Here we develop a three-dimensional analytic model for MR image contrast of collagen lamellae in the annulus fibrosus of the intervertebral disc of the spine, based on the dependence of the MRI signal on collagen fiber orientation.High-resolution MRI scans were performed at 1.5 and 7 T on intact whole disc specimens from ovine, bovine, and human spines. An analytic model that approximates the three-dimensional curvature of the disc lamellae was developed to explain inter-lamellar contrast and intensity variations in the annulus. The model is based on the known anisotropic dipolar relaxation of water in tissues with ordered collagen.Simulated MRI data were generated that reproduced many features of the actual MRI data. The calculated inter-lamellar image contrast demonstrated a strong dependence on the collagen fiber angle and on the circumferential location within the annulus.This analytic model may be useful for interpreting MR images of the disc and for predicting experimental conditions that will optimize MR image contrast in the annulus fibrosus.

ABSTRACTTissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4–L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel‐wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group‐level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc‐level mechanical response. Depending on the strain component, 81–99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264–1273, 2016.

Study objectives were to develop, validate, and apply a method to measure three-dimensional (3D) internal strains in intact human discs under axial compression. A custom-built loading device applied compression and permitted load-relaxation outside of the magnet while also maintaining compression and hydration during imaging. Strain was measured through registration of 300 μm isotropic resolution images. Excellent registration accuracy was achieved, with 94% and 65% overlap of disc volume and lamellae compared to manual segmentation, and an average Hausdorff, a measure of distance error, of 0.03 and 0.12 mm for disc volume and lamellae boundaries, respectively. Strain maps enabled qualitative visualization and quantitative regional annulus fibrosus (AF) strain analysis. Axial and circumferential strains were highest in the lateral AF and lowest in the anterior and posterior AF. Radial strains were lowest in the lateral AF, but highly variable. Overall, this study provided new methods that will be valuable in the design and evaluation surgical procedures and therapeutic interventions.

Intervertebral disc mechanics are affected by both disc shape and disc degeneration, which in turn each affect the other; disc mechanics additionally have a role in the etiology of disc degeneration. Finite element analysis (FEA) is a favored tool to investigate these relationships, but limited data for intervertebral disc 3D shape has forced the use of simplified or single-subject geometries, with the effect of inter-individual shape variation investigated only in specialized studies. Similarly, most data on disc shape variation with degeneration is based on 2D mid-sagittal images, which incompletely define 3D shape changes. Therefore, the objective of this study was to quantify inter-individual disc shape variation in 3D, classify this variation into independently-occurring modes using a statistical shape model, and identify correlations between disc shape and degeneration. Three-dimensional disc shapes were obtained from MRI of 13 human male cadaver L3L4 discs. An average disc shape and four major modes of shape variation (representing 90% of the variance) were identified. The first mode represented disc axial area and was significantly correlated to degeneration (R(2)=0.44), indicating larger axial area in degenerate discs. Disc height variation occurred in three distinct modes, each also involving non-height variation. The statistical shape model provides an average L3L4 disc shape for FEA that is fully defined in 3D, and makes it convenient to generate a set of shapes with which to represent aggregate inter-individual variation. Degeneration grade-specific shapes can also be generated. To facilitate application, the model is included in this paper׳s supplemental content.

PURPOSE:The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage positioned between the vertebral endplate and nucleus pulposus (NP) that functions both as a mechanical barrier and as a gateway for nutrient transport into the disc. Despite its critical role in disc nutrition and degeneration, the morphology of the CEP has not been well characterized. The objective of this study was to visualize and report observations of the CEP three-dimensional morphology, and quantify CEP thickness using an MRI FLASH (fast low-angle shot) pulse sequence.METHODS:MR imaging of ex vivo human cadaveric lumbar spine segments (N = 17) was performed in a 7T MRI scanner with sequence parameters that were selected by utilizing high-resolution T1 mapping, and an analytical MRI signal model to optimize image contrast between CEP and NP. The CEP thickness at five locations along the mid-sagittal AP direction (center, 5 mm, 10 mm off-center towards anterior and posterior) was measured, and analyzed using two-way ANOVA and a post hoc Bonferonni test. For further investigation, six in vivo volunteers were imaged with a similar sequence in a 3T MRI scanner. In addition, decalcified and undecalcified histology was performed, which confirmed that the FLASH sequence successfully detected the CEP.RESULTS:CEP thickness determined by MRI in the mid-sagittal plane across all lumbar disc levels and locations was 0.77 ± 0.24 mm ex vivo. The CEP thickness was not different across disc levels, but was thinner toward the center of the disc.CONCLUSIONS:This study demonstrates the potential of MRI FLASH imaging for structural quantification of the CEP geometry, which may be developed as a technique to evaluate changes in the CEP with disc degeneration in future applications.

Degeneration of the intervertebral disc (IVD) is implicated in low back pain, which is a costly and prevalent disease. Since the IVD is a mechanically active organ, it is important to consider its mechanical behavior as one factor in the degenerate pathology. Strain can be measured directly by imaging methods, but the stress distribution within the disc must be calculated. The stress distribution for a particular strain state is dependent on the IVD’s material properties and its geometry. While the material properties of the tissues comprising IVD have been extensively studied, its three-dimensional geometry remains incompletely characterized. Prior whole-disc models have been constructed from single IVDs. While this approach ensures that the geometry has a physiological basis, it is uncertain the degree to which results from a single IVD shape can be generalized to the entire population.

The intervertebral disc experiences combinations of compression, torsion, and bending that subject the disc substructures, particularly the annulus fibrosus (AF), to multidirectional loads and deformations. Combined tensile and shear loading is a particularly important loading paradigm, as compressive loads place the AF in circumferential hoop tension, and spine torsion or bending induces AF shear. Yet the anisotropy of AF mechanical properties in shear, as well as important structure-function mechanisms governing this response, are not well-understood. The objective of this study, therefore, was to investigate the effects of tissue orientation and enzymatic degradation of glycosaminoglycan (GAG) and elastin on AF shear mechanical properties. Significant anisotropy was found: the circumferential shear modulus, Gθz, was an order of magnitude greater than the radial shear modulus, Grθ. In the circumferential direction, prestrain significantly increased the shear modulus, suggesting an important role for collagen fiber stretch in shear properties for this orientation. While not significant and highly variable, ChABC treatment to remove GAG increased the circumferential shear modulus compared to PBS control (p=0.15). Together with the established literature for tensile loading of fiber-reinforced GAG-rich tissues, the trends for changes in shear modulus with ChABC treatment reflect complex, structure-function relationships between GAG and collagen that potentially occur over several hierarchical scales. Elastase digestion did not significantly affect shear modulus with respect to PBS control; further contributing to the notion that circumferential shear modulus is dominated by collagen fiber stretch. The results of this study highlight the complexity of the structure-function relationships that govern the mechanical response of the AF in radial and circumferential shear, and provide new and more accurate data for the validation of material models and tissue-engineered disc replacements.

Introduction The intervertebral disc consists of three major sub-structures: the nucleus pulposus (NP), the annulus fibrosus (AF), and the (superior/inferior) cartilaginous endplate (CEP). The CEP is a thin layer of hyaline cartilage between the vertebral body and the NP that provides a mechanical barrier and a nutritional conduit between the vertebral blood supply and the disc. There is evidence that with age and degeneration the CEP becomes thinner, calcifies, and may have reduced permeability [1]. MRI has been used to determine disc composition and volume [2,3] and to classify the stage of degeneration [4,5]. However, CEP geometry and relaxation times have not been quantified due to limitations in SNR and spatial resolution. The general method of cluster analysis has often been applied in the segmentation of brain structures, using the T1and/or T2-based contrast that is well understood for brain tissues. Here we have applied a similar concept to examine the nature of T1 and T2 relaxation in sub-structures of the intervertebral disc. Apart from the simple curiosity of these results, this analysis may facilitate segmentation of disc sub-structures towards the development of anatomically accurate finite element models in the study of disc biomechanics, as well as a more detailed method for classifying the degenerative grade of a disc.

Study Design. Prospective magnetic resonance imaging (MRI) study of patients low back pain (LBP) requiring discography as part of their routine clinical diagnoses and asymptomatic age-matched volunteers.Objective. To determine whether T-1 rho MRI and discography opening pressure (OP) are quantitative biomarkers of disc degeneration in LBP patients and in asymptomatic volunteers.Summary of Background Data. Disc degenerative disease, a common cause of LBP, is related to the patient's prognosis and serves as a target for therapeutic interventions. However, there are few quantitative measures in the clinical setting. Discography OP and T-1 rho MRI are potential biomarkers of disc degenerative disease related to biochemical composition of the intervertebral disc.Methods. The institutional review board approved all experiments, and informed consent was provided by each subject. Patients being treated for LBP (n = 17; 68 levels; mean age, 44 +/- 6 years; and range, 30-53) and control subjects (n = 11; 44 levels; mean age, 43 +/- 17 years; and range, 22-76) underwent T-1 rho and T2 MRI on a Siemens 3T Tim Trio clinical scanner (Siemens Medical Solutions, Malvern, PA). The LBP patients also received multilevel provocative discography before their MRI. OP was recorded as the pressure when fluid first enters the nucleus of the intervertebral disc.Results. T-1 rho was significantly lower in the painful discs (55.3 +/- 3.0 ms, mean +/- SE) from control (92.0 +/- 4.9 ms, P < 0.001) and nonpainful discs (83.6 +/- 3.2 ms, P < 0.001). Mean OP for the painful discs (11.8 +/- 1.0 psi, mean +/- SE) was significantly lower than that for nonpainful discs (19.1 +/- 0.7 psi, P < 0.001). Both T-1 rho and OP correlated moderately with Pfirrmann degenerative grade. Receiver-operating-characteristic area under the curve was 0.91 for T-1 rho MRI and 0.84 for OP for predicting painful discs.Conclusion. T-1 rho and OP are quantitative measures of degeneration that are consistent across both control subjects and LBP patients. A significant and strong correlation exists between T-1 rho values and in vivo OP measurements obtained by discography in LBP patients.

STUDY DESIGN:Cadaveric biomechanical study.OBJECTIVE:To quantify the effects of vertebral body augmentation on biomechanics under axial compression by a total disc replacement (TDR) implant.SUMMARY OF BACKGROUND DATA:TDR is a surgical alternative to lumbar spinal fusion to treat degenerative disc disease. Osteoporosis in the adjacent vertebrae to the interposed TDR may lead to implant subsidence or vertebral body fracture. Vertebral augmentation is used to treat osteoporotic compression fracture. This study sought to evaluate whether vertebral augmentation improves biomechanics under TDR axial loading.METHODS:Forty-five L1-L5 lumbar vertebral body segments with intact posterior elements were used. Peripheral quantitative computed tomography scans were performed to determine bone density, and specimens were block-randomized by bone density into augmentation and control groups. A semiconstrained keeled lumbar disc replacement device was implanted, providing 50% endplate coverage. Vertebral augmentation of 17.6% +/- 0.9% vertebral volume fill with Cortoss was performed on the augmentation group. All segments underwent axial compression at a rate of 0.2 mm/s to 6 mm.RESULTS:The load-displacement response for all specimens was nonlinear. Subfailure mechanical properties with augmentation were significantly different from control; in all cases, the augmented group was 2 times higher than control. At failure, the maximum load and stiffness with augmentation was not significantly different from control. The maximum apparent stress and modulus with augmentation were 2 times and 1.3 times greater than control, respectively. The subfailure stress and apparent modulus with augmentation were moderately correlated with bone density whereas the control subfailure properties were not. The augmented maximum stress was not correlated with bone density, whereas the control was weakly correlated. The maximum apparent modulus was moderately correlated with bone density for both the augmented and the control groups.CONCLUSION:Augmentation improved the mechanical properties of the lumbar vertebral body for compression by a TDR implant.

Background: The mechanical properties of extracellular matrix grafts that are intended to augment or replace soft tissues should be comparable to the native tissue. Such grafts are often used in fiber-reinforced tissue applications that undergo multi-axial loading and therefore knowledge of the anisotropic and nonlinear properties are needed, including the moduli and Poisson's ratio in two orthogonal directions within the plane of the graft. The objective of this study was to measure the tensile mechanical properties of several marketed grafts: Alloderm, Restore, CuffPatch, and OrthADAPT.Methods: The degree of anisotropy and non-linearity within each graft was evaluated from uniaxial tensile tests and compared to their native tissue.Findings: The Alloderm graft was anisotropic in both the toe- and linear-region of the stress-strain response, was highly nonlinear, and generally had low properties. The Restore and CuffPatch grafts had similar stress-strain responses, were largely isotropic, had a linear-region modulus of 18 MPa, and were nonlinear. OrthADAPT was anisotropic in the linear-region (131 MPA vs 47 MPa in the toe-region) and was highly nonlinear. The Poisson ratio for all grafts was between 0.4 and 0.7, except for the parallel orientation of Restore which was greater than 1.0.Interpretation: Having an informed understanding of how the available grafts perform mechanically will allow for better assessment by the physician for which graft to apply depending upon its application. (C) 2010 Elsevier Ltd. All rights reserved.

The annulus fibrosus (AF) is a highly organized structure made up of concentric lamellae of fibers embedded in a hydrated extrafibrillar matrix; the collagen fibers are oriented at alternating angles in each lamella. The AF undergoes multidirectional loading through combinations of compression, bending, torsion and shear of the motion segment. The composition and structure of the AF leads to mechanical stress-strain nonlinearity and anisotropy. Previous tissue-based studies of shear have tested the AF tissue under compressive simple shear and torsion, producing shear modulus on the order of 0.06–0.4 MPa [1, 2]. However, structural testing and mathematical models of the IVD have reported the shear modulus to be between 3–20 MPa [3–6]. We hypothesize that when the fibers of the AF are loaded the shear modulus will be on the same order as structural tests and mathematical models of the IVD. The objectives of this study are to measure the shear mechanical properties of the bovine outer AF and compare the regional variances between anterior and posterior AF.

BACKGROUND:Early diagnosis is a challenge in the treatment of degenerative disc disease. A noninvasive biomarker detecting functional mechanics of the disc is needed. T1rho-weighted imaging, a spin-lock magnetic resonance imaging technique, has shown promise for meeting this need in in vivo studies demonstrating the clinical feasibility of evaluating both intervertebral discs and articular cartilage. The objectives of the present study were (1) to quantitatively determine the relationship between T1rho relaxation time and measures of nucleus pulposus mechanics, and (2) to evaluate whether the quantitative relationship of T1rho relaxation time with the degenerative grade and glycosaminoglycan content extend to more severe degeneration. It was hypothesized that the isometric swelling pressure and compressive modulus would be directly correlated with the T1rho relaxation time and the apparent permeability would be inversely correlated with the T1rho relaxation time. METHODS:Eight cadaver human lumbar spines were imaged to measure T1rho relaxation times. The nucleus pulposus tissue from the L1 disc through the S1 disc was tested in confined compression to determine the swelling pressure, compressive modulus, and permeability. The glycosaminoglycan and water contents were measured in adjacent tissue. Linear regression analyses were performed to examine the correlation between the T1rho relaxation time and the other measured variables. Mechanical properties and biochemical content were evaluated for differences associated with degeneration. RESULTS:A positive linear correlation was observed between the T1rho relaxation time on the images of the nucleus pulposus and the swelling pressure (r = 0.59), glycosaminoglycan content per dry weight (r = 0.69), glycosaminoglycan per wet weight (r = 0.49), and water content (r = 0.53). No significant correlations were observed between the T1rho relaxation time and the modulus or permeability. Similarly, the T1rho relaxation time, swelling pressure, glycosaminoglycan content per dry weight, and water content were significantly altered with degeneration, whereas the modulus and permeability were not. CONCLUSIONS:T1rho-weighted magnetic resonance imaging has a strong potential as a quantitative biomarker of the mechanical function of the nucleus pulposus and of disc degeneration.

Endplate subsidence and vertebral body (VB) fracture are potential complications following lumbar total disc replacement (TDR) [1]. Early clinical evidence suggests that these events can be ameliorated in patients with osteopenia and osteoporosis by vertebral augmentation performed at the time of TDR [2]. However, the biomechanical basis to support vertebral augmentation of TDR has not been established. The objective of this study was to quantify the effects of vertebral augmentation with Cortoss on VB mechanics under compression by a TDR implant. We hypothesize that augmentation with Cortoss will improve the mechanical behavior in compression.