Solutes In Cartilage Research Articles

MRI of articular cartilage in OA: novel pulse sequences and compositional/functional markers

Osteoarthritis (OA) is a leading cause of disability worldwide. Magnetic resonance imaging (MRI), with its unique ability to image and characterize soft tissue non-invasively, has proven valuable in assessing cartilage in OA. The development of new, fast imaging methods with high contrast show promise to improve the magnetic resonance (MR) evaluation of this disease. In addition to morphologic MRI methods, MRI contrast mechanisms under development may reveal detailed information about the physiology of cartilage. It is anticipated that these and other MRI techniques will play an increasingly important role in assessing the success or failure of therapies for OA. On December 5 and 6, 2002, OMERACT (Outcome Measures in Rheumatology Clinical Trials) and OARSI (Osteoarthritis Research Society International) held a workshop in Bethesda, MD aiming at providing a state-of-the-art review of imaging outcome measures for OA of the knee to help guide scientists and pharmaceutical companies in the use of MRI in multi-site studies of OA. Applications of MRI were initially reviewed by a multidisciplinary, international panel of expert scientists and physicians from academia, the pharmaceutical industry and regulatory agencies. The findings of the panel were then presented to a wider group of participants for open discussion. The following report summarizes the results of these discussions with respect to novel MRI pulse sequences for evaluating articular cartilage of the knee in OA and notes any additional advances that have been made since.

Diffusion and partition of solutes in cartilage under static load

We describe experimental apparatus, methodology and mathematical algorithms to measure diffusion and partition for typical small ionic solutes and inulin (a medium size solute) in statically loaded cartilage. The partition coefficient based on tissue water ( K H 2O ) of Na + increased from 1.8 to 4.5 and for SO 4 −2 decreased from 0.5 to 0.1, when the applied presure was raised from zero to 22 atm K H 2O of inulin decreased from 0.3 to 0.05, for an increase in pressure from zero to 11 atm. Our theoretical interpretation of the results is that the partition coefficient can be expressed as a function of fixed charge density (FCD) for both loaded and unloaded cartilage. The partition coefficient shows good agreement with the ideal Gibbs–Donnan equilibrium, particularly when FCD is based on extrafibrillar water (EFW). The diffusion coefficients, D̄ also decreased with an increase in applied pressure; raising the pressure from 0 to 22 atm resulted in the following changes in the values of D̄: for Na + from 2.86×10 −6 to 1.51×10 −6 cm 2/s, for SO 4 −2 from 1.58×10 −6 to 7.5×10 −7 cm 2/s, for leucine from 1.69×10 −6 to 8.30×10 −7 cm 2/s and for inulin from 1.80×10 −7 to 3.30×10 −8 cm 2/s. For the three small solutes (two charged and one neutral) the diffusion coefficient D̄ is highly correlated with the fraction of fluid volume in the tissue. These experimental results show good agreement with the simple model of Mackie and Meares: hence solute charge does not affect the diffusion of small solutes under load. For inulin D̄ & K show some agreement with a modified Ogston model based on two major components, viz., glycosaminoglycans (GAG) and core protein. We conclude that the changes in the partition and diffusion coefficients of small and medium size solutes in statically loaded cartilage can be interpreted as being due to the reduction in hydration and increase in FCD. The change in the latter affects the partition of small ionic solutes and the partition and diffusion of larger molecules. Our results throw light on the ionic environment of chondrocytes in loaded cartilage as well as on the transport of solutes through the matrix.

Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging

The ability of water and solutes to move through the cartilage matrix is important to the normal function of cartilage and is presumed to be altered in degenerative diseases of cartilage such as osteoarthritis and rheumatoid arthritis. Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) techniques were used to measure a self diffusion coefficient (D) for small solutes in samples of explanted cartilage for diffusion times ranging from 13 ms to 2 s. With a diffusion time of 13 ms, the intratissue diffusivity of several small solutes (water, Na+, Li+, and CF3CO2-) was found consistently to be about 60% of the diffusivity of the same species in free solution. Equilibration of the samples at low pH (which titrates the charge groups so that the net matrix charge of -300 mM at pH 8 becomes approximately -50 mM at pH 2) did not affect the diffusivity of water or Na+. These data, and the similarity between the D in cartilage relative to free solution for water, anions, and cations, are consistent with the view that charge is not an important determinant of the intratissue diffusivity of small solutes in cartilage. With 35% compression, the diffusivity of water and Li+ dropped by 19 and 39%, respectively. In contrast, the diffusivity of water increased by 20% after treatment with trypsin (to remove the proteoglycans and noncollagenous proteins). These data and the lack of an effect of charge on diffusivity are consistent with D being dependent on the composition and density of the solid tissue matrix. A series of diffusion-weighted proton images demonstrated that D could be measured on a localized basis and that changes in D associated with an enzymatically depleted matrix could be clearly observed. Finally, evidence of restriction to diffusion within the tissue was found with studies in which D was measured as a function of diffusion time. The measured D for water in cartilage decreased with diffusion times ranging from 25 ms to 2 s, at which point the measured D was roughly 40% of the diffusivity in free solution. Although changes in matrix density by compression or digestion with trypsin led to a decrease or increase, respectively, in the measured D, the functional change in measured diffusivity with diffusion time remained essentially unchanged. In a different type of study, in which bulk transport could be observed over long periods of time, cartilage was submerged in 99% D2O and MRI studies were performed to demonstrate the bulk movement of water out of the cartilage matrix.(ABSTRACT TRUNCATED AT 400 WORDS)