Diffusion tensor microscopy of the intervertebral disc anulus fibrosus

Object The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration. Methods Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery. Results The 18- and 21-gauge needle–stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP–anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O– and collagen type II–stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration. Conclusions After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.

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Changes in mRNA and Protein Levels of Proteoglycans of the Anulus Fibrosus and Nucleus Pulposus During Intervertebral Disc Degeneration

Spine ◽

10.1097/00007632-200210150-00006 ◽

2002 ◽

Vol 27 (20) ◽

pp. 2212-2219 ◽

Cited By ~ 140

Author(s):

Gabriella Cs-Szabo ◽

Deborah Ragasa-San Juan ◽

Vani Turumella ◽

Koichi Masuda ◽

Eugene J-M.A. Thonar ◽

...

Keyword(s):

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Anulus Fibrosus ◽

Protein Levels

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Age-dependent microstructural changes of the intervertebral disc: a validation of proteoglycan-sensitive spectral CT

European Radiology ◽

10.1007/s00330-021-08028-z ◽

2021 ◽

Author(s):

Julian Pohlan ◽

Carsten Stelbrink ◽

Matthias Pumberger ◽

Dominik Deppe ◽

Friederike Schömig ◽

...

Keyword(s):

Computed Tomography ◽

Intervertebral Disc ◽

Chondroitin Sulfate ◽

Ex Vivo ◽

Microstructural Analysis ◽

Inverse Correlation ◽

Anulus Fibrosus ◽

Sulfate Content ◽

Age Related ◽

Age Related Changes

Abstract Objective To analyze the two major components of the intervertebral disc (IVD) in an ex vivo phantom, as well as age-related changes in patients. Methods Collagen 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). Results DECT 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). Conclusions DECT-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).

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