Noninvasive quantification of human nucleus pulposus pressure with use of T1rho-weighted magnetic resonance imaging.

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.

The effect of relative needle diameter in puncture and sham injection animal models of degeneration.

STUDY DESIGN: Biomechanical study and literature review. OBJECTIVES: To quantify the acute effect of needle diameter on the in vitro mechanical properties of cadaver lumbar discs in the rat and sheep. To review published in vivo animal studies and evaluate disc changes with respect to the relative needle size. SUMMARY OF BACKGROUND DATA: There are many cases where a disc needle puncture or injection is applied to animal models: puncture injuries to induce degeneration, chemonucleolysis to induce degeneration, and delivery of disc therapies. It is not clear what role the size of the needle may have in the outcome. METHODS: Mechanics were measured after sham phosphate buffered saline injection with a 27 G or 33 G needle in the rat and with a 27 G needle in the sheep. A literature review was performed to evaluate studies in which animal discs were treated with a needle puncture or a sham injection. For each study, the ratio of the needle diameter to disc height (needle:height) was calculated. RESULTS: When the rat was injected with a 27 G needle (52% of disc height), the compression, tension, and neutral zone stiffnesses were 20% to 60% below preinjected values and the neutral zone length was 130% higher; when injected with a 33 G needle (26% of disc height), the only affected property was the neutral zone length, which was only 20% greater. When the sheep was injected with a 27 G needle (10% of disc height), none of the axial properties were different from intact, the torsion stiffness was not different, and the torque range was 15% smaller. Twenty-three in vivo studies in the rat, rabbit, dog, or sheep were reviewed. The disc changes depended on the ratio of needle diameter to disc height as follows: significant changes were not observed for needle:height less than 40%, although between 25% and 40% results were variable and some minor nonsignificant effects were observed, disc changes were universal for needle:height over 40%. CONCLUSION: A needle puncture may directly alter mechanical properties via nucleus pulposus depressurization and/or anulus fibrosus damage, depending on the relative needle size. As more basic science research is aimed at treating disc degeneration via injection of therapeutic factors, these findings provide guidance in design of animal studies. Such studies should consider the relative needle size and include sham control groups to account for the potential effects of the needle injection.

Human internal disc strains in axial compression measured noninvasively using magnetic resonance imaging.

STUDY DESIGN: Internal deformations and strains were measured within intact human motion segments. OBJECTIVE: Quantify 2-dimensional internal deformation and strain in compression of human intervertebral discs using MRI. SUMMARY OF BACKGROUND DATA: Experiments using radiographic or optical imaging have provided important data for internal disc deformations. However, these studies are limited by physical markers and/or disruption of the disc structural integrity. METHODS: MR images were acquired before and during application of a 1000 N axial compression. Two-dimensional internal displacements, average strains, and the location and direction of peak strains were calculated using texture correlation, a pattern matching algorithm. RESULTS: The average height loss was 0.4 mm, which corresponded to 4.4% compressive strain. The inner AF radial displacement was outward, even with degeneration; the average outward displacement of the inner AF (0.16 mm) was less than the outer AF (0.36 mm). High shear peak strains (2%-26%) occurred near the endplate and at the inner AF. Shear was higher in the anterior AF compared to the posterior. CONCLUSION: This technique allows quantification of displacement and strain within the intact disc. The radial displacements of inner AF suggest NP translation under compression. Peak tensile radial strains occurred as vertical bands throughout the anulus, which may contribute to radial tears and herniations. The tensile axial and shear strains at the interface between the AF and endplate could be related to the occurrence of rim lesions. Peak strains at the endplate are likely due to the AF curvature and the oblique fibers angle at fiber insertion sites. In the future, this technique may be used to measure disc strain under a variety of loading conditions, such as bending or torsion, and could also be used to study the mechanical effects of disc degeneration and potential clinical interventions.

Disc mechanics with trans-endplate partial nucleotomy are not fully restored following cyclic compressive loading and unloaded recovery.

Mechanical function of the intervertebral disc is maintained through the interaction between the hydrated nucleus pulposus, the surrounding annulus fibrosus, and the superior and inferior endplates. In disc degeneration the normal transfer of load between disc substructures is compromised. The objective of this study was to explore the mechanical role of the nucleus pulposus in support of axial compressive loads over time. This was achieved by measuring the elastic slow ramp and viscoelastic stress-relaxation mechanical behaviors of cadaveric sheep motion segments before and after partial nucleotomy through the endplate (keeping the annulus fibrosus intact). Mechanics were evaluated at five conditions: Intact, intact after 10,000 cycles of compression, acutely after nucleotomy, following nucleotomy and 10,000 cycles of compression, and following unloaded recovery. Radiographs and magnetic resonance images were obtained to examine structure. Only the short time constant of the stress relaxation was altered due to nucleotomy. In contrast, cyclic loading resulted in significant and large changes to both the stiffness and stress relaxation behaviors. Moreover, the nucleotomy had little to no effect on the disc mechanics after cyclic loading, as there were no significant differences comparing mechanics after cyclic loading with or without the nucleotomy. Following unloaded recovery the mechanical changes that had occurred as a consequence of cyclic loading were restored, leaving only a sustained change in the short time constant due to the trans-endplate nucleotomy. Thus the swelling and redistribution of the remaining nucleus pulposus was not able to fully restore mechanical behaviors. This study reveals insights into the role of the nucleus pulposus in disc function, and provides new information toward the potential role of altered nucleus pulpous function in the degenerative cascade.

Assessment of human disc degeneration and proteoglycan content using T1rho-weighted magnetic resonance imaging.

STUDY DESIGN: T1rho relaxation was quantified and correlated with intervertebral disc degeneration and proteoglycan content in cadaveric human lumbar spine tissue. OBJECTIVE: To show the use of T1rho-weighted magnetic resonance imaging (MRI) for the assessment of degeneration and proteoglycan content in the human intervertebral disc. SUMMARY OF BACKGROUND DATA: Loss of proteoglycan in the nucleus pulposus occurs during early degeneration. Conventional MRI techniques cannot detect these early changes in the extracellular matrix content of the disc. T1rho MRI is sensitive to changes in proteoglycan content of articular cartilage and may, therefore, be sensitive to proteoglycan content in the intervertebral disc. METHODS: Intact human cadaveric lumbar spines were imaged on a clinical MR scanner. Average T1rho in the nucleus pulposus was calculated from quantitative T1rho maps. After MRI, the spines were dissected, and proteoglycan content of the nucleus pulposus was measured. Finally, the stage of degeneration was graded using conventional T2 images. RESULTS: T1rho decreased linearly with increasing degeneration (r = -0.76, P < 0.01) and age (r = -0.76, P < 0.01). Biochemical analysis revealed a strong linear correlation between T1rho and sulfated-glycosaminoglycan content. T1rho was moderately correlated with water content. CONCLUSIONS: Results from this study suggest that T1rho may provide a tool for the diagnosis of early degenerative changes in the disc. T1rho-weighted MRI is a noninvasive technique that may provide higher dynamic range than T2 and does not require a high static field or exogenous contrast agents.

In vivo quantification of human lumbar disc degeneration using T(1rho)-weighted magnetic resonance imaging.

Diagnostic methods and biomarkers of early disc degeneration are needed as emerging treatment technologies develop (e.g., nucleus replacement, total disc arthroplasty, cell therapy, growth factor therapy) to serve as an alternative to lumbar spine fusion in treatment of low back pain. We have recently demonstrated in cadaveric human discs an MR imaging and analysis technique, spin-lock T(1rho)-weighted MRI, which may provide a quantitative, objective, and non-invasive assessment of disc degeneration. The goal of the present study was to assess the feasibility of using T(1rho) MRI in vivo to detect intervertebral disc degeneration. We evaluated ten asymptomatic 40-60-year-old subjects. Each subject was imaged on a 1.5 T whole-body clinical MR scanner. Mean T(1rho) values from a circular region of interest in the center of the nucleus pulposus were calculated from maps generated from a series of T(1rho)-weighted images. The degenerative grade of each lumbar disc was assessed from conventional T(2)-weighted images according to the Pfirmann classification system. The T(1rho) relaxation correlated significantly with disc degeneration (r=-0.51, P<0.01) and the values were consistent with our previous cadaveric study, in which we demonstrated correlation between T(1rho) and proteoglycan content. The technique allows for spatial measurements on a continuous rather than an integer-based scale, minimizes the potential for observer bias, has a greater dynamic range than T(2)-weighted imaging, and can be implemented on a 1.5 T clinical scanner without significant hardware modifications. Thus, there is a strong potential to use T(1rho) in vivo as a non-invasive biomarker of proteoglycan loss and early disc degeneration.

Trans-endplate nucleotomy increases deformation and creep response in axial loading.

Knowledge of the functional role of the nucleus pulposus is critical for the development and evaluation of disc treatment strategies to restore mechanical function. While previous motion segment studies have shown that nucleotomy alters disc mechanics, disruption of the annulus fibrosus may have influenced these experiments. The objective of this study was to determine the mechanical role of the nucleus pulposus in support of axial loads via a trans-endplate nucleotomy procedure. Sheep motion segments were randomly assigned to three groups: control, limited nucleotomy, and radical nucleotomy. Mechanical testing consisted of 20 cycles of compression-tension, a 1-h creep, and a slow constant-rate compressive ramp test. Nucleotomy led to increased axial deformations, in particular an elongated neutral zone, a greater range of motion, and altered creep behavior. In general, the elastic properties exhibited a graded response with respect to the amount of nucleus material removed. This graded effect can be attributed to swelling of the nucleus pulposus in the limited nucleotomy group, whereas little swelling was observed in the radical group. The findings of the present study indicate that functional evaluation of nucleus pulposus replacements and disc implants should include range of motion measures (including neutral zone) and viscoelastic creep experiments in addition to considering compressive stiffness.

Effects of degeneration on the biphasic material properties of human nucleus pulposus in confined compression.

STUDY DESIGN: The biphasic compressive material properties of normal and degenerate human nucleus pulposus tissue were measured in confined compression. OBJECTIVES: The objective of this study was to determine the effects of degeneration and age on the mechanical properties of human nucleus pulposus. SUMMARY OF BACKGROUND DATA: The nucleus pulposus exhibits swelling behavior in proportion to proteoglycan content. In shear, the nucleus exhibits both fluid-like and solid-like properties, suggesting a biphasic nature. To date, biphasic compressive properties of human nucleus pulpous have not been reported. METHODS: Human nucleus pulposus samples were tested in confined compression. Isometric swelling stress and effective aggregate modulus were measured. Linear biphasic theory was used to determine the permeability of the tissue. Mechanical behavior was correlated with proteoglycan and water content. RESULTS: Degeneration produced significant decreases in swelling stress (Psw = 0.138 +/- 0.029 MPa nondegenerate, Psw = 0.037 +/- 0.038 MPa degenerate) and effective aggregate modulus (H(A)(eff) = 1.01 +/- 0.43 MPa nondegenerate, H(A)(eff) = 0.44 +/- 0.19 MPa degenerate). Both properties were inversely correlated with proteoglycan content. Permeability increased with degeneration (ka = 0.9 +/- 0.43 x 10(-15) m4/N-s nondegenerate, ka = 1.4 +/- 0.58 x 10(-15) m4/N-s degenerate). CONCLUSIONS: Swelling is the primary load-bearing mechanism in both nondegenerate and degenerate nucleus pulposus. Knowledge of the biphasic material properties of the nucleus pulposus will aid the development of new treatment strategies for disc degeneration aimed at restoring mechanical function of the intervertebral disc.

Intervertebral disc mechanics are restored following cyclic loading and unloaded recovery.

The objectives of this study were (1) to quantify changes in the mechanical behavior of the intervertebral disc in response to cyclic compressive loading and (2) to determine whether mechanical behavior would be restored following a period of unloading. The elastic and viscoelastic compressive mechanical behaviors of adult sheep motion segments were assessed. Ten thousand cycles of compressive loading resulted in increased elastic stiffness and decreased stress-relaxation. After 18 h of unloading in a PBS bath stiffness and relaxation were fully restored. Cyclic loading did not cause structural damage as determined by radiographs and magnetic resonance images. After cyclic loading, average stiffness increased from 603 to 800 N/mm (p = 0.015) and returned to initial levels after the recovery period. Cyclic loading caused a decrease in total relaxation (from 92 to 38 N, p < 0.001) that also returned to initial levels after recovery. The reversible, repeatable effects of cyclic loading and recovery demonstrated in this in vitro study may be attributed to fluid flow. Intervertebral disc fluid transport during the diurnal recovery cycle may be key to understanding intervertebral disc degeneration, as fluid exudation and recovery may be integral to maintaining adequate disc nutrition.

Effect of fiber orientation and strain rate on the nonlinear uniaxial tensile material properties of tendon.

Tendons are exposed to complex loading scenarios that can only be quantified by mathematical models, requiring a full knowledge of tendon mechanical properties. This study measured the anisotropic, nonlinear, elastic material properties of tendon. Previous studies have primarily used constant strain-rate tensile tests to determine elastic modulus in the fiber direction. Data for Poisson's ratio aligned with the fiber direction and all material properties transverse to the fiber direction are sparse. Additionally, it is not known whether quasi-static constant strain-rate tests represent equilibrium elastic tissue behavior. Incremental stress-relaxation and constant strain-rate tensile tests were performed on sheep flexor tendon samples aligned with the tendon fiber direction or transverse to the fiber direction to determine the anisotropic properties of toe-region modulus (E0), linear-region modulus (E), and Poisson's ratio (v). Among the modulus values calculated, only fiber-aligned linear-region modulus (E1) was found to be strain-rate dependent. The E1 calculated from the constant strain-rate tests were significantly greater than the value calculated from incremental stress-relaxation testing. Fiber-aligned toe-region modulus (E(1)0 = 10.5 +/- 4.7 MPa) and linear-region modulus (E1 = 34.0 +/- 15.5 MPa) were consistently 2 orders of magnitude greater than transverse moduli (E(2)0 = 0.055 +/- 0.044 MPa, E2 = 0.157 +/- 0.154 MPa). Poisson's ratio values were not found to be rate-dependent in either the fiber-aligned (v12 = 2.98 +/- 2.59, n = 24) or transverse (v21 = 0.488 +/- 0.653, n = 22) directions, and average Poisson's ratio values in the fiber-aligned direction were six times greater than in the transverse direction. The lack of strain-rate dependence of transverse properties demonstrates that slow constant strain-rate tests represent elastic properties in the transverse direction. However, the strain-rate dependence demonstrated by the fiber-aligned linear-region modulus suggests that incremental stress-relaxation tests are necessary to determine the equilibrium elastic properties of tendon, and may be more appropriate for determining the properties to be used in elastic mathematical models.