The Quantitative Structural and Compositional Analyses of Degenerating Intervertebral Discs Using Magnetic Resonance Imaging and Contrast-Enhanced Micro-Computed Tomography

Lin, Kevin; Tang, Simon Y.

doi:10.1007/s10439-017-1891-8

Cited by 18 publications

(22 citation statements)

References 40 publications

(42 reference statements)

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“…30 Quantitative magnetic resonance imaging (MRI) has been successfully applied to assess disc condition in humans and a range of animal models, including rats. 27,[35][36][37] T2 relaxation time, specifically, has been validated as an effective surrogate for disc composition, including hydration state and proteoglycan content. [38][39][40] To our knowledge, few studies have applied quantitative MRI to determine T2 relaxation values to assess disc condition in murine models, 37 and none, to our knowledge, have done so in mice.…”

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confidence: 99%

Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration

Piazza

Peck

Gullbrand

et al. 2018

Journal Orthopaedic Research

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Low back pain due to disc degeneration is a major cause of morbidity and health care expenditures worldwide. While stem cell-based therapies hold promise for disc regeneration, there is an urgent need to develop improved in vivo animal models to further develop and validate these potential treatments. The objectives of this study were to characterize a percutaneous needle injury model of intervertebral disc degeneration in the mouse caudal spine, and compare two non-invasive quantitative imaging techniques, microcomputed tomography and magnetic resonance imaging (MRI), as effective measures of disc degeneration in this model. Percutaneous needle injury of mouse caudal discs was undertaken using different needle sizes and injury types (unilateral or bilateral annulus fibrosus (AF) puncture). Mice were euthanized 4 weeks post-injury, and MRI and microcomputed tomography were used to determine T2 relaxation time of the NP and disc height index, respectively. Disc condition was then further assessed using semi-quantitative histological grading. Bilateral AF puncture with either 27 or 29G needles resulted in significantly lower T2 relaxation times compared to uninjured controls, while disc height index was not significantly affected by any injury type. There was a strong, inverse linear relationship between histological grade and NP T2 relaxation time. In this study, we demonstrated that quantitative MRI can detect disc degeneration in the mouse caudal spine 4 weeks following percutaneous needle injury, and may therefore serve as a surrogate for histology in longitudinal studies of both disc degeneration and cell-based therapies for disc regeneration using this model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2771-2779, 2018.

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confidence: 99%

Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration

Piazza

Peck

Gullbrand

et al. 2018

Journal Orthopaedic Research

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“…This approach was previously demonstrated in several ex vivo rodent models of IVD degeneration, and it achieved superior spatial resolution compared with microMRI. 9,10 By delivering Ioversol through tail-vein injection at a physiologically compatible dose, Ioversol was biologically available and accumulated preferentially in the IVD to increase the attenuation of all the scanned IVDs. We obtained disc height and volume measures of the IVDs expected from the aging mouse IVD.…”

Section: Resultsmentioning

confidence: 99%

“…To date, this is the first study to describe the in vivo use of CEμCT for the imaging of the mouse intervertebral disc. This approach was previously demonstrated in several ex vivo rodent models of IVD degeneration, and it achieved superior spatial resolution compared with microMRI . By delivering Ioversol through tail‐vein injection at a physiologically compatible dose, Ioversol was biologically available and accumulated preferentially in the IVD to increase the attenuation of all the scanned IVDs.…”

Section: Discussionmentioning

confidence: 99%

“…With a high molecular weight, 807.115 g/mol, Ioversol reduces the x‐rays that can pass through the tissue and increases the attenuation of blood vessels, organs, and other nonmineralized tissues. We have previously reported on a contrast‐enhanced microCT (CEμCT) technique using Ioversol to monitor and quantify IVD degeneration in vitro and ex vivo . Extending this work further, the objective of this study is to explore and validate the in vivo use of CEμCT technique using Ioversol to examine intervertebral discs at multiple spinal sites using growing and adult FVB/NJ mice.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously reported on a contrast-enhanced microCT (CEμCT) technique using Ioversol to monitor and quantify IVD degeneration in vitro and ex vivo. 9,10 Extending this work further, the objective of this study is to explore and validate the in vivo use of CEμCT technique using Ioversol to examine intervertebral discs at multiple spinal sites using growing and adult FVB/NJ mice.…”

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confidence: 99%

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In vivo contrast‐enhanced microCT for the monitoring of mouse thoracic, lumbar, and coccygeal intervertebral discs

Walk

Tang

2019

JOR Spine

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Mouse models are often used for studies of intervertebral disc (IVD) homeostasis and degeneration, yet the relatively small size of the IVD poses challenges for noninvasive, longitudinal imaging modalities. The recently developed contrast‐enhanced microCT (CEμCT) using Ioversol has been successful in detecting degenerative changes in the murine IVD ex vivo at the micrometer scale. Further leveraging the superior biocompatibility of Ioversol as a contrast agent, we demonstrate the in vivo use of this CEμCT technique to examine IVDs at multiple spinal sites. Ioversol was administered via tail vein injection (TVI) in growing and adult male FVB/NJ mice (n = 5 /group). The animals were anesthetized and underwent in vivo micro‐computed tomographic (microCT) at the coccygeal (CC5/CC6), lumbar (L5/6), and thoracic (T12/T13) IVDs. TVI of Ioversol was well‐tolerated by all animals. As Ioversol filtered through the kidneys and accumulated in the bladder, the attenuations of the mouse bladder and kidneys increased due to the high molecular weight of Ioversol, confirming that the Ioversol is biological available. Average IVD attenuations increased 3%‐15% following TVI (ANOVA; P < .01). The presence of Ioversol in the IVD combined with high‐resolution microCT allow for nondestructive visualization of structural features of the IVD. These results demonstrate CEμCT with Ioversol as a viable strategy for the in vivo monitoring of multiple mouse IVDs during degeneration, disease, and injury.

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Nondestructive, indirect assessment of the biomechanical properties of the rat intervertebral disc using contrast‐enhanced μCT

Newton

Hartner

Gawronski

et al. 2018

Journal Orthopaedic Research

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Mechanical characterization of the intervertebral disc involves labor-intensive and destructive experimental methodology. Contrast-enhanced micro-computed tomography is a nondestructive imaging modality for high-resolution visualization and glycosaminoglycan quantification of cartilaginous tissues. The purpose of this study was to determine whether anionic and cationic contrast-enhanced micro-computed tomography of the intervertebral disc can be used to indirectly assess disc mechanical properties in an ex vivo model of disc degeneration. L3/L4 motion segments were dissected from female Lewis rats. To deplete glycosaminoglycan, samples were treated with 0 U/ml (Control) or 5 U/ml papain. Contrast-enhanced micro-computed tomography was performed following incubation in 40% Hexabrix (anionic) or 30 mg I/ml CA (cationic) for 24 h (n = 10/contrast agent/digestion group). Motion segments underwent cyclic mechanical testing to determine compressive and tensile modulus, stiffness, and hysteresis. Glycosaminoglycan content was determined using the dimethylmethylene blue assay. Correlations between glycosaminoglycan content, contrast-enhanced micro-computed tomography attenuation, and mechanical properties were assessed via the Pearson correlation. The predictive accuracy of attenuation on compressive properties was assessed via repeated random sub-sampling cross validation. Papain digestion produced significant decreases in glycosaminoglycan content and corresponding differences in attenuation and mechanical properties. Attenuation correlated significantly to glycosaminoglycan content and to all compressive mechanical properties using both Hexabrix and CA . Predictive linear regression models demonstrated a predictive accuracy of attenuation on compressive modulus and stiffness of 79.8-86.0%. Contrast-enhanced micro-computed tomography was highly predictive of compressive mechanical properties in an ex vivo simulation of disc degeneration and may represent an effective modality for indirectly assessing disc compressive properties. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2030-2038, 2018.

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The Quantitative Structural and Compositional Analyses of Degenerating Intervertebral Discs Using Magnetic Resonance Imaging and Contrast-Enhanced Micro-Computed Tomography

Cited by 18 publications

References 40 publications

Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration

Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration

In vivo contrast‐enhanced microCT for the monitoring of mouse thoracic, lumbar, and coccygeal intervertebral discs

Nondestructive, indirect assessment of the biomechanical properties of the rat intervertebral disc using contrast‐enhanced μCT

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