients with neurological diseases. MS costs the Canadian economy over $1 billion dollars per year in prescription medications, medical services, and lost earnings. We believe that increasing the sensitivity of spinal cord MRI biomarkers would have a strong impact on the cost-effectiveness of developing new MS drugs, which would directly benefit the pharmaceutical industry and Canadian health care system. By making the drug development process more efficient, better drugs can get to market faster, and the burden of MS on Canadian patients and the economy can be reduced.