Monitoring Cartilage Tissue Engineering Using Magnetic Resonance Spectroscopy, Imaging, and Elastography

Abstract

A key technical challenge in cartilage tissue engineering is the development of a noninvasive method for monitoring the composition, structure, and function of the tissue at different growth stages. Due to its noninvasive, three-dimensional imaging capabilities and the breadth of available contrast mechanisms, magnetic resonance imaging (MRI) techniques can be expected to play a leading role in assessing engineered cartilage. In this review, we describe the new MR-based tools (spectroscopy, imaging, and elastography) that can provide quantitative biomarkers for cartilage tissue development both in vitro and in vivo. Magnetic resonance spectroscopy can identify the changing molecular structure and alternations in the conformation of major macromolecules (collagen and proteoglycans) using parameters such as chemical shift, relaxation rates, and magnetic spin couplings. MRI provides high-resolution images whose contrast reflects developing tissue microstructure and porosity through changes in local relaxation times and the apparent diffusion coefficient. Magnetic resonance elastography uses low-frequency mechanical vibrations in conjunction with MRI to measure soft tissue mechanical properties (shear modulus and viscosity). When combined, these three techniques provide a noninvasive, multiscale window for characterizing cartilage tissue growth at all stages of tissue development, from the initial cell seeding of scaffolds to the development of the extracellular matrix during construct incubation, and finally, to the postimplantation assessment of tissue integration in animals and patients.

Reduction of water diffusion coefficient with increased engineered cartilage matrix growth observed using MRI

“…However, many challenges remain unaddressed in realizing the full potential of this treatment path. Foremost among the technical challenges is the lack of noninvasive monitoring of tissue growth at all stages, from cell seeding to post-implantation [2]. This is important in order (a) to assess the efficacy of tissue engineering approaches at an early growth stage, (b) for providing an accurate assessment of engineered tissue growth postimplantation, and (c) for monitoring the healing of cartilage after treatment.…”

“…This is important in order (a) to assess the efficacy of tissue engineering approaches at an early growth stage, (b) for providing an accurate assessment of engineered tissue growth postimplantation, and (c) for monitoring the healing of cartilage after treatment. Magnetic resonance imaging (MRI) is a leading non-invasive characterization technique for monitoring growth in cartilage tissue engineering [2][3][4][5][6][7]. Research Cartilage tissue in its native state contains chondrocytes (~1%) imbedded in an extracellular matrix (ECM).…”

“…The diffusion-weighted MRI (dMRI) and particularly, the water apparent diffusion coefficient (ADC) has been used to probe the growth in cartilage tissue engineering [2]. Miyata et al [12] found a strong negative correlation of relative ADC (rADC, where rADC = ADC sample /ADC PBS , PBS = phosphate buffer saline) with an increasing amount of GAG as a function of the growth period in chondrocyte/agarose disks.…”

Biological and MRI characterization of biomimetic ECM scaffolds for cartilage tissue regeneration

“…Magnetic Resonance Imaging (MRI) is ideal for measuring the growth dynamics of cartilage tissue [12-14]. Our recent review article summarizes the development in the field of non-invasive monitoring of engineered cartilage using magnetic resonance techniques [12]. MRI observes the interaction of water protons with its surrounding and provides information about tissue microstructure non-invasively.…”

Monitoring Tissue Engineering and Regeneration by Magnetic Resonance Imaging and Spectroscopy

“…MRS is an established technique to investigate the atomic level structure and molecular dynamics of biological samples, whereas MRI provides volumetric maps of tissue based on the spin density, relaxation times, or diffusion of water protons or other high abundance NMR visible nuclei (such as sodium in cartilage tissue and phosphorous in bone tissue) [27][28][29][30]. The changes in the structure and composition of the growing tissue is reflected in changes in MR parameters, such as chemical shift, line broadening, T1 and T2 relaxation times, diffusion coefficient and many other MR expressed parameters [19,20,31]. These MR-visible parameters reflect the physical and biological environment around the observed nuclei and therefore, can provide non-destructive information about changes in local biochemical and mechanical properties of engineered tissue during the growth phase (both in vitro and in vivo) quantitatively and qualitatively.…”