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.

项目概要 该项目的目标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）退变（主要来源）效果的技术 慢性腰痛 (LBP) 是发病和残疾的常见原因，也是最常见的原因。 如果患者患有与工作相关的残疾，并且是导致美国缺勤的主要原因。 LBP有多个退变椎间盘，需要进一步检查以确定哪个椎间盘是退变的来源 在决定进行药物治疗或手术干预之前，没有诊断依据。 临床使用的方法有助于区分病理性疼痛和老化椎间盘。 另一方面，对于患有慢性腰痛的患者来说，没有好的手术解决方案，因为他们没有表现出 与保守治疗相比，长期缓解疼痛是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，这已表明 在这项建议中，我们追求的是最近几项研究的治疗效果。 多个 MR 参数 T1、T2、T1ρ、ADC 和 qCEST 可以检测疼痛的椎间盘并定量测量 向退变椎间盘注射间充质干细胞 (MSC) 对 LBP 的效果优于任何单一 MR 在目标 1 中，我们将开发一种高效、同步的多参数映射方法。 T1、T2、T1ρ、ADC 和 CEST 量化 技术开发的核心是我们的新产品。 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， 使用低秩张量重建进行高效、同步、多参数映射，利用 我们已将该技术应用于定量分析。 在目标 2 中，我们将验证该多参数。 与任何单独的参数相比，映射与分子疼痛标记的相关性更好，并且可以 检测MSC注射对小型猪椎间盘退变模型的治疗效果成功完成。 该项目有可能对我们诊断和治疗慢性腰痛的方式产生重大影响。 多参数量化MRI将为腰痛检测和指导提供可靠、无创的工具 医生还可以使用它来监测各种干细胞的治疗效果。 注射或目前正在开发的其他椎间盘靶向疗法。