Project Summary The intervertebral disc has a mechanical function, with degeneration and aging the disc structure and function are altered which can cause low back pain. Imaging is often used to evaluate disc structure and health via disc grading schemes but fail to identify clinically relevant disc changes. This may be due to the lack of mechanical function assessment in static MRI imaging. There is a critical need to measure disc mechanical function in vivo and evaluate disc health by functional capacity to diagnose and treat spine pathology. Mechanical function has been evaluated in cadaver models, but the relationship between the in vivo and cadaveric states is purely speculative, due to the lack of common reference state and unknown differences between them. The boundary and loading conditions of the in vivo condition have not been quantified and therefore cannot be replicated in cadaveric tests or finite element models (FEM). The objective of this proposal is to quantify the disc’s mechanical function in vivo, establish a function-based disc grading scheme, and create an in vivo human disc FEM. I will measure in vivo disc strain, use an animal model to establish a translational matrix between in vivo and cadaveric conditions, and use a FEM to predict the disc’s internal mechanical state in vivo. Aim 1: Quantify Mechanical Function of Human In Vivo Disc with Degeneration and Aging Current disc grading schemes are structure-based and cannot distinguish normal aging and degeneration from disc pathology; I will use multi-positional MRI to assess in vivo disc function and a statistical model to establish a novel multi-factorial disc grading scheme. Aim 2: Establish a Translational Matrix Between In Vivo and Cadaver States in a Porcine Model An animal model will be used to conduct paired MRI quantifications between in vivo and cadaver conditions. Ex vivo mechanical testing and paired in vivo FEM will enable further comparison between conditions. These quantifications will allow me to establish a translation matrix between the in vivo and cadaveric states. Aim 3: Create and Validate In Vivo Human Disc FEM MRI loading data from Aim 1, transformation matrix from Aim 2 and a previously validated disc model will be used to create and validate an in vivo human disc FEM for evaluating the internal mechanics of the in vivo disc. This study will yield a function-based disc grading scheme to replace prior structure-based schemes. It will establish a transformation matrix between in vivo and cadaveric states, an essential step for interpreting research data in the in vivo context and for appropriate setup for ex vivo mechanical testing and FEM. The main impact of this work will be the methods and techniques needed for research to investigate disc pathology and in the long term, clinical tools for the diagnosis and assessment of treatment options for low back pain.