Review
Magnetic resonance compositional imaging of articular cartilage: What can we expect in veterinary medicine?

https://doi.org/10.1016/j.tvjl.2015.04.035Get rights and content

Highlights

  • Compositional magnetic resonance imaging of cartilage aims to determine the biochemical composition of cartilage.

  • Technical issues still limit the use of some techniques for veterinary research or clinical practice.

  • dGEMRIC and T2 mapping seem to be most applicable for compositional imaging of animal cartilage.

  • GAG-CEST and sodium imaging are better used with high field magnets, which have limited availability.

  • Long acquisition times are sometimes required, for instance in T1ρ and diffusion-weighted imaging.

Abstract

Since cartilage has limited ability to repair itself, it is useful to determine its biochemical composition early in clinical cases. It is also important to assess cartilage content in research animals in longitudinal studies in vivo. In recent years, compositional imaging techniques using magnetic resonance imaging (MRI) have been developed to assess the biochemical composition of cartilage. This article describes MR compositional imaging techniques, and discusses their use and interpretation.

Technical concerns still limit the use of some techniques for research and clinical use, especially in veterinary medicine. Glycosaminoglycan chemical-exchange saturation transfer and sodium imaging are better used with high field magnets, which have limited availability. Long acquisition times are sometimes required, for instance in T1rho (ρ) and diffusion-weighted imaging, and necessitate general anaesthesia. Even in human medicine, some techniques such as ultra-short echo T2 are not fully validated, and nearly all techniques require validation for veterinary research and clinical practice. Delayed gadolinium-enhanced MRI of cartilage and T2 mapping appear to be the most applicable methods for compositional imaging of animal cartilage. Combining T2 mapping and T1ρ allows for the assessment of proteoglycans and the collagen network, respectively.

Introduction

Osteoarthritis (OA) is a degenerative process of the joint characterised by progressive degeneration of the articular cartilage and reduced joint function. Articular cartilage has biomechanical properties that are attributable to its extracellular matrix (ECM), which is composed of collagen, proteoglycans (PGs), hyaluronan (HA) and water (Lu and Mow, 2008).

Collagen fibres are organised into three zones (Fig. 1). In the radial zone, the fibres are perpendicular to the articular surface, forming rows; in the transitional zone, they overlap as thin lamellae, and in the superficial zone, they are tangential to the articular surface. This arcade-like orientation is involved in the dynamic behaviour of cartilage, reducing stresses in its deep part during loading and ensuring resistance to shearing forces in its superficial part (Halonen et al., 2013).

PGs are composed of a central core protein linked to hundreds of negatively charged polysaccharide chains called glycosaminoglycans (GAGs) and to HA (Fig. 1). Sulphate and carboxyl groups of GAGs carry negative charges (Maroudas et al., 1969). Each fixed negative charge requires a positive counter-ion (Na+) for the tissue to maintain overall electroneutrality. The high concentration of Na+ results in attraction to water.

Water linked to Na+ is called free water. It exists in two other forms when it is directly linked to collagen or PGs (Maroudas, 1976). When the joint is loaded, water flows through the ECM. Its flow is limited by the frictional resistance of collagen and attraction by ions. Water contributes to the viscoelastic behaviour of cartilage (Lu and Mow, 2008).

With progression of OA, synthesis is insufficient to compensate for the degradation of ECM; biochemical changes, such as a decrease in PGs and the degradation of collagen, occur as a consequence (Bijlsma et al., 2011). The alteration of the collagen network and the associated increase in water content modify the biomechanical properties of cartilage.

Since cartilage has limited ability to repair itself, biochemical changes associated with early OA should be identified as soon as possible in clinical cases. For research purposes, it would be extremely useful to determine the composition of cartilage in longitudinal studies in vivo. In recent years, compositional imaging techniques using magnetic resonance (MR) imaging have been developed to assess the biochemical composition of cartilage. This article reviews MR compositional imaging techniques and discusses their use and possible applications to veterinary medicine.

Section snippets

T2 mapping

The mobility of water protons varies with tissue type; it is high when protons are in free water and low when they are immobilised in ECM. This influences the transverse (T2) relaxation time, due to spin–spin (neighbouring) interactions (Watrin et al., 2001). In MR imaging (MRI) sequences highlighting T2 (T2 weighted, W), mobile water protons (e.g. in synovial fluid or in damaged collagen networks with increased free water content) give a hypersignal (long T2), whereas water protons immobilised

T2* mapping

In T2* mapping, when the radiofrequency (RF) pulse is 90°, the longitudinal magnetisation disappears and transverse magnetisation appears. The curve that represents the time needed for the transverse magnetisation to decrease should represent T2. This would be the case if the interaction between protons (spin–spin interaction) were the only reason for the reduction in phase coherence and for increasing entropy. However, the microscopic heterogeneity of the main field (i.e. constant

Ultra-short echo (UTE) – T2 mapping

Deep and calcified zones of articular cartilage, with their highly ordered collagen fibrils, limit the motion of protons. Protons are therefore more influenced by spin–spin interactions and lose phase coherence more quickly. T2 is very short, between 1 ms and 2 ms (Du et al., 2009). While standard T2 mapping uses echo times of 10 ms or more, UTE-T2 mapping uses echo times shorter than 1 ms (Bae et al, 2010, Williams et al, 2010). It has the potential to visualise cartilage at the osteochondral

T1rho (ρ) mapping

In the T1ρ technique, a supplementary low amplitude RF pulse is applied for a prolonged period of time during relaxation and appropriately aligned with the transverse magnetisation (Charagundla, 2004). The pulse, called spin-locking pulse, alters the tendency of the spin components to process at their own individual frequencies, instead locking them in an orientation aligned with the spin-locking pulse (Fig. 2). The magnetisation no longer relaxes according to T2, but instead relaxes according

Diffusion-weighted imaging (DWI)

DWI is based on the varying motion properties of water protons in different environments. Protons can move in all three directions in free water, but they are restricted by collagen or PG barriers in cartilage (Hagmann et al., 2006). In DWI, an RF pulse is applied with decreasing intensity over distance, the so-called ‘gradient pulse’. If the structure of the tissue allows diffusion (Fig. 3), such as when the direction of the gradient is parallel to the collagen fibres, the gradient pulse

Delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC)

Gadopentetate dimeglumine (Gd-DTPA2−), a contrast agent, can shorten T1 relaxation; an increased signal was demonstrated in a study comparing pre- and post-contrast images after IV injection of the agent (Bashir et al., 1996). Since the contrast is negatively charged and its concentration varies inversely from the concentration of the negatively charged GAGs, T1 is shorter in GAG-depleted cartilage. T1 values are mapped and translated in a colour scale. It can also be administered

Sodium imaging

In this technique, MRI targets the sodium nucleus, which is composed of 11 protons and 12 neutrons; the unequal number of protons and neutrons confers magnetic properties to sodium. In cartilage, sodium content is proportional to PG content, since it counter-balances the negative fixed charge density of GAGs. A loss of PG induces a decrease in FCD and thus a loss of sodium (Shapiro et al., 2002).

Though a better signal is obtained with high field magnets, imaging can be performed with a 1.5 T

GAG chemical-exchange saturation transfer (GAG-CEST) sequence

In conventional MRI, signals are detected from the protons of components (such as water) that have sufficiently long T2 relaxation times (>10 ms). The T2 of the restricted protons (with low mobility), such as protons of the amide group (−NH) and hydroxyl groups (−OH) of GAGs, are too short (<1 ms) to be detected.

An effect called ‘chemical exchange saturation transfer’ (CEST) refers to the induced exchange of protons between water and protons of specific molecules, such as GAGs (Fig. 1). For the

Applications in veterinary medicine

This review demonstrates that compositional imaging of cartilage in animals is primarily undertaken for research purposes, using small or large animal models. Technical concerns still limit the use of some techniques both for research and clinical use. Gag-CEST and sodium imaging necessitate high field magnets and long acquisition times (approximately 15 min and 20 min, respectively). UTE-T2 mapping has not been investigated in veterinary research. DWI was initially tested in vitro on fragments

Conclusions

So far, T2 mapping and dGEMRIC seem to be most applicable for compositional imaging of animal cartilage. Since the thickness of the cartilage varies with species, joints and anatomic sites in animals can be small and resolution must be optimised. The combination of T2 mapping and T1ρ might allow for the assessment of both PGs and the collagen network, respectively. Compositional imaging is currently a research tool rather than a clinical tool and it usually requires a high field magnet.

Conflict of interest statement

None of the authors of this paper has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of the paper.

Acknowledgements

This study was supported by the University of Namur (UNamur) and NARILIS (Namur Research Institute for Life Science).

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