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.