Purpose

To measure the T2* of the human cartilaginous end plate by using magnetic resonance (MR) imaging with very short echo times and to determine the effect of the orientation of the end plate on T2* and on relationships between T2* and biochemical composition.

Materials and methods

This study was exempt from institutional review board approval, and informed consent was not required. Thirty-four samples of three cadaveric lumbar spines (from subjects who died at ages 51, 57, and 66 years) containing cartilaginous end plates and subchondral bone were prepared. Samples were imaged with a 3-T imager for T2* quantification by using a three-dimensional very short echo time sequence (repetition time msec/echo times msec, 30/0.075, 2, 5, 12, 18). Samples were imaged with the end plate at three orientations with respect to the constant magnetic induction field: 0°, 54.7°, and 90°. After imaging, the cartilage was assayed for its water, glycosaminoglycan, and collagen content. Pearson correlations were used to investigate the effect of orientation on the relationships between T2* and biochemical composition.

Results

T2* was significantly longer when measured at an orientation of 54.7° (21.8 msec ± 2.8 [± standard error of the mean]) than at 0° (10.0 msec ± 0.7, P < .001) or 90° (9.9 msec ± 0.4, P < .001). At 54.7°, T2* was highly correlated with glycosaminoglycan content (r = 0.85, P < .001), the collagen-to-glycosaminoglycan ratio (r = -0.79, P < .001), and water content (r = 0.62, P = .02); at 0° and 90°, there were no significant differences in these relationships, with a minimum P value of .19.

Conclusion

T2* evaluation can allow noninvasive estimation of the degeneration of the cartilaginous end plate; however, the accuracy of T2*-based estimates of biochemical composition depends on the orientation of the end plate.

To provide mechanistic insight into the etiology of osteoporotic wedge fractures, we investigated the spatial distribution of tissue at the highest risk of initial failure within the human vertebral body for both forward flexion and uniform compression loading conditions. Micro-CT-based linear elastic finite element analysis was used to virtually load 22 human T9 vertebral bodies in either 5° of forward flexion or uniform compression; we also ran analyses replacing the simulated compliant disc (E=8 MPa) with stiff polymethylmethacrylate (PMMA, E=2500 MPa). As expected, we found that, compared to uniform compression, forward flexion increased the overall endplate axial load on the anterior half of the vertebra and shifted the spatial distribution of high-risk tissue within the vertebra towards the anterior aspect of the vertebral body. However, despite that shift, the high-risk tissue remained primarily within the central regions of the trabecular bone and endplates, and forward flexion only slightly altered the ratio of cortical-to-trabecular load sharing at the mid-vertebral level (mean±SD for n=22: 41.3±7.4% compression; 44.1±8.2% forward flexion). When the compliant disc was replaced with PMMA, the anterior shift of high-risk tissue was much more severe. We conclude that, for a compliant disc, a moderate degree of forward flexion does not appreciably alter the spatial distribution of stress within the vertebral body.

Nutrient and metabolite transport through the cartilage endplate (CEP) is important for maintaining proper disc nutrition, but the mechanisms of solute transport remain unclear. One unresolved issue is the role of dynamic loading. In comparison to static loading, dynamic loading is thought to enhance transport by increasing convection. However, the CEP has a high resistance to fluid flow, which could limit solute convection. Here we measure solute transport through site-matched cadaveric human lumbar CEP tissues under static vs. dynamic loading, and we determine how the degree of transport enhancement from dynamic loading depends on CEP porosity and solute size. We found that dynamic loading significantly increased small and large solute transport through the CEP: on average, dynamic loading increased the transport of sodium fluorescein (376 Da) by a factor of 1.85 ± 0.64 and the transport of a large dextran (4000 Da) by a factor of 4.97 ± 3.05. Importantly, CEP porosity (0.65 ± 0.07; range: 0.47-0.76) strongly influenced the degree of transport enhancement. Specifically, for both solutes, transport enhancement was greater for CEPs with low porosity than for CEPs with high porosity. This is because the CEPs with low porosity were susceptible to larger improvements in fluid flow under dynamic loading. The CEP becomes less porous and less hydrated with aging and as disc degeneration progresses. Together, these findings suggest that as those changes occur, dynamic loading has a greater effect on solute transport through the CEP compared to static loading, and thus may play a larger role in disc nutrition.

Background context

Magnetic resonance imaging (MRI) has limited diagnostic value for chronic low back pain because of the unclear relationship between any anatomic abnormalities on MRI and pain reported by the patient. Assessing the innervation of end plate and disc pathologies-and determining the relationship between these pathologies and any abnormalities seen on MRI-could clarify the sources of back pain and help identify abnormalities with enhanced diagnostic value.

Purpose

To quantify innervation in the vertebral end plate and intervertebral disc and to relate variation in innervation to the presence of pathologic features observed by histology and conventional MRI.

Study design/setting

A cross-sectional histology and imaging study of vertebral end plates and intervertebral discs harvested from human cadaver spines.

Methods

We collected 92 end plates and 46 intervertebral discs from seven cadaver spines (ages 51-67 years). Before dissection, the spines were scanned with MRI to grade for Modic changes and high-intensity zones (HIZ). Standard immunohistochemical techniques were used to localize the general nerve marker protein gene product 9.5. We quantified innervation in the following pathologies: fibrovascular end-plate marrow, fatty end-plate marrow, end-plate defects, and annular tears.

Results

Nerves were present in the majority of end plates with fibrovascular marrow, fatty marrow, and defects. Nerve density was significantly higher in fibrovascular end-plate marrow than in normal end-plate marrow (p<.001). Of the end plates with fibrovascular and fatty marrow, less than 40% were Modic on MRI. Innervated marrow pathologies collocated with more than 75% of the end plate defects; hence, innervation was significantly higher in end plate defects than in normal end plates (p<.0001). In the disc, nerves were observed in only 35% of the annular tears; in particular, innervation in radial tears tended to be higher than in normal discs (p=.07). Of the discs with radial tears, less than 13% had HIZ on T2 MRI. Innervation was significantly less in radial tears than in fibrovascular end-plate marrow (p=.05) and end-plate defects (p=.02).

Conclusions

These findings indicate that vertebral end-plate pathologies are more innervated than intervertebral disc pathologies and that many innervated end-plate pathologies are not detectable on MRI. Taken together, these findings suggest that improved visualization of end-plate pathologies could enhance the diagnostic value of MRI for chronic low back pain.

Cartilage endplate (CEP) biochemical composition may influence disc degeneration and regeneration. However, evaluating CEP composition in patients remains a challenge. We used T2* mapping from ultrashort echo-time (UTE) magnetic resonance imaging (MRI), which is sensitive to CEP hydration, to investigate spatial variations in CEP T2* values and to determine how CEP T2* values correlate with adjacent disc degeneration. Thirteen human cadavers (56.4 ± 12.7 years) and seven volunteers (36.9 ± 10.9 years) underwent 3T MRI, including UTE and T1ρ mapping sequences. Spatial mappings of T2* values in L4-S1 CEPs were generated from UTE images and compared between subregions. In the abutting discs, mean T1ρ values in the nucleus pulposus were compared between CEPs with high vs low T2* values. To assess in vivo repeatability, precision errors in mean T2* values, and intraclass correlation coefficients (ICC) were measured from repeat scans. Results showed that CEP T2* values were highest centrally and lowest posteriorly. In the youngest individuals (<50 years), who had mild-to-moderately degenerated Pfirrmann grade II-III discs, low CEP T2* values associated with severer disc degeneration: T1ρ values were 26.7% lower in subjects with low CEP T2* values (P = .025). In older individuals, CEP T2* values did not associate with disc degeneration (P = .39-.62). Precision errors in T2* ranged from 1.7 to 2.6 ms, and reliability was good-to-excellent (ICC = 0.89-0.94). These findings suggest that deficits in CEP composition, as indicated by low T2* values, associate with severer disc degeneration during the mild-to-moderate stages. Measuring CEP T2* values with UTE MRI may clarify the role of CEP composition in patients with mild-to-moderate disc degeneration.

Purpose of review

The endplates form the interface between the rigid vertebral bodies and compliant intervertebral discs. Proper endplate function involves a balance between conflicting biomechanical and nutritional demands. This review summarizes recent data that highlight the importance of proper endplate function and the relationships between endplate dysfunction, adjacent disc degeneration, and axial low back pain.

Recent findings

Changes to endplate morphology and composition that impair its permeability associate with disc degeneration. Endplate damage also associates with disc degeneration, and the progression of degeneration may be accelerated and the chronicity of symptoms heightened when damage coincides with evidence of adjacent bone marrow lesions.

Summary

The endplate plays a key role in the development of disc degeneration and low back pain. Clarification of the mechanisms governing endplate degeneration and developments in clinical imaging that enable precise evaluation of endplate function and dysfunction will distinguish the correlative vs. causative nature of endplate damage and motivate new treatments that target pathologic endplate function.

Study design

Experimental and computational assessment of thickness, porosity, biomechanical behavior, and adjacent disc glycosaminoglycan content in double- and single-layer bony endplate samples harvested from human cadaver spines.

Objective

To determine if the second layer of bone in double-layer vertebral endplates allows the superficial layer to achieve a more optimal balance between its biomechanical and nutritional functions.

Summary of background data

Proper disc health requires the endplate to balance opposing biomechanical and nutritional functions. Previous studies investigating endplate function report seeing double: some endplates have a second layer of bone. However, it remains unclear whether the second layer of bone has any functional advantage. Such information could shed light on the factors that protect against disc degeneration.

Methods

Six lumbar spines were obtained from human cadavers (32-84 yr) and scanned with magnetic resonance imaging. Cylindrical cores that included the endplate and underlying trabecular bone were harvested from the center of the superior vertebral endplates (6 double- and 12 single-layer endplates) and imaged using micro-computed tomography. The thickness and porosity of the bony endplate layers were measured for each core. High-resolution finite element analysis was performed to assess biomechanical behavior. Glycosaminoglycan content within the adjacent nucleus tissue was quantified using the dimethylmethylene blue technique.

Results

The superficial layer of the double-layer endplates was 50% thinner (P = 0.009) and tended also to be more porous than single-layer endplates. Strains were higher in thinner endplates; however, the second layer of bone in the double-layer endplates had a stiffening effect so that despite being thinner than single-layer endplates, the superficial layer of the double-layer endplates had a similar risk of damage. After adjusting for age, glycosaminoglycan content was significantly higher in the nucleus tissue adjacent to the double-layer endplates (P = 0.01).

Conclusion

Compared with single-layer endplates, double-layer endplates seem to permit a more optimal balance between endplate biomechanical and nutritional functions, and may therefore offer a significant protective factor against disc degeneration.

How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechano-responsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.

How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechano-responsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.

Individual trabecula segmentation (ITS) technique can decompose the trabecular bone network into individual trabecular plates and rods and is capable of quantifying the plate/rod-related microstructural characteristics of trabecular bone. This novel technique has been shown to be able to provide in-depth insights into micromechanics and failure mechanisms of human trabecular bone, as well as to distinguish the fracture status independent of area bone mineral density in clinical applications. However, the plate/rod microstructural parameters from ITS have never been correlated to experimentally determined mechanical properties of human trabecular bone. In this study, on-axis cylindrical trabecular bone samples from human proximal tibia (n=22), vertebral body (n=10), and proximal femur (n=21) were harvested, prepared, scanned using micro computed-tomography (µCT), analyzed with ITS and mechanically tested. Regression analyses showed that the plate bone volume fraction (pBV/TV) and axial bone volume fraction (aBV/TV) calculated by ITS analysis correlated the best with elastic modulus (R(2)=0.96-0.97) and yield strength (R(2)=0.95-0.96). Trabecular plate-related microstructural parameters correlated highly with elastic modulus and yield strength, while most rod-related parameters were found inversely and only moderately correlated with the mechanical properties. In addition, ITS analysis also identified that trabecular bone at human femoral neck had the highest trabecular plate-related parameters while the other sites were similar with each other in terms of plate-rod microstructure.