In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI
Introduction
The articular cartilage can be thought of as a fiber-reinforced anisotropic composite material. The mechanical properties of articular cartilage are a function of the essential mechanical properties of the tissue components and the interplay of these components during loading. Articular cartilage is a bi-phasic material: the permeable solid section is represented by a solid matrix that consists of collagen fibers and proteoglycan molecules, and the fluid section is composed of extracellular water with dissolved ions and nutrients. Most of the fluid can move through the collagen network during loading. Experimental data from articular cartilage can be assessed by single-, bi- or multi-phasic models [1], [2], [3], [4].
The mechanical properties of articular cartilage arise from the complex structure and interactions of its biochemical constituents: mostly water, electrolytes, and a solid matrix composed primarily of collagen and proteoglycan. Laasanen et al. showed that collagen primarily controls the dynamic tissue response while proteoglycans affect more the static properties [5]. In the ex-vivo study published by Appleyard et al. there was found a strong and significant correlation between shear modulus and collagen content, whereas correlation between shear modulus and water content was not significant [6]. Stiffness and strength of articular cartilage tissue depended on the density and orientation of collagen fibers, and the type or amount of collagen cross-linking [7].
Various imaging methods have been applied to assess articular cartilage. These include standard radiography [8], CT arthrography [9], ultrasonography [10], and MR imaging [11], [12]. MRI offers excellent soft tissue contrast and multi-planar imaging capability, and therefore, it has become the method of choice to diagnose cartilage diseases. It also provides valuable information on composition and structural changes in cartilage. For determination of glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was developed and has been used to answer clinical questions [13], [14]. Since transversal relaxation time, T2, is related to collagen matrix composition and is primarily influenced by collagen fiber orientation [15] and water content [16], T2 has been successfully used for in vitro [17] and in vivo [18], [19] cartilage tissue assessment. Another useful parameter that reflects the functional properties of cartilage tissue is diffusivity. The idea of using gradients to make the MR imaging signal sensitive to the molecular motion of water was introduced by Stejskal and Tanner in 1965 [20], and currently, there are a few sequences based on diffusion weighting that have been successfully used for evaluation of cartilage function and its structure [21], [22], [23], [24].
The mechanical properties of articular cartilage can be evaluated on different levels, from an in vivo investigation of intact joints by indentation [25] to in vitro studies of explants [26] and to cellular and molecular levels [26]. For viscoelastic materials like cartilage, two biomechanical parameters play a role: firstly the instantaneous modulus (I), which describes the initial stiffness upon loading, and secondly the equilibrium modulus (Eq) which describes only the time independent share of the stiffness. The ratio between I and Eq gives a measure of the viscoelastic character. If I/Eq is close to unity the material is merely elastic, and is better termed spontaneous elastic. If I/Eq is greater than two, the material is strongly viscoelastic. For cartilage it may be said that the smaller I/Eq the more vital is the cartilage, which means it is able to better withstand static loading (carrying heavy loads for instance) as well as fast and extremely high load cycles (from jumping or running for instance). The mechanical properties of cartilage tissue are strongly related to the OA stage of cartilage [27]. Changes in the biomechanical properties of articular cartilage are one of the first signs of the tissue degeneration. For cartilage degeneration, it is necessary to know how cartilage maintains its functionality and how cartilage responds to the ever-changing mechanical environment. The biomechanical properties of articular cartilage can be assessed relatively precisely, however, ex-vivo [28] or invasively during an arthroscopic procedure [29]. MRI provides the possibility to non-invasively assess the biomechanical properties of articular cartilage provides MRI. In the past, several studies suggested the way how MRI parameters might be used for biomechanical parameters assessment [28], [30], [31]. However, to the best of our knowledge, the correlation between biomechanical properties and MR parameters of degenerated human articular cartilage stages has not been previously determined.
Therefore, in the presented study we hypothesized that biochemical parameters derived non-invasively from MRI as a non-invasive imaging method can predict the biomechanical properties of naturally degenerated human articular cartilage. Thus the aim of this work was to determine the correlation of MR relaxation times and diffusion constants at 3 T with an instantaneous and an equilibrium modulus.
Section snippets
Sample preparation
Bone-cartilage specimens from patients who underwent total knee replacement surgery in an orthopedic hospital were delivered to our laboratory, several hours after surgery, in a frozen state. Thirteen specimens were harvested from the same site of the weight bearing area in lateral femoral condyles with different stages of osteoarthritis. Samples with extensively eroded cartilage tissue were excluded from the study. The size of the sample was chosen in order to fit into the micro-imaging device
Results
Histological evaluation revealed seven samples with mild OA, four with moderate OA and one with advanced OA.
In the comparison between mechanical properties and MRI parameters of cartilage samples in different OA stages a high correlation for some parameters was found, e.g., the correlation between I/Eq and bulk [Gd-DTPA] (r = 0.9320). In general, T1Gd and [Gd-DTPA] were in high correlation with the majority of the tested mechanical parameters, moreover, T1Gd correlated with Eq, I/Eq ratio and τ
Discussion
This study revealed a high correlation between some quantitative MR parameters (post-contrast T1 and contrast agent concentration) and biomechanical parameters (Eq, I/Eq, and τ) in naturally degenerated human articular cartilage.
It is generally accepted that the biomechanical properties of articular cartilage depend on the biochemical composition, the ultrastructural organization, and the interaction of the matrix molecules. Since alterations of the structural and biochemical properties are one
Acknowledgments
The authors thank Dr. Reinhard Fuiko for providing cartilage specimens. Funding for this study was provided by the Austrian Science Fund (FWF) FWF—Project P-18110-B15 and Slovak Scientific Grant Agency VEGA 2/0142/08.
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2021, Journal of BiomechanicsCitation Excerpt :Previous studies with bovine and leporine articular cartilage have associated the OA-related changes in the constituent-specific mechanical parameters with structure and composition (Julkunen et al., 2009, 2007; Mäkelä et al., 2014). In humans, cartilage structure has been extensively evaluated using microscopy and magnetic resonance imaging, but the function is primarily characterized using only simple elastic properties of the tissue (Juras et al., 2009; Kaplan et al., 2017; Rautiainen et al., 2015; Robinson et al., 2016). Further, only a few studies have reported relationships between constituent-specific mechanical properties and tissue structure at different stages of osteoarthritis in humans (Ebrahimi et al., 2020, 2019; Julkunen et al., 2008; Kaplan et al., 2017; Mäkelä et al., 2012).
Bi-component T2 mapping correlates with articular cartilage material properties
2021, Journal of BiomechanicsCitation Excerpt :Correlation coefficients between MRI parameters and PG content were 0.73 to 0.82 for dGEMRIC (Tiel et al., 2016; Watanabe et al., 2006), −0.24 to −0.48 for T2 (Keenan et al., 2015; Li et al., 2011), and −0.04 to −0.64 for T1p (Keenan et al., 2011; Li et al., 2011; Tiel et al., 2016). Correlation coefficients between MRI parameters and elastic modulus were 0.81 for dGEMRIC (Juras et al., 2009), −0.16 for T1ρ (Keenan et al., 2011), and −0.09 to −0.47 for T2 (Juras et al., 2009; Keenan et al., 2011). One study reported a correlation coefficient of −0.32 between T1ρ and energy dissipation (Tang et al., 2011).