Quantitative Multiparametric MRI to Assess the Effect of Stem Cell Therapy on Chronic Low Back Pain

项目摘要 该项目的目标是开发多参数标测磁共振成像（MRI） 评估干细胞治疗对椎间盘（IVD）退变影响的技术，这是一个主要来源 慢性腰痛（LBP）LBP是发病和残疾的常见原因，也是最常见的 在美国，与工作有关的残疾的原因和错过工作的主要原因。如果一个病人 LBP有几个退行性椎间盘，需要进一步检查以确定哪个椎间盘是LBP的来源。 疼痛，在决定医疗或手术干预之前。然而，没有诊断 临床使用的方法有助于区分病理性疼痛和老化的椎间盘。上 另一方面，对于患有慢性LBP的患者没有很好的手术解决方案，因为他们没有表现出 与保守治疗相比，长期疼痛缓解。一种潜在的替代手术方法 手术是使用注射的干细胞作为再生椎间盘的潜在治疗方法， 在最近的几项研究中有很好的治疗效果。在这个提议中，我们假设， 多个MR参数T1、T2、T1 ρ、ADC和qCEST可以检测疼痛的椎间盘，并定量测量 间充质干细胞（MSCs）注射到退变椎间盘对LBP的影响优于任何单一MR 参数.在目标1中，我们将开发一种高效的同时多参数映射方法， T1、T2、T1 ρ、ADC和CEST定量。技术发展的核心是我们新的 开发了多任务框架，于2018年发表在Nature BME上，该框架允许运动补偿， 高效，同时，多参数映射使用低秩张量重建，利用 在多个时间维度之间的大量数据冗余。我们已经将该技术应用于定量 心血管和身体成像具有优异的效果。在目标2中，我们将验证多参数 映射与分子疼痛标记物的相关性比任何单独的参数更好， 检测MSC注射在小型猪椎间盘退变模型中的治疗效果。成功完成 该项目的研究有可能对我们诊断和治疗慢性LBP的方式产生重大影响。 多参数定量MRI将为LBP的检测和引导提供一种可靠的、无创的工具 它还可以用来监测各种干细胞治疗的效果， 注射或目前正在开发的其他椎间盘靶向疗法。

PROJECT SUMMARY The goal of the proposed project is to develop multiparametric mapping magnetic resonance imaging (MRI) techniques to assess the effect of stem cell therapy on Intervertebral Disc (IVD) degeneration, a major source of chronic low back pain (LBP). LBP is a common cause of morbidity and disability, and the most common cause of job-related disability and a leading contributor to missed work in the United States. If a patient with LBP has several degenerate discs, further examination is required to determine which disc is the source of pain, prior to a decision of medical treatment or surgical intervention. However, there are no diagnostic methods in clinical use that help to differentiate between a pathologically painful and an aging disc. On the other hand, there are no good surgical solutions for patients suffering from chronic LBP as they failed to show long term pain relief compared to conservative treatment. A potential alternative approach to surgical procedures is the use of injected stem cells as a potential treatment to regenerate the discs, which have shown promising therapeutic effects in several recent studies. In this proposal, we hypothesize that a combination of multiple MR parameters T1, T2, T1ρ, ADC, and qCEST can detect painful discs and quantitatively measure the effect of mesenchymal stem cells (MSCs) injection to degenerate discs on LBP better than any single MR parameter. In Aim 1, we will develop a highly efficient and simultaneous multiparametric mapping approach for T1, T2, T1ρ, ADC, and CEST quantification. The centerpiece of the technical development is our newly developed Multitasking framework, published in Nature BME in 2018, which allows motion compensated, highly efficient, simultaneous, multiparametric mapping using low rank tensor reconstruction, taking advantage of the vast data redundancy among multiple time dimensions. We have applied the technique to quantitative cardiovascular and body imaging with excellent results. In Aim 2, we will validate that multiparametric mappings are better associated with molecular pain markers than any individual parameters alone and can detect the therapeutic effect of MSC injection in a minipig model of disc degeneration. Successful completion of this project has the potential to make major impact on the way we diagnose and treat chronic LBP. Multiparametric quantification MRI will provide a reliable and noninvasive tool for LBP detection and guide physicians which discs to treat. It could also be used to monitor the therapeutic effect of various stem cell injections, or other disc-targeted therapies that are currently in development.