Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo

Gullbrand, Sarah E.; Peterson, Joshua; Mastropolo, Rosemarie; Roberts, Timothy T.; Lawrence, James P.; Glennon, Joseph C.; DiRisio, Darryl J.; Ledet, Eric H.

doi:10.1016/j.spinee.2014.12.003

Cited by 40 publications

(37 citation statements)

References 26 publications

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“…In general, higher T2 values are interpreted as high hydration. However, this is a simplified model since T2 values reflect not only the composition between proteoglycans, collagen, and water but also depend on tissue anisotropy, i.e., matrix organization [ 14 , 15 , 21 , 22 , 29 , 30 ]. Why certain EPZs respond to load in different ways are obviously complex and probably multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Axial loading during MRI induces significant T2 value changes in vertebral endplates—a feasibility study on patients with low back pain

et al. 2018

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Background: The function of the endplate (EP) is the most important factor influencing nutritional supply to the avascular intervertebral disc (IVD). It is desired to have a non-invasive method to assess functional EP characteristics in vivo. Assessment of functional EP characteristics is important in order to understand its relation to IVD degeneration, which in turn might deepen the understanding of the pathophysiology behind low back pain (LBP). It was hypothesized that, by comparing quantitative MRI of EPs performed with conventional supine MRI (unloaded MRI) with axial loading during MRI (alMRI), dynamical properties of the EP can be displayed. The aim was therefore to investigate the feasibility of axial loading during MRI (alMRI) to instantaneously induce quantitative EP changes. Methods: T2 mapping of 55 vertebral EPs (L1-S1) in five LBP patients was performed during conventional supine MRI (unloaded MRI) and subsequent alMRI. With T2 mapping, the cartilaginous EP and bony EP cannot be separated; hence, the visualized EP was termed EP zone (EPZ). Each EPZ was segmented at multiple midsagittal views, generating volumetric regions of interest. EPZs demonstrating signal inhomogeneity and/or adjacent Modic changes (MC) were termed abnormal EPZs. EPZ mean T2 values were compared between unloaded MRI and alMRI, and their relationship with abnormal EPZs was determined. Results: alMRI induced significantly higher (p = 0.01) EPZ mean T2 values compared with unloaded MRI. Significantly higher mean T2 values were seen in inferior EPZs compared with superior EPZs, both with unloaded MRI (35%, p < 0.001) and with alMRI (26%, p = 0.04). Significant difference between unloaded MRI and alMRI was seen in normal (p = 0.02), but not in abnormal EPZs (p = 0.5; n = 12). Conclusions: alMRI induces changes in human EPZ characteristics in vivo. The T2 value significantly increased in normal EPZs, with lack of such in abnormal EPZs. Combining T2 mapping with alMRI provides a clinical feasible, non-invasive method with potential to reveal biochemical behavioral patterns, thus adding another dimension of the EPZs characteristics compared with information obtained with solely unloaded MRI.

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Section: Discussionmentioning

confidence: 99%

Axial loading during MRI induces significant T2 value changes in vertebral endplates—a feasibility study on patients with low back pain

et al. 2018

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“…The difference in T2-value most likely reflects known structural differences in EP and vertebral composition. It has been shown in vitro and in animal studies that the inferior EP is thicker, is stiffer, resists load better and has different transport kinetics in comparison with superior EPs [17]. Moreover, the difference in tissue composition between EPs at different positions has indirectly been shown in humans as superior EPs being more prone to burst fractures [18].…”

Section: Discussionmentioning

confidence: 99%

Low back pain patients and controls display functional differences in endplates and vertebrae measured with T2-mapping

2018

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Purpose The aim was to (1) verify our previous finding that endplates (EPs) display load-induced T2-changes, (2) investigate whether vertebrae display load-induced T2-changes and (3) investigate whether EPs and vertebrae in LBP patients and controls display T2-differences during conventional unloaded MRI and axial loaded MRI (alMRI). Methods Twenty-seven patients (mean 39 years) and 12 (mean 38 years) controls were examined with T2-mapping on a 1.5 T scanner during conventional unloaded MRI and subsequently during alMRI (Dynawell ® loading device), separated by approximately 20 min. For determination of EP and vertebral T2-values, volumetric regions of interest were manually segmented. Each vertebra was then divided into half to obtain superior and inferior units. The presence of EP changes (visual inhomogeneity in the EP zone), Schmorl's nodules and Modic changes were registered. Results For conventional unloaded MRI, the T2-values in the superior and inferior vertebral units and the EPs were significantly higher in the patients compared with controls (p < 0.03, p < 0.006) even when adjusted for the presence of Modic changes, Schmorl's nodules and EP signal changes. alMRI induced significant changes in the superior EPs of the patients (p < 0.001). Additionally, the T2-value differed significantly between the superior and inferior EP, as well as between the superior and inferior vertebra with higher values in the inferior units (p < 0.001). Conclusion This study demonstrated significantly higher EP and vertebral T2-values in LBP patients in comparison with controls. In addition, alMRI induced significant T2-changes in the superior EPs for patients but not for controls. Importantly, the T2-differences between the groups may indicate that EPs and vertebrae in LBP patients have altered biodynamical characteristics compared to controls and the higher T2-values measured in patients may represent early inflammation or impaired nutritional transport.Graphical abstract These slides can be retrieved from electronic supplementary material.

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“…Static compressive loading has been shown to induce changes in cell biosynthesis and gene expression for collagens and proteoglycans, and protease activation, as well as cell death when applied in vivo and to explants or isolated cells. Static compressive loading is thought to inhibit nutrient transport and necessary gas exchange that may be essential for promoting cellular biosynthesis and maintaining cell survival, whereas dynamic compression promotes convection that increases large molecular weight nutrient uptake into the disc. Interestingly, transport of small molecules such as oxygen and glucose are predominantly governed by diffusion rather than convection that are modulated under dynamic loading.…”

Section: Mechanical Loading Effects On Ivd Cellsmentioning

confidence: 99%

Mechanotransduction and cell biomechanics of the intervertebral disc

et al. 2018

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Mechanical loading of the intervertebral disc (IVD) initiates cell-mediated remodeling events that contribute to disc degeneration. Cells of the IVD, nucleus pulposus (NP) and anulus fibrosus (AF), will exhibit various responses to different mechanical stimuli which appear to be highly dependent on loading type, magnitude, duration, and anatomic zone of cell origin. Cells of the NP, the innermost region of the disc, exhibit an anabolic response to low-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure, while higher magnitudes promote a catabolic response marked by increased protease expression and activity. Cells of the outer AF are responsive to physical forces in a manner that depends on frequency and magnitude, as are cells of the NP, though they experience different forces, deformations, pressure, and osmotic pressure in vivo. Much remains to be understood of the mechanotransduction pathways that regulate IVD cell responses to loading, including responses to specific stimuli and also differences among cell types. There is evidence that cytoskeletal remodeling and receptor-mediated signaling are important mechanotransduction events that can regulate downstream effects like gene expression and posttranslational biosynthesis, all of which may influence phenotype and bioactivity. These and other mechanotransduction events will be regulated by known and to-be-discovered cell-matrix and cell-cell interactions, and depend on composition of extracellular matrix ligands for cell interaction, matrix stiffness, and the phenotype of the cells themselves. Here, we present a review of the current knowledge of the role of mechanical stimuli and the impact upon the cellular response to loading and changes that occur with aging and degeneration of the IVD.

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Low rate loading-induced convection enhances net transport into the intervertebral disc in vivo

Cited by 40 publications

References 26 publications

Axial loading during MRI induces significant T2 value changes in vertebral endplates—a feasibility study on patients with low back pain

Axial loading during MRI induces significant T2 value changes in vertebral endplates—a feasibility study on patients with low back pain

Low back pain patients and controls display functional differences in endplates and vertebrae measured with T2-mapping

Mechanotransduction and cell biomechanics of the intervertebral disc

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