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.

项目总结 拟议项目的目标是开发多参数标测磁共振成像(Mri)。 评估干细胞疗法对主要来源--椎间盘退变的影响的技术 慢性下腰痛(LBP)。LBP是导致疾病和残疾的常见原因，也是最常见的 与工作相关的残疾的原因，也是美国缺勤的主要原因。如果一名患者患有 LBP有几个退化的盘，需要进一步检查才能确定哪个盘是 疼痛，在决定进行内科治疗或外科手术之前。然而，目前还没有诊断出 有助于区分病理性疼痛和老化的椎间盘的临床使用方法。论 另一方面，慢性下腰痛患者没有很好的手术治疗方案，因为他们没有表现出 与保守治疗相比，长期缓解疼痛。一种潜在的外科手术替代方法 手术是使用注射的干细胞作为一种潜在的治疗方法来再生椎间盘，这已经表明 在最近的几项研究中显示了良好的治疗效果。在这项提案中，我们假设 多个MR参数T1、T2、T1、ρ、ADC和QCEST可以检测出疼痛的椎间盘并定量测量 骨髓间充质干细胞(MSCs)注射治疗退变腰椎间盘的效果优于单一MR 参数。在目标1中，我们将开发一种高效且同时的多参数映射方法 T1、T2、T1ρ、ADC和CEST量化。技术发展的核心是我们的新技术 开发的多任务框架，于2018年发表在自然BME上，允许运动补偿， 使用低秩张量重建的高效、同时、多参数映射，利用 多个时间维度之间的海量数据冗余。我们已经将该技术应用于定量 心血管和身体成像，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关联更好，并且可以 检测骨髓间充质干细胞注射对小型猪椎间盘退变的治疗作用。成功完成 这一项目的进展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的检测和引导提供可靠的、非侵入性的工具 内科医生对哪些椎间盘进行治疗。它还可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

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

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

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