Intervertebral disc degeneration, quantified by T2* MRI, biochemistry, and compressive mechanics, correlated to global functional mechanics of the lumbar spine

University of Minnesota Ph.D. dissertation. Major: Biomedical Engineering. May 2013. Advisor: David J. Nuckley. 1 computer file (PDF); xii, 149 pages, appendix p. 143-149.Low back pain is one of the most prevalent health complaints in the US, with an estimated 70-85% of the population developing back pain at some point in their life, creating a significant financial burden. Although the causes of low back pain are poorly defined and indistinct, most often implicated as the origin of pain, is the intervertebral disc. The disc affords the spine its extensive multidirectional motion due to the complex interaction between two morphologically, biomechanically, and biochemically distinct tissues: the annulus fibrosus and the nucleus pulposus. With advancing age, injury, pathology or a combination of these, a degenerative cascade of biomechanical, biochemical, and nutritional alterations diminish the discs' ability to maintain its structure and function. Unfortunately, measurement of these properties in vivo is currently not a viable option due to the invasiveness of the procedures. Therefore, an indirect method is needed to evaluate the multifarious characteristics of a patient's disc health. Of critical interest is the relationship that functional spinal mechanics has with the morphologic, biochemical, and biomechanical properties of the intervertebral disc as they change with degeneration. Eighteen osteoligamentous cadaveric lumbar spines that spanned the degenerative spectrum were utilized in a correlation study design to evaluate the relationships between each factors of disc health: imaging, biochemical content, biomechanical competency, and functional mechanics. Each specimen was first imaged using quantitative T2* MRI techniques, where the site-specific relaxation times and features of the Pfirrmann grading system, including signal intensity and distinction between the nucleus pulposus and surrounding annulus fibrosus, were measured. Then their functional spinal mechanics were evaluated and range of motion, neutral zone ratio, bending stiffness and helical axis patterns were computed. Local biochemical content and compressive biomechanical properties were subsequently analyzed. Each outcome measure was then assessed with respect to the others using correlation statistical methods in an effort to understand the multifactorial relationships surrounding disc degeneration. The T2* relaxation times and newly defined variables, T2* Intensity Area and Transition Zone Slope, were significantly correlated to the standard Pfirrmann grading, showing the T2* MR imaging parameters are sensitive to the morphological changes associated with disc degeneration. Also, these features enable the quantitative grading of disc degeneration without subjectivity or bias but with clinically recognized features of distinction. Furthermore, T2* relaxation times were found to have a high sensitivity for detecting the proteoglycan content of the intervertebral disc, which may potentially have a profound impact on the early diagnosis of degeneration. The T2* relaxation times were also significantly correlated to the residual stress and excised strain of the disc. These multi-faceted changes that occur with degeneration impact the global mechanics of the spinal unit by increasing the neutral zone to range of motion ratio, or joint instability, and altering the bending stiffness and range of motion. Even stronger correlations were measured with alterations in the helical axis patterns of lateral bending. There was a marked increase of out-of-plane rotations and a larger migration of the instantaneous axis of rotation with worsening degeneration evaluated by MRI, local biochemistry, and local residual mechanics. Quantitative T2* MRI has the sensitivity to predict the local biochemical and biomechanical properties of the intervertebral disc. Complementary to MRI analysis, the measurement of the pathway of motion throughout the degenerative progress, using the helical axis approach, can enhance the disc assessment. Altogether, these clinically viable methods may immediately improve the characterization of the intervertebral disc for enhanced treatment and care

Validation of an automated shape-matching algorithm for biplane radiographic spine osteokinematics and radiostereometric analysis error quantification

Biplane radiography and associated shape-matching provides non-invasive, dynamic, 3D osteo- and arthrokinematic analysis. Due to the complexity of data acquisition, each system should be validated for the anatomy of interest. The purpose of this study was to assess our system’s acquisition methods and validate a custom, automated 2D/3D shape-matching algorithm relative to radiostereometric analysis (RSA) for the cervical and lumbar spine. Additionally, two sources of RSA error were examined via a Monte Carlo simulation: 1) static bead centroid identification and 2) dynamic bead tracking error. Tantalum beads were implanted into a cadaver for RSA and cervical and lumbar spine flexion and lateral bending were passively simulated. A bead centroid identification reliability analysis was performed and a vertebral validation block was used to determine bead tracking accuracy. Our system’s overall root mean square error (RMSE) for the cervical spine ranged between 0.21-0.49mm and 0.42-1.80º and the lumbar spine ranged between 0.35-1.17mm and 0.49-1.06º. The RMSE associated with RSA ranged between 0.14-0.69mm and 0.96-2.33º for bead centroid identification and 0.25-1.19mm and 1.69-4.06º for dynamic bead tracking. The results of this study demonstrate our system’s ability to accurately quantify segmental spine motion. Additionally, RSA errors should be considered when interpreting biplane validation results.Eunice Kennedy Shriver National Institute of Child Health and Human Development K12HD073945 Eunice Kennedy Shriver National Institute of Child Health and Human Development F31HD087069 National Institute of Arthritis and Musculoskeletal and Skin Diseases T32 AR050938 Foundation for Physical Therapy Minnesota Partnership for Biotechnology and Medical Genomics MHP IF #14.0

Macrophages and Intervertebral Disc Degeneration

The intervertebral disc (IVD) aids in motion and acts to absorb energy transmitted to the spine. With little inherent regenerative capacity, degeneration of the intervertebral disc results in intervertebral disc disease, which contributes to low back pain and significant disability in many individuals. Increasing evidence suggests that IVD degeneration is a disease of the whole joint that is associated with significant inflammation. Moreover, studies show elevated macrophage accumulation within the IVD with increasing levels of disease severity; however, we still need to understand the roles, be they causative or consequential, of macrophages during the degenerative process. In this narrative review, we discuss hallmarks of IVD degeneration, showcase evidence of macrophage involvement during disc degeneration, and explore burgeoning research aimed at understanding the molecular pathways regulating macrophage functions during intervertebral disc degeneration