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Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression.

ABSTRACT: BACKGROUND: The present study was conducted to address whether the intervertebral disc of rabbit could be considered (i) as a valuable model to provide new insights into the tissue and cellular changes of Nucleus pulposus aging and (ii) as an appropriate tool to investigate the efficacy of Nucleus pulposus cell-based biotherapies. METHODS: Lumbar intervertebral disc from rabbits with increasing ages (1, 6 and 30 month-old) were compared by MRI and histological observation using Pfirrmann's grading and Boos' scoring respectively. The expression of transcripts (COL2A1, AGC1, COL1A1, MMP13, BMP2, MGP and p21) in Nucleus pulposus cells were analysed by quantitative real-time PCR. RESULTS: MRI analysis indicated an early age-dependent increase in the Pfirrmann's grading. Histological Boos' scoring was also increased. The analysis of transcript expression levels showed that COL2A1 and AGC1 were down-regulated as a function of age. Conversely, COL1A1, MMP-13, BMP-2, MGP and p21 were significantly up-regulated in the Nucleus pulposus cells of aged rabbit intervertebral disc. CONCLUSIONS: Our study describes the consistency of the rabbit as a model of intervertebral disc changes as a function of age by correlating tissue alteration with cellular modification measured.

SUBMITTER: Clouet J

PROVIDER: S-EPMC3150337 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression.

Clouet Johann J Pot-Vaucel Marianne M Grimandi Gaël G Masson Martial M Lesoeur Julie J Fellah Borhane H BH Gauthier Olivier O Fusellier Marion M Cherel Yan Y Maugars Yves Y Guicheux Jérôme J Vinatier Claire C

BMC musculoskeletal disorders 20110704

<h4>Background</h4>The present study was conducted to address whether the intervertebral disc of rabbit could be considered (i) as a valuable model to provide new insights into the tissue and cellular changes of Nucleus pulposus aging and (ii) as an appropriate tool to investigate the efficacy of Nucleus pulposus cell-based biotherapies.<h4>Methods</h4>Lumbar intervertebral disc from rabbits with increasing ages (1, 6 and 30 month-old) were compared by MRI and histological observation using Pfir ...[more]

PMID: 21726455

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Project description:ObjectiveTo analyze the two major components of the intervertebral disc (IVD) in an ex vivo phantom, as well as age-related changes in patients.MethodsCollagen and chondroitin sulfate were imaged at different concentrations in agar solution. Age-related changes in disc density were retrospectively analyzed in normal-appearing discs in dual-energy computed tomography (DECT) images from a patient cohort with various spinal pathologies (n = 136). All computed tomography (CT) scans were acquired using single-source DECT at 80 and 135 kVp with automatic exposure calculation. In 136 patients, the attenuation of normal-appearing discs on collagen/chondroitin maps (cMaps) correlated with the patients' age with Pearson's r using standardized regions of interest in the anterior anulus fibrosus (AAF) and nucleus pulposus (NP).ResultsDECT collagen mapping revealed concentration-dependent Hounsfield units (HU) of IVD components. For collagen, we found Pearson's r = 0.9610 (95% CI 0.6789-0.9959), p = 0.0023 at 120 kVe, and r = 0.8824 (95% CI 0.2495-0.9871), p = 0.0199 in cMap. For chondroitin sulfate, Pearson's r was 0.9583 (95% CI 0.6603-0.9956), p = 0.0026 at 120 kVp, and r = 0.9646 (95% CI 0.7044-0.9963), p = 0.0019 in cMap. Analysis of normal-appearing IVDs revealed an inverse correlation of density with age in the AAF: Pearson's r = - 0.2294 at 135 kVp (95% CI - 0.4012 to - 0.04203; p=0.0141) and r = - 0.09341 in cMap (95% CI - 0.2777 to 0.09754; p = 0.0003). In the NP, age and density did not correlate significantly at 135 kVp (p = 0.9228) and in cMap (p = 0.3229).ConclusionsDECT-based collagen mapping allows microstructural analysis of the two main intervertebral disc components-collagen and chondroitin sulfate. IVD density declines with age, presumably due to a reduction in collagen and chondroitin sulfate content. Age-related alterations of disc microstructure appear most pronounced in the AAF.Key points• DECT-based collagen mapping allows precise analysis of the two main intervertebral disc components-collagen and chondroitin sulfate. • Intervertebral disc (IVD) density declines with age, presumably due to a reduction in collagen and chondroitin sulfate content. • Age-related alterations of disc microstructure are most pronounced in the anterior anulus fibrosus (AAF).

Project description:Introduction:Estimation of intervertebral disc degeneration on magnetic resonance imaging (MRI) is challenging. Qualitative schemes used in clinical practice correlate poorly with pain and quantitative techniques have not entered widespread clinical use. Methods:As part of a prior study, 25 New Zealand white rabbits underwent annular puncture to induce disc degeneration in 50 noncontiguous lumbar discs. At 16?weeks, the animals underwent multi-echo T2 MRI scanning and were euthanized. The discs were stained and examined histologically. Quantitative T2 relaxation maps were prepared using the nonlinear least squares method. Decay Variance maps were created using a novel technique of aggregating the deviation in the intensity of each echo signal from the expected intensity based on the previous rate of decay. Results:Decay Variance maps showed a clear and well demarcated nucleus pulposus with a consistent rate of decay (low Decay Variance) in healthy discs that showed progressively more variable decay (higher Decay Variance) with increasing degeneration. Decay Variance maps required significantly less time to generate (1.0?±?0.0 second) compared with traditional T2 relaxometry maps (5 (±0.9) to 1788.9 (±116) seconds). Histology scores correlated strongly with Decay Variance scores (r = 0.82, P?<?.01) and weakly with T2 signal intensity (r = 0.32, P?<?.01) and quantitative T2 relaxometry (r = 0.39, P?<?.01). Decay Variance had superior sensitivity and specificity for the detection of degenerate discs when compared to T2 signal intensity or Quantitative T2 mapping. Conclusion:Our results show that using a multi-echo T2 MRI sequence, Decay Variance can quantitatively assess disc degeneration more accurately and with less image-processing time than quantitative T2 relaxometry in a rabbit disc puncture model. The technique is a viable candidate for quantitative assessment of disc degeneration on MRI scans. Further validation on human subjects is needed.

Project description:IntroductionLow-back pain (LBP) has been correlated to the presence of intervertebral disc (IVD) degeneration on T2-weighted (T2w) MRI. It remains challenging, however, to accurately stage degenerative disc disease (DDD) based on T2w MRI and measurements of IVD height, particularly for early DDD. Several quantitative MRI techniques have been introduced to detect changes in matrix composition signifying early DDD. In this study, we correlated quantitative T2, T1rho and Apparent Diffusion Coefficient (ADC) values to disc mechanical behavior and gold standard early DDD markers in a graded degenerated lumbar IVD caprine model, to assess their potential for early DDD detection.MethodsLumbar caprine IVDs were injected with either 0.25 U/ml or 0.5 U/ml Chondroïtinase ABC (Cabc) to trigger early DDD-like degeneration. Injection with phosphate-buffered saline (PBS) served as control. IVDs were cultured in a bioreactor for 20 days under axial physiological loading. High-resolution 9.4 T MR images were obtained prior to intervention and after culture. Quantitative MR results were correlated to recovery behavior, histological degeneration grading, and the content of glycosaminoglycans (GAGs) and water.ResultsCabc-injected IVDs showed aberrancies in biomechanics and loss of GAGs without changes in water-content. All MR sequences detected changes in matrix composition, with T1rho showing largest changes pre-to-post in the nucleus, and significantly more than T2 and ADC. Histologically, degeneration due to Cabc injection was mild. T1rho nucleus values correlated strongest with altered biomechanics, histological degeneration score, and loss of GAGs.ConclusionsT2- and T1rho quantitative MR-mapping detected early DDD changes. T1rho nucleus values correlated better than T2 and ADC with biomechanical, histological, and GAG changes. Clinical implementation of quantitative MRI, T1rho particularly, could aid in distinguishing DDD more reliably at an earlier stage in the degenerative process.

Dataset Information

Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression.

Publications

Characterization of the age-dependent intervertebral disc changes in rabbit by correlation between MRI, histology and gene expression.

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