Changes In Lumbar Intervertebral Discs Research Articles

Application of a semiautomatic classifier for modic and disk hernia changes in magnetic resonance

OBJECTIVE: Early detection of degenerative changes in lumbar intervertebral disc by magnetic resonance imaging in a semiautomatic classifier for prevention of degenerative disease. METHOD: MRIs were selected with a diagnosis of degenerative disc disease or back pain from January to May 2014, with a sample of 23 patients and a total of 170 disks evaluated by sagittal T2 MRI image, first evaluated by a specialist physician in training and them were introduced into the software, being the results compared. RESULTS: One hundred and fifteen discs were evaluated by a programmed semiautomatic classifier to identify MODIC changes and hernia, which produced results "normal or MODIC" and "normal or abnormal", respectively. With a total of 230 readings, of which 141 were correct, 84 were reading errors and 10 readings were undiagnosed, the semiautomatic classifier is a useful tool for early diagnosis or established disease and is easy to apply because of the speed and ease of use; however, at this early stage of development, software is inferior to clinical observations and the results were from around 65% to 60% certainty for MODIC rating and 61% to 58% for disc herniation, compared with clinical evaluations. CONCLUSION: The comparative results between the two doctors were 94 consistent results and only 21 errors, which represents 81% certainty.

Age related reduction of T1rho and T2 magnetic resonance relaxation times of lumbar intervertebral disc.

This report aims to study the age related T1rho and T2 relaxation time changes in lumbar intervertebral disc. Lumbar sagittal magnetic resonance imaging (MRI) was performed with a 3 Tesla scanner in 52 subjects. With a spin-lock frequency of 500 Hz, T1rho was measured using a rotary echo spin-lock pulse embedded in a 3D balanced fast field echo sequence. A multi-echo turbo spin echo sequence was used for T2 mapping. Regions-of-interest were drawn over the T1rho and T2 maps, including nucleus pulposus and annulus fibrosus. For L1/2-L4/5 discs, results showed the age associated reduction of T1rho of nucleus pulposus had a of slope of -1.06, the reduction of T2 of nucleus pulposus had a slope of -1.47, the reduction of T1rho of annulus fibrosus had a slope of -0.25, and the reduction of T2 of annulus fibrosus had a slope of -0.18, with all the slopes significantly non-zero. In nucleus pulposus the slope of T2 was slightly steeper than that of T1rho (P=0.085), while in annulus fibrosus the slope of T1rho was slightly steeper than that of T2 (P=0.31). We conclude that significant age related reduction of T1rho and T2 magnetic resonance relaxation times of lumbar intervertebral disc was observed, however, the relative performances of T1rho vs. T2 were broadly similar.

N-Cadherin-Mediated Cell Signaling in Nucleus Pulposus Cells of the Intervertebral Disc

Introduction Immature nucleus pulposus (NP) cells of the intervertebral disc (IVD) are large, vacuolated cells that form cell clusters with strong cell-cell interactions.1 With maturation and aging, NP cells lose their ability to form these cell clusters, with aging-associated changes in NP cell phenotype, morphology, and proteoglycan synthesis that may contribute to IVD degeneration.2-4 Therefore it is important to understand the mechanisms governing immature NP cell cluster behavior toward the goal of revealing factors that can promote immature, healthy NP cell phenotypes. Prior work has shown healthy, immature NP cells preferentially bind laminin proteins, exhibit potential for cell cluster formation, and maintain matrix production when cultured upon soft, laminin-containing substrates.2 N-cadherin has been identified as a cell-cell adhesion marker that is present in immature NP cells, but disappears with age.5-6 The goal of this study was to determine if N-cadherin was an important molecule in regulating cell-cell interactions in immature NP cell cluster formation and to test for a regulatory role in maintaining an immature NP phenotype for IVD cells in vitro. Materials and Methods Porcine nucleus pulposus (NP) cells were isolated from IVD of immature pigs (3-6 mos).2 Laminin-rich substrates were constructed from basement membrane extract (BME, 13.7 mg/mL, Trevigen) to generate soft (300 Pa) or stiff (BME-coated glass, > 2,900 Pa) substrates; similar substrates were constructed of “soft” and “stiff” type I collagen (col 1, 4 mg/mL, Sigma). NP cells were plated (65,000 cells/cm2) on the substrates with the following treatment conditions for up to 4 days: N-cadherin (40 μg/mL) blocking antibody, E-cadherin (20 μg/mL) blocking antibody or no treatment control. NP cells were stained for polymerized F-actin (phalloidin, Invitrogen), anti-N-cadherin (Abcam), or anti-E-cadherin (Abcam) antibodies with propidium iodide nuclei counterstain. Changes in matrix production were analyzed in collected media and recovered cells via biochemical assays for sGAG (DMMB assay) and DNA (picogreen). Additionally, gene expression for immature NP markers, N-cadherin, Brachyury-T, aggrecan and type I collagen, were analyzed via quantitative real-time PCR. Results NP cells cultured upon soft BME substrates maintained their rounded morphology at all times with formation of 3D cell clusters ( Fig. 1A ). On stiff BME and all col 1 substrates, NP cells spread out and attached with formation of numerous actin stress fibers. Higher N-cadherin expression was observed on soft BME compared with all other substrates; E-cadherin expression was absent in porcine NP cells on all substrates. Additionally, significantly higher matrix production was observed on soft BME substrates compared with soft col 1 ( Fig. 1B ), and higher gene expression for NP markers was observed on soft BME substrates compared with all other substrates ( Fig. 1C ). NP cell cluster formation, proteoglycan synthesis and NP marker gene expression on soft BME substrates was influenced by N-cadherin blocking antibody but not E-cadherin blocking antibody ( Fig. 1A -C). [Figure: see text] Conclusion Soft BME substrates promote NP cell clustering in vitro with an associated expression of N-cadherin. In NP cells, it appears that N-cadherin-mediated signaling helps promote matrix production and elevated expression for multiple molecular markers of an immature NP phenotype. Treatment with an N-cadherin blocking antibody resulted in loss of all features of the immature NP cell on soft BME substrates. These findings establish the importance of N-cadherin in mediating immature NP cell cluster formation and maintenance of the immature phenotype. Ongoing studies aim to understand the downstream signaling mechanisms governed by N-cadherin-mediated signaling that promote the immature NP phenotype. Acknowledgments This study was supported with funds from NIH R01EB002263, R01AR047442, R01AR057410, T32GM008555, North Carolina Biotechnology Center, and with the NSF Graduate Research Fellowship. Disclosure of Interest None declared References Trout JJ, Buckwalter JA, Moore KC, Landas SK. Ultrastructure of the human intervertebral disc. I. Changes in notochordal cells with age. Tissue Cell 1982;14(2):359–369 Gilchrist CL, Darling EM, Chen J, Setton LA. Extracellular matrix ligand and stiffness modulate immature nucleus pulposus cell-cell interactions. PLoS ONE 2011;6(11):e27170 Boos N, Weissbach S, Rohrbach H, Weiler C, Spratt KF, Nerlich AG. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine 2002;27(23):2631–2644 Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine 1995;20(11):1307–1314 Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA. Transcriptional profiling of bovine intervertebral disc cells: implications for identification of normal and degenerate human intervertebral disc cell phenotypes. Arthritis Res Ther 2010;12(1):R22 Minogue BM, Richardson SM, Zeef LA, Freemont AJ, Hoyland JA. Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation. Arthritis Rheum 2010;62(12):3695–3705

The involvement of ADAMTS‐5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

Low back pain is a global health problem in which more than 40% is caused by lumbar intervertebral disc degeneration (LDD). ADAMTS-5 (A disintegrin and metalloproteinase with thrombospondin motifs-5) was shown to be involved in LDD by functional analyses. To identify whether there is an association between ADAMTS-5 and LDD, and what is the contribution of ADAMTS-5 genetic polymorphisms to MD (Mean diffusivity) changes in lumbar IVD (Intervertebral disc). We firstly genotyped selected ADAMTS-5 SNPs (Single nucleotide polymorphisms) in a Chinese Han population. After the primary analyses of allelic, genotypic, and haplotypic association, we performed SNP-SNP interaction analysis. We subsequently genotyped another 50 participants and acquired the corresponding MD values from individual lumbar IVDs. The association analysis between the genotypic groups divided by the above positive SNPs and the corresponding MD values were also performed. Significant associations were identified in rs151058, rs229052, and rs162502. None of the 2-SNP haplotypic analysis survived the 10,000 permutation test. The following interaction analysis demonstrated that rs151058 was strong associated with LDD when conditioning on rs162502. Significant difference of MD values between AA and G+ carriers was identified in rs162502. This is the first study indicating that the SNPs of ADAMTS-5 may contribute to predisposition of LDD. An interaction between rs151058 and rs229052 may exist in ADAMTS-5 with LDD. The rs162502 might be associated with altered MD values.

Three-dimensional morphological and signal intensity features for detection of intervertebral disc degeneration from magnetic resonance images

Advances in MRI hardware and sequences are continually increasing the amount and complexity of data such as those generated in high-resolution three-dimensional (3D) scanning of the spine. Efficient informatics tools offer considerable opportunities for research and clinically based analyses of magnetic resonance studies. In this work, we present and validate a suite of informatics tools for automated detection of degenerative changes in lumbar intervertebral discs (IVD) from both 3D isotropic and routine two-dimensional (2D) clinical T2-weighted MRI. An automated segmentation approach was used to extract morphological (traditional 2D radiological measures and novel 3D shape descriptors) and signal appearance (extracted from signal intensity histograms) features. The features were validated against manual reference, compared between 2D and 3D MRI scans and used for quantification and classification of IVD degeneration across magnetic resonance datasets containing IVD with early and advanced stages of degeneration. Combination of the novel 3D-based shape and signal intensity features on 3D (area under receiver operating curve (AUC) 0.984) and 2D (AUC 0.988) magnetic resonance data deliver a significant improvement in automated classification of IVD degeneration, compared to the combination of previously used 2D radiological measurement and signal intensity features (AUC 0.976 and 0.983, respectively). Further work is required regarding the usefulness of 2D and 3D shape data in relation to clinical scores of lower back pain. The results reveal the potential of the proposed informatics system for computer-aided IVD diagnosis from MRI in large-scale research studies and as a possible adjunct for clinical diagnosis.

AB0674 Spine osteoarthritis - clinical and morphological comparisons

BackgroundSpine osteoarthritisis one of the leading places in the structure of the Rheumatic Diseases. Until recently, the degeneration of the intervertebral disc (IVD), reflected in the reduction of the number...

Association between visual degeneration of intervertebral discs and the apparent diffusion coefficient

The value of apparent diffusion coefficient (ADC) measurements in intervertebral disc has been studied because ADC provides an estimate of free diffusion of unbound water and could be used as a quantitative tool to estimate degenerative changes. However, the challenging nature of diffusion imaging of spine and limited numbers of subjects in earlier studies has produced contradictory findings. We aimed to determine the relation between ADC and visual degenerative changes in lumbar intervertebral discs in a sufficiently large homogeneous study group. Lumbar spines of 228 volunteer middle-aged men were MR imaged at 1.5 T including anatomic and diffusion-weighted imaging. ADC values, T2 signal intensity and height, and width of the three lowest lumbar intervertebral discs were measured and disc degeneration visually graded. The calculated average ADC of 530 measured discs was 2.01 x 10(-3) mm(2)/s+/-0.29 (+/-S.D.). The reduction in ADC between visually normal and moderately degenerated discs was 4%. Severely degenerated discs showed 5% larger ADC values than normal discs, presumably due to free water in cracks and fissures of those discs. T2 signal intensity of the disc was significantly correlated with the ADC values, whereas other measured parameters did not show correlation. There was no evident difference in ADC between the studied anatomic lumbar levels. Because there is considerable overlap between ADC values of normal and degenerated discs, we conclude that ADC measurements of intervertebral discs, at least with current technology, have limited clinical value.

Transabdominal ultrasonography in the diagnosis of lumbar disc herniation

The aim of our study was to assess the value of transabdominal ultrasonography in the diagnosis of a lumbar herniated disc and to investigate the influence of the quality of the ultrasonography investigation on detection of pathological changes in lumbar intervertebral disc. 119 patients (55 female, 64 male, mean age 41 years) were included in our study. Patients were suffering from lower back pain and were investigated by transabdominal ultrasonography, using a 3.5 MHz scanner. The results of the ultrasonography investigation were compared with MRI and intraoperative findings The quality of the ultrasonography documentation shows distinct differences between the segments of the lower lumbar spine (L3/4 86.6 %, L4/5 85.7 %, L5/S1 70.6 %). The sonographic evaluations were correct in 75.4 % of cases. Sensitivity of ultrasonography for the detection of an intradiscal lesion was 0.46 for L3/4, 0.83 for L4/5 and 0.78 for L5/S1. Specificity was 0.91 for L3/4, 0.65 for L4/5 and 0.67 for L5/S1. Compared to MRI investigation transabdominal ultrasonography of the lumbar herniated disc proved to be distinctly inferior because of methodical limitations and lower diagnostic accuracy. This method, however, can be used as a preliminary diagnostic procedure.

Classification of Age-Related Changes in Lumbar Intervertebral Discs

Study Design. A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. Objectives. To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. Summary of the Background Data. No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). Methods. A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. Results. A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (κ values, 0.49–0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age (P < 0.0001) and macroscopic grade of degeneration (P < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. Conclusions. Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.

Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science.

A histologic study on age-related changes of the human lumbar intervertebral disc was conducted. To investigate comprehensively age-related temporospatial histologic changes in human lumbar intervertebral disc, and to develop a practicable and reliable classification system for age-related histologic disc alteration. No comprehensive microscopic analysis of age-related disc changes is available. There is no conceptual morphologic framework for classifying age-related disc changes as a reference basis for more sophisticated molecular biologic analyses of the causative factors of disc aging or premature aging (degeneration). A total of 180 complete sagittal lumbar motion segment slices obtained from 44 deceased individuals (fetal to 88 years of age) were analyzed with regard to 11 histologic variables for the intervertebral disc and endplate, respectively. In addition, 30 surgical specimens (3 regions each) were investigated with regard to five histologic variables. Based on the semiquantitative analyses of 20,250 histologic variable assessments, a classification system was developed and tested in terms of validity, practicability, and reliability. The classification system was applied to cadaveric and surgical disc specimens not included in the development of the classification system, and the scores were assessed by two additional independent raters. A semiquantitative analyses provided clear histologic evidence for the detrimental effect of a diminished blood supply on the endplate, resulting in the tissue breakdown beginning in the nucleus pulposus and starting in the second life decade. Significant temporospatial variations in the presence and abundance of histologic disc alterations were observed across levels, regions, macroscopic degeneration grades, and age groups. A practicable classification system for age-related histologic disc alterations was developed, resulting in moderate to excellent reliability (kappa values, 0.49-0.98) depending on the histologic variable. Application of the classification system to cadaveric and surgical specimens demonstrated a significant correlation with age ( < 0.0001) and macroscopic grade of degeneration ( < 0001). However, substantial data scatter caution against reliance on traditional macroscopic disc grading and favor a histology-based classification system as a reference standard. Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.

An Observation of Ruptured Annulus Fibrosus in Lumbar Discs

To observe anatomical or pathological changes in lumbar intervertebral discs, discography and computed tomography-discography (CTD) were performed on fresh human cadavers. The results of discograms and CTD were compared with histological findings of cross sections of discs. Preoperative CTD of lumbar disc herniation was investigated based on these results. Ruptures of the annulus fibrosus were divided into two categories: circumferential rupture and radial rupture. In CTD images of fresh human cadavers, most images of rupture of the annulus fibrosus showed anterior to lateral circumferential rupture. As disc degeneration progressed, circumferential rupture tended to coexist with radial rupture in many cases. In CTD cases of lumbar disc herniation, most images of ruptures of the annulus fibrosus showed a posterior radial rupture, which was the route for herniated nucleus. The greater the degree of degeneration, the more the images tended to show radial ruptures coexisting with circumferential ruptures.