Magnetization transfer in cartilage and its constituent macromolecules

Abstract

The goal of this work was to investigate magnetization transfer (MT) in cartilage by measuring water proton signals Ms/Mo, as an indicator of MT, in (i) single-component systems of the tissue's constituent macromolecules and (ii) intact cartilage under control conditions and after two pathomimetic interventions. Ms/Mo was quantified with a 12-microT saturation pulse applied 6 kHz off resonance. Both glycosaminoglycans (GAG) and collagen exhibited concentration dependent effects on Ms/Mo, being approximately linear for GAG solutions (Ms/Mo = -0.0137[% GAG] + 1.02) and exponential for collagen suspensions (Ms/Mo = 0.80 x exp[-(%collagen)/6.66] + 0.20); the direct saturation of water could not account for the measured Ms/Mo. Although the effect of collagen on Ms/Mo is much stronger than for a corresponding concentration of GAG, Ms/Mo is not very sensitive to changes in collagen concentration in the physiological range. Tissue degradation with 25 mg/ml trypsin led to an increase in Ms/Mo from the baseline value of 0.2 (final/initial values = 1.15 +/- 0.13, n = 11, P < 0.001). In contrast, a 10-day treatment of cartilage with 100 ng/ml of interleukin-1 beta (IL-1 beta) caused a 19% decrease in Ms/Mo (final/initial values = 0.81 +/- 0.08, n = 3, P = 0.085). The changes in hydration and macromolecular content for the two treatments were comparable, suggesting that Ms/Mo is sensitive to macromolecular structure as well as concentration. In conclusion, whereas the baseline Ms/Mo value in cartilage may be primarily due to the tissue collagen concentration, changes in Ms/Mo may be due to physiological or pathophysiological changes in GAG concentration and tissue structure, and the measured Ms/Mo may differentiate between various pathomimetic degradative procedures.

Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI

“…This method is applicable to a wide range of applications, from living tissue in culture on a near-histologic scale, to isolated samples in vitro, to in vivo clinical (or animal) studies. Complementary methods that provide information on collagen are under development (23)(24)(25)(26)(27)(28) and would enrich the interpretation of these studies. We now have a unique opportunity to study developmental and degenerative disease processes in cartilage and monitor the efficacy of medical and surgical therapeutic measures, for ultimately achieving a greater understanding of cartilage physiology in health and disease.…”

Quantitative MRI of cartilage and bone: degenerative changes in osteoarthritis

“…T 2 , diffusion and magnetization transfer are sensitive to the molecular structure and concentration of both collagen and GAG (161)(162)(163)(164)(165)(166). Sodium MRI was the first technique proposed for specifically imaging the GAG concentration in cartilage, based on the fact that the charged sodium ion would distribute in cartilage in relation to the concentration of the charged GAG molecules (167) and has been shown to be clinically viable (168).…”

Three‐dimensional delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) at 1.5T and 3.0T

“…Previous implementations of dGEMRIC in vivo used timeconsuming single-slice two-dimensional (2D) imaging to obtain the data necessary for the T1 map (2-7). Interleaved multislice acquisitions cannot be used because magnetization transfer effects will introduce errors into the T1 measurement (8). Therefore, it has not been possible to perform a full-joint assessment of the GAG distribution in a single imaging session.…”