Utilizing Magnetic Resonance Imaging to Quantify Lumbar Intervertebral Disc Mechanics and Composition in Participants with and without Low Back Pain

Abstract

Low back pain (LBP) is a highly prevalent medical condition experienced by approximately 80% of the population at least once, and it disproportionately affects females more than males. Most of the existing treatments focus on addressing the symptoms of LBP rather than the underlying cause because clinical magnetic resonance (MR) imaging, the most commonly used diagnostic tool, is often insufficient to determine the source of pain. LBP has many potential etiological factors, but intervertebral disc (IVD) degeneration is thought to be a leading cause as it is found in around 40% of cases. However, IVD degeneration can also be observed in asymptomatic individuals, and the exact mechanisms linking IVD degeneration to LBP remain unclear. It is hypothesized that alterations in IVD composition and mechanics may play a role in LBP and occur before IVD degeneration can be visibly detected with clinical MR imaging. The understanding of in vivo IVD composition and mechanics is limited, however, because most prior studies have been performed in vitro, and these studies are unable to fully replicate in vivo conditions or make connections with LBP. Recent advances in experimental MR imaging have made it possible to examine in vivo lumbar IVD mechanics and height. There is a need to obtain consist levels of IVD height before evaluating in vivo IVD mechanics because IVD mechanical properties are impacted by diurnal fluctuations in IVD height. Since in vivo IVD height recovery times remain poorly understood, Aim 1A of this dissertation used MR imaging to measure IVD height in asymptomatic participants after resting supine for 45 minutes on two separate days, one first thing in the morning and the other later in the day. Differences in IVD height measurements across the different times of day were on the same order of magnitude as those for MR image segmentation repeatability, suggesting that the 45-minute supine rest is sufficient to produce consistent measurements of IVD height at different times of day. Future in vivo analyses of IVD mechanics, including those in the remainder of this dissertation, can therefore utilize this 45-minute supine rest to perform data collections at different times of day, increasing research throughput. However, the loading conditions leading up to the 45-minute rest were unknown, and only examining one timepoint made it impossible to ascertain if the recovery time was even faster than 45 minutes. Therefore, Aim 1B expanded upon Aim 1A by assessing the IVD height recovery across eight evenly spaced timepoints from six to 55 minutes after a 30-minute treadmill walk in asymptomatic participants. IVD height was no longer significantly different from pre-exercise values by 48 minutes post-exercise, supporting the results of Aim 1B. IVD strain at each post-exercise timepoint was also calculated as the percentage change in IVD height from pre-exercise, normalized to the pre-exercise height. This strain data over time post-exercise was fit to a two-parameter Kelvin-Voight viscoelastic model to quantify a characteristic recovery time of 24 minutes. The characteristic recovery time can be used in future studies to probe the relationship between in vivo IVD mechanics and LBP. Furthermore, the results of Aim 1B suggest that in vivo IVD recovery time is similar to loading time and, together with Aim 1A, expand upon the limited knowledge of in vivo IVD recovery time. There is still, however, a poor understanding of in vivo lumbar IVD composition and mechanical response to loading. Thus, Aim 2 of this dissertation investigated IVD degeneration level, water content, height, and strain in asymptomatic participants. Since LBP is more common in females, comparisons were made between males and females. An MR imaging and exercise protocol consisting of a 45-minute supine rest, pre-exercise MR imaging, a 30-minute treadmill walk, and post-exercise MR imaging was utilized. Newly developed custom software was used to calculate T2 relaxation time, which is correlated with IVD water content, and previously developed methods for calculating IVD height and strain were implemented. No statistically significant differences were detected between males and females, but the study still provided new insights about IVDs in males compared to females which may help guide future studies focused on sex differences in LBP. It also improved the understanding of in vivo IVD composition and mechanical response to loading in asymptomatic individuals. How this IVD composition and mechanical response to loading in asymptomatic individuals compares to those in individuals with LBP is yet to be discovered. Therefore, Aim 3A utilized the same methods and participants as Aim 2 but recruited additional participants with non-specific acute LBP. The acute LBP participants were further categorized based on their pain impact levels (mild, moderate, or severe). IVD water content, height, and strain were all correlated with IVD degeneration level, but only strain was correlated with pain. Participants with bothersome acute LBP (moderate and severe acute LBP) experienced significantly greater IVD compressive strain than participants with minimal symptoms. These results suggest that IVD strain is the superior predictor of acute LBP, and IVD strain measurements from the MR imaging and exercise protocol may be a valuable tool to identify if an IVD is the source of LBP earlier than clinical MR imaging. Additionally, future treatment interventions aimed at addressing these alterations in IVD strain may help mitigate the transition from acute to chronic LBP. Participants with chronic LBP were evaluated in Aim 3B. Since it was only a pilot study, no significant differences were detected between asymptomatic and chronic LBP participants, but trends towards higher IVD degeneration, lower water content, and greater compressive strain with chronic LBP were observed. Thus, strain may be a valuable biomarker of both acute and chronic LBP, while IVD degeneration and water content may be helpful biomarkers of chronic LBP. Although, chronic LBP must be investigated further in the future. Overall, helpful advancements were made towards distinguishing whether IVD composition and mechanics are possible mechanisms of LBP. These insights may be useful for the future improvement of diagnostic tools and treatments for LBP.