PROJECT SUMMARY Chronic low back pain (cLBP) is the world's leading debilitating condition and the most common reason for opioid prescription in the US. While axial cLBP is commonly considered non-specific and multifactorial, it is often suspected a dysfunction of the spinal stabilization system that includes the intervertebral disc (IVD) and adjacent paraspinal muscles (PSMs). Axial cLBP is notoriously challenging to treat because of uncertainty about patient-specific causal mechanisms preventing effective matching to treatments. IVD degeneration is easily appreciated with clinical imaging and often studied. Less is known about the role of PSM degeneration, including atrophy and fat infiltration (FI), which are assumed to relate to cLBP, although existing evidence does not provide a clear association. Given the availability of advanced MRI sequences that quantify FI, it is now possible to investigate PSM FI patterns that will inform how it may relate to functional outcomes in cLBP patients. The current working hypothesis is that degenerative IVD pathology promotes PSM FI as a result of a compensatory biomechanical response of the muscle in an attempt to stabilize an affected spinal segment that overtime leads to neuromuscular fatigue and/or from direct exposure to pro-inflammatory factors from IVD damage. We hypothesize that PSM FI spatial distribution patterns (fat maps) have significant correlation with 1) patient-specific kinematics and PSM activation patterns (i.e. motor control), and 2) bimolecular factors, derived from patient PSM muscle biopsy. To test this hypothesis, we will quantify PSM FI, degenerative IVD pathology, trunk and full-body kinematics, and paraspinal muscle activation in 40 axial cLBP subjects and 40 age-matched controls. We will also collect a muscle tissue sample from the cLBP patients to uncover the biomolecular mechanisms of PSM FI. In this study, we are proposing to 1) quantify spatial distribution of paraspinal muscle fat infiltration