Non-invasive evaluation of in vivo intervertebral disc mechanical function
Date
2024
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
The intervertebral discs are musculoskeletal soft tissues, situated between the vertebrae in the spine, that enable distribution of large, multiaxial loads as a part of daily activity and motion. Disc degeneration is the structural and compositional deterioration of the disc, with associated changes in mechanical properties and function. Disc degeneration is often implicated as a primary cause of low back pain (LBP). With normal aging degeneration there is disc breakdown that progresses steadily with increasing age. In accelerated degeneration, disc breakdown exceeds normal aging degeneration due to multifactorial, largely unknown causes. It has been notoriously difficult to distinguish between normal aging degeneration and accelerated degeneration. The relationship and associations between low back pain likely differ between aging degeneration and accelerated degeneration, such that assessing these relationships with no regard for subject age complicates study outcomes. ☐ Magnetic resonance imaging (MRI) is a non-invasive method commonly used to evaluate disc health, but structural and biomarker assessments from MRI have been largely unsuccessful in distinguishing between aging degeneration and accelerated degeneration. In the present work, baseline MRI parameters were evaluated for adults across the lifespan (n = 84, ages 18-83 years old) to quantify the impact of age on MRI outcomes. Given the known age-dependence of degeneration, we sought to develop a novel, age-dependent disc degeneration model. We developed a Disc Effective Age model, which requires subject traits and baseline MRI measures and outputs a Disc Effective Age. Following stepwise regression and assessment of several models, we found that a 4 parameter model optimally estimates the disc effective age. The model calculates disc effective age by disc level with inputs: subject height, nucleus T2 relaxation time, mid-sagittal disc area, and disc 3D volume. The model output can be directly compared to the subject’s true age to determine whether the degree of disc degeneration is expected due to aging or accelerated compared to asymptomatic subjects of the same age. The effective age model is objective, quantitative, continuous, and can be directly compared to a subject’s true age, enabling identification of discs with accelerated degeneration. ☐ Furthermore, the impact of aging degeneration on discs’ mechanical function in vivo is unknown. Another objective of this work was to evaluate disc mechanical function in vivo with repeated MRI in an asymptomatic adult population to quantify changes in disc mechanical function due to aging. MRI was acquired in flexion, extension, and diurnal loading conditions. Flexion and extension were applied as bending often inhibits or exacerbates LBP, such that these loading states have potential clinical relevance. Diurnal loading was evaluated as it is a natural, daily recurring loading state related to both disc loading and fluid flow. ☐ For many MRI parameters, the magnitude and distribution of outcomes were age-dependent. Generally, disc height and nucleus T2 relaxation times decreased while disc width and annulus T2 relaxation times increased with increasing subject age. Notably, in flexion, the changes in wedge angle and strain for younger subjects were greater in the lower lumbar discs whereas older subjects exhibited a greater flexion response in the upper lumbar discs. These findings highlight changes in disc mechanical function with age and can be further used as baseline expectations for evaluating mechanical response of subjects with LBP to help isolate potential sights of disc dysfunction. ☐ Another method for evaluating disc mechanical function is with ex vivo mechanical testing of cadaveric discs; unfortunately, it is unknown how directly these outcomes translate to the in vivo context. There are significant differences between the in vivo and the ex vivo states, including active loading, fluid flow, and surrounding tissues. It is necessary to quantify differences between the in vivo and ex vivo experimental states in order to accurately and effectively interpret ex vivo mechanical outcomes in the in vivo context. Given the necessity of paired samples between in vivo and ex vivo states, this quantification is only possible with the use of an animal model. We conducted sequential MRI on minipig spines throughout the dissection process to enable evaluation of the differences that arise between subsequent experimental states. The disc geometry, MRI T2 relaxation time, and opening pressure were all altered by progressive dissection, specimen preparation, and imposed loading conditions. The main finding of this study was that in the minipig model, an imposed axial stress of 0.20-0.33 MPa successfully recovered live, in vivo disc geometry and opening pressure. ☐ Besides mechanical testing, finite element modelling (FEM) can also be used to evaluate the ex vivo disc. FEM can evaluate disc response, isolate the impact of particular features, and provide internal stress and strain distributions, which are generally unrealistic to acquire with typical imaging and mechanical testing. The usefulness of a FEM is similarly limited by how well it can mimic the biological disc. To this end, the final objective of this work was to develop an intervertebral disc finite element model with geometry based on disc MRI and tissue properties from mechanical testing and evaluated its ability to mimic multiaxial disc mechanical function. We successfully incorporated residual strain due to swelling and multigeneration fibers in a FEM of intervertebral disc and validated human disc models against uniaxial quasi-static and multiaxial dynamic tests. The inclusion of swelling and fiber-induced residual strain in the multigeneration model was necessary for achieving a physiological residual strain state and for replicating disc mechanical behavior across uniaxial quasi-static and multiaxial dynamic test cases. ☐ The outcomes of this dissertation include a Disc Effective Age model which quantified aging degeneration, in vivo disc mechanical response across the adult lifespan with flexion, extension, and diurnal loading, quantified differences between the in vivo and ex vivo states in a porcine model, and validated an intervertebral disc finite element model with residual strain.
Description
Keywords
Intervertebral discs, Low back pain, Magnetic resonance imaging