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: 10689204
• 负责人: Debiao Li
• 金额: $ 71.62万
• 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/10689204
• 关键词: Absenteeism at work; Aging; American; Anatomy; Back Pain; Biology; Chemicals; Chronic low back pain; Clinical; Compensation; 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; 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; accurate diagnosis; bone marrow mesenchymal stem cell; cardiovascular imaging; data acquisition; disability; disc regeneration; healthy volunteer; imaging modality; improved; intervertebral disk degeneration; molecular marker; multitask; new therapeutic target; nucleus pulposus; pain patient; pain relief; 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）。 LBP 是发病和残疾的常见原因，也是最常见的 在美国，这是与工作相关的残疾的原因之一，也是导致缺勤的主要原因。如果患者患有 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 在决定医疗或手术干预之前。但目前尚无诊断依据 临床使用的方法有助于区分病理性疼痛和老化椎间盘。上 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，可以长期缓解疼痛。手术的潜在替代方法 程序是使用注射的干细胞作为再生椎间盘的潜在治疗方法，这已表明 最近的几项研究显示出有希望的治疗效果。在这个提案中，我们假设结合 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 范围。在目标 1 中，我们将开发一种高效、同步的多参数映射方法，用于 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 多个时间维度之间的大量数据冗余。我们将该技术应用于定量 心血管和身体成像效果极佳。在目标 2 中，我们将验证多参数 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。顺利完成 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 医生要治疗哪些椎间盘。它还可以用于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。

项目成果

Chemical exchange saturation transfer fingerprinting for exchange rate quantification.

• DOI: 10.1002/mrm.27363
• 发表时间: 2018-10
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Zhou Z;Han P;Zhou B;Christodoulou AG;Shaw JL;Deng Z;Li D
• 通讯作者: Li D

Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration.

• DOI: 10.3390/cells10092241
• 发表时间: 2021-08-29
• 期刊: Cells
• 影响因子: 6
• 作者: Krut Z;Pelled G;Gazit D;Gazit Z
• 通讯作者: Gazit Z

Quantitative chemical exchange saturation transfer MRI of intervertebral disc in a porcine model.

• DOI: 10.1002/mrm.26457
• 发表时间: 2016-12
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Zhou Z;Bez M;Tawackoli W;Giaconi J;Sheyn D;de Mel S;Maya MM;Pressman BD;Gazit Z;Pelled G;Gazit D;Li D
• 通讯作者: Li D

Detection of low back pain using pH level-dependent imaging of the intervertebral disc using the ratio of R1ρ dispersion and -OH chemical exchange saturation transfer (RROC).

• DOI: 10.1002/mrm.25186
• 发表时间: 2015-03
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Liu Q;Tawackoli W;Pelled G;Fan Z;Jin N;Natsuaki Y;Bi X;Gart A;Bae H;Gazit D;Li D
• 通讯作者: Li D

Whole-brain steady-state CEST at 3 T using MR Multitasking.

• DOI: 10.1002/mrm.29109
• 发表时间: 2022-05
• 期刊: MAGNETIC RESONANCE IN MEDICINE
• 影响因子: 3.3
• 作者: Han, Pei;Cheema, Karandeep;Lee, Hsu-Lei;Zhou, Zhengwei;Cao, Tianle;Ma, Sen;Wang, Nan;Han, Hui;Christodoulou, Anthony G.;Li, Debiao
• 通讯作者: Li, Debiao