Project Summary / Abstract Low back pain (LBP) is the leading cause of disability worldwide and lumbar imaging has become ubiquitous in its standard course of care. However, typical clinical imaging offers only a qualitative assessment of spine anatomy and “new research to improve prognostic stratification of patients with chronic low back pain” was recently called for by the NIH Pain Consortium Task Force on Research Standards for Chronic LBP. Intervertebral disc (IVD) degeneration, a primary or secondary cause of LBP, is characterized by the progressive breakdown of the tissue's structure and composition resulting in altered mechanical behaviors and internal disruptions that can provide a means for nerve ingrowth, a precursor for discogenic pain. Magnetic resonance elastography (MRE) is a non-invasive imaging technique that tracks propagating strain waves as they move through soft tissues and allows the measurement of tissue material properties in-vivo. Supporting data demonstrates that MRE-derived shear stiffness can serve as a biomarker sensitive to this disease process and can detect internal disruptions within operated IVDs compared to non-operated controls. Yet, improved MRE scan sequences to reduce scan time, mechanical validation of MRE-derived viscoelastic properties, and determination of the limits of MRE-detected internal disruptions are required prior to clinical utilization. The long-term goal of this research is to provide a safe and non-invasive method to quantify the mechanical function of musculoskeletal soft-tissues within the spine to allow early diagnosis of injury and disease, improve patient stratification and facilitate in-vivo evaluation of restorative interventions for LBP. Aim 1 develops a custom spin-echo echo-planar imaging MRE sequence to reduce scan times while simultaneously increasing SNR. Aim 2 validates the MRE-derived viscoelastic material properties of healthy and degenerated IVD tissue against material testing and also determines the type, orientation and minimum defect size that MRE can detect in cadaveric tissue. Aim 3 determines if MRE-derived measurements of material properties and internal defects together with MR measurements of spatial variations in tissue composition can differentiate a painful and non- painful IVD from asymptomatic subjects and disc-related chronic LBP patients, respectively. This work will improve data collection in a reduced time, which is applicable to all MRE applications, and allow in-vivo assessment of viscoelastic mechanical properties and internal damage. Non-invasive in-vivo assessment of IVD mechanical function may allow the prognostic stratification of LBP patients and serve as a novel “patient specific” clinical tool to identify damage and quantify the functional consequences of disease and treatment.