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

定量多参数 MRI 评估干细胞疗法对慢性腰痛的效果

• 批准号: 10454354
• 负责人: Debiao Li
• 金额: $ 71.58万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10454354
• 关键词: Aging; American; Anatomy; Back Pain; Biology; Chemicals; Chronic low back pain; Clinical; Consumption; Data; Dehydration; Detection; Development; Diagnosis; Diagnostic Procedure; Diffusion; Dimensions; Family suidae; Goals; Grant; Height; Human; Image; Imaging Techniques; Immobilization; Individual; Injections; Intervertebral disc structure; Longitudinal Studies; Low Back Pain; Magnetic Resonance Imaging; Maps; Measures; Medical; Mesenchymal Stem Cells; Metabolism; Methods; Miniature Swine; Modeling; Molecular; Monitor; Morbidity - disease rate; Motion; Natural regeneration; Nature; Occupations; Operative Surgical Procedures; Pain; Pathologic; Patients; Physicians; Process; Property; Protons; Publishing; Reproducibility; Scanning; Source; Spinal Fusion; System; T2 weighted imaging; Techniques; Therapeutic Effect; Time; Tissues; United States; Vertebral column; Water; Work; accurate diagnosis; base; bone marrow mesenchymal stem cell; cardiovascular imaging; data acquisition; disability; healthy volunteer; imaging modality; improved; intervertebral disk degeneration; molecular marker; multitask; new therapeutic target; nucleus pulposus; pain patient; pain relief; parametric imaging; porcine model; reconstruction; solute; stem cell therapy; stem cells; targeted treatment; tool; treatment response

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.

项目摘要 拟议项目的目的是开发多参数映射磁共振成像（MRI） 评估干细胞疗法对椎间盘（IVD）变性的影响的技术，这是主要来源 慢性下腰痛（LBP）。 LBP是发病率和残疾的常见原因，也是最常见的 与工作有关的残疾原因，是美国错过工作的主要贡献者。如果患者患有 LBP具有几个退化的椎间盘，需要进一步检查以确定哪个光盘是 疼痛，在做出治疗或手术干预的决定之前。但是，没有诊断 临床用途的方法有助于区分病理疼痛和衰老的椎间盘。在 另一方面，对于患有慢性LBP的患者，没有出色的手术解决方案，因为他们未能显示 与保守治疗相比，长期缓解疼痛。手术的潜在替代方法 程序是使用注射干细胞作为再生椎间盘的潜在治疗方法，这已显示 在最近的几项研究中有希望的治疗作用。在此提案中，我们假设 多个MR参数T1，T2，T1ρ，ADC和QCEST可以检测到疼痛的椎间盘并定量测量 间充质干细胞（MSC）注射对LBP的归化盘的影响比任何单个MR都要好 范围。在AIM 1中，我们将开发一种高效且简单的多参数映射方法 T1，T2，T1ρ，ADC和CEST定量。技术发展的核心是我们新的 开发的多任务框架，于2018年发表于自然BME，允许完成运动， 利用低级张量重建，高效，同时的多参数映射，利用优势 多个时间维度之间的巨大数据冗余。我们已经将该技术应用于定量 心血管和身体成像，效果很好。在AIM 2中，我们将验证该多参数 与单独的任何参数相比，映射与分子疼痛标记相关，可以 检测MSC注射的治疗作用在椎间盘退化模型中。成功完成 这个项目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检测和指南提供可靠且无创的工具 光盘治疗的医师。它也可用于监测各种干细胞的治疗作用 注射剂或其他目前正在开发的椎间盘靶向疗法。